Adenoma - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References 0497000253, 9780497000257, 9781417541300

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ADENOMA A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES

J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS

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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2004 by ICON Group International, Inc. Copyright 2004 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Adenoma: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-497-00025-3 1. Adenoma-Popular works. I. Title.

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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.

Copyright Notice If a physician wishes to copy limited passages from this book for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications have copyrights. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs, or other materials, please contact us to request permission (E-mail: [email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International, Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this book.

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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on adenoma. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.

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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications. Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.

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About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes&Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health

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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON ADENOMA ................................................................................................ 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Adenoma ....................................................................................... 5 E-Journals: PubMed Central ....................................................................................................... 67 The National Library of Medicine: PubMed ................................................................................ 71 CHAPTER 2. NUTRITION AND ADENOMA..................................................................................... 117 Overview.................................................................................................................................... 117 Finding Nutrition Studies on Adenoma .................................................................................... 117 Federal Resources on Nutrition ................................................................................................. 121 Additional Web Resources ......................................................................................................... 122 CHAPTER 3. ALTERNATIVE MEDICINE AND ADENOMA .............................................................. 125 Overview.................................................................................................................................... 125 National Center for Complementary and Alternative Medicine................................................ 125 Additional Web Resources ......................................................................................................... 137 General References ..................................................................................................................... 139 CHAPTER 4. PATENTS ON ADENOMA ........................................................................................... 141 Overview.................................................................................................................................... 141 Patents on Adenoma .................................................................................................................. 141 Patent Applications on Adenoma .............................................................................................. 151 Keeping Current ........................................................................................................................ 156 CHAPTER 5. BOOKS ON ADENOMA ............................................................................................... 157 Overview.................................................................................................................................... 157 Chapters on Adenoma ................................................................................................................ 157 CHAPTER 6. PERIODICALS AND NEWS ON ADENOMA ................................................................. 167 Overview.................................................................................................................................... 167 News Services and Press Releases.............................................................................................. 167 Academic Periodicals covering Adenoma................................................................................... 171 CHAPTER 7. RESEARCHING MEDICATIONS .................................................................................. 173 Overview.................................................................................................................................... 173 U.S. Pharmacopeia..................................................................................................................... 173 Commercial Databases ............................................................................................................... 174 Researching Orphan Drugs ....................................................................................................... 174 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 179 Overview.................................................................................................................................... 179 NIH Guidelines.......................................................................................................................... 179 NIH Databases........................................................................................................................... 181 Other Commercial Databases..................................................................................................... 183 APPENDIX B. PATIENT RESOURCES ............................................................................................... 185 Overview.................................................................................................................................... 185 Patient Guideline Sources.......................................................................................................... 185 Finding Associations.................................................................................................................. 187 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 189 Overview.................................................................................................................................... 189 Preparation................................................................................................................................. 189 Finding a Local Medical Library................................................................................................ 189 Medical Libraries in the U.S. and Canada ................................................................................. 189 ONLINE GLOSSARIES................................................................................................................ 195 Online Dictionary Directories ................................................................................................... 195

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ADENOMA DICTIONARY......................................................................................................... 197 INDEX .............................................................................................................................................. 279

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FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with adenoma is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about adenoma, using the most advanced research tools available and spending the least amount of time doing so. In addition to offering a structured and comprehensive bibliography, the pages that follow will tell you where and how to find reliable information covering virtually all topics related to adenoma, from the essentials to the most advanced areas of research. Public, academic, government, and peer-reviewed research studies are emphasized. Various abstracts are reproduced to give you some of the latest official information available to date on adenoma. Abundant guidance is given on how to obtain free-of-charge primary research results via the Internet. While this book focuses on the field of medicine, when some sources provide access to non-medical information relating to adenoma, these are noted in the text. E-book and electronic versions of this book are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). If you are using the hard copy version of this book, you can access a cited Web site by typing the provided Web address directly into your Internet browser. You may find it useful to refer to synonyms or related terms when accessing these Internet databases. NOTE: At the time of publication, the Web addresses were functional. However, some links may fail due to URL address changes, which is a common occurrence on the Internet. For readers unfamiliar with the Internet, detailed instructions are offered on how to access electronic resources. For readers unfamiliar with medical terminology, a comprehensive glossary is provided. For readers without access to Internet resources, a directory of medical libraries, that have or can locate references cited here, is given. We hope these resources will prove useful to the widest possible audience seeking information on adenoma. The Editors

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From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.

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CHAPTER 1. STUDIES ON ADENOMA Overview In this chapter, we will show you how to locate peer-reviewed references and studies on adenoma.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and adenoma, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “adenoma” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: •

Preliminary Steps in the Diagnosis of the Pleomorphic Adenoma Source: New York State Dental Journal (NYSDJ). 68(5): 28-31. May 2002. Contact: Available from Dental Society of the State of New York. 7 Elk Street, Albany, NY 12207. (518) 465-0044. Summary: Patients with parotid (one of the salivary glands) swellings are often first seen in the dental office. The dental practitioner must be able to differentiate a neoplastic (new growth, including cancers) lesion from other causes of parotid swelling. Pleomorphic adenoma, or benign mixed tumor, is the most frequently occurring type of benign (not cancerous) neoplasms that involves the salivary glands. The authors of this article about the diagnosis of pleomorphic adenoma (PA) stress that knowledge of the diagnostic modalities used to determine the presence of a tumor is mandatory for dental

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care providers. The authors present a case report to illustrate the techniques that are used in the preliminary diagnosis of the benign pleomorphic adenoma. Final diagnosis awaits the microscopic examination of a surgical specimen. The PA tumor can easily and effectively be treated while in their early stage. Delay in treatment leads to a greater chance of malignant transformation (to cancer), increases the risk of recurrence, and leads to greater morbidity (associated disease or complications). 3 figures. 9 references. •

Family History of Colorectal Adenomatous Polyps and Increased Risk for Colorectal Cancer Source: Annals of Internal Medicine. 128(11): 900-905. June 1, 1998. Summary: The risk of colorectal cancer among family members of patients with this kind of cancer is well established, but the risk for family members of patients with colorectal adenomas is less well established. This article reports on a study undertaken to examine the risk of colorectal cancer among first degree relatives of patients with adenoma, compared with that among first degree relatives of controls without adenoma. The reconstructed cohort study consisted of 1,554 first degree relatives of 244 patients with newly diagnosed adenomas and 2,173 first degree relatives of 362 endoscopically normal controls. Structured interviews were used to obtain family history. The risk of colorectal cancer was elevated among first degree relatives of patients with newly diagnosed adenomas. This increased risk was the same for parents and siblings. First degree relatives of patients with adenomas did not have an elevated risk of other cancers. The risk of colorectal cancer among family members increased with decreasing age at diagnosis of adenoma in probands. Among first degree relatives of patients who were 50 or younger when the adenoma was diagnosed, the risk was more than four times greater than among first degree relatives of patients who were older than 60 when the adenoma was diagnosed. The authors conclude that first degree relatives of patients with newly diagnosed adenomas, particularly those who are 50 or younger at diagnosis, have an increased risk of colorectal cancer and should undergo screening similar to that recommended for relatives of patients with colorectal cancer. 5 tables. 34 references. (AA-M).

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Endoscopic Therapy of Colorectal Villous Adenoma Source: Endoscopy Review. 7(8): 18-20, 25. October 1990. Summary: Villous adenomas are a fairly distinctive entity among adenomatous polyps of the colon. This article discusses endoscopic therapy of colorectal villous adenoma. The author notes that when adopting an endoscopic protocol, the following limits in the methodology should be kept in mind: extension of neoplasia in depth into the digestive wall (which limits endoscopic destruction of the lesion); extension of the neoplasia in surface (which affects healing after destruction); the malignant potential of a villous adenoma; the location of the lesion; and the risk of recurrence. Specific endoscopic procedures discussed include Nd:YAG lasers, CO2 lasers, photodynamic therapy, cryotherapy, and injection of absolute alcohol. Additional topics include colonic preparation; colonic motility and pain; complications, including hemorrhage, perforation, and infection; indications for laser photodestruction; villous adenoma in the rectum, sigmoid, and proximal colon; and surveillance after laser therapy. The author concludes that laser photodestruction in colorectal neoplasia is proposed in about onethird of indications for palliation of symptoms from an advanced rectal cancer.

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Federally Funded Research on Adenoma The U.S. Government supports a variety of research studies relating to adenoma. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to adenoma. For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally funded studies use animals or simulated models to explore adenoma. The following is typical of the type of information found when searching the CRISP database for adenoma: •

Project Title: A PANHYPOPITUTITARY MOUSE MUTATION Principal Investigator & Institution: Camper, Sally A.; Professor; Human Genetics; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 01-APR-1993; Project End 30-JUN-2007 Summary: (provided by applicant): Ames (df) dwarf mice provide an entree for understanding the molecular events that regulate pituitary gland organogenesis. Mutants exhibit panhypopituitarism, or multiple pituitary hormone deficiency, failing to produce adequate amounts of prolactin, growth hormone, thyroid stimulating hormone, or gonadotropins. A missense mutation in the homeodomain of the transcription factor Propi is responsible for the defect. This partial loss of function mutation affects development of the pituitary gland early in organogenesis, causing cytodifferentiation failure of several cell types that ultimately results in a hypocellular anterior pituitary lobe. PROP1 mutations cause multiple pituitary hormone deficiency in humans as well, although the phenotype is variable, occasionally involving loss of adrenocorticotropin production. Using genetic engineering in mice we generated both null and gain of function alleles of Prop. Homozygotes for the null allele exhibit lethality with 50% penetrance, which may result from adrenal insufficiency, as observed in some human pedigrees with PROP1 mutations. Propi expression is normally restricted to a short window of pituitary development, and prolonged expression causes transient hypogonadism and delayed puberty due to delayed differentiation of pituitary gonadotropin producing cells. In addition, mice with this gain of function allele develop adult onset hypothyroidism and have increased risk of pituitary adenomas. Pituitary adenomas are the most common type of intracranial tumor in humans, although little is known about the genetic changes that lead to adenoma formation. We have delineated many of the sequential steps in the commitment process of organogenesis, placing Prop 1 in the genetic hierarchy relative to several other critical homeobox genes. During the next grant cycle we propose to characterize the Propi null allele to discover the basis for the failure of cytodifferentiation. We will dissect the interactions of Propi with pituitary

2 Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).

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transcription factors and secreted signaling molecules that are important in early development using genetics, explant and cell culture, DNA sequence analysis, and differential expression analysis. These studies will expand our understanding of pituitary organogenesis and tumorigenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ALTERNATIVE ESTROGEN REPLACEMENT THERAPY FOR COLON CANC* Principal Investigator & Institution: Campbell-Thompson, Martha L.; Pathology, Immunol & Lab Med; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 01-JUN-2005 Summary: (provided by applicant): Botanical products are becoming increasingly popular as alternatives to estrogen replacement therapy (ERT). Clinical evidence strongly supports an association between ERT and reduced risk of colon cancer in postmenopausal women. After follow-up of women taking combined estrogenprogestin replacement therapy, the Women's Health Initiative recently reported a 37% reduction in colorectal cancer cases compared to women on placebo. In another 20 published studies, half support an inverse association and another quarter shows a significant reduction in risk. Despite these findings, few investigations are underway to determine the mechanisms by which this preventive effect is achieved. Estrogenic effects are mediated by binding to a nuclear receptor and we determined that the second estrogen receptor subtype, ERbeta, is the subtype found in the colonic epithelium. Our studies also showed reduced expression of ERbeta mRNA in colon tumors compared to normal mucosa in female patients. Furthermore, following over-expression of ERbeta, human colon cancer cells displayed reduced proliferation rates and anchorage independent growth. These data imply that ERbeta could mediate the chemoprotective effects for ERT. The overall hypothesis being tested is that alternative ERT based on phytoestrogens with high ERbeta binding activity will reduce colon carcinogensis. Specific aims are proposed to test the following hypotheses: (1) Overexpression of ERbeta in human colon cancer cells will decrease tumorigenic phenotype in vitro (cells in culture) and in vivo (xenograph growth in mice) by interference of EGFR signaling pathways, and (2) A phytoestrogen-enriched diet will reduce experimentally induced aberrant crypt foci by decreasing proliferative activity in the colonic epithelium. The goal of this application is to define how activation of ERbeta-mediated responses can modulate human colon cancer cell growth and whether a red clover extract with ERbetaselectivity can decrease carcinogen initiated colon tumorigenesis. If phytoestrogens show a chemopreventive effect on colon cancer development and the mechanism is related to ERbeta, these data would clearly expand our understanding of colon cancer and provide a new therapeutic strategy. The ability to pinpoint how an alternative ERT inhibits the adenoma-carcinoma sequence could also lead to more effective methods in preventing cancer recurrence in female patients, as well as developing better chemoprevention strategies in post-menopausal women. The clinical translational potential of this hypothesis lies in the ability of ERbeta positive epithelial cells to respond to phytoestrogens. These results would also suggest additional potential for chemoprevention strategies based on selective estrogen receptor (ERbeta) therapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ANALYSIS OF THE PROTEOME IN HUMAN PITUITARY TUMORS Principal Investigator & Institution: Desiderio, Dominic M.; Professor of Neurology; Neurology; University of Tennessee Health Sci Ctr Memphis, Tn 38163

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Timing: Fiscal Year 2002; Project Start 15-JUN-2001; Project End 31-MAY-2006 Summary: (Adapted from applicant's abstract) The human pituitary proteome includes all proteins that are expressed in the given time. Unlike a genome, the proteome is not fixed, but it changes depending on the conditions. Proteome science (proteomics) employs a combination of state-of-the-art separation techniques, mass spectrometry, and bioinformatics for the study of proteomes. A promising prospect is the application of proteome research for the investigation of tumor pathologies. Qualitative and quantitative changes in the proteome that are associated with tumor formation can be monitored by a comparison of healthy (control) vs. tumor tissue, and the proteins of interest can be characterized, Here, the proteomics approach will be applied to the study of the proteome in human pituitary macroadenomas (hormonally silent tumors). The objective of the proposed research program is to generate a two-dimensional reference map of human pituitary proteins, and to characterize the proteins whose expression is modified in pituitary macroadenomas. The proteins will be separated by twodimensional gel electrophoresis, and the 2D maps will be digitized. 2D gel images from control versus tumor proteomes will be compared, and protein spots will be quantified. The proteins whose abundance is altered in pituitary tumors will be identified and characterized. The protein of interest will be digested, and the masses of the resulting peptides will be measured by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Amino acid sequence of the peptides will be determined by electrospray-ion trap mass spectrometry. Using these peptide-mapping and/or sequencing data, the protein will be identified by searching a protein sequence database. Characterization of differentially expressed pituitary proteins will also include a detailed investigation of changes in posttranslational protein modifications. In addition, a number of prominent proteins from the control pituitary proteome will also be characterized, and a 2D reference database of the human pituitary will be constructed. Knowledge of the changes in protein expression in pituitary macroadenomas will help clarify fundamental mechanisms of macroadenoma formation, which may lead to the development of more effective means to treat and manage these tumors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BIOLOGY AND DIAGNOSIS OF HNPCC Principal Investigator & Institution: Boland, C. Richard.; Chief; Medicine; University of California San Diego La Jolla, Ca 920930934 Timing: Fiscal Year 2002; Project Start 10-MAY-1996; Project End 31-JAN-2003 Summary: Hereditary non-polyposis colorectal cancer (HNPCC) is caused by a germline mutation in one of the DNA mismatch repair (MMR) genes. Tumors that develop in a person with HNPCC have a very large number of microsatellite instability (MSI). Approximately 15% of all colorectal cancers have MSI and in most instances this is due to acquired genetic defects in the DNA MMR system, rather than a germline mutation. Therefore, in addition to being perhaps the most common form of an inherited predisposition to cancer, HNPCC has been a model for the understanding of genomic instability in sporadic tumors. We are interested in HNPCC for two reasons. First, our laboratory has established in vitro models in which to study the biology of normal DNA MMR activity and how mutations in the MMR genes affect the cell cycle. Secondly, as a laboratory dedicated to transnational investigation, we are interested in the clinical side of HNPCC. A central theme of this application is that we can find the germline basis of HNPCC in only about half of such families. We have hypothesized that there are additional genes participating in the DNA MMR system that may be responsible for HNPCC. We have data suggesting that there is another DNA MMR gene on

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chromosome 3. We have hypothesized that different types of mutations in the known HNPCC genes alter the DNA MMR system in different ways which may be responsible for the various phenotypes seen in this disease. We are part of the UC Irvine-UC San Diego collaborative Cancer Genetics Network, which will provide us with a large data base of familial colorectal tumors. We will use this data base to obtain tumor tissue and blood from patients with familial forms of colorectal cancer. We will first determine whether all colorectal cancers can be divided into one of the two known mechanisms of genomic instability. We will look for new germline mutations that might be responsible for HNPCC. Finally, we will microdissect tumors with MSI and determine which genes are mutated in the tumor progression sequence. We have hypothesized that the traditional "gatekeepers" for adenoma formation and conversion to carcinoma may not be the same as those that occur in tumors without MSI. In summary, we propose to study the basic biology of the DNA MMR system in vitro, and use this information to develop insight into the clinical behavior and the diagnostic strategies for HNPCC, predisposition to cancer, HNPCC, has been a model for understanding genomic instability in sporadic tumors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CA2+-RECEPTOR: IMMUNE MODULATION IN VIVO AND IN VITRO Principal Investigator & Institution: Brown, Edward M.; Professor of Medicine; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2008 Summary: (provided by applicant): Autoimmunity is the cause of several common endocrine disorders. Graves' disease and nongoitrous hypothyroidism are examples of diseases caused by activating and inhibitory antibodies, respectively, to a G proteincoupled cell surface receptor (GPCR). The extracellular calcium-sensing receptor (CaR) is a GPCR that plays a crucial role in maintaining mineral ion homeostasis by virtue of its capacity to sense small changes in the extracellular ionized calcium concentration (Ca2+o). The physiological relevance of the CaR was established by the discovery of patients with activating or inactivating mutations that produce hypo- or hypercalcemic conditions, respectively. The former is termed autosomal dominant hypocalcemia (ADH) and the latter familial hypocalciuric hypercalcemia (FHH). Similar to inactivating or activating mutations, there might be patients with inactivating or activating antibodies to the CaR. Indeed, we recently described 4 patients with inactivating antibodies to the CaR, three of whom had a picture of FHH while one had biochemical findings more like primary hyperparathyroidism (PHPT). Surprisingly, further preliminary studies have identified inactivating antibodies in two individuals who had undergone removal of a parathyroid (PT) adenoma for a diagnosis of PHPT, raising the possibility that anti-CaR antibodies can contribute to the development of PHPT in a subset of patients. Additional preliminary studies have also identified two hypocalcemic individuals with activating antibodies to the receptor, who have a biochemical picture compatible with hypoparathyroidism. The overall goal of this proposal is to document that activating and inactivating CaR antibodies can cause forms of hypoparathyroidism and PTH-dependent hypercalcemia, respectively, that should be distinguished from other causes of these disorders and may be amenable to specific CaR-based medical therapy. The following aims are addressed at achieving this goal: (1) To identify and characterize inactivating antibodies to the CaR in persons with PTH-dependent hypercalcemia. (2) To identify and characterize activating antibodies to the CaR in

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persons with hypoparathyroidism. (3) To develop an animal model of activating and/or inactivating antibodies by immunization with the CaR's extracellular domain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CALCIUM IN THE PREVENTION OF NEOPLASTIC POLYPS Principal Investigator & Institution: Baron, John A.; Professor of Medicine; Medicine; Dartmouth College 11 Rope Ferry Rd. #6210 Hanover, Nh 03755 Timing: Fiscal Year 2002; Project Start 30-SEP-1988; Project End 31-DEC-2003 Summary: This application, a resubmission for the renewal of "Calcium Prevention of Neoplastic Polyps," is a proposal to collect further information on subjects in our randomized, placebo-controlled trial of calcium supplementation for the prevention of colorectal adenomas. The study began in response to animal and human experimental data and some epidemiological findings suggesting that calcium intake may exert a protective effect on large bowel neoplasia. The trial studied whether supplementation with calcium carbonate (1200 mg calcium per day) prevented the recurrence of colorectal adenomas in 930 patients with a recent history of these tumors. Treatment in the trial ended in December, 1996. Calcium lowered the risk of any recurrent adenoma by 18% (95% CI 0.66-0.98), and reduced the number of adenomas by 25% (95% CI 0.550.94). We now propose to investigate whether the effect of calcium persisted beyond active treatment, or if there was a subsequent rebound. We also plan to study some related biological mechanisms. Studies of calcium supplementation and mucosal proliferation in the bowel have been conflicting, but the relationship between calcium intake and apoptosis has been investigated and merits study. Further evidence that dietary calcium may preferentially affect the risk of adenomas harboring ras mutations needs confirmation. As well, animal models and some epidemiological data suggest that vitamin D may protect against bowel carcinogenesis. We propose to investigate this in the context of our trial, and to examine polymorphisms in the vitamin D receptor gene. With the funds requested here, we will use our established subject population and available biological specimens to study these mechanisms. We will follow the subjects in the study until the year 2003, monitor their medical history, and track adenoma recurrence after the end of treatment in the trial. All subjects provided blood specimens at study entry and at study exit. Using these samples, we will measure 25-OH vitamin D and 1,25-OH vitamin D to document how calcium supplementation affected these levels, and how the baseline levels and polymorphisms in the vitamin D receptor related to adenoma occurrence. We will also obtain slides from each adenoma detected during the risk period of the trial or during the additional follow-up period and investigate the association between calcium treatment and ras mutation. Finally, we propose to conduct a pilot study in preparation for a study of calcium supplementation and apoptosis both in normal rectal mucosa and in adenomas. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CHEMOPREVENTION OF DUODENAL POLYPS IN FAP Principal Investigator & Institution: Disario, James A.; Associate Professor; Huntsman Cancer Institute; University of Utah Salt Lake City, Ut 84102 Timing: Fiscal Year 2003; Project Start 01-JUN-1999; Project End 31-MAR-2005 Summary: (provided by applicant): This is a Phase II/lll study to evaluate the effects of exisulind for treatment on duodenal adenomatous polyps and on adenoma and mucosal apoptosis assays in Familial Adenomatous Polyposis (FAP) patients who have had colectomy or Attenuated Adenomatous Polyposis Coli (AAPC) patients whom may or

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may not have undergone colectomy. These subjects have a defined high genetic risk of developing duodenal cancer (relative risk 300). This is a double blind, placebo controlled, single center study. One hundred subjects, fifty each arm, will be enrolled. Eligible subjects who harbor 10 to 40 duodenal polyps within a measured segment are randomized to receive exisulind 150 mg p.o. qid or an identical placebo for the duration of one year. (Persons with AAPC whom still have colon intact will receive 200 mg bid for the same duration. Gastroduodenoscopy will be performed at baseline to assess polyp status and place, where applicable, a tattoo 10 cm beyond the papilla of Vater. Duodenal polyps are mapped for number and size at baseline and at follow up at year one. Polyp and mucosal biopsies will be obtained for apoptosis. Subjects are contacted bi-monthly for assessments. Drug is dispensed every three months and a pill count is recorded monthly. Chemistries, CBC and urinalysis is performed at baseline and at 1, 3, 6 and 12 months. A beta-HCG is performed initially on all fertile women. The NCI common toxicity criteria is employed to detect toxicities and an external Data Safety Monitoring Committee serves to review all adverse events and any protocol issues. A 5year study is proposed. The randomized treatment period is 1 year. There will be a 6 month termination phase to include data analysis, manuscript preparation and closure of all study procedures. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHEMOPREVENTION OF EARLY PULMONARY LESIONS IN MICE Principal Investigator & Institution: Malkinson, Alvin M.; Professor; Pharmaceutical Sciences; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2002; Project Start 28-JUN-2002; Project End 31-MAY-2005 Summary: (provided by applicant): At UCHSC, we have assembled mature Genomics and Proteomics and mouse carcinogenesis groups to study preclinical chemoprevention of lung cancer in former-smokers. Our rationale is that anti-inflammatory drugs inhibit chemically-induced lung tumorigenesis, early lung lesions are reversible, and no verified biomarkers exist for human lung neoplasia. Mouse hyperplastic foci and microadenomas model the small nodules present in the lungs of former smokers, and a better understanding of the progression to cancer will lend insight into human lung cancer chemoprevention. A two-stage carcinogenesis regimen, in which 3methylcholanthrene (MCA) is injected ip followed by four weekly ip doses of butylated hydroxytolulene (BHT), induces these lung lesions in male BALB mice. Budesonide, a synthetic glucocorticoid, and three other anti-inflammatory drugs, each with a unique mechanism of action, will be administered (orally) singly and in combination after foci and microadenomas have developed. The three other drugs are LM4111 (a COX-2 specific inhibitor), PBIT (an iNOS-specific inhibitor), and Iloprost (a stable prostacyclin agonist). The number of foci, and the number and sizes of microadenomas and pleural surface adenomas will be quantified at established time points up to 20 weeks after the MCA injection. Several proteins whose expression increases in early mouse lung lesions will be examined by immunohistochemistry to see if they can predict successful chemoprevention. These include pro-inflammatory enzymes (COX-1, COX-2, and iNOS) and hnRNP proteins (AUF1 , HuR, and A1). We have combined two global strategies, genomics and proteomics, as discovery tools for novel surrogate markers. RNA and protein expression patterns will be examined by microarray, LC/MS/MS, and 2DPAGE/MS analyses, respectively. Expression in normal lungs will be compared with dissectable adenomas, and then our analyses will move proximally to examine samples more practically obtainable from humans (bronchoalveolar lavage cells and fluid, and

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serum). Our goals are: (1) to successfully inhibit lung tumor progression when antiinflammatory drugs are applied after early lesions have forms; and (2) to identify novel early-stage predictive biomarkers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHEMOPREVENTION OF TOBACCO RELATED CANCER IN ANIMALS Principal Investigator & Institution: Pereira, Michael A.; Director; Pathology; Medical College of Ohio at Toledo Research & Grants Admin. Toledo, Oh 436145804 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2005 Summary: (provided by applicant): Our overall goal is to develop biomarkers for chemoprevention studies of cigarette smoke-related cancers that can be translated to clinical studies in former smokers. To obtain this aim, we propose: Specific Aim 1: Develop biomarkers for chemoprevention of lung cancer in former smokers using a mouse model for lung cancer and related biological and molecular alterations; and Specific Aim 2: Develop biomarkers for chemoprevention of bladder cancer in exsmokers using a rat model for urinary bladder cancer and associated biological and molecular alterations. Our hypothesis is that chemopreventive agents will decrease cancer incidence by modulating and reversing biological and molecular alterations in phenotypically normal tissue, precancerous tissues and tumors. Further, we hypothesize that the modulation of the biological and molecular alterations can be developed as biomarkers for chemoprevention in animal and clinical studies including studies in former smokers. To accomplish Aim 1, lung tumors will be induced in strain A mice by exposure to cigarette smoke, benzo(a)pyrene and 4-(Methyl nitrosamino)-1-(3- pyridyl)1-butanone (NNK) and to accomplish Aim 2, bladder tumors will be induced in F344 rats by N-butyl-N-hydroxybutyl)nitrosamine (OH-BBN). After exposure to the carcinogens including cigarette smoke has ceased the animals will be administered the chemo-preventive agents: budesonide and the farnesyl transferase inhibitor, R115777 in the lung studies and budesonide, ketoprofen and sulindac in the bladder study. Biological and molecular alterations of cell proliferation, apoptosis, methylation of genes (both hypomethylation of protooncogenes and hypermethylation of tumor suppressor genes) and alteration in mRNA and protein expression will be determined in phenotypically normal tissues, precancerous lesions and tumors at different times during the progression to cancer. The ability of the chemopreventive agents to modulate and reverse these biological and molecular alterations in tissue and lesions will be determined in parallel with the ability of the agents to prevent cancer. Thus, biological and molecular alterations that are modulated in parallel with the prevention of cancer by the chemopreventive agents will be indicated as biomarkers for chemoprevention studies including those in former smokers where the agents will similarly be administered after exposure to cigarette smoke had ceased. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CHEMOPREVENTIVE RESPONSES TO INHALED ISOTRETINOIN Principal Investigator & Institution: Dahl, Alan R.; Senior Research Scientist; Battelle Memorial Institute 505 King Ave Columbus, Oh 43201 Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 31-DEC-2002 Summary: (provided by applicant): Former and current smokers and individuals who have been successfully treated for aerodigestive cancer would greatly benefit from drugs that prevent progression of lung neoplasia. This group of people is vast,

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comprising over one-third of the adult population of the United States. Isotretinoin exhibits excellent potential as a lung cancer chemopreventative in vitro and for this reason has been the subject of a number of clinical trials, with generally disappointing results. We reasoned that the discrepancy between lab and clinic could be explained by pharmacokinetics-orally administered isotretinoin is >99 percent bound by blood protein, leaving too little to diffuse to the target lung epithelium-and we conducted a pilot study with inhaled isotretinoin aerosol in carcinogen-treated A/J mice, with quite promising results. From this and other pilot studies, we found that: retinoic acid receptor (RAR) upregulation in the lungs correlated with efficacy; inhaled isotretinoin did not upregulate liver RARs; and, oral isotretinoin upregulated liver, but not lung, RARs. Based on these observations and in vitro results, we derived a hypothesis for the mechanism of action: upregulated RARs inhibit the growth-stimulating action of AP-1 whose activity in the absence of an inhibitor would be increased via a Ras initiated cascade. The proposed research will test the hypothesis in NNK-treated A/J mice by determining AP- 1 DNA binding activity and upregulated biomarker proteins or mRNAs in both isotretinoin-exposed and unexposed animals. In addition, RAR upregulation as a direct predictor of efficacy will be examined and the possibly complex relationships between inhaled dose and efficacy will be explored. RAR and RXR upregulation and other endpoints will be determined in the lungs of mice exposed to a range of pulmonary doses for up to 11 days. In long-term exposures of up to 34 weeks, tumor multiplicities will be determined in addition to biomarkers. Completion of the proposed research will have a number of benefits including: providing a paradigm for studying inhaled drugs that may act similarly to isotretinoin; validating RAR levels as an indicator of an efficacious dose; and dose guidance for potential studies in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COLON POLYP SURVEILLANCE WITH DNA ANALYSIS OF STOOL Principal Investigator & Institution: Schoenfeld, Philip S.; Assistant Professor of Medicine; Internal Medicine; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 24-SEP-2002; Project End 30-JUN-2004 Summary: Clinical practice guidelines state that individuals with a history of colon adenomas should undergo surveillance colonoscopy to identify and remove newly formed colon adenomas. Cost-effectiveness studies suggest that the cost of repeated surveillance colonoscopies drives the cost of colorectal cancer prevention, and surveillance colonoscopy is also associated with significant endoscopic complications. Therefore, it is preferable to develop accurate, non-invasive, and more economical surveillance tests. Multi-target DNA-based assay panels (MTAP) of stool may accurately diagnose colon adenomas. Small preliminary studies (n=39) demonstrate that fecal MTAP accurately diagnoses colon adenomas> 10 mm in diameter (sensitivity = 82 percent (95 percent Cl: 48 percent-98 percent); specificity = 93 percent (95 percent Cl: 76 percent-99 percent)). If this non-invasive test truly mimics the accuracy of the goldstandard test, surveillance colonoscopy, then fecal MTAP may offer a safer and more economical approach to colon adenoma surveillance. However, no studies about the diagnostic accuracy of fecal MTAP have been performed among patients with a personal history of colon adenomas. It is also important to assess patient satisfaction and anxiety associated with fecal MTAP vs. colonoscopy since this test must also be acceptable to patients in order to be effective. Therefore, we propose an observational study about the diagnostic accuracy of fecal MTAP for colon adenomas among 405 patients with a personal history of colon adenomas. Surveillance colonoscopy will be

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used as the gold standard diagnostic test for identification of colon adenomas. Results of surveillance colonoscopy will be compared to results of fecal MTAP to determine the diagnostic accuracy of fecal MTAP for colon adenomas. Patient satisfaction and anxiety for colonoscopy vs. fecal MTAP as a surveillance tool will also be assessed. The three Specific Aims of this trial are to: 1) Measure the diagnostic accuracy (i.e., sensitivity, specificity, positive and negative predictive values) of fecal MTAP for colon adenomas (any size) among a cohort of individuals with a personal history of colon adenomas; 2) Quantify the diagnostic accuracy of fecal MTAP for colorectal cancers and advanced adenomas (adenoma> 10 mm in diameter, villous adenoma, or adenoma with highgrade dysplasia) among a cohort of patients with a personal history of colon adenomas; 3) Use appropriate questionnaires to assess patient satisfaction and anxiety for fecal MTAP vs. colonoscopy as a surveillance tool. Ultimately, this trial will produce pilot data to determine if a randomized controlled trial of fecal MTAP vs. colonoscopy for colon adenoma surveillance should be performed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MODELING

COLORECTAL

CANCER

SURVEILLANCE

WITH

MISCAN

Principal Investigator & Institution: Zauber, Ann G.; Associate Attending Biostatistician; Sloan-Kettering Institute for Cancer Res New York, Ny 100216007 Timing: Fiscal Year 2002; Project Start 13-SEP-2002; Project End 31-AUG-2006 Summary: (provided by applicant)Despite recent declines in both mortality and incidence, colorectal cancer is currently the third most common cancer diagnosed and the third leading cause of cancer death in the United States for both men and women. It is not known to what extent this decline is attributable to changes in use of screening, changes in exposures to "lifestyle" risk and protective factors, changes in treatment, or combinations of these factors. Theoretically more than 50% of colorectalcancer could be prevented by modification in screening, lifestyle, and chemoprevention practices. Mathematical modeling of the colorectal cancer incidence and mortality rates over time can estimate the separate and joint effects of screening, lifestyle changes, and changes in treatment for different subgroups of the population. The Department of Public Health, Erasmus University Rotterdam, has developed a comprehensive micro-simulation model of the adenoma-carcinoma sequence for colorectal cancer (MISCAN) which has been used to assess the potential effects of screening interventions and can incorporate varying risk groups in its description and outcomes. This model simulates a full dynamic population which makes it particularly suitable for surveillance of population trends. We will refine this model further to include more flexibility for risk strata and to incorporate the advanced adenoma as the intermediate marker for colorectal cancer risk, and to allow for differential survival post-diagnosis based on treatment. The key question we plan to address concerns the impact of colorectal cancer screening on mortality trends. The specific aims of this study are to 1) update and refine the MISCAN model with best estimates of risk factors, screening, and treatment practices; 2) use the MISCAN microsimulation model to estimate the absolute and relative contribution of colorectal cancer screening, risk factors, and improved therapy on observed colorectal cancer incidence and mortality trends; 3) use the MISCAN model to predict how changes in colorectal cancer screening and treatment practices will affect future incidence and mortality. This study will provide an understanding of the absolute and relative contribution of screening, lifestyle factors, and improved therapy on incidence and mortality trends. This is essential for directing medical and public health resources to the most effective interventions in the appropriate risk groups.

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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CONTRAST ASSISTED ULTRASOUND IMAGING OF TUMORS Principal Investigator & Institution: Ferrara, Katherine W.; Professor; Biomedical Engineering Div; University of California Davis Sponsored Programs, 118 Everson Hall Davis, Ca 956165200 Timing: Fiscal Year 2002; Project Start 11-DEC-1997; Project End 30-NOV-2002 Summary: Second and third generation ultrasonic contrast agents have created an exciting new opportunity to image local microvascular perfusion. Physicians and physiologists have long recognized the significance of tissue perfusion, however, important questions remain unanswered due to the lack of assessment tools. Our initial observations show promise for a new family of diagnostic tools that could be applied to assess cancer, cardiovascular disease, glaucoma and wound healing. The techniques described in this proposal could provide the opportunity to map microvascular density and heterogeneity at the correct scale for the detection of tumors and to assess the maximum local microvascular transit time. Using a unique new experimental system, we have established that a set of physical phenomena affect the scattered signal from ultrasound contrast agents, and provide significant opportunities for new tools for the assessment of vascular function as well as structure. In this application, we propose to extend these studies to evaluate these effects through intravital microscopy, and to take advantage of these phenomena to tailor a new imaging mode to assess vascular density and microvascular transit time. Due to our expertise in tumor vascularity, we propose to focus our investigations on applications in this area. However, the proposed techniques could have far wider clinical application. We propose to map vascular density and transit time. A new mode called recovery imaging will be employed in which microbubbles are destroyed in a local region and the timing for echo restoration determined. These new methods will be evaluated in phantoms, through intravital microscopy in an ischemic rat model, and in a final comparative study of four mouse tumor cell lines and a benign fibroadenoma model. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CORE--CELL AND TISSUE PATHOLOGY FACILITY Principal Investigator & Institution: Bernstein, Harris; University of Arizona P O Box 3308 Tucson, Az 857223308 Timing: Fiscal Year 2002 Summary: APPLICANT'S Core A will provide endpoint analyses for experiments involving apoptosis in both cell culture systems and in animal and human tissues. Apoptosis analyses for cell culture will include bright field examination (LM) using Romanowsky-type dyes or polychrome stains and transmission electron microscopy (TEM). Apoptosis will be quantitated in animal and human colonic specimens using light microscopy. The core will be responsible for maintaining and testing flat mucosa from colon resections and from colonoscopies (from cancer patients, adenoma patients, and "normal" patients). Tests would include measurements of apoptosis and specific proteins of interest to the project directors. We will use fluorochrome tags on secondary antibodies to detect specific proteins in conjunction with Leica Laser Scanning Confocal Microscopy (LSCM), or produce permanent slides using immunohistochemical procedures. By these approaches we will identify and quantify gene products of significance to the three projects, including proteins which may prove valuable as biomarkers of colon cancer risk (e.g. Hsp70, Cox-2, Gadd153, and others. Quality control

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studies will be performed to measure expression of potential biomarkers in each of the different regions of the colon of normal individuals as a basis for identifying abnormal expression in high risk individuals. The core will also measure expression of potential biomarkers in the normal appearing mucosa of cancer patients at various distances from the cancer. The core will establish, maintain, subclone and test apoptosis resistant colonic epithelial cell lines for altered gene expression. Cellular effects of chemopreventive agents, of other drugs and of transfections will be evaluated by microscopic methods applicable to the particular experimental situation. Procedures to be made available are ultrastructural cytochemistry (including cryosectioning), fluorescent apoptosis/necrosis assay, bright-field examination of cytospin preparations, semi-thin plastic sectioning, and paraffin embedding. The core will also assist in developing special microscopic procedures to answer specific questions that emerge as experimental data are obtained and analyzed. Two experienced research specialists will be available in the core to provide this assistance. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORE--HUMAN TISSUE RESOURCE AND LOGISTICS Principal Investigator & Institution: Montgomery, Elizabeth A.; Associate Professor; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2007 Summary: (provided by applicant): The purpose of this shared resource is to provide human tissues and expert pathologic interpretation for investigators on all of the projects under the direction of expert pathologists. The Histopathology and Tissue/Biological Fluids Resource has been in existence since 1986 and expanded under the support of the GI SPORE. At the end of the year 2000, the Resource includes 1495 banked colorectal carcinoma resection specimens, 306 colorectal adenoma samples, 207 hepatic metastases of colorectal carcinoma, 702 pancreatic carcinoma specimens, 401 xenografts of colorectal carcinoma, 6 pancreatic carcinoma xenografts, 4252 blood specimens from individuals at risk for colorectal carcinoma, and 120 blood specimens from patients with pancreatic cancer. Paraffin-embedded material is also available on the cases with frozen materials and clinical and outcome data are available for the vast majority of resection specimens. Further, the Core includes a collection of 74 pancreatic biopsy specimens (paraffin-embedded) with clinical follow-up and known DPC4 status and a collection of 101 cytologic specimens from pancreatic carcinomas with known clinical outcome and k-ras, p53 and DPC4 gene status. 123 stool specimens are stored from patients with known outcome. Recently 34 pancreatic juice specimens have been collected from patients with a variety of pancreatic diseases. Ten fully characterized pancreas carcinoma cell lines have been prepared from human tumors and reported to ATCC and another 6 lines are fully developed. The various specimens are harvested and banked efficiently for the molecular analyses proposed in the SPORE. Distribution of these specimens to SPORE investigators has resulted in over 100 publications concerning colorectal and pancreatic carcinoma. Furthermore, the pathology expertise developed through this core has been successfully exported to other centers. For example, SPORE support was instrumental in the establishment of an internationally accepted set of morphologic criteria for the categorization of precursor lesions of the pancreas. This resource provides for the procurement of fresh frozen pancreatic carcinomas and for collection of blood and pancreatic juice as well as for expert pathologic consultation to investigators. The resource further supports xenografting of colorectal and pancreatic carcinomas into nude mice. Clinical and family histories are entered into a computerized database that is managed through this core. A mechanism

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Adenoma

is in place for prioritization of distribution of requested resources to investigators within and external to the Johns Hopkins GI cancer SPORE. Collaboration with investigators at other centers allows the accrual of rare tumor types. Specimens are collected under the supervision of pathologists with expertise in pancreatic neoplasia in close collaboration with clinical specialists in these areas and in similarly close collaboration with basic research investigators to maximize translational impact of the projects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORE--MEASUREMENT Principal Investigator & Institution: Selhub, Jacob; Harvard University (Sch of Public Hlth) Public Health Campus Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 18-SEP-2003; Project End 31-AUG-2008 Summary: The overall goal of the core laboratory is to provide measurements of blood and other biological samples for the assessment of folate and one carbon metabolism states. Our working hypothesis is that assessing these states is best attained by multiple measurements. These measurements are divided into a number of categories: 1) Measurement of blood vitamin levels. 2) Measurements of blood total homocysteine level, as a functional indicator of B vitamin status particularly folate (and B12) 3) Measurements of genomic DNA methylation, which provides an insight into folate (and other B vitamins) status, particularly as it relates to the C667T mutation in the MTHFR gene, and as a possible biomarker for colorectal adenoma 4) Measurements of uracil misincorporation into DNA which is an indication of a low folate (and other B vitamins) status, and as a possible biomarker for colorectal adenoma and 5) measurements of folate form distribution in cell extracts, which provides an insight of relative rates of one carbon flow into the various metabolites. The specific aims are: To use the methods which have been routinely used in our lab in samples provided by the various sites, for the determination of plasma and red blood cell folates (microbial assays), plasma vitamin B12 (radiometric assay), plasma pyridoxal 5'-phosphate (radioenzymatic assay), plasma B2 (HPLC with fluorimetric detection) and plasma homocysteine (HPLC with fluorimetric detection). To compare folate, B12, PLP, B2 and tHcy values in representative plasma samples, between our laboratory and that of Dr Per Magnum Ueland from the University of Bergen in Norway and determine common denominators, that will allow integration of data from the EPIC study with those from the US. To determine in circulating lymphocytes and colorectal biopsies, genomic DNA methylation using our newly developed method which is based on the determination of methylcytosine concentration in hydrolyzed DNA using LCMS. To determine in circulating lymphocytes and colorectal biopsies, uracil misincorporation into DNA using GCMS of hydrolyzed DNA. To determine in same colorectal biopsies folate forms distribution using our new affinity/HPLC method for the assessment of folate status in these biopsies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CORE--TISSUE CORE Principal Investigator & Institution: Washington, Mary K.; Professor of Pathology; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 24-SEP-2002; Project End 30-APR-2007 Summary: (provided by applicant): The specific aims of this proposal are 1)To collect, process, bank, and distribute human colorectal neoplasms and matched normal tissue samples to investigators in the Vanderbilt University Medical Center (VUMC) GI

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SPORE and other GI SPORES; 2) To collect and bank biopsies of grossly normal mucosa and mucosa adjacent to adenomas to facilitate research in adenoma recurrence; 3) To perform quality control to ensure that the relevant tissue is supplied to the researcher, and that tissues are suitable for the planned research (not necrotic or involved by unsuspected disease processes); 4) To protect patient confidentiality through use of an explicit pre-surgical consent form that specifically addresses use of extraneous tissue for research purposes and through de-identification of specimens, or through anonymization of specimens if informed consent is waived; 5) To work with the Biomedical Informatics Core to establish an informatics strategy for networking of requests, specimen tracking, and for extraction of de-identified data relating to specimens of interest. The Biomedical Informatics Core will help identify suitable specimens from the pathology archives, either by diagnosis, histologic features, demographics, clinical features, or other outcomes data, and will develop and maintain a centralized database of prospectively collected and banked specimens; 6) To provide laser microdissection services to the GI SPORE investigators; 7) To provide tissue microarray services to the GI SPORE investigators; 8) To provide correlation of tumor morphology with image mass spectroscopy findings 9)To provide expertise in evaluation of histopathology of mouse models of colorectal neoplasia and correlation with human disease; 10)To provide expertise in developing, performing and evaluating immunohistochemical stains for G1 SPORE investigators. Establishment of a GI SPORE Tissue Core at VUMC will build upon two already established mechanisms for tissue collection: the Tissue Acquisition Shared Resource of the Vanderbilt-Ingram Comprehensive Cancer Center (VICCC) and the Tissue Collection Core for the Program Project Grant Molecular Mechanisms of Chemoprevention of Colorectal Cancer by ArSAIDS (hereafter referred to as the COX-2 PPG), and a third mechanism in development, the newly-awarded VUMC-led site for the Cooperative Human Tissue Network (CHTN). Mechanisms for collection of human GI tissue and quality assurance are already in place and are used on a daily basis. By building upon the infrastructure of the VUMC CHTN, which collects tissue at three additional hospitals, a large number of GI specimens will be captured that would otherwise be unavailable for the GI SPORE. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORE--TISSUE PROCUREMENT AND CULTURE Principal Investigator & Institution: Noble, Mark D.; Professor; University of Utah Salt Lake City, Ut 84102 Timing: Fiscal Year 2002 Summary: The Tissue Procurement and Culture Core will support investigation broadly within the Program by processing tissues and providing cultures of colon epithelium ranging from normal to fully transformed cells. Well- characterized growth protocols for colonic epithelial cells will be used to establish cultured from all biopsies obtained. These will include specimens derived from normal colon, from adenomas and from carcinomas. Of specific concern is to develop cell cultures from patients with APC, HNPC and sporadic polyps and malignancies. In addition, this Core will be responsible for analyzing antigenic markers of colon differentiation in the resulting populations, so as to provide the analytical laboratories with well-characterized populations for their research efforts. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Adenoma

Project Title: DIET, GENETIC SUSCEPTIBILITY AND COLORECTAL NEOPLASIA Principal Investigator & Institution: Le Marchand, Loic; Professor; None; University of Hawaii at Manoa Honolulu, Hi 96822 Timing: Fiscal Year 2002; Project Start 19-SEP-1997; Project End 31-JUL-2007 Summary: (provided by applicant): Smoking, overnutrition and a high red meat and low folate and calcium diet have been associated with colorectal cancer (CRC) and adenoma. The epidemiologic features of CRC among migrants and native populations in Hawaii suggest the modifying effects of genetic susceptibility factors on most of these associations. Taking advantage of the genetic and dietary diversity of our population, we have made good progress in investigating specific gene variants that affect one's capacity to bioactivate dietary carcinogens or utilize one-carbon groups for DNA synthesis or methylation. We also showed that a genetic variant associated with lower circulating IGF-I hormones may protect against colorectal neoplasia. We seek to renew grant 1 -R01-CA72520 to extend a case-control study of colorectal adenoma in order to test these gene-diet interactions in a large series of adenoma cases and controls, as well as to examine several new variants in these pathways in relation to adenoma, as well as CRC using existing samples/data from a companion study. New aims also include discovering new SNPs and mapping haplotypes in major genes related to the activation of heterocyclic amines and assessing population stratification in our subjects using random genetic markers. A diet and lifestyle questionnaire will be administered in person to another 904 new adenoma cases and 904 endoscopically normal controls (for a total study sample of 1,204 adenoma cases and 1,404 controls) frequency-matched on age, sex, race/ethnicity, date and mode of endoscopy. Usual consumption of meat and fish items prepared by high-temperature methods and doneness of meats will be assessed, in addition to estimating the total intake of energy, nutrients, and other dietary components. Subjects will be phenotyped for several P450 enzymes by caffeine challenge. A blood sample will also be collected to genotype subjects for variants in a number of genes related to growth hormones, carcinogen activation and folate metabolism. Sequencing of genes related to heterocyclic amine activation in colorectal cancer patients of Japanese, Caucasian, African American, Latino or Native Hawaiian origin will allow for the construction of haplotypes. Correlations with CYP1A2 phenotype will help to select functional haplotypes which will then be tested for associations with adenoma and colorectal cancer. Genotyping for random markers will permit to exclude residual confounding by ethnicity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DIETARY HETEROCYCLIC AMINES, GENETIC SUSCEPTIBILITY, AND Principal Investigator & Institution: Martinez, Maria Elena.; Associate Professor; None; University of Arizona P O Box 3308 Tucson, Az 857223308 Timing: Fiscal Year 2002; Project Start 30-SEP-1998; Project End 29-SEP-2004 Summary: (Applicant's Description) A number of studies on the molecular genetics of colorectal cancer have revealed that mutations and defects of several tumor-related genes are responsible for tumorigenesis. Among the genes affected, mutations in K-ras oncogene and p53 tumor suppressor gene are thought to play an important role in the multistep process of tumorigenesis. In addition, the role of genetic susceptibility to colorectal cancer is supported by results of recent studies, such that the role of a variety of genetic polymorphisms on colorectal carcinogenesis are actively being investigated. Heterocyclic amines, environmental products that are found in high concentrations in

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meats cooked at high temperatures, are known to be potent carcinogens and mutagens. The metabolism of these products varies among individuals and is known to depend on polymorphisms in genes involved in activation or detoxification of these substrates. To date, accurate data on exposure to heterocyclic amines in the diet are lacking, due to the lack of dietary instruments and analytic methodology. In this study, we propose to investigate the role of exposure to dietary heterocyclic amines and polymorphic genotypes and phenotypes on risk of adenoma genetic mutations and adenoma recurrence in a two-phase analytic approach. This study will be conducted in the ongoing phase III trial of ursodeoxycholic acid on adenoma recurrence. In the first phase, we will conduct case-series analyses among 1,200 individuals using genetic mutations in the K-ras oncogene and p53 tumor suppressor gene as the endpoints. As part of this phase, we will pilot and develop a self-administered dietary questionnaire to assess exposure to heterocyclic amines. In the second phase, we will follow individuals prospectively during the trial and focus on adenoma recurrence as the end-point. By conducting this study, we will have the opportunity to assess whether the metabolic activation or detoxification of heterocyclic amines is related to genetic alterations in adenomas or to adenoma recurrence. This two-phase analysis provides a strong approach to address these study questions and enhance our understanding of the mechanisms related to the inherited susceptibility markers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DNA-BASED ARRAYS OF CROSS-REACTIVE MOLECULAR SENSORS Principal Investigator & Institution: Stojanovic, Milan N.; Medicine; Columbia University Health Sciences Po Box 49 New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2005 Summary: (provided by applicant): The mammalian olfactory system is composed of 1000 different receptors on over 1000 cells each, and although individual receptors may be only modestly sensitive and selective, in the aggregate they are capable of fine differentiation of trace odorants through parallel molecular recognition events The interplay between multiple copies of the same receptor and parallel processing of crossreacting receptors is an area of current interest. Artificial sensors susceptible to facile variations of the binding site would permit investigation of parallel recognition as a strategy for analyte identification. Our recent discovery of oligonucleotides with a hydrophobic variable domain within the fixed frameworks of three- and four-way junctions allows construction of the several thousand distinct molecular sensors needed for such an investigation. Therefore, an array of cross-reacting hydrophobic sensors based on DNA will be constructed to model the olfactory system. The array will provide an instantaneous fingerprint of all molecules with hydrophobic domains present in a solution A typical array at the end of funding period will consist of one to several hundred selected molecular sensors organized in 1586-well plates with multiple readings per sensor. The arrays will be validated on urine specimens collected for metabolite screening. The hydrophobic fingerprints will be correlated with disease states. This approach will be initially demonstrated on Cushing's disease, adrenal adenoma, adrenal carcinoma, hirsutism and congenital adrenal hyperplasia. In the next phase, DNA-based cross-reactive sensors for oligosaccharides will be incorporated into arrays to expand the panel of metabolites that could be profiled in a single-step assay. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Adenoma

Project Title: EFFECTS OF BRASSICA ON MARKERS OF COLON CANCER RISK Principal Investigator & Institution: Fowke, Jay H.; Medicine; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 06-SEP-2001; Project End 31-AUG-2004 Summary: (provided by applicant): There is considerable basic science research to suggest that isothiocyanates (ITC) or several indole analogs (e.g., indole-3carbinol (I3C)) slow cellular proliferation, re-instate apoptotic action, and reduce colon tumor incidence. Humans are exposed to these agents primarily through consuming Brassica vegetables (e.g., broccoli), but it is unknown if greater Brassica consumed could affect colon cancer risk. We propose a short-term pilot dietary intervention to investigate the effects of greater Brassica consumption on markers colon cancer progression. Twenty adenoma patients will participate in a randomized controlled cross-over trial. Recruitment, intervention, and lab protocols have been developed through other ongoing studies, improving the cost-efficiency of this pilot project. The intervention-arm of the trial is based on a model developed for the Women's Health Initiative, and provides social support and information to help participants incorporate these vegetables into their daily diet. Biomarkers measured from rectal biopsies will include Bcl-2 (inhibits apoptosis), Bak and Bax (promote apoptosis), Mib-1 (marker of cellular proliferation), and p21 (marker of cellular differentiation). Multiple 24-hour dietary recalls will measure each participant's adherence to the intervention. Dietary adherence will be measured further by urinary ITC level (combined with GST enzyme genotype), a unique and specific biomarker of Brassica vegetable intake. Using mixed-model repeatedmeasures ANOVA, we will compare molecular marker expression when participants consume Brassica vegetables to when these same participants consume an over-thecounter fiber and vitamin supplement. This pilot study will provide the needed estimates of variance in biomarker response to the dietary change for sample size calculations for future applications. Previously, we found that healthy people were able to increase the consumption of these vegetables with minimal social and instructional support, and we used those pilot data to gain funding for a larger randomized trial enrolling breast cancer survivors. Since Brassica vegetables are widely available, inexpensive, and consumed without harm, a change in molecular marker expression consistent with reduced proliferation and enhanced differentiation and apoptosis would suggest further research to evaluate the application of Brassica consumption to reduce colon cancer risk. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ENVIRONMENTAL/GENETIC EPIDEMIOLOGY OF COLORECTAL ADENOMA Principal Investigator & Institution: Kadlubar, Fred; University of Arizona P O Box 3308 Tucson, Az 857223308 Timing: Fiscal Year 2002 Summary: Risk of colorectal neoplasias probably involves the interactions of genetic and environmental factors. Among these, abnormal DNA methylation is relatively common, although little is known about its etiology. In this project, we propose to conduct investigations of several environmental and genetic factors as they relate to a commend end-point in the Program Project, adenoma recurrence. Using data and biological samples from our recently completed Wheat Bran Fiber (WBF) trial, our ongoing study of ursodeoxycholic acid (UDCA), and those from our propose trial of selenium and celecoxib, we propose to: 1) examine if folate status (assessed by dietary intake and

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plasma levels), high plasma homocysteine, or the methylenetetrahydrofolate reductase (MTHFR) gene is associated gene methylation, assessed by the presence of the CpG island methylator phenotype (CIMP); 2- compare the effects of selenium or celecoxib intervention on the recurrence of adenomatous polyps among individuals with low gluathione S-transferase (GST) status (assessed as GSTM null and/or GSTT1 null genotypes and those with the high activity groups; 3) assess whether the presence of the MTHFR polymorphism modifies the effect between selenium or cerecoxib intervention on the recurrence of adenomatous polyps among individuals with low gluathione Stransferase (GST) status (assessed as GSTM1 null and/or GSTT1 null genotypes) and those with the high activity groups; 3) assess whether the presence of the MTHFR polymorphism modifies the effect between selenium and/or celecoxib intervention and adenoma recurrence; and, 4) assess the modifying effect between selenium and/or celecoxib intervention and adenoma recurrence; and, 4) assess the modifying effect of the N-acetyltransferase 1 and 2 genes, and the cytochrome P40 1A2 phenotype in the association of dietary heterocyclic aromatic amines and adenoma recurrence. The proposed studies will evaluate the role of prominent genetic and epidemiologic factors as they relate to gene methylation and adenoma recurrence in a large sample of prospectively collected data. The relative importance of the proposed interactions can only be appreciated through their investigation in a large comprehensive setting using a well-characterized population, as proposed in this project. While we estimate that we will have over 4,000 study participants available, we have designed these studies in a cost-effective manner, with adequate power to test the proposed hypotheses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EPIDEMIOLOGIC STUDY OF PREDICTORS FOR ADENOMA RECURRENCE Principal Investigator & Institution: Zheng, Wei; Professor; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 24-SEP-2002; Project End 30-APR-2007 Summary: (provided by applicant): Most colorectal cancers arise from adenomatous polyps, and a large proportion of adenoma patients will develop new adenomas after their initial polypectomy. There is considerable controversy regarding an appropriate surveillance interval for adenoma patients following the removal of their initial adenomas. Therefore, studies assessing predictors for recurrent adenoma, particularly among patients with multiple or pathologically advanced adenoma(s), will provide valuable information for designing individualized, cost-effective surveillance and chemoprevention strategies for adenoma patients. Some tumor markers (genetic or epigenetic alternations) involved in the formation of colorectal neoplasms are promising predictors for recurrent adenomas, as they are believed to reflect a field cancerization process or a genetic predisposition to colon adenomas. We hypothesize that patients whose initial adenomas have certain altered genetic or epigenetic profiles may have an elevated risk of adenoma recurrence, and these tumor markers, along with pathologic features of initial adenomas can be used to predict the risk of adenoma recurrence. To evaluate these hypotheses we propose in this application a series of investigations, consisting of both hypothesis-testing and hypothesis-generating components as described below. For the reasons described in section BI, the major focus of this application will be on the study of predictors for recurrent adenomas among patients with multiple or pathologically advanced adenoma(s). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EPIDEMIOLOGY OF RECTAL MUCOSAL PROLIFERATION Principal Investigator & Institution: Sandler, Robert S.; Professor of Medicine; Medicine; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2002; Project Start 15-FEB-1988; Project End 30-MAR-2004 Summary: Colorectal cancer is common in the United States and other Western countries. The biology of colorectal cancer provides unique opportunities for etiologic research. Because colorectal cancer arises from an ordered series of pathological precursor stages, epidemiologists can conduct studies that examine where various potential risk factors operate in the cancer sequence. This is a competing renewal application of a study that has been examining the epidemiologic aspects of colorectal cancer precursors for the past twelve years. The proposed study will explore the insulinlike growth factor (IGF) axis as it relates to events in rectal mucosa that lead to neoplasia. In so doing, the study will test a more mature set of hypotheses that link lifestyle and exposure information with specific endocrine and paracrine factors. The specific aims of the study are: (1) To compare body weight (and anthropometric measures), glycemic load, and physical activity in patients with colorectal adenomas to adenoma-free controls. (2) To evaluate the association between circulating levels of IGF-I and IGF-II and adenomas/apoptosis. (3) To evaluate the association between circulating levels of IGF binding proteins IGFBP 1, IGFBP3 and adenomas/apoptosis. (4) To evaluate the association between tissue levels of IGF-I, IGF-II and IGFBP3 and adenomas/apoptosis. As a secondary aim the study will collect buffy coat specimens from blood. The white cell and tissue archive, combined with extensive exposure information, will provide a resource for future studies. Study subjects will be 400 consenting male and female patients who meet eligibility criteria. Rectal mucosal pinch biopsies will be taken during routine colonoscopy and immediately processed. Apoptosis will be measured using in-situ end-labeling and light microscopy. Circulating levels of IGF-axis hormones will be measured by ELISA. Tissue levels of IGF's and binding protein will be measured by quantitative competitive RT-PCR. The study is a logical extension of current research. The concept that lifestyle factors operate through endocrine and paracrine effects on the rectal mucosa has not been previously examined in comprehensive epidemiologic studies. By using meticulous laboratory methods, and by obtaining detailed information on diet and lifestyle, the proposed study has the potential to improve our understanding of mucosal factors associated with colorectal carcinogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PATHOLOGY

EPITHELIAL

GENE

TRANSCRIPTION

IN

INTESTINAL

Principal Investigator & Institution: Wu, Gary D.; Associate Professor of Medicine; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-AUG-1999; Project End 31-JUL-2004 Summary: The intestinal epithelium is spatially segregated into a proliferating, undifferentiated compartment and a non- proliferating, differentiated compartment in both the small and large intestine. The differentiated columnar epithelium is the interface between the contents of the intestinal lumen and the internal environment of higher vertebrates and, therefore, expresses genes important for the functional activity at this interface. To date, however, little is known about the following: 1) The molecular mechanism by which genes are targeted to the colonic epithelium, 2) The processes

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underlying differentiation in the colonic epithelium, or 3) The mechanisms by which intestinal gene regulation is altered in pathologic disease states. Therefore, based upon the following hypothesis, we propose to study the transcriptional regulation of a gene known as DRA (Down Regulated in Adenoma): 1) The regulation of DRA gene expression may be used as a model to understand how gene expression is directed to the differentiated surface epithelium of the colon. DRA encodes a sulfate/chloride anion transporter that is expressed principally by the differentiated epithelium in the colon and whose expression is lost in colonic adenomas and adenocarcinomas. DRA has been recently identified by positional cloning as the gene which is mutated in congenital chloride diarrhea and represents the only gene yet identified that, in isolation, plays a role in the pathogenesis of diarrhea. We have demonstrated that two zinc finger transcription factors, YY1 and GATA, play an important role in the transcriptional activation of the DRA promoter in vitro. Transgenic animals demonstrate that 3.6 kb of the DRA 5'-flank directs high level reporter gene expression to the differentiated epithelium of both the small and large intestine. Three specific aims will be pursued to understand how the DRA gene is regulated: 1) To elucidate the transcriptional mechanisms by which the DRA 5'-flank is activated using sodium butyrate induction of DRA in LS174T cells as an in vitro model system, 2) To identify potential cis-acting regions within the DRA promoter which interact which nuclear proteins isolated from murine small and large intestine, and 3) To characterize the mechanisms that regulate DRA gene expression in vivo using transgenic mice. Ultimately, once the mechanisms by which DRA gene transcription is regulated in the normal colon have been elucidated, DRA may be a useful model with which to investigate how gene expression is altered in pathobiology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ERBB2 KINASE SIGNALING IN COLON CARCINOGENESIS Principal Investigator & Institution: Dawson, Dawn M.; Pathology; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2002; Project Start 21-AUG-2000; Project End 31-JUL-2005 Summary: Altered or over-expression of growth factors or their receptors is thought to significantly contribute to tumorigenesis. The erbB kinases, especially the protooncogene erbB2, and major ligands (EGF and neuregulin groups) are implicated in epithelial malignancies such as breast and colon. EGFR and TGFalpha co- expression in colon cancer is associated with neoplastic progression through growth factor independence. Immunohistochemical studies of the erbB kinase family in colon adenomas with concurrent invasive cancer demonstrate increased expression of erbB2 in the neoplastic cell population. In addition, I present the new finding of co-expressed heregulin (cognate ligand for human erB3 and 4) and erbB2 in these polyps and cancers as well as in colon adenoma and carcinoma cell lines. I demonstrate a significant biologic response to heregulin, not previously described in colon cell lines, and loss of cell growth by blockade of the erB2 receptor, emphasizing the importance of activated erbB2 as a mechanism for cell growth in the colon. As both EGFR and erbB3 will signal through erbB2 as heterodimers, I propose that activation of erbB2 is central to the control of down stream signaling and that activated erbB2 receptor is pivotal in the progression of colon cancer. To study the role of erbB2 and related kinases and ligands in colon carcinogenesis, four colon cell lines have been characterized for the role of erbB signaling: a benign adenoma line, two growth factor dependent (GFD) carcinoma lines, and a growth factor independent (GFI) carcinoma cell line. They were selected to represent stages in the multi-step progression of colon carcinogenesis. Blockade of EGFR

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and erbB2 receptor activation in these cell lines is associated with dramatic biologic response further supporting a role for functional erbB2 on colon carcinogenesis. Employing these unique cell lines, representative of colon cancer progression that exhibit autocrine activation by TGFalpha and heregulin, I propose to study erbB2 signaling in colon carcinogenesis. The objective is to define the role of the erbB2 activation through TGFalpha and heregulin in this in vitro model of tumor progression, specifically to determine: 1) the functional expression profile of the erbB kinases and these ligands in the model cell lines and characterize tissue expression of the same to support the biologic relevance of erbB kinases in carcinogenesis, 2) the signal pathways and biologic response mediated by erbB2 activation, and 3) the effects of erbB signalbased modulation through erbB2, PI3K, and MED/MAPK pathways that contributes to neoplastic progression as characterized by cell growth and resistance to apoptosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EVALUATION OF BIOLOGICAL RELEVANCE OF CHOLINE INTAKE Principal Investigator & Institution: Cho, Eunyoung; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2004; Project Start 07-MAY-2004; Project End 30-APR-2006 Summary: (provided by applicant): Choline is an essential nutrient for human and is involved in many metabolic pathways, including methyl-group transfer. Animal studies have demonstrated choline deficiency as a condition sufficient for the development of hepatocellular carcinoma in the absence of other carcinogens. A methyl-group-deficient diet with no choline and low methionine promotes chemically induced carcinogenesis in animals. A methyl-group-deficient diet with low folate and methionine intake has been related to cancers of several organs in humans. However, understanding the role of choline in humans has been hampered by lack of food composition data for dietary choline intake. Recently, we obtained choline composition data for foods measured by our food frequency questionnaire. Before we use the intake data in populations, we propose to examine the biological relevance of variation in choline intake over the range of intake in a general population. Using data from the Framingham Offspring Study, we will examine the relation between choline intake and plasma levels of homocysteine, an intermediate product in methyl-group metabolism and an indicator of the body's methyl-group availability. We will characterize the relationship between choline intake and other dietary and life-style factors. We will also examine choline intake in relation to colorectal adenoma risk in the Nurses' Health Study, a large prospective study of women. These data will provide evidence whether measurable and physiologically important variation in choline intake exists within populations. The results from the proposed grant will enhance understanding of the role of choline intake in humans and lay the groundwork for future studies on choline intake and overall methyl-groupdeficient diet and cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EXPRESSION AND FUNCTION OF THE GUANYLIN LIGAND FAMILY Principal Investigator & Institution: Cohen, Mitchell B.; Professor; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, Oh 452293039 Timing: Fiscal Year 2002; Project Start 30-SEP-1995; Project End 31-AUG-2004

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Summary: The overall objectives of this application are: 1) to use the expression patterns of the paired ligands guanylin and uroguanylin to understand the factors which contribute to transcriptional regulation in intestinal epithelial cells and 2) to identify the specific physiologic and pathophysiologic functions of these ligands by generating and studying transgenic animal models. Because of the defined spatial patterns of expression of guanylin and uroguanylin, their high levels of intestinal expression, and the tools which we currently possess, these paired genes represent a unique opportunity to identify mechanisms of gene expression, especially in the colon and in the small intestinal crypts. In vitro techniques, including transient transfection assays, DNasel hypersensitivity and footprinting will be used to guide in vivo studies of gene expression. Transgenic mice expressing various portions of the guanylin and uroguanylin promoter elements linked to the luciferase reporter gene will be used to define sequences that direct tissue specific expression. In order to accomplish our second objective we will create a guanylin and a uroguanylin knockout mouse. Our initial efforts at gene targeting by homologous recombination have produced a perinatal-lethal and/or embryo-lethal phenotype. In order to determine the mechanism(s) responsible for this phenotype, we will identify the sites of expression of guanylin and uroguanylin in the developing mouse embryo, embryoid bodies, placenta and yolk sac; to do this we will use RT-PCR, whole mount and tissue slice in situ hybridization. This will identify whether guanylin or uroguanylin is expressed in the developing intestine as well as in critical organs outside the intestine in the developing mouse. Based on the results and interpretation of these studies, we will pursue a strategy to effect tissue-specific ablation of guanylin by taking advantage of an in vitro or an in vivo conditional targeting approach. This will generate transgenic mice lacking guanylin and/or uroguanylin in the intestine. To discern the role of guanylin and uroguanylin in vivo, we will measure basal and stimulated intestinal secretion using bioelectric, ion flux and in situ ligated loop measurements. Based on the observed physiologic actions of guanylin, we will investigate the effect of guanylin and uroguanylin loss on salt tolerance, bicarbonate buffering, an acute phase injury, intestinal motility and intestinal adenoma formation. We will determine whether guanylin or uroguanylin receptors are upregulated in these mice and whether receptors other than guanylyl cyclase C (GC-C), play a role in any identified phenotype. Should guanylin or uroguanylin inactivation result in "no basal phenotype," we will search for compensatory or redundant mechanisms which permit this "normal" phenotype. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EXPRESSION MONITORING IN COLORECTAL CANCER Principal Investigator & Institution: Notterman, Daniel A.; University Professor and Chair; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2002; Project Start 30-AUG-2002; Project End 30-JUN-2006 Summary: Our long-term objective is to describe the molecular events that underlie colorectal cancer. Advances in technology permit the simultaneous measurements of thousands of different mRNA transcripts. There have also been notable advances in rapidly and efficiently scoring DNA abnormalities in mathematical approaches for organizing and exploring this information. Our plan is to harness all of these abilities in the service of a molecular understanding of tumor formation, progression, and metastasis. This should both enable us to discern new cancer pathway genes and to replace the current morphological classification of cancer with a more precise system based upon the molecular state of the abnormal cell. Our specific aims are: (i) Array Development: To develop and validate a colon cancer cDNA microarray. Using the

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Affymetrix U 95 Chip Set (60,000 full-length genes and ESTs), we will screen 120 microdissected tissue samples (90 abnormal, 30 normal) representing the full range of colorectal neoplasia. Approaches that are delineated and described in Project 3 will be used to select 4,000 to 6,000 features for a colon-oriented cDNA microarray. Features representing other known or suspected cancer pathway genes (see Project 1, and from the literature) will also be included in the colon-oriented cDNA microarray array. (ii) Gene Discovery: To identify expression changes in individual and groups of transcripts as colonic epithelium is transformed through aberrant crypts, adenomatous polyps, adenocarcinomas, and metastatic tissue. To target the associated genes for mutational analysis (in concert with Project 1 and Project 3) and assess their role in neoplasia. Genes will be identified that are abnormally expressed in neoplastic epithelium and in concert with Project 1 are shown to have an associated genetic or epigenetic abnormality. These candidate oncogenes or tumor suppressor genes will be characterized by: (i) in situ hybridization, (ii) promoter and coding sequence analysis, (iii) clonogenic and tumorigenic assays, (iv) cell cycle analysis, (v) animal models, and (vi) mechanistic studies. (iii) Outcome prediction: To develop a molecular taxonomy of colorectal cancer by relating concerted patterns of gene expression to clinical and genetic information. In concert with Projects 1 and 3, we propose to develop an approach to tumor classification and clinical outcome prediction that is grounded in a comprehensive evaluation of transcript abundance, DNA markers, and clinico-pathological status. By relating patterns of gene expression and gene mutation to fundamental indicators of disease status, we may be more able to precisely predict the clinical behavior of a tumor. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FOLATE, 1-CARBON NUTRIENTS, GENE VARIANTS & COLON CANCER Principal Investigator & Institution: Hunter, David J.; Director; Epidemiology; Harvard University (Sch of Public Hlth) Public Health Campus Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 18-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): Most of the over twenty epidemiologic studies that have examined the relationship between dietary folate intake and the risk of developing colorectal neoplasms, have reported that higher folate intakes are associated with lower risk. Animal studies, using either carcinogen-induced or genetically engineered rodent models of colorectal cancer, have indicated an inverse relationship between dietary folate and the risk of colorectal cancer. The folate metabolic pathway influences genomic methylation and the supply of nucleotides for DNA synthesis; these can also be influenced by adequacy of supply of vitamins B12, B6, and B2, all co-factors for critical enzymatic reactions in the pathway. The overall long-term objective of our Team is to establish the role of folate and other nutritional contributors to one-carbon metabolism in colorectal cancer by combining animal, mechanistic, human observational studies and clinical trials. We will accomplish this by establishing a Cooperative Specialized Center for the study of Folate, One carbon nutrients, Gene variants and Colorectal cancer. This Center will be a Collaborative Program between Harvard and Tufts Universities in Boston, Dartmouth University in New Hampshire, the International Agency for Research in Cancer and the University of Bergen in Europe, Variagenics Inc. in Boston, and the Division of Cancer Prevention and the Center for Cancer Research at the NCI. We are organized into three projects, developmental projects, and two cores. Project 1 will pool data from three large prospective cohort studies with 2,700 expected colorectal cancer cases to establish whether higher intake of folic acid reduces risk of colorectal cancer and examine whether this reduced risk is greater among persons with low

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methionine intake, low plasma folate, vitamins B12, B6, and B2 levels, consumers of more than one alcoholic beverage per day, and homozygotes for the methylenetetrahydrofolatereductase (MTHFR) C677T polymorphism, and compound heterozygotes for the MTHFR A1298C polymorphism. Project 2 will validate mouse models of colon carcinogenesis as systems to examine modification of risk by folate and other contributors to one-carbon metabolism. Project 3 will assess whether the degree of uracil misincorporation and genomic methylation in peripheral blood lymphocytes and distal colon biopsies represent biomarkers of one-carbon nutrient adequacy and colorectal adenoma risk, using data and samples from two randomized clinical trials of folate supplementation. The projects will be supported by innovative Developmental Projects. In initial Developmental Project 1 transgenic mice with the null allele of MTHFR, and the homologous C677T polymorphism; these mice will be available for incorporation into feeding studies in Project 2. In Developmental Project 2 we will explore five folate-metabolism genes for polymorphisms that influence plasma folate and homocysteine levels. All Projects will be supported by the Administrative and Statistical Core (based at the Harvard School of Public Health), and the Measurement Core (based at the Human Nutrition Research Center at Tufts University). These highly interrelated studies will help integrate epidemiologic and mechanistic observations and help provide a basis for public health recommendations on optimal levels of folate and B vitamin intake. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENE-ENVIRONMENT CARCINOGENESIS

INTERACTION

AND

COLON

Principal Investigator & Institution: Chen, Jia; Community and Preventive Med; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2002; Project Start 21-SEP-1998; Project End 31-DEC-2003 Summary: Jia Chen received her Sc.D. in 1994 in the fields of Toxicology and Environmental Engineering from Massachusetts Institute of Technology. Since 1995 she has been working as a Research Associate in Medicine at Harvard Medical School and a Research Fellow at Harvard School of Public Health. She is interested in an academic research career in molecular epidemiology studying genetic susceptibility to cancer. David J. Hunter, MBBS, MPH, ScD, has extensive experience in chronic disease and molecular epidemiology. He has mentored numerous graduate students and postdoctoral fellows; two graduate students he co- supervised are now postdoctoral fellows in the NCI Genetic Epidemiology Program. He is a co-investigator of the Nurses' Health Study I and Health Professionals Follow-Up Study based at Harvard. Dr. Hunter is familiar with the research methods proposed in this project and he will oversee Dr. Chen's research activities and education. Dr. Chen proposes to use the resources of three large well-characterized cohort studies (the Nurses' Health Study I, the Health Professionals Follow-Up Study, and the Physicians Health Study) to prospectively assess gene-nutrient and other gene-environment interactions in the etiology of colorectal adenoma and carcinoma. Specifically, she will assess whether polymorphisms in the alcohol dehydrogenase type 3 (ADH3), cytochrome P450IIE1 (CYP2E1), and methylenetetrahydrofolate reductase (MTHFR) genes are associated with these cancers and whether they modify associations with intake of folate, methionine and alcohol, as well as other potentially carcinogenic or anticarcinogenic nutrients on risk of colon cancer and polyps. In addition, she will modify the existing PCR- RFLP based genotyping methods and adapt more flexible and efficient technologies while maintaining high accuracy. The proposed study would be valuable as positive

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Adenoma

associations would clearly implicate the substrates of the gene product as environmental carcinogenic exposures, clarifying colon cancer etiology and pointing to preventive dietary and other lifestyle modifications. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENES CONTROLLING NEOPLASIA OF THE INTESTINAL EPITHELIUM Principal Investigator & Institution: Dove, William F.; Professor of Oncology and Medical Geneti; Oncology; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2002; Project Start 22-SEP-1993; Project End 31-DEC-2002 Summary: The Min mouse strain develops multiple intestinal neoplasms on sensitive genetic background. It is heterozygous for a nonsense allele of the Adenomatous polyposis coli gene of the mouse, Apc. We first shall aim to settle controversial issues concerning the strict adherence of adenoma formation to the one-locus Knudson model and the clonality of early tumors. Then, we shall explore the involvement of several candidate molecular systems in the Min phenotype, including the Wingless signaling pathway. Our work culminates in developing a sensitized genetic screen for mutant modifiers of the Min phenotypes. This screen, novel in mammalian cancer genetics, may identify a series of factors acting in this tumor lineage and in the tumor-bearing host. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENES, ANTICARINOGENS AND COLON NEOPLASMS Principal Investigator & Institution: Lin, Henry J.; Professor; Harbor-Ucla Research & Educ Inst 1124 W Carson St Torrance, Ca 905022052 Timing: Fiscal Year 2002; Project Start 30-SEP-1996; Project End 31-JUL-2006 Summary: (provided by applicant): The long-term goal is to use genetics and epidemiology to identify targets for prevention of colon cancer. The application is on prostaglandin biosynthesis as a promising target, because aspirin prevents some cases of colon cancer. The hypothesis is that genetic variation in prostaglandin production may mimic aspirin effects and shed light on preventive mechanisms. Work will focus on naturally-occurring mutations in people and targeted mutations in mice in a nuclear prostaglandin pathway defined by: cytosolic phospholipase A prostaglandin H synthase 2 (PTGS2/Cox-2), hematopoietic prostaglandin D synthase (H-PGDS), and peroxisome proliferator-activated receptor gamma. The project builds on discovery among 10 percent of African Americans of a PTGS2/Cox-2 mutation (Val5llAla) near the active site of the enzyme. Specific aims are to: (1) conduct case-control analyses on prevalence of colorectal adenomas and cancer in relation to genetic variants in PTGS2/Cox-2 and H-PGDS; (2) assess human interindividual variation in PTGS2/Cox-2 activity in relation to the Va151 1 Ala enzyme variant; (3) develop in vitro expression assays for novel variants identified in H-PGDS; and (4) develop a knockout mouse model of variation in H-Pgds to complement human epidemiologic studies. Three case-control studies will be used to assess effects of genetic variation on colon neoplasms: a Kaiser sigmoidoscopy study of adenomas (1,700 subjects); a Univ. of North Carolina colonoscopy study of adenomas (800 subjects); and African American cancer cases and controls (roughly 400) from the Multiethnic Cohort Study. Results may lead to better understanding of protective mechanisms involving aspirin and nonsteroidal anti-inflammatory drugs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENETIC ALTERATIONS OF P53R2 AND COLORECTAL ADENOMA Principal Investigator & Institution: Xie, Dawen; Epidemiology and Biostatistics; University of South Carolina at Columbia Byrnes Bldg., Room 501 Columbia, Sc 29208 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2004 Summary: (provided by applicant): Colorectal cancer is the second most common cause of cancer mortality in the United States. The maintenance of genomic integrity after DNA damage depends on the coordinated action of cell cycle checkpoint controls and DNA damage repair systems. Molecular biological studies have clearly indicated that colon cancer is a disease caused by an accumulation of multiple genetic defects. One of the most studied genetic defects has involved the p53 gene. It is the major target for genetic alterations or biochemical activations in human cancer. However, the mechanism by which p53 exerts its effects or alters other signaling systems is largely unknown. In recent years a number of specific p53 target genes have been discovered and are likely to be involved in downstream target effects of altered p53 protein including cell cycle arrest, apoptosis, and tumor suppression. Recently, an important p53 downstream target gene, p53-inducible ribonucleotide reductase small subunit 2 (p53R2) was identified in a colon cancer cell line. p53R2 is a gene that is essential for DNA repair, and loss of function of this gene results in dysfunctional repair mechanisms. The p53R2 gene is mutated in either the regulatory region or the coding region. In preliminary work we have identified several germline mutations/polymorphisms in the first intron (the regulatory region of p53R2) in six of twenty patients with incident colorectal adenomas. We hypothesize that germline mutations/polymorphisms of p53R2 result in differential susceptibility to colorectal neoplasia. We propose to 1) determine distributions and frequencies of germline mutations/polymorphisms of p53R2 in participants in a recently concluded community, colonoscopy-based case-control study of incident sporadic colorectal adenoma (n=174 cases and 226 controls); 2) investigate associations of these mutations/polymorphisms with risk for adenoma; 3) identify the precise mutation(s)/polymorphism(s) in the p53R2 gene responsible for altered DNA repair system mechanisms; and 4) conduct preliminary work on the functional significance of genetic variants in the regulatory region of p53R2. This project will provide insight and preliminary data for further study of a novel downstream target gene of p53 signaling that ultimately may be responsible for dysfunctional DNA repair, thus contributing to greater vulnerability for developing colon cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENETIC AND EPIGENETIC CHANGES IN COLORECTAL CANCER Principal Investigator & Institution: Barany, Francis; Professor; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2002; Project Start 30-AUG-2002; Project End 30-JUN-2006 Summary: The long-term research objective of Project 1 is to correlate molecular changes in DNA and RNA with establishment, progression, and metastasis of colon cancer. We will use three technologies developed in our laboratory: Multiplexed Ligase Detection Reaction (LDR) assays, Universal DNA arrays, and EndoV/DNA ligase mutation scanning assay. These technologies will identify point mutations, deletions, LOH, gene copy number, methylation status, and gene expression level in dozens of oncogenes and tumor suppressor genes within individual colon tumors. By capturing these genetic and epigenetic changes in important genes, the molecular profiles will allow us to identify new patterns and mechanisms of cancer gene activation and repression. Further, we will

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identify the genetic changes most important for metastatic progression to specific secondary sites, and in concert with Projects 2 and 3 construct and validate a molecular prognostic scoring system based upon genes that independently influence prognosis. Our specific aims are: (i), (ii) To identify important interactions between both known and putative oncogenes and tumor suppressor genes from (a) defined signaling pathways, and (b) candidate genes identified in adenocarcinomas and precursors by cDNA expression array analysis and prioritized in Project 2 and 3. Tumor sample (360 total), including aberrant crypts, adenomas, adenocarcinomas, liver and lung metastasis will be analyzed. We will use molecular changes in key genes from the p53, cell cycle, apoptosis, Wnt signaling, RPTK signaling, and TGFbeta signaling pathways as the foundation for interpreting how such changes provide a cell survival advantage, and contribute to progressive autonomous growth and metastasis of colon cancers. (iii) To ascertain which mutations or alterations in gene expression correlate with colon cancer metastasis, in (a) receptor protein kinases (RPTKs), their known ligands, and (b) candidate genes identified in liver and lung metastases and prioritized in Projects 2 and 3. We will identify the autocrine and paracrine activation loops mediated by specific RPTKs and their ligands in primary and metastatic tumors. (iv) To employ biostatistical and bioinformatic approaches (Project 3) to determine which alteration(s) identified in Projects 1 and 2, and Core B correlate with recurrence and survival. Two separate cohorts of resected Stage 2/3 primary colon cancers (400 total) with good and poor outcomes will be analyzed to identify and validate genes that independently influence prognosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETIC BASIS OF COLON ADENOMA SYNCHRONOUS TO CARCINOMA. Principal Investigator & Institution: Yen, Yun C.; Chief of Biochemical Pharmacology; City of Hope/Beckman Research Institute Helford Building Duarte, Ca 910103000 Timing: Fiscal Year 2004; Project Start 01-MAY-2004; Project End 30-APR-2006 Summary: (provided by applicant): The colorectal adenoma-carcinoma paradigm is well established and is responsible for over 70% of colorectal cancers (CRC), for both sporadic and hereditary types. The adenoma has also become the surrogate marker for prevention studies. The synchronous adenoma (SA) to sporadic cancers occur commonly, about 25%, and the associated clinical parameters have not been well studied. It is known to be associated with higher rates of adenoma recurrence, such as metachronous adenoma (MA), and second CRC. It is more likely to be proximal in location in the colon, microsatellite instable (MSI) and have a 20% better 5 year-survival than CRC without SA. All this information indicates that CRC+SA is biologically different than the usual CRC. The aims of this study are to characterize SA in a well defined population of CRC and with respect to new CRC and MA. The molecular parameters with gene expression array analysis will be employed to answer some questions regarding: 1. Nature of adenoma to carcinoma development in sporadic CRC with and without SA. 2. Biological differences of proximal compared to distal CRC. 3. Significance of MSI in sporadic CRC. 4. Molecular basis for survival differences of CRC+SA, MSI instable CRC compared to the CRC without SA and MSI stable CRC. The methodology will involve collecting archival stored tissue of CRC and SA, laser microdissect out the tumor tissue and test it on gene microarray chip against genes of several categories: cell cycle, apoptosis, tumor suppressors, signal transduction, microsatellite markers, DNA repair, methylation and specific genes involved in tumorigenesis. These results will help our understanding of the adenoma, specifically

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the SA, and improve the use of this precursor in prevention studies. We will understand better the biology of different subsets of sporadic CRC, namely CRC+SA, proximal tumors and MSI instable tumors. Our findings will impact on future clinical therapeutic studies of CRC. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETIC EPIDEMIOLOGIC STUDIES OF POLYPS AND CANCER Principal Investigator & Institution: Potter, John D.; Member & Program Head; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2002; Project Start 30-SEP-1994; Project End 31-AUG-2004 Summary: (Adapted from applicant's abstract): The etiology of colorectal cancer and polyps involves genetic as well as environmental factors. The colon is exposed to a large number of genotoxic compounds both from exogamous and endogamous sources. Hereditary non-polyposis colorectal cancer illustrates the importance of DNA repair mechanisms in colorectal carcinogenesis. We hypothesize that polymorphisms in common DNA repair enzymes may also affect the risk of colorectal neoplasia. In the first 4 years of this grant, we have measured several polymorphic enzymes a) related to the metabolism of specific carcinogens from diet and tobacco smoke and b) in the folate pathway. Polymorphisms in other enzymes related to alcohol metabolism (also a source of DNA damage) and rotate metabolism linked to DNA repair via the provision of nucleotides) may also modulate risk. The goals of this competing renewal are to investigate the risk of colon cancer, colorectal adenoma, and colorectal hyperplastic polyps associated with 1) polymorphisms in DNA repair enzymes, specifically in hMLHI, hMSH2, MSH6, hOGGI, XRCC1, XRCC3, XPD, and AGT; 2) polymorphisms related to alcohol metabolism, specifically alcohol dehydrogenases 2,3, and 4; and 3) polymorphisms in enzymes in folate metabolism, specifically in MTHFR, thymidylate synthase (TS), and methionine synthase. We further plan to investigate possible interactions in determining risk of colorectal neoplasia: 1) between relevant environmental exposures and genetic polymorphisms (e.g., dietary intakes of folate and TS polymorphisms; cooked meat and nucleotide-excision repair enzymes); and 2) between polymorphisms in DNA repair genes and those in folate, or alcohol-related enzymes. Two large completed case-control studies of colorectal polyps (adenoma n=550 cases, n=700 controls, and hyperplastic polyps, n=200 cases) and colon cancer (n=1650 cases, n=1950 controls) - with extensive data on diet, alcohol intake, smoking history, and family history, as well as genotype information on other relevant genes will provide the basis for this study. Information on a number of DNA damage-repair pathway polymorphisms and their interactions with relevant exposures will help build our understanding of the molecular mechanisms involved in the stages of colorectal neoplasia; ultimately, the findings should provide directions for future screening and prevention strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENETIC REGULATION OF ANGIOGENESIS IN COLONIC POLYPS Principal Investigator & Institution: Chung, Daniel C.; Professor; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: (provided by applicant): The controlled induction of angiogenesis plays a critical role in a variety of both physiological and pathological states. In particular the formation of new blood vessels in response to the hypoxic environment that develops

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within a tumor mass is crucial for the survival of advanced malignancies. However, the role of angiogenesis in the pathogenesis of benign precursor lesions is unknown. In the well-described progression of colon cancer, angiogenesis begins early at the stage of the premalignant adenomatous polyp. In colonic epithelial cells, this is associated with upregulation of the key pro-angiogenic factor VEGF. The genetic mechanisms underlying this upregulation of VEGF in benign colonic polyps are poorly described. Activation of the Wnt (APC beta-catenin) and K-ras signaling pathways is characteristically observed in these colon polyps. Preliminary studies demonstrate the novel upregulation of VEGF by Wnt signaling. In addition, K-ras regulates VEGF expression in a phosphatidyl inositol 3-kinase dependent manner. Furthermore, K-ras functions synergistically with the Wnt pathway to upregulate VEGF. To address the hypothesis that these signaling pathways that are frequently altered in early colonic neoplasia may also play an important role in angiogenesis through the regulation of VEGF, the following specific aims are proposed: (1) to define the critical cis-regulatory elements in the VEGF promoter that mediate Wnt signaling. (2) to define the K-ras effector pathways that regulate VEGF expression, and (3) to define the interaction of hypoxia with Wnt signaling in the upregulation of VEGF. Collectively, these studies will highlight the important role of angiogenesis in premalignant colonic polyps and provide the foundation for novel strategies that specifically target angiogenesis in the prevention of these colon cancer precursors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETIC VARIABILITY IN COLORECTAL NEOPLASIA Principal Investigator & Institution: Gerner, Eugene W.; Professor; University of Arizona P O Box 3308 Tucson, Az 857223308 Timing: Fiscal Year 2002; Project Start 05-SEP-2002; Project End 31-MAR-2007 Summary: (provided by applicant): The translational goal of this project is to develop simple blood tests to predict colon cancer risk and to tailor therapy for colorectal intraepithelial neoplasia (IEN). Diagnosis of colon cancer at an early stage continues to be problematic, and response to treatment is limited in late stage colon cancer. Better measures of risk will contribute to colon IEN prevention or earlier detection. Earlier detection combined with methodologies to predict response to therapy will decrease colon cancer incidence and mortality. The hypothesis to be tested in this proposal is that the risk of colorectal cancer is influenced by genetic variability affecting the expression/function of the adenomatous polyposis coli (APC) tumor suppressor gene and/or APC modifier genes, such as ornithine decarboxylase (ODC). Measures of this genetic variability may be prognostic and/or predictive factors for colorectal IEN. To test this hypothesis, four specific aims are proposed. First, we will measure specific mutations in the APC tumor suppressor gene in colorectal adenomas from participants in colon cancer prevention trials. Second, we will measure germline polymorphism frequencies in codon 1822 of APC. We will determine associations between genetic variability in APC with dietary factors and adenoma recurrence in this patient group. Third, we will measure the genetic variability in the c-myc-dependent region of the ODC promoter in groups at risk for colorectal IEN, and determine whether polymorphisms are associated with adenoma recurrence. Finally, we will ascertain the functional significance of these polymorphisms in intestinal carcinogenesis. Future studies will measure variability in other downstream mediators of APC. These other mediators include networks regulating polyamine and arachidonic acid metabolism. Since these pathways are targets for IEN therapy (e.g., DFMO, NSAIDs), genetic

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variability in these pathways may be predictive factors for therapeutic response to treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETICS OF MAXILLARY/MANDIBULAR DISCREPANCIES Principal Investigator & Institution: Krebs, Linda J.; None; University of Connecticut Sch of Med/Dnt Bb20, Mc 2806 Farmington, Ct 060302806 Timing: Fiscal Year 2003; Project Start 29-SEP-2003; Project End 31-MAY-2008 Summary: (provided by applicant): The proposed plan for the K22 award is a one-year scholar phase, followed by a four-year faculty development phase. The scholar phase will provide for advanced postdoctoral training in the laboratory of Dr. Andrew Arnold at the University of Connecticut Health Center. This phase of mentored training will afford me the opportunity to focus my efforts on research and career development. During this phase, we will study the molecular mechanisms of hyperparathyroidism (HPT). Most cases of primary HPT are due to a solitary benign adenoma in one of the parathyroid glands. Molecular allelotyping and CGH have been used to identify areas in the genome where tumor suppressor genes involved in parathyroid tumorigenesis might be located. Interestingly, the frequent findings of LOH on chromosome 6 and 15 are commonly present in adenomas, but have not been noted in parathyroid carcinomas, suggesting that parathyroid adenomas and carcinomas may develop along separate pathways. This study will focus on deciphering the genetic changes that are particular to parathyroid adenomas through analysis of genetic losses and gene expression on chromosome 6 and 15. The hypothesis of this study is that the areas of LOH on chromosomes 6 and 15 are indicative of tumor suppressor genes, that when inactivated by mutation, contribute to benign parathyroid neoplasia. The research proposed for the faculty phase will study the genetic basis of non-syndromic maxillary/mandibular discrepancies, using many of the same techniques as the scholar phase project. The emergence of technologies to investigate complex human trait genetics has made it possible to begin to sort out the genetic basis of specific and quantifiable phenotypes. Relatively common skeletally based dentofacial dysmorphologies can result from discrepancies in the size, shape and/or position of the mandible and/or the maxilla. Such skeletal discrepancies can be classified into specific phenotype groups in order to construct genotype-phenotype maps for such dysmorphologies. The proposed research plan is to perform a genome wide screen to identify the quantitative trait loci (QTL) associated with the phenotypes being studied, and to narrow these regions to identify the candidate and/or novel genes involved in the craniofacial dysmorphologies investigated in this proposed project. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GONADOTROPH ADENOMAS: PREVALENCE & PHARMACOLOGY Principal Investigator & Institution: Snyder, Peter J.; Professor of Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GONADOTROPINS & COX-2 IN OVARIAN CANCER PREVENTION Principal Investigator & Institution: Xu, Xiangxi; Member; Fox Chase Cancer Center Philadelphia, Pa 191112434 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 30-APR-2008 Summary: (provided by applicant): The gonadotropin stimulation hypothesis is a leading idea in the etiology of ovarian cancer explaining the association of cancer risk with the number of ovulatory cycles. However, gonadotropins have only unremarkable effects on the growth of ovarian surface epithelial cells in culture. Thus, a convincing mechanism for the ovarian carcinogenic activity of gonadotropins is lacking. Recently, we found that pre-neoplastic ovarian surface epithelia that are located immediately adjacent to morphologically neoplastic lesions often lack basement membranes and have proposed that the loss of basement membrane is an early step in ovarian tumorigenicity. Thus, we hypothesize a mechanism for the carcinogenic effect of gonadotropins, that the hormones stimulate the loss of basement membranes similar to pre-ovulatory events. As a result, the frequent placement of the ovarian surface epithelium in such a basement membrane-less, pre-neoplastic stage by repeated gonadotropin stimulation increases the frequency for tumor prone cells to transform Gonadotropins induce Cox-2 in both granulosa and surface epithelial cells to mediate ovulation, and the loss of basement membrane and other ovulatory events can be blocked by inhibition of the Cox enzymes. The W or Wv mice are predisposed to tubular adenoma formation from the ovarian surface epithelium. The cause of ovarian neoplasm is thought to be the elevated serum gonadotropins in these spontaneously mutant mice. Another genetically engineered mutant mouse, the Disabled-2 (Dab2) heterozygous knockout model, is also predisposed to the development of ovarian surface epithelial dysplasia and papillomatosis, the premalignant lesions of ovarian cancer. We speculate that the combination of Wv/Wv and Dab2 () genotypes will augment the predisposition to ovarian neoplasm. We will test if the inhibition of Cox enzymes reduces the gonadotropin stimulated basement membrane loss, and inhibits or reduces the predisposition of the Wv/Wv, Dab2 () mice to develop ovarian tumors. To investigate the mechanisms, we will also examine the effects of gonadotropin stimulation on the expression of Cox-2, collagen IV, laminin, and MMPs in ovarian surface epithelial cells in culture. These studies will help to understand the etiology of ovarian cancer related to gonadotropins, and provide a mechanism(s) for the chemopreventive activity of Cox-2 inhibitors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GREAT LAKES NEW ENGLAND CLINICAL AND EPIDEMIOLOGY CENTER Principal Investigator & Institution: Brenner, Dean E.; Professor; Internal Medicine; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 15-MAY-2000; Project End 28-FEB-2005 Summary: We propose to establish a Clinical-Epidemiology Center Consortium consisting of the collaboration of the following Institutions and their respective consortium partners: University of Michigan Medical Center- University of Michigan Cancer Center, Dartmouth Medical School- Norris Cotton Cancer Center, the Dana Farber Cancer Institute, Wellesley-St. Michael Hospital of Toronto, and the Henry Ford Medical System. We propose to pool our clinical experience to address the needs of the Early Detection Network by providing a large human subject pool for prevention clinical research, by devising innovative approaches to the validation of biomarkers, by

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sharing samples with Network laboratories and clinical centers, and by closely interacting with Network Biomarkers Development and Validation Laboratories. The following Specific Aims are proposed: l. Initiate validation studies for selected biomarkers for colorectal adenomas and cancers; 2. Refine statistical criteria for a clinical biomarker validation program, 3. Establish organizational structure for clinical studies of biomarkers for research in colon and other cancers, 4. Establish mechanisms for use of development funds; and 5. Describe quality assurance procedures. Specific Aim #1 will be addressed through a four stage biomarker validation paradigm. The first stage consists of characterization studies to individual variability of a biomarker. The second stage consists of an intermediate size cross sectional validation trial. The third stage consists of a longitudinal observational trial. The fourth stage consists of a randomized, double blinded chemoprevention validation trial. In this application, we propose to validate five potential serum biomarkers and aberrant crypt foci as a pathologic biomarker. Specific Aim #2 will be addressed through the development and prospective testing of newly developed statistical methods designed to assess biomarker efficacy in panels. Specific Aim #3 will be addressed by establishing an Operations Center at the University of Michigan, a Data Management Unit at Dartmouth Medical School, and staffing all clinical sites with a dedicated clinical research associate experienced in sample collection, handling, tracking, shipment and data management. Specific Aim #4 will be addressed through two proposed development projects, one assessing K-ras in stool guaiac samples and a second studying cytochrome P-450 isozymes in tissue samples. The a procedure for review of development projects is described. Specific Aim #5 is addressed through description of data management, laboratory, pathology, and endoscopic quality control procedures. Our consortium, while focused upon the validation of biomarkers for colorectal cancer provides extensive, diverse human populations from which to validate early detection biomarkers for high priority cancers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HEMOSTASIS SYSTEM IN TUMOR GROWTH AND METASTASIS Principal Investigator & Institution: Ploplis, Victoria A.; Research Professor; University of Notre Dame 511 Main Bldg Notre Dame, in 46556 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2009 Summary: Previous studies have identified relationships between hemostasis and tumor growth and metastasis. Clinically, elevated plasma levels of these proteins have been suggested as prognostic markers for relapse and reduced survival. While these correlates exist, specific in vivo mechanisms by which this system contributes to the pathology of the disease remains largely unknown. Several clinical studies have identified components of the hemostasis system in regulating the pathology of a number of cancers. While a number of genes have been implicated in various stages of colon cancer, mutations in the adenomatous polyposis coli (APC) gene have been found during the early stages of adenoma formation, and it is believed that this gene is involved in tumor development and progression. Mutations of this gene result in familial adenomatous polyposis (FAP), which is characterized by the formation of multiple colonic adenomatous polyps. These adenomas predispose to the development of colon carcinoma. A mouse model (APC[Min+/o] )has been developed that mimics the clinical features of FAP. Therefore, studies to directly determine the role of hemostasis in this cancer can be effectively studied in APC[Min+/o] mice with additional alterations inexpression of hemostasis proteins. Specifically this study is focused on: 1) utilization of the spontaneous tumor model, APC[Min+/o], with additional alterations in expression of components of the hemostasis system and

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comparisons of tumor development and dissemination in these various genotypicallydistinct groups. This will involve analyses of tumor growth rate, spatial and temporal involvement of proteins and other host cells, and extent of vascularization, associated with tumor progression; 2) identification and quantitation of the relative abundance of angiogenic factors in primary and metastatic tumors utilizing quantitative real-time RTPCR (Q-RT-PCR) and determination of the spatial expression patterns by in situ hybridization. Since preliminary studies in our laboratory have demonstrated an attenuation of the pathology in APC[Min+/o]/UPA-/- mice relative to APC [Min+/o] or APC[Min+/o]/PG-/- mice 3) characterization of the mechanism associated with the uPA/uPAR system in the regulation of intestinal/colonic tumor formation will be assessed. This will include in vitro and in vivo analyses of effects on proteins associated with cell signaling pathways, and generation of mice with targeted mutations of uPA with specific alterations of domains associated with receptor interaction and proteolytic activity, in order to further elucidate functional domains of uPA involved in regulating tumor formation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HEPCIDIN EXPRESSION IN THE ANEMIA OF CHRONIC DISEASE Principal Investigator & Institution: Weinstein, David A.; Children's Hospital (Boston) Boston, Ma 021155737 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): The pathogenesis of the anemia of chronic disease is not understood. A recently identified peptide, hepcidin, has been found to be aberrantly expressed in hepatic adenomas in GSD (GSD), resulting in an iron-resistant irondeficiency anemia similar to that seen in the anemia of chronic disease. Hepcidin is postulated to be involved in the pathogenesis of the anemia of chronic disease, and these investigations are aimed at characterizing the role of hepcidin in both normal iron homeostasis and in subjects with the anemia of chronic disease. The specific aims are the following: 1) To evaluate the relationship between adenoma tumor burden and anemia; 2) To characterize iron absorption and distribution in normal controls, anemic patients, and patients with GSD Type 1 at (GSD1a; 3) To compare hepcidin expression in normal individuals and patients with GSD1a, and 4) To determine the role of hepcidin as a mediator of the anemia of chronic disease in patients with other inflammatory conditions. Methodology: The relationship between iron homeostasis and hepcidin expression will be studied in normal and pathologic states including GSD1a, juvenile rheumatoid arthritis, and inflammatory bowel disease. As inappropriate hepcidin expression has been demonstrated in hepatic adenomas in patients with GSD, direct observational studies in this population will be performed to allow further clinical correlation between these lesions and indices of erythropoiesis and iron status. Oral absorption of iron will be investigated in all subjects to define the relationship between hepcidin and iron absorption. For the inflammatory disorders, the oral iron challenge tests and direct measurement of hepcidin will be performed during periods of disease remission and exacerbation. The relationship between hepcidin and inflammatory markers will also be investigated. Through these studies, the role of hepcidin as a mediator of anemia of chronic disease will be elucidated. Improved understanding of the pathophysiology of the anemia of chronic disease will lay the foundation for new treatments for anemia and disorders of iron homeostasis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HORMONE REGULATION AND PATHOGENESIS OF PITUITARY TUMORS Principal Investigator & Institution: Klibanski, Anne; Professor of Medicine; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 01-MAR-1989; Project End 28-FEB-2003 Summary: Human pituitary tumors of a gonadotroph cell origin represent up to 30% of all diagnosed pituitary neoplasms. Clinically, these tumors cause considerable morbidity because of mass effect, resulting in cranial nerve compression syndromes, including visual loss and other neurologic deficits, and there are no established adjunctive medical therapies to control tumor growth. A major finding regarding the pathogenesis of human pituitary tumors in our previous grant period was that such tumors are monoclonal in origin, demonstrating that somatic mutation is a requisite event in tumor formation. The next critical questions are what mechanisms underlie selective clonal proliferation in pituitary tumors, and what mechanisms underlie the pathogenesis of specific adenoma phenotypes. Activins are TGF beta- related cytokines which function as both growth and differentiation factors, and have been shown to the synthesized by human pituitary tumors. Locally secreted activin has been demonstrated to be a novel, potent and selective growth and differentiation factor in normal pituitary. Novel preliminary data presented in this proposal demonstrates that exogenous activin can decrease cellular proliferation in vitro in human tumors of a gonadotroph or, somatotroph cell origin, This is the first demonstration of a pituitary-derived autocrine factor which has anti-proliferative effects in a significant percentage of these tumors. However, a subset of human gonadotroph tumors do not respond to exogenous activin. A lack of responsiveness to activin by a subset of human tumors strongly suggests that there are underlying receptor, and/or, intracellular signal defects in such tumors, a hypothesis which will be investigated in this proposal. Alterations in cell-surface receptor gene expression by pituitary adenomas may be an underlying cellular mechanism modulating cell proliferation. The loss of activin-responsiveness by the significant number of tumors may be indicative of loss of functional activin cell-surface receptors, as has been shown for, human lymphoid and colorectal cancers. This proposal will examine activin receptor, gene expression in human pituitary tumors. We have now identified novel human pituitary tumor-specific activin type I receptor isoforms which lack a full-length intracellular serine/threonine kinase signaling domain. Our proposed studies will investigate tumor-specific expression of these potential dominant- negative truncated receptor forms and whether expression of these receptor forms prevents activin anti-proliferative effects. We will functionally test this hypothesis by introducing full length Alk4 type I receptor into primary human pituitary tumor cultures and reestablishing activin responsiveness to exogenous activin. The hypothesized dominant negative phenotype of truncated Alk4 receptor, isoforms will also be functionally tested in human cell lines,including an erythroleukemic cell line known to growth arrest in response to activin, as well as established pituitary somatotroph and corticotroph cell lines. Our proposal focuses on the molecular, mechanisms of pituitary tumorigenesis and the potential anti-proliferative role of activin and its receptors in regulating pituitary tumor growth. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HUMAN INTESTINAL DRA--FUNCTION AND REGULATION Principal Investigator & Institution: Alrefai, Waddah A.; Medicine; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2005

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Summary: (provided by applicant): The current proposal is aimed at providing the PI with extensive training in advanced molecular biology along with formal courses at the graduate level to enhance his research and laboratory skills. The experienced sponsorand co-sponsor, along with a highly interactive basic-research environment at the section of Gastroenterology at the Univ. of IL at Chicago, offer a great training opportunity for the PI to achieve his career goals in becoming an independent basicresearch investigator in the area of the physiology of intestinal transport. The proposed studies are aimed at examining the exact role of the DRA (Down Regulated in Adenoma) gene in the intestinal Cl- absorption. The DRA gene was shown to be mutated in patients with Congenital Chloride Diarrhea (CLD) disease, where the basic defect is an impaired intestinal apical membrane Cl-/HCO3 exchange process. However, DRA cDNA has a high sequence homology with sulfate transporters. DRA was initially shown to be a sulfate/oxalate transporter. Data from few recent studies also indicated that DRA might function as a Cl- transporter. However, in contrast, our recent studies along with studies from other laboratories provide strong evidence that DRA itself may not encode for the conventional intestinal luminal Cl-/HCO3' exchanger. Therefore, it is critical to investigate the precise functional role of DRA in Cltransport. In Specific Aim 1, we will examine the role of DRA utilizing the anti-sense technique to attenuate its endogenous expression in Caco2 cells and study its effect on SO4--and Cl- transport processes, along with Structure/Function studies to reveal the mechanism(s) by which DRA mutations affects the intestinal Cl- transport. Specific Aim 2 will focus on the mechanism(s) involved in DRA targeting to the plasma membrane. In Specific Aim 3, we will elucidate the transcriptional regulation of DRA, whereas in Specific Aim 4, we will identify proteins interacting with DRA, and possibly a novel intestinal apical membrane Cl- /HCO3 exchanger by screening human colonic cDNA library utilizing the Yeast Two-Hybrid System. The proposed studies will significantly enhance our understanding of the pathophysiological basis of Congenital Chloride Diarrhea and diarrhea in other colonic diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HUMAN PROLACTIN SECRETION IN VARIOUS ENDOCRINE DISORDERS Principal Investigator & Institution: Arafah, Baha M.; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2002; Project Start 01-DEC-2001; Project End 30-NOV-2002 Summary: Prolactin levels are determined in patients with pituitary dysfunction during dynamic provocative stimulation. The emphasis is on patients with prolactin secreting pituitary adenomas, pre and post surgical adenomectomy. Patients with hyperprolactinemia and hypopituitarism are also being studied under this protocol. The dynamic studies in the latter group is likely to help define the mechanism of hypopituitarism in these patients. The data documenting the usefulness of prolactin dynamic studies in predicting the long term benefit from transsphenoidal surgery in patients with prolactin secreting pituitary adenomas were published in 1986. Prolactin levels are often elevated in patients with functioning or non functioning adenomas associated with hypopituitarism. Our study has demonstrated that the degree of prolactin level elevation under these situations, correlate with the potential for recovery of pituitary function after decompressive surgery. We are in the process of comparing and contrasting data on the dynamics of prolactin secretion with that obtained from evaluating the pulsatile aspect of prolactin secretion in the same patients. The long term follow up of patients who had surgical resection of pituitary adenomas 10 to 25 years

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ago, is being assessed. We have a major advantage in following a relatively large number of these patients to allow us to do these long-term studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INHIBITION OF COLON TUMOR PROGRESSION BY INK4A/ARF Principal Investigator & Institution: Enders, Gregory H.; Assistant Professor; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-APR-2008 Summary: (provided by applicant): Colon carcinoma is the second most common fatal human malignancy and has served as a prototype for studies of tumor progression. Recently, vascularity has emerged as a limiting factor in solid tumor development and a clinically important feature in the detection, recurrence, and therapy of colon tumors. The Ink4a/Arf locus encodes p16Ink4a (p16) and p19Arf (Arf; alternative reading frame). Both proteins are tumor suppressors and potent mediators of cell cycle arrest and senescence in vitro. The Ink4a/Arf locus is frequently silenced by methylation in colon adenoma and carcinoma. This observation suggests that the locus may suppress colon tumorigenesis, but direct evidence has been lacking. We examined the effect of a deletion of the locus in mice with multiple intestinal neoplasia (Min). We have found that Min colon tumors show accelerated tumor progression in the absence of p16 and Aft. These tumors are larger, show histologic features of carcinoma, and, most prominently, are more vascular. The latter feature is accompanied by increased vascular endothelial growth factor (VEGF) content. We propose here to dissect the molecular basis of the phenotype. In Aims 1 and 2, respectively, we will determine the individual impacts of p16 and Arf on Min colon tumor progression, using mice selectively deficient in each protein. We will analyze expression of p16 and Arf in Min colon tumors and assess whether methylation and silencing of the p16 or Arf promoters correlates with features of tumor progression. We will assess the impacts of p16 and Arf on tumor cell cycle arrest and senescence. In Aim 3 we will explore the significance of the vascular phenotype for tumor progression. We will generate Min mice with targeted deletion of the VEGF gene in the intestinal epithelium, in Ink4a/Arf-null and -wild type backgrounds, and examine the consequences for colon tumor progression. In Aim 4, we will examine the regulation of VEGF expression in Min colon tumor cells in vivo and in vitro and will test whether antibodies directed against VEGF disrupt the ability of tumor cells to recruit vascular endothelial cells. In summary, these studies will define key determinants of colon tumor progression and vascularity, improve our understanding of p16 and Arf function in physiologic settings of tumor suppression, and address the significance of the enhanced vascularity for colon tumor progression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: INSULIN RESISTANCE AND ADENOMAS OF THE COLORECTUM Principal Investigator & Institution: D'agostino, Ralph B.; Associate Professor; Public Health Sciences; Wake Forest University Health Sciences Winston-Salem, Nc 27157 Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 30-JUN-2004 Summary: There is considerable evidence that insulin and/or insulin-like growth factors (IGFs) can increase risk of colorectal neoplasia. Epidemiologic risk factors for colorectal neoplasia are similar to those for insulin resistance syndromes, and prospective studies have shown both diabetes and higher levels of IGF-1 to be associated with colorectal cancer risk. No previous studies have included direct measures of insulin resistance, nor have any included complete ascertainment of colorectal neoplasia by direct examination

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of the entire colorectum. This study will assess the relationship between insulin resistance and colorectal neoplasia by taking advantage of a unique opportunity to examine a multi-ethnic cohort on whom prior measures of insulin sensitivity have been made. The Insulin Resistance and Atherosclerosis Study (IRAS) is a cohort study supported by the National Heart Lung and Blood Institute. IRAS examined 1628 people of average age 55 in 1991-1994 for atherosclerosis risk factors. The cohort, assembled in four clinical centers (Alamosa, Co., Los Angeles, Oakland, and San Antonio) was established to be multi-ethnic (34 percent Hispanic, 28 percent African American, and 38 percent non-Hispanic white), bi-gender, and varied in diabetes risk. In 1998-1 999 over 85 percent of the surviving cohort was re-examined. Both of the examinations have included measures of self-reported risk factors for atherosclerosis (diet, physical activity, tobacco use, family history) as well as anthropometry and, most importantly, oral glucose tolerance testing and frequently-sampled intravenous glucose tolerance tests (FSIGT). The FSIGT is a sensitive and specific measure of insulin resistance. All surviving cohort members (estimated 1518) will be invited to have a screening colonoscopy. Feasibility data indicate that 1000 will agree to have a colonoscopic exam, among whom we estimate 240 (range 206-274) will have adenomas. Mucosal biopsies will be taken from the cecum and rectum of all subjects, and all adenomas will be removed and examined for histologic features, Ki-ras mutations, proliferation, and apoptosis. Serum samples will be assayed for insulin, IGF-1, IGFBPI, and IGFBP3 levels for all cohort members at both the time of colonoscopy, as well as at the time of two earlier examinations (199 1-4 and 1998-9) using stored serum samples. This study offers the advantage of the availability of prospective measures of glucose tolerance, insulin resistance, measurements of most colorectal neoplasia risk factors, and the availability of stored blood samples from a multi-ethnic and bi-gender cohort. Complete colorectal visualization of this entire cohort will enable unbiased estimates of colorectal neoplasia risk related to these factors. This study therefore offers a time-efficient and a costefficient method to test the hypothesis that colorectal neoplasia risk is increased substantially by factors related to insulin resistance, and to examine the biologic mechanisms whereby that risk is increased. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INSULIN, THE IGF AXIS, AND COLORECTAL NEOPLASIA Principal Investigator & Institution: Limburg, Paul J.; Senior Associate Consultant; Mayo Clinic Coll of Medicine, Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 30-JUN-2006 Summary: (provided by applicant): The Cancer Prevention, Control, and Population Sciences Career Development Award will provide an excellent opportunity for me to acquire and refine the skills necessary to conduct high-quality gastrointestinal cancer prevention research at a population level. My proposed research plan involves the rigorous evaluation of a timely central hypothesis with direct relevance to colorectal cancer prevention. Using a series of different general, molecular, and genetic epidemiologic approaches, I intend to explore unresolved or unexamined issues related to the possibility that hyperinsulinemia, either alone or in combination with insulin-like growth factor (IGF) axis proteins, is causally linked to colorectal carcinogenesis. Existing data from cell culture experiments, animal model systems, and human observational studies support this hypothesis, yet many essential questions remain to be addressed. In the context of mentored research, I plan to perform (1) a historical cohort study of type 2 diabetes mellitus (DM) and colorectal adenocarcinoma risk, (2) a case-control study of type 2 DM and colorectal adenoma risk, (3) a nested case-control study of serum

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insulin/IGF axis protein concentrations and colorectal adenocarcinoma risk, (4) a pilot study of IGF axis mRNA expression levels in neoplastic versus non-neoplastic colorectal mucosa, and (5) a prospective cohort study of IGF axis gene polymorphisms among subjects with or without colorectal neoplasia. These studies should provide meaningful scientific data, while simultaneously affording me a broad exposure to and considerable experience with several important investigational tools. To further enhance my career development, I plan to obtain didactic training in areas relevant to gastrointestinal cancer prevention research (including the responsible conduct of research). Additionally, I intend to serve as an instructor for a cancer epidemiology course at Mayo Graduate School. The resources of my sponsoring institution are excellent and will facilitate the successful, efficient completion of my overall objectives. Following achievement of these goals, I am confident that I will be ready to continue my career as a successful independent investigator committed to academic research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MAGNETIC RESONANCE METHODS FOR GUIDING THERMAL THERAPY Principal Investigator & Institution: Mulkern, Robert V.; Associate Professor; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 06-SEP-2002; Project End 31-AUG-2004 Description (provided by applicant): Thermal treatment of some breast cancers may become an effective, minimally invasive, therapeutic tool given proper guidance of the thermal deposition. Proper guidance implies that the diseased tissue must be clearly identified and heated to an appropriate temperature for an appropriate length of time to insure effective cell destruction while cell damage to neighboring, healthy tissue is minimized to as great a degree as possible. Clearly an advantage can be gained if the thermal treatment can be combined with an imaging modality capable of monitoring the tissue temperature changes which occur during the heating process in order to maximize damage to diseased tissue while minimizing damage to healthy tissue. We believe that Magnetic Resonance Imaging (MRI) provides such a modality but that the full potential of MR for guidance of thermal therapy remains largely untapped due to the need for further technical development. For instance, a major limitation with current state-of-the art MR thermometry pulse sequence design is the dependence on baseline subtraction methods for temperature change measurement. Interscan motion, largely unavoidable in clinical situations, makes the dependence on baseline subtraction methods highly problematic for robust temperature monitoring. Another limitation, particularly pertinent to the breast, is interference from the lipid signal which confounds MR temperature measurements made on the assumption that the signal arises solely from the water resonance, the current method of choice in most experimental MR thermometry studies to date. The focus of this proposal is to develop novel MR pulse sequences which take advantage of state-of-the-art gradient hardware to overcome these limitations so that MR guidance of breast tumor ablation can become an efficient therapeutic reality. A cornerstone of the work is that the temperature sensitive water frequency can be referenced to the temperature insensitive fat frequency to allow for internally referenced temperature change measurements. It is proposed that this novel approach will simultaneously solve problems associated with interscan motion and baseline subtraction methods as well as lipid contamination. The proposal focuses on the development and testing of techniques for MR guided thermal therapy in the breast. These techniques have some unique properties which may, however, prove useful in

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other areas of medical imaging such as breathhold spectroscopic studies in the abdomen or functional MRI studies of the brain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MATRILSIN AND TUMOR PROGRESSION Principal Investigator & Institution: Matrisian, Lynn M.; Professor and Chair; Cancer Biology; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2003; Project Start 04-AUG-1993; Project End 31-MAR-2007 Summary: (provided by applicant): This application is a continuation of studies focused on the role of the matrix metalloproteinase MMP-7 (matrilysin) in colorectal cancer. In previous funding periods, we demonstrated that MMP-7 gene expression is directly regulated by signal transduction pathways activated by the loss of function of the "gatekeeper" APC gene, and that the induction of the MMP-7 gene product significantly contributes to early stage intestinal tumorigenesis. Pharmacological or genetic elimination of MMP-7 results in fewer adenomas and prolonged survival in a mouse model of hereditary polyposis. Synthetic MMP inhibitors have been tested in Phase III clinical trials in advanced cancer settings with disappointing results. The overall goal of this application is to apply the lessons learned from the initial clinical trials to optimize the use of MMPIs for colon cancer prevention and treatment, and to identify novel targets for the development of chemopreventive agents to treat patients at risk for colon cancer. In aim 1, we will develop a surrogate assay for inhibition of MMP activity and optimize the use of MMPIs in the prevention of intestinal adenomas and the control of liver metastasis. In aim 2, we will determine if the tumor promoting effects of MMP-7 are mediated by a direct effect on intestinal epithelial cells or are dependent on microenvironmental influences using a cellular reconstitution assay. In aim 3, we will use tissue proteomics to identify MMP-7 substrates relevant to intestinal tumorigenesis. In aim 4, in conjunction with the "Protease Consortium", we will test the hypothesis that multiple proteolytic pathways contribute to intestinal tumor progression by using oligonucleotide microarrays to identify extracellular proteases that are upregulated in adenomas, and determine their potential as targets for the prevention of colorectal cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MECHANISM /EFFICACY /CHEMOPREVENTION AGENTS /LUNG CANCER Principal Investigator & Institution: Anderson, Marshall W.; Director; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2003; Project Start 23-MAY-2003; Project End 30-APR-2008 Summary: Lung cancer is the leading cancer killer in the US with 160,000 deaths and 178,000 new cases diagnosed in 1997. Our long-term goal is to develop chemoprevention strategies to prevent the progression of lung tumorigenesis in high-risk current and former smokers. This Project will focus on the agents budesonide, Polyphenon E (a green tea extract), difluoromethylornitihine (DFMO) and myo-inositol as these agents are 1) effective in the post-initiation phase of lung tumorigenesis; 2) effective in rodent lung adenocarcinoma models and 3) have a history of therapeutic or dietary use. The Project will test the hypothesis that the efficacy of these compounds in combinations during adenoma formation and progression of adenomas to dysplasias and adenocarcinomas of lung tumorigenesis in A/J mice will be greater than the efficacy of any single agent with the goal of lowering doses, and potentially harmful side effects,

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without decreasing efficacy. As budesonide, a glucocorticoid agonist, and (-)epigallocatechin gallate (EGCG, the major component of Polyphenon E) are known to block activation by the AP-1 and NF-kB family of transcription factors, the levels of AP1 and NF-kB activity in mouse lung adenocarcinomas will be determined with and without treatment with chemopreventive agents using AP-1 or NF-kB responsive reporter genes in transgenic mice. The second hypothesis that AP-1 and NF-kB inhibition is a major mechanism of lung cancer chemoprevention will be tested directly by assaying tumor formation in transgenic animals that inducibly express dominant negative mutants of c-jun (AP-1 pathway) and IkBa (NF-kB pathway) in the respiratory epithelium. Upon completion of this project we will have defined if lower doses of known chemopreventive agents, when used in combination, are less toxic and more effective than single agents and whether AP-1 and/or NF-kB blockade in the respiratory epithelium is an important mechanism for suppression of lung tumor initiation and progression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISM OF TUMOR SUPPRESSION BY P27 Principal Investigator & Institution: Fero, Matthew L.; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2002; Project Start 28-SEP-2001; Project End 31-AUG-2004 Summary: Matthew Fero is a medical oncologist with research interests which focus on the role of cell cycle genes the development of cancer and in the control of cell growth. This award permits Dr. Fero to further our understanding of tumor suppression by the cell cycle inhibitor (CKI) gene p27kip1, while making a transition in his career from the position of a mentored researcher to an independent investigator. The proposed studies utilize the skills Dr. Fero has acquired in the manipulation of the mouse embryo to produce mutations in laboratory mice which are specific both to genes of interest and confined to particular tissues. These novel gene mutations will then be combined with well defined murine models of induced carcinogenesis and gene expression analysis to define the mechanism of tumor suppression of p27 and it's biochemical effects in tumorigenesis. By developing mice which harbor cell cycle gene mutations confined to the pituitary or thymus it will be determined whether the p27kipI can induce adenomas and lymphomas in these tissues in an autonomous fashion, that is independent of the influence of factors from surrounding cells or tissues. Likewise analysis of intestinal tumors, lymphomas and prostate tumors developing in mice which are genetic mosaics for p27 gene mutations will determine whether these tumors also arise in an autonomous fashion. The mechanism of tumor suppression by p27 will be further defined in each model system and the patterns of altered gene expression and cell cycle protein function will be characterized. If p27 mutations cause tumors in a cell nonautonomous fashion it will be important to determine the signaling pathway which acts between the p27 deficient cell and the neoplastic cell. Therapeutic agents may then be targeted at either the cell cycle proteins or the intracellular molecules which mediate cancer development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MECHANISMS FOR PITUITARY TUMORIGENESIS Principal Investigator & Institution: Melmed, Shlomo R.; Professor and Director; CedarsSinai Medical Center Box 48750, 8700 Beverly Blvd Los Angeles, Ca 900481804 Timing: Fiscal Year 2002; Project Start 15-DEC-1998; Project End 30-NOV-2003

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Summary: Pituitary adenomas are common benign neoplasms giving rise to disorders of growth, reproductive function, cortisol production and local central pressure effects. Although recently determined to be monoclonal, the genetic mechanisms involved in pituitary cell transformation are unclear. This proposal will characterize the transforming properties of PTTG, a novel pituitary tumor derived protein. We used differential RNA display to identify a rat pituitary derived transforming gene (PTTG) which encodes a 199 a.a. novel protein. Now, we will isolate and study human PTTG and assign its chromosomal locus. PTTG expression will be tested in hormone- secreting (PRL, GH, ACTH) and non-functional pituitary tumors, and its abundance assessed as a function of pituitary adenoma grading, invasinenes, hormonal activity and ultimately long-term clinical outcome. Cellular localization of PTTG will also be determined in these tumors by double immunostaining and in situ techniques. Models of pituitary enlargement (pregnancy and estrogen-induced prolactinomas) will be used to determine PTTG expression in the pathogenesis of the pituicyte to hyperplasia to adenoma formation. PTTG in vitro and in vivo transforming properties will be determined in double agar transformation assays, nude mouse tumorigenesis and growth factor regulation will be assessed. Effects of inducible PTTG expression on cell proliferation will also be assessed. These studies will thus provide mechanistic insight into the pathogenesis of prolactinomas, acromegaly, Cushing's Disease and non-secreting pituitary tumors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MINORITY PREDOCTORAL FELLOWSHIP PROGRAM Principal Investigator & Institution: Rios, Yesenia; Molecular, Cellular & Dev Biol; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2003; Project Start 21-AUG-2003; Project End 20-AUG-2007 Summary: (provided by applicant): Pituitary tumorgenesis is likely to be associated with mutations or derangements of normal corticotrophspecific regulatory pathways. Understanding how corticotroph-lineage develops in normal embryos will help elucidate mechanisms underlining corticotroph tumor ontogeny. Corticotroph ontogeny during vertebrate development involves molecular pathways distinct from other pituitary cell lineages. The critical determinants of corticotroph differentiation remain largely unclear. Both transcription factors and soluble molecules signaling via Jak/STAT pathways are involved in corticotroph development and pro-opiomelanocortin (POMC) expression. Using POMC expression as an entry point, I propose to study genetic and molecular mechanisms underlying corticotroph determination and differentiation in zebrafish. The aims of this proposal are (1) to elucidate the critical roles of STAT 3 in POMC lineage development; (2) to participate in a genetic screen to identify and characterize essential genes required for development of POMC lineage. My mentor, Dr. Shuo Lin, is an co-PI for a NIH-funded organ-specific genetic screen that utilizes live transgenic zebrafish harboring fluorescent tissues. Transgenic zebrafish expressing green fluorescent protein driven by the POMC promoter offer a unique in vivo model allowing a detailed genetic analysis of POMC-specific cells in living embryos. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MODELS OF DRA GROWTH SUPPRESSION IN COLON CANCER Principal Investigator & Institution: Schweinfest, Clifford W.; Hollings Cancer Center; Medical University of South Carolina P O Box 250854 Charleston, Sc 29425

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Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2007 Summary: The Down-Regulated in Adenoma gene (DRA) was originally identified by subtractive hybridization between a colon adenocarcinoma and adjacent, normal mucosa. It was found to be transcriptionally extinguished in the overwhelming majority of colon adenomas and adenocarcinomas. DRA protein is expressed in the terminally differentiated absorptive mucosal epithelium and, to a lesser degree, in the goblet cells, but not in the stem cell population deeper within the crypt. We (and others) have previously demonstrated that DRA is an anion transporter capable of the inward transport of chloride and sulfate ions. Such a function is consistent with its protein localization. However, we have also discovered another function of DRA that is of more direct interest to the subject of colon tumorigenesis: expression of DRA causes growth suppression. This function is independent of the anion exchange function of DRA. Our working hypothesis is that the Dra knockout mouse, in combination with the p53 knockout and/or the Min mouse will demonstrate colon tumor progression at the level of morphology, histology and/or molecular assessment of cell cycle criteria. The possibility that DRA may be a specific growth suppressor of colonic epithelial cells is a highly innovative concept and of great potential importance given the frequent downregulation of this gene in human colon tumors. The possibility that a mouse strain could be developed that would better mimic the stages of development of the human disease will add a valuable approach to the study of colon cancer. Our long-term goal is to elucidate the pathway between loss of Dra expression at the cell surface and loss of growth control. This proposal will focus on the growth suppressing function of DRA by simultaneously employing several approaches: 1) we will use a Dra knockout mouse model to explore the in vivo effects of loss of Dra expression on the pathology of tumor development in the mouse intestine and on the cell cycle of the intestinal epithelium, 2) we will use a cell culture model in which DRA expression is expressed ectopically in an Adenoviral construct or controlled with a tetracycline-repressible promoter to examine cell cycle alterations, and 3) we will characterize the molecular domain(s) of DRA that are required for growth suppression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR CHARACTERIZATION OF ACF (ABBERANT CRYPT FOCI) Principal Investigator & Institution: Rosenberg, Daniel W.; Associate Professor; None; University of Connecticut Sch of Med/Dnt Bb20, Mc 2806 Farmington, Ct 060302806 Timing: Fiscal Year 2004; Project Start 01-AUG-1999; Project End 30-APR-2009 Summary: (provided by applicant): Colon cancer develops from a combination of genetic and environmental influences. Aberrant crypt loci (ACF) represent a morphologically identifiable premalignant lesion that is associated with colon cancer pathogenesis. We and others have identified a number of alterations in tumor-related genes that may predict their outcome. We intend to fully characterize ACF in terms of their significance in the dysplasia-adenoma-carcinoma sequence. To accomplish this goal, we will examine potential genetic aberrations and expression profiles of ACF at their earliest stages of formation. We will also test how luminal factors induce their growth, focusing on bile acid (BA) composition and bacterial colonization. Finally, we will extend our recent studies on dysregulation of the ARF-p53 circuit, using pdmary epithelial tumor cells (SP-2 cells) recently established from NJ mice. Aim 1 will determine whether genomic instability contributes to colon tumor pathogenesis in AOM-treated mice. We will use CGH and SKY to analyze colon tumors from a panel AOM sensitive strains (A,SWR, FVB/N,Balb/c). We will then use focused BAC arrays

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and global mutational analyses to study ACF that have been stratified by histomorphology. We will confirm altered genes by TaqMan/IHC analysis and representative known genes involved in colon tumorigenesis will be selected for analysis from regions of gain/loss and mutational alterations. Parallel gene profiling of ACF will be undertaken to determine molecular signatures that predict cancer risk in ACF stratified by tumorigenic potential. RNA from laser-captured ACF of varying morphology and predicted growth characteristics will be linear amplified and applied to high-density arrays. Finally, we will use focused BAC arrays to characterize human ACF using candidate regions identified above. Aim 2 will establish the luminal conditions that favor ACF progression, focusing on chemical exposures, bile acids and bacterial colonization. We will test whether bile acids induce altered luminal redox status and inactivate p53 and whether ACF that form reflect these early alterations. We will also test the effects of bacterial colonization on bile acid metabolism and ACF promotion. Aim 3 will determine the mechanism for functional inactivation of p53 that we recently reported in NJ tumors. This is the first in vivo model demonstrating loss of p53 function (DNA binding, target gene regulation) with sequence-normal cDNA. We will use our epithelial tumor cells (SP-2 cells) to study mechanisms and consequences of p53 inactivation. We will examine the responsiveness of p53 in AOM-induced colon cancer cells to p53 activators and determine the posttranslational modification status of p53. We will determine which proteins associate with p53 in the SP-2 cells and determine the influence of identified p53 modifications on p53 activity. Finally, we will evaluate the effects of BAs on p53 function both YAMC and SP-2 cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR EPIDEMIOLOGY OF COLORECTAL ADENOMAS Principal Investigator & Institution: Haile, Robert W.; Professor; Preventive Medicine; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2006 Summary: (provided by applicant): Our overall objective is to conduct more directed studies of main effects of genes and gene-gene and gene environment interactions within selected metabolic pathways of interest in the etiology of colorectal adenomas, accepted precursors of colorectal cancer (CRC). In the parent study for this application, we have DNA and risk factor data on 1,610 subjects (778 cases and 832 controls). We have the following specific aims: 1) Study selected genes and environmental factors relevant to a folate-related pathway. Specifically, we propose to study MTHFR, MTRR, ADH3, which may affect folate metabolism, and XRCC1, XRCC3, OGG1, and MGMT, which may be involved in DNA repair of damage associated with folate metabolism. In addition, we have data already in hand on RBC folates, homocysteine, and DNA methylation that will be incorporated into statistical analyses of these data where appropriate. 2) Study genes that may be involved in the metabolism or transport of bile acids. Specifically, we propose to study SLC10A2, the gene encoding the ilieal sodiumdependent bile acid transporter (ISBT), along with the VDR and EPHX1 genes. We will also conduct analyses to investigate if the main effects of these genes appear to be modified by selected environmental factors that have been hypothesized to affect risk of colorectal adenomas or cancer via an effect on bile acids. 3) To characterize systematically in vitro all non-synonymous SNPs in selected genes of epidemiologic interest, such as EPHXl (alias mEH) and MTHFR, by site-directed mutagenesis of the cloned enzyme, overexpression and appropriate assays, and to characterize systematically in vitro all SNPs in the 5' and 3' UTRs (untranslated region) of selected genes of epidemiologic interest in appropriate reporter constructs, e.g. expressing

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modified firefly luciferase. Our rationale for selecting alleles to be characterized is described in the Study Design and Methods section; 4) As a statistical method to better analyze complex metabolic pathways is further developed by Drs. Thomas and Cortessis, we will apply this method to data generated by this study. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR GENETIC MARKERS OF PRE-MALIGNANT AND PRE-INVASIVE BREAST DISEASE Principal Investigator & Institution: O'connell, Peter; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, Tx 78229 Timing: Fiscal Year 2002 Summary: Morphologically defined non-invasive breast lesions can be organized into categories, from those with little malignant potential (proliferative disease without atypia, PDWA), to those that may be 'initiated' (atypical ductal hyperplasia, ADH), to 'transformed' lesions that are considered to be malignant (ductal carcinoma in situ, DCIS). This series of progressively more abnormal lesions may be examples of evolutionary stages in the development of breast cancer, with each morphological stage representing the impact of cumulative genetic changes, culminating in a transformed cell lineage capable of overcoming controls on growth and differentiation. Our study of these early breast lesions (PDWA, ADH, DCIS), based on genetic loci known to show allelic imbalance (LOH) in invasive breast cancers, has indicated that the majority of these early lesions are themselves clonal neoplasms, the majority of early breast lesions can be thought of as ductal adenomas, with an evolutionary relationship to the invasive and that they commonly share many of the same LOH events found in invasive breast cancer in the same breast. Thus, the majority of early breast lesions can be thought of as ductal adenomas, with an evolutionary relationship to the invasive breast cancers that accompany them. That is, they represent true premalignant breast lesions. We therefore propose: (1) To seek common patterns in the emergence of LOH events as lesions evolve toward higher evolutionary stages, and also to seek patterns which may indicate the risk of a particular lesion's progressing to invasive cancer; (2) To confirm the association of particular LOH patterns in early lesions with progression to invasive disease, in order to guide clinical patient management decisions; and (3) To define in non-familial breast cancer specimens the role of tumor suppressor genes already identified in familial breast cancer, and also to study the role of these genes in the new families collected by our Familial Breast Cancer Registry (Resource B). The overall goal of this project is to identify genetic changes in premalignant breast cells which herald the progression to true malignancy and subsequent invasion, in order to more accurately diagnose and ultimately treat those premalignant lesions with a significant probability of becoming malignant. Measuring these genetic changes could identify patients who would benefit from chemo-prevention therapy. At the same time, we will learn more about the genetic loci which may be involved in the critical early stages of breast cancer evolution. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MOLECULAR GENETICS & EPIGENETICS OF COLORECTAL ADENOMAS Principal Investigator & Institution: Hamilton, Stanley; University of Arizona P O Box 3308 Tucson, Az 857223308 Timing: Fiscal Year 2002

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Summary: (Applicant's Description) Colon carcinogenesis is a multi-step process, with the colorectal adenoma as an intermediate step in the development of cancer. Previous studies have shown that there a two distinct pathways to colon cancer involving specific epigenetic and genetic events: one is associated with the CpG-island methylator phenotype (CIMP) that is characterized by the methylation of specific CpG islands; and the other which does not involve altered DNA methylation. The role of CIMP status in the pathogenesis of adenomas is a new and potentially critical area of investigation. This project tests novel hypotheses related to the role of gene methylation in the pathogenesis of colorectal adenomas. We will verify existing theories relating methylation to specific genetic and biologic events in both adenomas and rectal mucosa. The primary goal of this project is to investigate the hypothesis that presence of the CIMP phenotype adversely affects the recurrence of colorectal adenomas. Secondly, we propose that selenium and celecoxib will differentially affect the CIMP status of recurrent adenomas from Project Ib. Thirdly, we will verify, again in a large population, the association of CIMP status with specific genetic alterations (Ki-ras, p53), and biologic events (COX expression, apoptosis and proliferation). Lastly, we will explore the involvement of a field defect in adenoma pathogenesis by determining the association of age-related DNA methylation and nuclear chromatin alterations in baseline rectal mucosa and the ability of these variables to predict adenoma recurrence. State of the art methods, including microdissection of adenoma tissue, Bisulfite-PCR and MCA for methylation status, automated sequencing for Ki-ras, immunohistochemistry for p53, PCNA, Cox-1, Cox-2, and in-situ TUNEL, and nuclear chromatin texture analysis through photometric imaging will be supported by an extensive QA/QC program. The analyses will be performed in laboratories at MD Anderson, TX (Drs. Hamilton and Issa) and Univ. of Arizona, AZ (Drs. Alberts, Einspahr and Bartels) supported by sophisticated tissue and data management systems. The comprehensive preliminary data demonstrate that this team of collaborators has both the experience and intellectual depth to accomplish the goals of this project. As we describe in detail, we have carefully selected from adenoma and rectal mucosa tissue blocks banks and databases from the completed Phase III WBF Trial and the continuing UDCA (Project Ia) trial and will utilize samples from the proposed selenium and celecoxib trial described in Project Ib. While we have a large and novel population to draw from, we have designed this project to answer complex questions of the pathogenesis of adenomatous polyps while conserving valuable resources. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR GENETICS OF CANCER SUSCEPTIBILITY Principal Investigator & Institution: Siracusa, Linda D.; Associate Professor; Microbiology and Immunology; Thomas Jefferson University Office of Research Administration Philadelphia, Pa 191075587 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2008 Summary: (provided by applicant): The study of genes that influence cancer susceptibility is a rapidly evolving field. The power of mouse genetics coupled with the ability to scan entire genomes of individual animals has led to the discovery that several chromosomal regions harbor genes conferring susceptibility or resistance to different types of cancers. This proposal is focused on identifying and characterizing genes that influence the development of cancers in the gastrointestinal tract. Our goals are to use newly established congenic mouse lines to identify additional loci influencing cancer susceptibility. The system we have chosen involves the tumor suppressor gene Adenomatous Polyposis Coli (APC). Mutations in APC cause inherited and sporadic

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colorectal cancers. Apc Min mice have a mutation in the homologue of the APC gene and develop multiple adenomas throughout their small and large intestines. QTL studies identified a locus, Modifier of Min (Mom1), which maps to the distal region of chromosome 4 that dramatically modifies ApcMin-induced tumor number. We previously reported that the secretory type II Phospholipase A2 (Pla2g2a) gene is a strong candidate for Mom1. Inbred strains of mice display 100% concordance between Pla2g2a allele type and tumor susceptibility. Expression and sequence analysis revealed that Mom1 susceptible strains are null for Pla2g2a activity. We have established mice congenic for the C57BL/6J Pla2g2a-/- region on the CAST/Ei resistant inbred strain background. Using this newly developed congenic strain in crosses with ApcMin /+ mice, we will analyze offspring for several parameters measuring tumor phenotype and perform QTL analyses on the genome of offspring to identify additional loci that can influence polyp multiplicity. The identified regions of the genome will be further subjected to molecular dissection to determine their influence on cancer susceptibility; these studies will lead to the identification and characterization of gene(s) responsible for altering susceptibility. Ultimately, examination of newly identified modifier loci in human tumors should allow an understanding of the relationship between the effects of modifier genes on human tumor initiation, growth and progression. Further investigations will ultimately lead to insights regarding the value of these modifier genes in cancer diagnostics, prevention and treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR MECHANISMS ADENOMA/FOLLICULAR CARCINOMA

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Principal Investigator & Institution: Zeiger, Martha A.; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002 Summary: Over 28,000 thyroidectomies are performed in the United States annually for suspected malignancy. However, up to 18,000 of these are benign on permanent histology. This phenomenon is due to the fact that fine needle aspirations (FNA) of the thyroid that are suspicious for malignancy ultimately turn out to represent a benign process in 60% of cases. Because of this phenomenon we chose to examine follicular neoplasms of the thyroid for molecular markers that would distinguish a follicular adenoma from a carcinoma. Up to 40 follicular neoplasms of the thyroid were screened by microsatellite polymorphism analysis that might distinguish the two. Although there was no difference between follicular adenomas and follicular carcinomas, Hijrthle cell neoplasms of the thyroid appeared to have greater loss of heterozygosity on chromosomes 1q and 2p that could distinguish Hijrthle cell adenomas from Hijrthle cell carcinomas. These abnormalities could also be demonstrated on FNA samples with 100% sensitivity and 75% specificity; a potential dramatic improvement over what can now be accomplished by cytology. Because Hiirthle cell neoplasms of the thyroid represent a very small percentage of thyroid carcinomas that still left the clinical dilemma of distinguishing follicular adenomas from carcinomas as well as lesions that were suspicious for papillary thyroid carcinoma. We, therefore, examined follicular neoplasms and lesions that were suspicious for papillary cancer for telomerase activity. We found that 100% of follicular carcinomas and 67% of papillary thyroid cancer have a positive telomerase activity. As a result of this above work, we are prospectively collecting FNA samples from patients who have suspicious lesions on thyroid cytology. The collaborating institutions include the University of Pittsburgh and Mayo Clinic at Jacksonville. To date we have collected 127 samples and are currently examining the use

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of telomerase as a marker to distinguish benign from malignant. Should we be able to accomplish this and apply it to FNA then theoretically this technique could result in the obviation of up to 18,000 thyroidectomies performed annually in this country. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOUSE MODELS OF LUNG CANCER Principal Investigator & Institution: Boivin, Gregory P.; Associate Professor; Pathology and Lab Medicine; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): Dr. Boivins's immediate career objectives are to excel in primary and collaborative research efforts, to start a fellowship program in Mouse Pathology, and a training program in Laboratory Animal Medicine. This proposal will alleviate service work so that the fellowship and training program can be pursued and will provide funding for developing a primary research focus. Training and mentoring of high school students, undergraduates, graduate students, postdoctoral fellows, and faculty members will also continue to be performed in two general categories: unstructured or one-on-one time and structured time spent in courses or classes. Alleviation of service work will allow expansion in these areas. Lung cancer is the most common malignant tumor worldwide and is subsequently the greatest cause of cancerrelated mortality. The identification of genes mutated in lung cancer has pointed to some of the signal transduction abnormalities, such as changes in RAS signaling, that occur in the establishment of these tumors. Additionally, mouse-modeling experiments have shown that transgenic mice over expressing Fgf-7, Fgf-10, or activated K-Ras in lung epithelium exhibit epithelial hyperplasia, adenoma, and carcinoma, respectively. Preliminary data have shown that tumor formation in the mouse can be promoted by altering the genotype of mice at the BIm locus. The experiments proposed here will establish and validate mouse models of lung cancer by manipulating the genetic background of the mouse to increase the expression of tumor-promoting factors by increasing somatic recombination and mutation. Tumors will be characterized genomically and by transcription profiling in order to identify other genes altered in the lung tumor formation. This work will test the hypothesis that haploinsufficiency of BIm will increase tumor progression in transgenic mouse models of lung tumorigenesis by increasing mutation rates. The long term aims are to establish in vivo models of lung neoplasia in the mouse in order to identify and characterize the signaling pathways and genes that are disrupted in the development of these tumors, to use these models to identify early markers of tumor development in the lung, and to identify therapeutic targets for human lung cancer therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MR GUIDED FOCUSED ULTRASOUND SURGERY Principal Investigator & Institution: Hynynen, Kullervo H.; Associate Professor; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002 Summary: During the current phase of this grant, the feasibility of using single focused ultrasound transducer guided by MRI has been demonstrated in clinical treatments of fibroadenomas of the breast. In addition, several basic safety and monitoring issues related to the therapy were investigated in animal experiments and it was shown that MRI monitoring can be used not only to guide and monitor the location of the focal spot but also shown that MRI monitoring can be used not only to guide and monitor the

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location of the focal spot but also to detect the actual temperature elevation achieved. This result exceeded our expectations and will allow us to use MRI to provide online dosimetry. The overall objective of this proposal is to test the hypothesis that MRI guided and monitored focused ultrasound surgery can be effectively used in combination with radiation therapy to coagulate small malignant tumors of the breast. As was shown by our treatments of fibroadenoma of breast the small focal spot size of the clinical device makes the treatment of typical target volumes required for breast cancer impractical. To overcome this, we have developed phased array systems (under another grant) that can increase the focal volume and reduce the treatment time. The utilization of the phased arrays allow us to make the thermal exposure distribution uniform and use the minimum amount of power to reduce the total treatment time. However, previous experience with tissue coagulation has been primarily with single focused transducers that deliver very non-uniform and high thermal dose in the target volume. Thus, we plan to execute a series of rabbit VX2 carcinoma sonications to establish the dose. In addition the clinical treatments of the fibroadenomas will be continued to test the treatment procedures in clinical settings. Finally, we plan to execute a clinical phase I trial to test the feasibility of treating malignant breast tumors by using MRI guided focused ultrasound. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OVARIAN TUMOR PROJECT Principal Investigator & Institution: Cho, Kathleen R.; Professor; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002 Summary: The long-term goal of the proposed studies is to exploit existing technologies to generate comprehensive profiles of molecular alteration in ovarian cancers in order to identify clinically relevant molecular tumor signatures. Although the currently employed morphology-based ovarian tumor classification system has laid the groundwork for viewing ovarian cancer as several overlapping, but distinct disease entities, the existing scheme has significant limitations in its ability to allow prediction of the clinical course of an individual ovarian cancer patient. The major thrust of this proposal is to generate comprehensive molecular profiles of the most common histologic type of ovarian carcinoma, i.e., serious carcinoma, and to provide a basis for the identification of molecular markers of serious carcinoma with potential clinical relevance (Aim 1). The studies will deliberately focus on one histologic type in order to increase the likelihood of identifying biomarkers on which to base new and more informative tumor classification schemes. In the course of these studies, a series of related questions pertaining to ovarian cancer biology and tumor biology in general, will also be addressed (Aim 2). Aim 1: To define protein and gene expression profiles in 250-300 serous ovarian carcinomas, in order to identify molecular markers that distinguish clinically or biologically distinct subgroups of patients, including those with early versus advanced stage disease, low versus high grade tumors, and those with survival versus death. Aim 2: To define data on protein and gene expression patterns in ovarian carcinomas and other common tumor types (colorectal and lung carcinomas) to pursue the following objectives: 1) To identify specific patterns of gene/protein expression or genomic alteration that characterize serous versus other major types of ovarian carcinoma (mucinous, endometrioid, and clear cell) 2) To identify markers unique to ovarian carcinomas that can be used to distinguish them from normal ovarian tissues as well as tumors from other primary sites (specifically colorectal and lung cancers) 3) To identify novel molecular markers of ovarian, serous carcinomas with

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which to evaluate serous cystadenomas and serous tumors of low malignant potential as candidate serous carcinoma precursor lesions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PATHOPHYSIOLOGY AND MANAGEMENT OF PITUITARY TUMORS Principal Investigator & Institution: Cryer, Philip E.; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002 Summary: This study assesses pathophysiology mechanism in patients with functioning pituitary tumors, especially prolactinoma and growth hormone secreting adenomas. Studies include measurements of somatomedins and growth hormone by a variety of assays. Further, through systematic followup of these patients who are admitted primarily for studies of pathophysiologic mechanisms, we will assess the efficacy of therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PHASE III COLON CANCER PREVENTION TRIAL Principal Investigator & Institution: Meyskens, Frank L.; Professor of Medicine; Medicine; University of California Irvine Irvine, Ca 926977600 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by the applicant): The long-range objective of our work is to develop safe and effective drugs to prevent colon cancer, which is the fourth most common incident cancer in America with over 58,000 people dying of the disease in the year 2000. Our specific aims in this application are: 1.To conduct a randomized, doubleblind placebo-controlled phase III clinical chemoprevention trial of the combination of DFMO plus sulindac to decrease the rate of new adenomatous polyp formation. 2. To correlate the effects of the combination on polyamine and prostaglandin contents in the flat mucosa to the rate of adenoma formation. 3. To determine the rate of side effects in patients randomized to the combination therapy over the course of the intervention. The major objectives of this investigation are to reduce the recurrence rate of adenomatous colonic polyps without producing toxicity greater than that seen in the placebo group. The overall goal of our work is to develop safe combinations of chemoprevention agents that can be used in the practice setting and complement current surveillance efforts. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PHASE III TRIALS OF CHEMOPREVENTIVE AGENTS ON COLON CA Principal Investigator & Institution: Alberts, David S.; Professor of Medicine and Pharmacology; University of Arizona P O Box 3308 Tucson, Az 857223308 Timing: Fiscal Year 2002 Summary: Colorectal cancer continues as the third leading cause of cancer death in both males and females in the United States. Data from the National Poly Study show that repeated colonoscopic surveillance with United States. Data from the National Poly Study show that repeated colonoscopic surveillance with removal of any discovered adenomas reduces colonic cancer occurrence; however, the results also show that adenoma recurrence is common (>40% at 3 years), that compliance with scheduled follow-up colonoscopic examinations is problematic and that the cost is significant for

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the cancer prevention achieved. Clearly, there is a need to develop dietary and chemopreventive intervention strategies that can be applied to large populations to reduce both adenoma recurrence and colorectal cancer risk. In Project 1a, we focus on reducing the risk of adenoma recurrence by lowing the relative concentration of deoxycholic acid, a putative tumor promoting secondary bile acid in fecal contents, through the use of ursodeoxycholic acid and in Project 1b, by changing intrinsic colon mucosal cell metabolic pathways with a drug, celecoxib )A COX-2 inhibitor), and a nutritional supplement, selenium (formulated in baker's yeast), that can modify elements of signal transduction pathways that are thought to affect neoplastic progression. The use of all three of these exciting chemopreventive agents are supported by strong epidemiologic, preclinical and preliminary clinical data and all appear to have excellent safety profiles. Project 1a completes an ongoing, placebo- controlled, doubleblind, cancer control, phase III study of ursodeoxycholic acid in participants with a recent history of resected colorectal adenomas. Enrollment of the required 1200 participants was achieved in the late fall 1999. The rates of participants going off drug treatment and the occurrence of significant adverse events are exceptionally low. All participants and data processing aspects of the study will be completed within the next four years. Project 1b is a new placebo-controlled, double-blind, phase II trial of factorial design, evaluating prevention of recurrent colon adenomas by treatment with the COX2 inhibitor, celecoxib, or selenium in the form of baker's yeast, or a combination of the two agents versus placebo The study will be conducted in 1,600 evaluable participants with a history of resected adenomas chosen to be similar to those evaluated in the Project 1a ursodeoxycholic acid study. A major strength obtained by using a comparable study design and participants (n=2,800) will be the opportunity to evaluate several risk factors that may affect polyp recurrence, progression and response to intervention, in this large study population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SECRETION

PHYSIOLOGICAL

MODEL

OF

PARATHYROID

HORMONE

Principal Investigator & Institution: Petrasek, Danny; None; California Institute of Technology Mail Code 201-15 Pasadena, Ca 91125 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant) In human physiology, the rapid and coordinated secretion of PTH by the parathyroid gland is essential for maintaining healthy levels of serum calcium. Small decrements in serum calcium concentration are routinely demonstrated to produce five to ten fold increases in serum parathyroid concentrations within a few minutes. The extracellular calcium binding to a calcium sensing receptor is thought to inhibit the exocytosis of stored parathyroid hormone into the intercellular spaces. In vitro PTH secreting cells (chief cells) are reported to exhibit greater calcium sensitivity (inhibition of PTH release) when they exist as isolated single cells in comparison to when residing in a connected group of cells: suggesting that a network has emergent regulatory properties. In an adenoma, the parathyroid secreting cells (chief cells) are large and densely packed, the calcium receptor number is diminished, and the PTH secretion per cell is much higher than in healthy tissue. Calcium ions regulatory effect on the secretion of PTH is significantly dampened in adenomatous tissue. The sensitivity of the cells is substantially recovered however, when the adenoma is dispersed into smaller cellular collections. We posit that gland geometry and interstitial PTH in combination alter the interstitial diffusion of calcium and endow the cell network with the capacity for dynamic secretory responses. In order to explore this

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hypothesis, a series of computational and mathematical models will be constructed. The models will investigate the calcium-PTH physiology, both in the context of small cellular networks as well as the macro physiological scale of organ level responses corresponding to published animal and human clinical experiments. The objective of this proposal is to construct higher-level quantitative models: by using realistic geometric structures, and careful addition of cellular and biophysical processes. In a broader view, our preliminary results suggest that in addition to the cellular mechanisms, glandular networks may have regulatory prowess at the level of interstitial transport. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: POLYMORPHISMS IN PG/COX PATHWAY AND COLORECTAL POLYPS Principal Investigator & Institution: Ulrich, Cornelia M.; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2002; Project Start 05-JUN-2001; Project End 31-MAY-2004 Summary: Aspirin and other non-steroidal inflammatory drugs (NSAIDs) reduce the recurrence of colorectal polyps among patients with familial adenomatous polyposis (FAP) and are associated with a lower risk of both adenoma and colorectal cancer. Primary targets for these drugs are cyclooxygenases (COX1 and COX2) in the prostaglandin (PG) pathway. The goal of this study is to evaluate the association between colorectal polyps and polymorphisms in enzymes, growth factors, and receptors linked to prostaglandin synthesis or COX activity. Currently, very few polymorphisms in this pathway have been reported, and, of those, the population allele frequency is not known. Thus, several steps in this proposal (Projects 1-3) aim to systematically identify new genetic polymorphisms in this pathway, and to establish allele frequency and potential impact on enzyme function. Methods include screening of enzymes in the COX/PG pathway for new polymorphisms both by searching genetic databases and by using other techniques (dHPLC, enzyme mismatch cleavage, DNA sequencing). Genotyping of a population of 75 Caucasians and 75 African Americans for candidate polymorphisms will be used to establish allele frequency. Subsequently (Project 4) we propose to investigate a selected 5 to 10 genetic polymorphisms in COX1,COX2, and other enzymes in the PG/COX pathway, or growth factors and receptors related to it, and their association with colorectal polyps. We propose to genotype 550 cases with adenomatous polyps, 200 cases with hyperplastic polyps only, and 700 polyp-free controls. Study participants were recruited as part of the Minnesota case-control study in 1991-4 and comprehensive questionnaire information on health status, family history, diet, physical activity, and use of aspirin and other NSAIDs has been obtained. We will 1) investigate the main effects of the genetic polymorphisms, and 2) investigate whether these polymorphisms modify the association between environmental factors (in particular aspirin and NSAID use) and colorectal polyps. Finally, we plan to develop a model for integrating information on genetic variability at multiple points in this metabolic pathway. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: POSITIONAL CLONING OF THE PAS 1 QTL IN MICE Principal Investigator & Institution: You, Ming; Professor; Surgery; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 30-JUN-2007

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Summary: (provided by applicant): The goal of this proposal is to identify the pulmonary adenoma susceptibility 1 gene (Pas 1), which is responsible for lung tumor susceptibility to chemical carcinogens. Chemical carcinogenesis in mouse lung may involve changes in at least three classes of genes: tumor susceptibility genes, protooncogenes, and tumor suppressor genes. A major quantitative trait locus (QTL) responsible for lung tumor susceptibility to chemical carcinogens has been mapped to distal chromosome 6 in mice which accounts for approximately 50% of variance in tumor multiplicity between the susceptible A/J mouse and the resistant C57BL/6J mouse. The existence of Pas 1 locus will be confirmed by the construction of congenic strains in which high lung tumor susceptibility (A/J) allele is substituted onto the genetic background of the C57BL/6J mouse. The congenic chromosomal segment containing the Pas 1 QTL will then be progressively reduced by congenic mouse strain construction until the region is small enough for positional cloning of the Pas 1 gene, which requires a congenic region of approximately 0.5 - 1 centiMorgan. Based on flanking marker sequences, the DNA sequences of the entire region will be obtained from Celera mouse genome database. New and known genes in the target region will also be identified through the annotated Celera sequence database and the annotated public mouse sequence database. Candidate genes will be sought based on known or deduced function and/or differences in expression between lungs from A/J mice and those from C57BL/6J mice. Finally, the functional role of the candidate Pas 1 gene will be evaluated by constructing knock-in mice with the A/J Pas 1 allele to be replaced with the C57BL/6J allele. The resulting mouse will be subjected to lung carcinogenesis assay to confirm the Pas 1 gene. The significance of these studies is that they will identify the Pas 1 gene whose human homologue may predispose some individuals to lung cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MUSHROOM

PREVENTION

OF

CANCER

BY

CORIOLUS

VERSICOLOR

Principal Investigator & Institution: Toth, Bela; Eppley Institute for Research in Cancer & Allied Diseases; University of Nebraska Medical Center Omaha, Ne 681987835 Timing: Fiscal Year 2003; Project Start 15-APR-2003; Project End 31-DEC-2004 Summary: (provided by applicant): Protein-bound polysaccharide K (PSK), a hot water extract from the fruiting body and mycelia of the Coriolus versicolor (CV) mushroom, has significant adjuvant activity in combination with oral fluorouracil chemotherapy for the treatment of gastric cancer and is approved for this indication in Japan. Recently, hot water extracts from the CV mushroom have been used as nutritional supplements by cancer patients in the US. Given the extensive use of these supplements, comparative studies into the bioactivity of the clinical (PSK) and nutritional supplement (VPS) preparations are warranted and we propose to compare their tumor preventative, and therapeutic activities, as well as extend our understanding of their mechanism of action based on immune augmentation. This proposal will address the hypothesis that the oral administration of PSK and VPS results in immunomodulatory activity and preventative and therapeutic activity in mice for colorectal cancer. This hypothesis will be tested using two autochthonous tumor models: 1,2-dimethylhydrazine (DMH) induced colorectal tumors and the Apcmin transgenic model of gastrointestinal polyps and adenomas. Our long-term objective is to initiate clinical studies in colorectal cancer, if warranted by these studies, using VPS and the immune surrogates identified by this proposal to support the phase I dose-finding protocols. Three Specific Aims are proposed to test our hypothesis: 1: Determine and compare the preventative and therapeutic activity of PSK and VPS for DMH induced preneoplastic lesions, adenomas

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and adenocarcinomas of the large intestine in mice. 2: Determine and compare the immune augmenting properties of PSK and VPS and correlate these parameters with tumor preventative and therapeutic activity. 3: Study the preventative and therapeutic activity of PSK and VPS activity in an Apc transgenic model of intestinal polyp and adenoma formation and its association with immune augmentation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROMOTING COLON CANCER SCREENING IN AT RISK FAMILIES Principal Investigator & Institution: Schroy, Paul C.; Associate Professor of Medicine; Boston Medical Center Gambro Bldg, 2Nd Fl, 660 Harrison Ave, Ste a Boston, Ma 02118 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-AUG-2004 Summary: (provided by applicant): Colorectal cancer is the second leading cause of cancer-related death in U.S. Screening rates among individuals at increased risk of the disease because of a family history colorectal cancer or adenomas are suboptimal. Preliminary studies highlight the need for novel strategies to increase both provider and patient awareness of familial risk factors, promote compliance with appropriate screening recommendations, and facilitate risk communication between providers, affected patients and at-risk family members. Accordingly, the specific aims described herein address each of these needs by proposing novel interventions targeted at providers, adenoma patients and at-risk relatives. Specific Aim #1 is to design, implement and evaluate an educational program for primary care housestaff and assess its impact on their knowledge, risk assessment and screening behavior. The educational program will incorporate both didactic and interactive teaching sessions as well as distribution of a colorectal cancer risk assessment "tool kit." The actual content of the sessions and "tool kit" will be defined during Year 1 using existing literature, focus groups and an expert panel. A randomized controlled trial will be conducted in Year 2 to evaluate the program's effectiveness. A pretest/post-test format will be used to assess knowledge, patient exit interviews will be used to assess risk assessment skills, and chart audit with feedback will be used to assess documentation and screening behavior. Specific Aim #2 is to evaluate the efficacy of an educational program aimed at promoting increased awareness about familial risk and notification of first-degree relatives among adenoma patients. The program employs a standardized computerbased educational intervention that is conducted at the "bedside" immediately postpolypectomy, followed by a tailored notification of risk and recommendations in the form of a personalized letter. A three-arm randomized trial comparing the dual intervention to the bedside computer-based intervention alone versus standard care will be conducted to assess the program's effectiveness. Telephone surveys will be used to assess patient knowledge and extent of communication to at-risk siblings. Specific Aim #3 is to explore patient preferences and the role of shared decision-making as a strategy for promoting compliance with colorectal cancer screening recommendations among individuals with a family history of colorectal adenomas or cancer. Structured interviews will be conducted to assess patient preferences for the five recommended screening strategies colorectal cancer screening strategies, identify factors influencing their choices, and determine the extent to which such patients wish to participate in tho decision-making process using a validated "decision aid" and "Colorectal Cancer Autonomy Index/Autonomy Preference Index." Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: RANDOMIZED TRIAL OF FOLATE AND COLORECTAL ADENOMA Principal Investigator & Institution: Giovannucci, Edward L.; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 15-SEP-1995; Project End 29-FEB-2004 Summary: Given the high rates of colorectal cancer and the potential chemopreventive properties of folate or folic acid, it is crucial to demonstrate in a randomized setting that folic acid supplementation reduces the occurrence of colorectal neoplasia. We thus propose to continue to examine the hypothesis that folic acid supplementation of 1,000 micrograms daily will reduce the recurrence rate of colorectal adenomas, precursors of cancers using a randomized, placebo-controlled intervention trial. This study has been successfully initiated and has been ongoing since 1996 among 750 individuals within two ongoing cohort studies, the Health Professionals Follow-Up Study and the Nurses' Health Study. As planned, we will examine whether any influence of folate is modified by various factors, including baseline folate and vitamin B12 levels, aspirin use, family history of colorectal cancer, and intakes of alcohol and methionine. For this submission, we now propose extending follow-up from three to five years because of recent evidence of a long induction period between folate intake and colorectal cancer, and because recent fortification of food products with folic acid may reduce the contrast of folate status between intervention and placebo groups. We further propose to measure additional folate- related factors (plasma homocysteine, methylene-tetrahydrofolate reductase (MTHFR) genotype) and insulin-like growth factor (IGF) parameters (insulinlike growth factor-1 and insulin-like growth factor binding protein-3), which we have found to be the strongest cluster of etiologic factors for colorectal carcinogenesis in our cohorts. Thus, it is of interest to examine the independent and interacting roles of folaterelated and IGF-related factors in adenoma recurrence. Within our existing cohorts, the intervention trial, as well as the proposed additional biomarker and genotype measures, can be conducted at a fraction of the cost of a similarly sized intervention trial of colorectal adenoma recurrence in other typical settings. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: REAL FLUORESCENCE

TIME

IN

VIVO

DIAGNOSIS

OF

DYSPLASIA

BY

Principal Investigator & Institution: Feld, Michael S.; Director; Center for Cancer Research; Massachusetts Institute of Technology Room E19-750 Cambridge, Ma 02139 Timing: Fiscal Year 2002; Project Start 21-DEC-1990; Project End 31-MAR-2004 Summary: The objective of this proposal is to develop and improve endoscopiccompatible spectroscopic techniques based on excitation-emission matrix (EEM) fluorescence, reflectance and light scattering for real-time in vivo analysis and diagnosis of dysplasia in the colon, esophagus and urinary bladder. We have developed three models to analyze tissue reflectance and fluorescence. The diffuse reflectance model furnishes information about tissue scatterers (such as mitochondria and the fiber network of connective tissue) and absorbers (such as hemoglobin). The light scattering spectroscopy (LSS) model yields information about nuclear size and crowding in the epithelial layer of tissue. The intrinsic fluorescence model isolates the contributions of fluorophores (such as structural proteins, NADH, porphyrins etc.) from the interference of absorbers and scatterers. Clinical EEM fluorescence/reflectance data will be collected for colonic adenoma, Barrett's esophagus and urothelial carcinoma, and will be analyzed using these models. Information about tissue structure and composition will be extracted and used to formulate new models and diagnostic algorithms. Validation of

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Adenoma

the algorithms will be performed prospectively with extended clinical data sets. In addition, we will extend the excitation wavelength range of our clinical EEM system down to 308 nm, to access more information about epithelial cellular proteins, update our data acquisition systems, and integrate data analysis software for real-time diagnosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION BY KRUPPEL LIKE FACTOR IN THE COLON Principal Investigator & Institution: Tseng, Chi-Chuan C.; Boston Medical Center Gambro Bldg, 2Nd Fl, 660 Harrison Ave, Ste a Boston, Ma 02118 Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 30-JUN-2006 Summary: (provided by applicant): Colorectal carcinogenesis is a multi-step process including both the activation of oncogenes and the loss of tumor suppressor genes. Most of the neoplastic lesions in the colon arise through the progression from normal to hyperproliferative epithelium, adenoma and carcinoma, It is hypothesized that cellular hyperproliferation resulting from either spontaneous mutation or increased in intestinal proliferation leads to clonal expansion and carcinogenesis. Although multiple genetic mutations have been described, the molecular events governing intestinal hyperproliferation is unknown. Recently, an eukaryotic zinc finger protein, gut-enriched Kruppel-like factor (GKLF/KLF4), has been identified to be an important factor in controlling growth arrest. Our laboratory has shown that GKLF gene expression is reduced in colon cancer tissue and that constitutive expression of an antisense GKLF DNA in a colon tumor cell line results in cell hyperproliferation. These data suggest that down-regulation of GKLF may lead to uninhibited cell growth. Furthermore, GKLF mRNA levels increased as colonic epithelium acquired more differentiated phenotype. We hypothesize that up-regulation of GKLF is essential for colonic epithelium to become differentiated and that down-regulation of GKLF will render colonic cells to become hyperproliferated and ultimately neoplastic transformation. The precise physiological function of GKLF in the colon is not clear and its up- and down-stream targets are currently unknown. The aims of the current study are: (1) to elucidate the physiological properties of GKLF by examining the effect of constitutive overexpression of sense, antisense or dominant-negative mutant GKLF DNA on cell growth and differentiation in normal colon epithelial; adenoma; and cancer cell lines; (2) to investigate the role of GKLF in cell cycle progression by examining its effect on cyclins, cyclin-dependent kinases (cdks) expression, and on transcriptional regulation of the cyclin D1 gene; and (3) to examine molecular mechanisms governing basal transcription of the GKLF gene as well as vit D3- or interferon-gama-promoted GKLF expression. Collectively, the information gained from this proposal will add to our understanding the contribution of GKLF to growth, differentiation, and malignant transformation of the colonic epithelial cells. Ultimately, if the GKLF down-regulation process can be manipulated, it may be possible to use inhibitors of this process for chemoprevention of cancer formation in the gastrointestinal tract. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: REGULATION OF INTESTINAL CL:HCO3 EXCHANGE Principal Investigator & Institution: Coon, Steven D.; Medicine; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2002; Project Start 13-FEB-2002

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Summary: The overall goal of the research proposal is to determine the mechanism of regulation of CI:HCO3 exchange in the chronically inflamed intestine and to determine the prostanoid responsible for altered transport during inflammation. Once this is accomplished, next will be to investigate the cellular messengers involved in these processes and to determine which of the isoforms of the DI:HCO3 exchanger are altered during inflammation. Principal Investigator (P.I.) will learn to investigate transport in intact cells using fluorescence and these techniques will help to determine the prostanoid responsible for the alterations during inflammation. In addition, P.I. will learn the techniques to measure second messengers in live cells using single cell fluorescence techniques. PI will also learn techniques related to molecular biology such as Northern and Western blotting and PCR to study those isoforms altered during chronic inflammation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RECEPTOR

REGULATION

OF

THE

POLYMERIC

IMMUNOGLOBULIN

Principal Investigator & Institution: Kaetzel, Charlotte S.; Professor; Pathology and Lab Medicine; University of Kentucky 109 Kinkead Hall Lexington, Ky 40506 Timing: Fiscal Year 2002; Project Start 01-APR-1990; Project End 31-JAN-2004 Summary: IgA is transported into external fluids by the polymeric immunoglobulin receptor (pIgR), whose expression is tissue specific and cytokine regulated. Expression of pIgR is abnormally regulated during colon carcinogenesis and has been used a prognostic variable in colon cancer. Investigators have demonstrated that pIgR is expressed in well differentiated human intestinal adenoma and carcinoma cell lines, but not in a human liver cell line or in less differentiated colon carcinoma cell lines and that it is upregulated by interferon gamma. The investigators have located a segment of promoter-proximal region of the pIgR gene which is necessary and sufficient to confer cell-type specificity and interferon gamma inducibility on a reporter gene. They have identified a putative tissue-specific cis-acting element, the pIgR Xbox; binding of nucleoproteins to this element is positively correlated with pIgR expression and transcription activity of pIgR promoter. They have also identified an interferon gamma responsive element which binds interferon regulatory factor I (IRF-I). Deletion of the IRF-I site abolishes interferon gamma inducibility with the pIgR promoter. Significantly the IRF-I site is located within the first exon of the pIgR gene rather than in the 5 prime flanking region. This is the first demonstration of an IRF-I binding site in a promoterproximal exon and suggests a novel mechanism for transcriptional regulation by interferon gamma. The central hypothesis of this proposed research is that binding of IRF-I to the interferon gamma response element and binding of tissue specific transcription factors to the Xbox element are important mechanisms for regulating transcription of the polymeric immunoglobulin receptor gene. Three specific aims are proposed: 1. The investigators will characterize the role of the IRF-I element in the interferon gamma inducibility of the human pIgR promoter, especially in its unique location within the first exon. 2. The investigator will characterize the role of Xbox element in tissue specific expression of the human pIgR promoter. 3. The investigators will characterize the biochemical and functional properties of proteins that bind the Xbox element both in vitro and in the nuclei of living cells. These studies offer the potential for identifying novel molecular mechanisms which relate expression of the pIgR gene which may offer insights into: a. Immune regulation in the human intestine. b. Specific gene regulation. c. Novel mechanisms of gene regulation by interferon gamma. d. Regulation of gene expression during colon carcinogenesis.

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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE AND REGULATION OF INTESTINAL NA/H EXCHANGER Principal Investigator & Institution: Chang, Eugene B,.; Martin Boyer Professor of Medicine; Medicine; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2003; Project Start 01-JUL-1986; Project End 31-MAR-2008 Summary: (provided by applicant): An essential function of the intestinal mucosa is to regulate Na absorption appropriately in response to potentially large variations in daily oral intake and metabolic perturbations. In this competitive renewal application, we will examine the cellular events involved in the regulation of the apical membrane Na-H exchangers, NHE2 and NHE3, in this process, as they are major pathways for nonnutrient dependent Na absorption. We hypothesize that their acute regulation is in large part dependent on an orchestrated movement in and out of the apical membrane that is highly dependent on actin cytoskeleton and other integral membrane and adaptor proteins. We also hypothesize that they are not randomly distributed in the apical membrane, but found in highly ordered lipid domains (non-caveolin lipid rafts) and clathrin-coated regions. Their distribution in these specialized membrane domains is essential for their function and regulation, specifically in clustering them with other transporters such as the anion exchanger, DRA (Down-Regulated in Adenoma), the dipeptidy1 transporter hPepT1, adaptor proteins (E3KARP and NHERF), and other key molecules such as v- and t-SNARES required for membrane endo- and exocytosis. Finally, we believe disease-related perturbations of intestinal Na absorption are mediated by their specific effects on components of these events and/or proteins. To examine these hypotheses, we propose three specific aims: (1) To define the process and mechanisms of induced membrane trafficking of NHE2 and NHE3 involved in their regulation by intestinal epithelial cells, (2) To examine the potential functional and physical interactions between NHEs and DRA and hPepT1, two transporters brush border transporters that we believe are coupled with and regulated by apical NHEs, and (3) To define mechanisms of disease-related perturbations in NHE function and regulation using two experimental conditions - inflammation-associated oxidant stress and metabolic acidosis, which inhibit and enhance gut Na absorption, respectively. We will use a combination of functional, biochemical, and imaging approaches to provide detailed mechanistic and novel insights into how NHEs are regulated physiologically, their relative roles in coupled dipeptide and anion transport, how their dysfunction and aberrant regulation by certain disease processes ultimately cause alterations in net water and electrolyte transport by the gut. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ROLE OF TUMOR CELL SURFACE LECTIN IN METASTASIS Principal Investigator & Institution: Raz, Avraham; Director of Tumor Prog & Metastasis; Pathology; Wayne State University 656 W. Kirby Detroit, Mi 48202 Timing: Fiscal Year 2002; Project Start 01-JUL-1987; Project End 31-MAR-2007 Summary: (provided by applicant): Metastasis, the epitome of cancer progression, is a pathophysical process of profound significance, because much of the lethality from malignant neoplasms is attributed directly to their ability to develop metastasis in distant organs. Carbohydrate-mediated recognition leads to the formation of multi-cell emboli in the circulation, a process directly related to the development of metastases. The role of galectin-3 in this process is now established through the efforts of this continued research. Galectin-3 is a member of the galectin gene family, composed of at

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least twelve members. Galectin-3 is a chimeric gene product with monomer subunit of about 30,000 daltons, composed of three distinct structural motifs, a short NH2-origin preceding an amino half-domain containing Gly-X-Y tandem repeats characteristic of collagens and carboxy-terminal half which encompasses the N-acetyllactosamine (Galbeta-4GlcNac)-binding site. Galectin-3 is an unusual protein, in that it is localized and functions in the cytoplasm, cell membrane, nucleus and the extracellular milieu and undergoes for function a non-covalent homodimerization and post-translation phosphorylation that regulate carbohydrate-recognition. It contains the NWGR antideath motif of the BH1 domain of the bcl-2 family members. Galectin-3 has distinct functions and recognition sites involving different cell lineages at different developmental and pathological stages including cell growth, apoptosis-resistance, adhesion, differentiation, inflammation, transformation, angiogenesis, invasion and metastasis. We now propose to define in greater detail the structural-functional relationship of galectin-3 as it relates to cellular localization, cell growth, apoptosisresistance, cell-cell recognition, angiogenesis, tumor growth and hematogenous spread of tumor cells. To this end we propose the following: 1) To determine the molecular basis of the anti-apoptotic property of galectin-3; 2) To determine the functional consequence of galectin-3 phosphorylation on cell regulation and apoptosis; 3) To study the effect of antigalectin-3 therapy on cancer progression and metastasis. It is expected that the results to be obtained from this study will provide a better understanding of galectin-3 and its interacting ligands in tumor progression and metastasis and will further the developments of specific reagents for the detection and interventions in these processes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SCREENING COLONOSCOPY FEASIBILITY TRIAL Principal Investigator & Institution: Winawer, Sidney J.; Sloan-Kettering Institute for Cancer Res New York, Ny 100216007 Timing: Fiscal Year 2003; Project Start 01-SEP-1999; Project End 31-MAY-2008 Summary: (provided by applicant): In 2002 colorectal cancer will be diagnosed in 148,300 men and women and cause 56,600 deaths, account for 785,000 life years lost, and cost this country 6 billion dollars. Colonoscopy is increasingly being used as a screening option even though there is uncertainty as to the benefit and harms of this approach in comparison to FOBT. A recent study of V.A. men showed that a single colonoscopy may be a better option than FOBT because of its detection of advanced adenomas as well as early stage cancers. This approach has not been studied in 'general population' men and women and has not been compared directly to a program of annual FOBT. The longterm objective of this proposal is to compare a single screening colonoscopy directly to programmatic FOBT in general population men and women. The study in progress demonstrated a lower rate (6%) of advanced neoplasia (advanced adenoma or early cancer) detected by screening colonoscopy as compared to the V.A. Trial (10.5%). This raised the question of how much better a single screening colonoscopy is than an FOBT directed colonoscopy. We therefore designed a trial to compare the benefits and harms of the two strategies. Participation in a single colonoscopy may be higher than with a program of annual FOBT. However, the number of colonoscopies needed to detect advanced neoplasia also may be greater than with FOBT directed colonoscopy. The trial will involve three clinical centers, a Pathology Review Center, and a Coordinating Center. The organization of this study will build on the ongoing randomized trial of screening colonoscopy vs. usual care, using the same infrastructure and accumulating colonoscopy data from the proposed study and the present study. This data will be used

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as a basis for calculating in the general population the benefits, harms, and medical resource burden of potentially the most effective screening test (colonoscopy) as compared to the most commonly used screening test (FOBT). The results of this study will have major implications in prioritizing national guidelines and in clarifying financial and clinical resources and manpower issues. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SELENIUM ADENOCARCINOMAS

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Principal Investigator & Institution: Connelly, Alexandra E.; Epidemiology; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 30-APR-2005 Summary: (provided by applicant): Colorectal cancer is the second leading cause of cancer mortality in the United States, with an estimated 56,700 deaths in 2001. Most colorectal adenocarcinomas arise from benign, neoplastic adenomatous polyps. Because colorectal cancer has an identifiable precursor lesion (adenomatous polyps), a unique opportunity for early detection and intervention exists if modifiable risk factors for polyps can be identified. Variations in incidence of colorectal cancer with respect to geography and migration suggest an important environmental component to colorectal cancer risk. Selenium, an essential trace element found in cereals, wheat, dairy products, meat and fish, may prevent carcinogenesis through a number of biochemical pathways. One way that selenium might reduce cancer risk is by increasing apoptosis, or programmed cell death. This process provides a mechanism to remove damaged cells, which decreases the chance that abnormal cells will proliferate and develop into malignancies. Clinical trial data suggest a strong protective effect of selenium on cancer incidence; however, results from observational studies are inconclusive. Many of the case-control studies of selenium and colon cancer did not exclude participants with advanced disease, making it difficult to draw a conclusion given the impact that advanced disease and cancer treatment have on selenium levels in the body. Very few studies have addressed the association between selenium and colorectal adenomas and all studies that have were very small. Finally, no epidemiologic studies have assessed the potential biological pathway through apoptosis. The proposed study will make use of existing biological samples from two large studies to investigate the relation between serum selenium and early stage colorectal adenocarcinoma, in addition to its precursor lesion (adenomatous polyps). Most notably, we propose to investigate the biologic mechanism of apoptosis, which has not been previously evaluated in a human population. This research is of public health importance because selenium is a potential chemopreventive agent for colorectal cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SIMULATION MODELING OF COLORECTAL CANCER Principal Investigator & Institution: Dittus, Robert S.; Professor of Medicine; Medicine; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 15-APR-2002; Project End 31-MAR-2005 Summary: The goals of this research are to build a new and more powerful discreteevent simulation model based on an existing, validated computer model of the natural history of colorectal neoplasia and use the new model to address questions concerning the clinical outcomes, cost, effectiveness, cost- effectiveness, and resource utilization of various colorectal cancer (CRC) control strategies for patients and for complex and

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dynamic populations. These goal will be achieved through the translation of an existing model into C++, an object-oriented programming language that would improve the model's ease of modification, decrease the time needed to complete an analysis, and allow direct interaction between the model and other commonly available programming applications. The new model will be programmed to allow the simulation of populations whose individual members are characterized by multiple and interacting cancer risk factors, have varying degrees of adherence with established cancer control protocols, and receive their care in settings where the resources needed to provide cancer control interventions are limited. The parameterization of this model will be based on a rigorous review of the literature and the model will be validated by several methods, including existing cancer control outcome data. After completion of its programming, parameterization and validation, the applicant will demonstrate the power and versatility of this new computer model by employing it in various complex analyses concerning the expected outcome over time of implementing new cancer control strategies in both the general U.S. population and specific subpopulations representing relevant geopolitical and payer/provider groupings. In addition, the applicant will examine the impact of resource constraints (such as manpower) on the outcomes of proposed cancer control strategies and the implications of disparities in such resources across geopolitical boundaries and healthcare provider markets. The completed model will be able to predict the outcomes of any given CRC control strategy, among specific risk-defined patient subgroups, in any given population, during and over any period of time. This model could serve as a template and modeling paradigm for the examination of the cost-effectiveness of prevention and treatment strategies for other cancers and for diseases other than cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SPORE IN GL CANCER Principal Investigator & Institution: Coffey, Robert L.; Medicine; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 24-SEP-2002; Project End 30-APR-2007 Summary: (provided by applicant): This Gastrointestinal SPORE application is being submitted by the Vanderbilt-Ingram Comprehensive Cancer Center (VICCC) and its affiliated institutions. This proposal is from a group of basic science researchers and clinical investigators with long-standing collaborative interactions that have resulted in significant NCI extramural funding. In this proposal, we apply the translational research strengths of the VICCC and its affiliated institutions towards reducing the incidence, morbidity and mortality of colorectal cancer by focusing on established (EGF receptor and cyclooxygenase-2), promising (p120) and to-be-identified molecular targets for prevention and therapy. We propose five projects. In Project 1, we will examine molecular correlates of EGF receptor blockade in an ECOG-approved Phase II trial of ZD 1839. In parallel with this, we will use polarizing colon cancer cells in vitro to evaluate ways in which blockade of the EGF receptor axis can be optimized. In Project 2, we will evaluate combined blockade of the EGF receptor signaling pathway and cyclooxygenase-2 in Phase I and, subsequently, Phase II trials in patients with colorectal cancer. These trials will be complemented by genetic studies to examine the importance and interaction of these two pathways in three mouse models of intestinal cancer. Project 3 is designed to utilize DNA microarray and imaging mass spectrometry to identify and, ultimately, predict rectal cancer patients most likely to respond to neoadjuvant chemoradiotherapy. Project 4 will examine the role of p120-a protein first identified by Vanderbilt investigators-in colorectal metastasis. Project 5 is designed to

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test and identify markers for adenoma recurrence that could eventually serve in the early detection or prevention of colorectal cancer. To support these research projects, we propose six cores: administrative, tissue, clinical trials, emerging Technologies, biostatistics and biomedical informatics. The proposed developmental (pilot) research and career development programs are tightly integrated with established institutional initiatives that have documented track records of identifying and funding promising projects and individuals. We will use these established mechanisms to fund gastrointestinal cancer-targeted pilot projects and to support career development. The strong institutional commitment from both VICCC and Vanderbilt University Medical Center to the success of this program is outlined in the application and supporting documents. We believe that the projects, cores, pilot projects and career development awards outlined in this application will lead to major improvements in the prevention, diagnosis and treatment of colorectal cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STATISTICAL MODELS IN EPIGENOMICS Principal Investigator & Institution: Siegmund, Kimberly D.; Preventive Medicine; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2006 Summary: The primary objective of this proposal is to develop statistical models for the analysis of DNA methylation data. Questions that are currently posed for gene expression profiles, such as how to classify samples based on cell-wide gene expression patterns or how to classify genes with unknown function, based on their expression patterns across samples, may be similarly posed for DNA methylation patterns. Our focus is on the discovery of new subgroups based on patterns of DNA methylation. We view DNA methylation patterns as an intermediate variable along a pathway from exposures to outcomes and take a flexible hierarchical modeling approach that can incorporate measured and unmeasured covariates. Our aims are motivated by ongoing and planned future studies in the Department of Preventive Medicine and Norris Cancer Center at the University of Southern California. Specifically, we propose to: 1. Develop model-based class discovery methods (cluster analysis/unsupervised learning approaches) using quantitative measures of DNA methylation, adjusting for locusspecific and sample-specific covariate effects. a. Analysis of paired samples of tumor tissue and normal tissue taken from the margin of the tumor. b. Extend model to allow for multiple tumors per subject. c. Extend model to a two-dimensional cluster analysis of samples and loci. 2. Develop models for characterizing methylation patterns as an intermediate variable by modeling a) the association between risk factors and methylation pattern clusters, and b) the association between methylation pattern clusters and outcome. 3. Apply methods to studies of DNA methylation in colorectacl adenomas and lung cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: STUDIES IN PRIMARY HYPERPARATHYROIDISM Principal Investigator & Institution: Snyder, William B.; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2002 Summary: The utility of various parathyroid localization studies (double isotope, ultrasound, MRI, and CT) continues to be evaluated. A series is in progress on angiographic ablation of mediastinal parathyroid adenomas, as an alternative to sternal-

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splitting surgery. Risk factors for kidney stone formation are also undergoing further evaluation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STUDIES OF NORMAL AND NEOPLASTIC HUMAN PITUITARIES Principal Investigator & Institution: Lloyd, Ricardo V.; Professor of Pathology; Mayo Clinic Coll of Medicine, Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2002; Project Start 15-MAY-2001; Project End 30-APR-2006 Summary: Pituitary neoplasms are associated with a great deal off morbidity of excessive hormone production and/or as space occupying lesions in the central nervous system. The mechanisms regulating pituitary tumor growth in humans are poorly understood. Recent studies have shown that pituitary adenomas are monoclonal and that some specific genetic alterations are present in these tumors. However, very little is known about the regulation of the pituitary tumor growth and why only few of these neoplasms become malignant, which usually leads to the patient's demise in spite of aggressive treatment. Our laboratory has recently developed human pituitary cell lines immortalized with a replication-defective recombinant human adenovirus which should provide stable cell lined for many of the proposed studies. We plan to examine the mechanisms regulating pituitary growth and tumor progression using cell and molecular biological approaches. Preliminary studies indicate that pancreastain, a proteolytic product of chromogranin, which is processed by PC 1/3 and PC 2 in pituitary cells, has autocrine and paracrine regulatory functions on pituitary tumor cells. Our preliminary studies also showed that pancreastain inhabits cell proliferation in vitro. The haploid insufficiency paradigm will be explored to possibly explain some of the effects of p27 on pituitary tumor development and progression. Our laboratory was the first to discover leptin production and secretion by anterior pituitary cells. We also noted that leptin inhabit plan to examine the mechanism of leptin action in the pituitary. The specific aims include: I. Determine the role of chromogranin/secretogranin proteolytic products and neuroendocrine-specific proconvertases in pituitary tumor growth and differentiation. II. Determine the role of specific cell cycle inhibitors in the development of pituitary tumors. a. Examine the mechanism regulating p27 expression in pituitary tumor development and progression. b. Determine the role of p16 methylation in pituitary tumor development. III. Examine the role of leptin, leptin receptors, STAT and SOCS proteins in pituitary tumor development and progression. The information derived from these studies should provide insight into the pathobiology of pituitary tumors and lead to more effective treatment modalities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TGF BETA RECEPTOR MUTATIONS AND HUMAN CANCER Principal Investigator & Institution: Grady, William M.; Assistant Professor of Medicine; Medicine; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 01-MAY-1998; Project End 28-JUL-2002 Summary: (Applicant's Description): Dr. William Grady completed an Internal Medicine residency at the University of Washington and is now completing a Gastroenterology fellowship at Case Western Reserve University. He has also commenced a research postdoctoral fellowship with Dr. Sanford Markowitz aimed at studying the role of TGFbeta receptor mutations in causing human g a strointestinal cancers. Dr. Markowitz's laboratory will provide a stimulating environment that will allow Dr. Grady to advance toward his long-term goal of becoming an independent investigator studying the

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molecular defects that give rise to human gastrointestinal cancers. The broad long-range objectives of this proposal are to define the role of TGF-beta receptor mutations in the genesis of gastrointestinal cancers. TGF-beta inhibits the growth of and induces apoptosis in human colonic epithelial cells. Previous studies in Dr. Markowitz's lab have demonstrated that TGF-beta receptor subunit type II (RII) mutations are found in 80%95% of colon and gastric cancers that have the replicative error phenotype (RER) and that TGF-beta RII acts as a tumor suppressor gene in RER colon cancer. The aims of this proposal are: 1) to determine the timing of RII mutations in the sequence of RER colon adenoma to colon carcinoma progression; 2) to determine the clinical subset of human gastric cancers which arise via RII mutations and the RER cancer pathway; 3) to determine the contributions of TGF-beta resistance, TGF-beta receptor type II (RII) and type I (RI) mutations, and defects in post-TGF-beta receptor signaling in the genesis of NonRER human colon cancers; 4) to use TGF-beta RII viral vectors to determine the antitumor activity of restored wild-type RII in suppressing colon cancer cell line growth, both in culture and in nude mice xenografts, and to determine the role of induction of apoptosis as part of the mechanism by which TGF-beta RII exerts its anti-tumor activity; and 5) to determine in the azoxymethane model of mouse colon carcinogenesis the promotion of colon adenoma and/or carcinoma formation resulting from introduction of a heterozygous RII gene knockout, and to confirm the role of RII inactivation in augmenting formation of these tumors by establishing the presence in them of mutational inactivation of the remaining wild-type RII allele. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THERAPEUTIC TARGETING OF BETA-CATENIN IN COLON CANCER Principal Investigator & Institution: Drebin, Jeffrey A.; Professor and Chief, Division of Gastroi; Surgery; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2007 Summary: (provided by applicant): Genetic deletions of the adenomatous polyposis coil (APC) tumor suppressor gene occur in the majority of colon cancers Loss of the APC gene products' ability to down-regulate the beta-catenin protein is hypothesized to represent a critical mechanism by which APC loss contributes to the etiology of colon cancer However, the APC protein interacts with multiple other proteins, including gamma-catenin and hDLG, that may play a role in neoplastic cell growth To date there has been little direct examination of the role of beta-catenin in the neoplastic behavior of human colon cancer cells The precise mechanisms by which beta-catenin signaling enhances the growth and survival of neoplastic cells are unknown, and the characterization of changes in gene expression resulting from beta-catenin-mediated transcriptional effects has been limited The overall goal of this project is to directly evaluate the role of beta-catenin on the neoplastic properties of APC-mutant intestinal neoplasms Antisense oligodeoxynucleotides capable of specifically suppressing betacatenin expression in human cancer cells have been identified The ability of the antibiotic doxycycline, at clinically achievable concentrations, to inhibit beta-catenin expression has also been elucidated These beta-catenin-suppressive agents will be used to define beta-catenin-dependent effects on cell cycle and apoptotic regulatory mechanisms in APC-mutant colon cancer cells Effects of beta- catenin on c-myc expression and function will be characterized Changes in gene expression profiles of APC-mutant colon cancer cells resulting from suppression of beta-catenin expression will be evaluated, and compared with changes induced by upstream alterations in APC or downstream alterations in Tcf4 activity Effects of suppressing beta-catenin on

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spontaneous adenoma formation will be evaluated using APC-mutant min mice and antitumor effects resulting from the in vivo suppression of beta-catenin expression will be evaluated in APC-mutant human colon cancer xenografts Collectively, these studies will define the role of beta-catenin in the neoplastic growth of APC-mutant colon cancer cells and will characterize the efficacy of chemopreventive and therapeutic strategies that target beta-catenin in vivo. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “adenoma” (or synonyms) into the search box. This search gives you access to fulltext articles. The following is a sample of items found for adenoma in the PubMed Central database: •

A CA repeat 30 --70 KB downstream from the adenomatous polyposis coli (APC) gene. by Spirio L, Joslyn G, Nelson L, Leppert M, White R.; 1991 Nov 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=329171

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Activation of the c-Ki-ras Oncogene in Aflatoxin B1-Induced Hepatocellular Carcinoma and Adenoma in the Rat: Detection by Denaturing Gradient Gel Electrophoresis. by Soman NR, Wogan GN.; 1993 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=46017

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Analysis of chromosomal instability in human colorectal adenomas with two mutational hits at APC. by Sieber OM, Heinimann K, Gorman P, Lamlum H, Crabtree M, Simpson CA, Davies D, Neale K, Hodgson SV, Roylance RR, Phillips RK, Bodmer WF, Tomlinson IP.; 2002 Dec 24; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=139243

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Analysis of masked mutations in familial adenomatous polyposis. by Laken SJ, Papadopoulos N, Petersen GM, Gruber SB, Hamilton SR, Giardiello FM, Brensinger JD, Vogelstein B, Kinzler KW.; 1999 Mar 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=26782

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APC mutations are sufficient for the growth of early colorectal adenomas. by Lamlum H, Papadopoulou A, Ilyas M, Rowan A, Gillet C, Hanby A, Talbot I, Bodmer W, Tomlinson I.; 2000 Feb 29; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=15782

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Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.

With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.

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Association of adenoma and focal nodular hyperplasia: experience of a single French academic center. by Laurent C, Trillaud H, Lepreux S, Balabaud C, Bioulac-Sage P.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=161818

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AT repeat polymorphism at the D5S122 locus tightly linked to adenomatous polyposis coli (APC). by Breukel C, Tops C, Van Leeuwen C, Van Der Klift H, Fodde R, Khan PM.; 1991 Dec 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=329275

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CA repeat polymorphism from YAC JW25 at the D5S318 locus, distal to adenomatous polyposis coli (APC). by Wijnen J, Tops C, Breukel C, Van Leeuwen C, Goverde A, Van Der Klift H, Fodde R, Khan PM.; 1991 Dec 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=329349

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Concurrent pleomorphic adenoma in parapharyngeal space and submandibular gland. by Ladeinde AL, Adeyemo WL, Bamgbose BO, Ogunlewe MO, Ajayi FO.; 2004; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=419374

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Core I gene is overexpressed in Hurthle and non-Hurthle cell microfollicular adenomas and follicular carcinomas of the thyroid. by Maximo V, Preto A, Crespo A, Rocha AS, Machado JC, Soares P, Sobrinho-Simoes M.; 2004; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=404464

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CpG island clones from a deletion encompassing the gene for adenomatous polyposis coli. by Varesco L, Thomas HJ, Cottrell S, Murday V, Fennell SJ, Williams S, Searle S, Sheer D, Bodmer WF, Frischauf AM, et al.; 1989 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=298656

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Direct effects of thyrotropin-releasing hormone, cyproheptadine, and dopamine on adrenocorticotropin secretion from human corticotroph adenoma cells in vitro. by Ishibashi M, Yamaji T.; 1981 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=370889

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Effects of p53 mutations on apoptosis in mouse intestinal and human colonic adenomas. by Fazeli A, Steen RG, Dickinson SL, Bautista D, Dietrich WF, Bronson RT, Bresalier RS, Lander ES, Costa J, Weinberg RA.; 1997 Sep 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=23339

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Evidence that the familial adenomatous polyposis gene is involved in a subset of colon cancers with a complementable defect in c-myc regulation. by Erisman MD, Scott JK, Astrin SM.; 1989 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=287431

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Germ-line mutations of the APC gene in 53 familial adenomatous polyposis patients. by Miyoshi Y, Ando H, Nagase H, Nishisho I, Horii A, Miki Y, Mori T, Utsunomiya J, Baba S, Petersen G, et al.; 1992 May 15; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=49100

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GH3 pituitary adenoma cells can reverse thymic aging in rats. by Kelley KW, Brief S, Westly HJ, Novakofski J, Bechtel PJ, Simon J, Walker EB.; 1986 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=386349

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Growth stimulation by coexpression of transforming growth factor-alpha and epidermal growth factor-receptor in normal and adenomatous human colon epithelium. by Markowitz SD, Molkentin K, Gerbic C, Jackson J, Stellato T, Willson JK.; 1990 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=296730

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Hyperpolarization of the membrane potential caused by somatostatin in dissociated human pituitary adenoma cells that secrete growth hormone. by Yamashita N, Shibuya N, Ogata E.; 1986 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=386467

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Identification of a Colon Mucosa Gene That is Down-Regulated in Colon Adenomas and Adenocarcinomas. by Schweinfest CW, Henderson KW, Suster S, Kondoh N, Papas TS.; 1993 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=46467

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Importance of epidermal growth factor receptor signaling in establishment of adenomas and maintenance of carcinomas during intestinal tumorigenesis. by Roberts RB, Min L, Washington MK, Olsen SJ, Settle SH, Coffey RJ, Threadgill DW.; 2002 Feb 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=122223

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Intestinal adenomas can develop with a stable karyotype and stable microsatellites. by Haigis KM, Caya JG, Reichelderfer M, Dove WF.; 2002 Jun 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=124400

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Lack of correlation between Ki-67 labelling index and tumor size of anterior pituitary adenomas. by Mastronardi L, Guiducci A, Puzzilli F.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=56633

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Molecular cloning and chromosomal mapping of DNA rearranged with the parathyroid hormone gene in a parathyroid adenoma. by Arnold A, Kim HG, Gaz RD, Eddy RL, Fukushima Y, Byers MG, Shows TB, Kronenberg HM.; 1989 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=303928

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Molecular mechanisms of [beta]-catenin recognition by adenomatous polyposis coli revealed by the structure of an APC --[beta]-catenin complex. by Spink KE, Fridman SG, Weis WI.; 2001 Nov 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=125720

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OXIDATIVE PHOSPHORYLATION AND RESPIRATORY CONTROL IN MITOCHONDRIA FROM NORMAL, ADENOMATOUS, AND HYPERPLASTIC THYROID GLANDS. by Turkington RW, Nordwind B.; 1962 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=291094

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Pituitary adenomas in man and mouse: oncogenic potential of a truncated fibroblast growth factor receptor 4. by Low MJ.; 2002 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=150826

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Pleomorphic adenoma of minor salivary gland in the parapharyngeal space. by Varghese BT, Sebastian P, Abraham EK, Mathews A.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=156027

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Polyclonal structure of intestinal adenomas in Apc Min / + mice with concomitant loss of Apc + from all tumor lineages. by Merritt AJ, Gould KA, Dove WF.; 1997 Dec 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28409

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PPAR-[gamma] receptor ligands: novel therapy for pituitary adenomas. by Heaney AP, Fernando M, Melmed S.; 2003 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154441

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Pronounced reduction in adenoma recurrence associated with aspirin use and a polymorphism in the ornithine decarboxylase gene. by Martinez ME, O'Brien TG, Fultz KE, Babbar N, Yerushalmi H, Qu N, Guo Y, Boorman D, Einspahr J, Alberts DS, Gerner EW.; 2003 Jun 24; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=164678

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Stereotactic radiation for pituitary adenoma. by Mulroy L, Rheaume DE, Fleetwood I, Schella J, Robar J.; 2004 Feb 3; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=331369

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Stimulation of human thyroid growth via the inhibitory guanine nucleotide binding (G) protein Gi: constitutive expression of the G-protein alpha subunit Gi alpha-1 in autonomous adenoma. by Selzer E, Wilfing A, Schiferer A, Hermann M, GrubeckLoebenstein B, Freissmuth M.; 1993 Feb 15; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=45924

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Synchronous sebaceous lymphadenoma with squamous cell carcinoma -- case report. by Shukla M, Panicker S.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=324416

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The adenomatous polyposis coli-binding protein EB1 is associated with cytoplasmic and spindle microtubules. by Berrueta L, Kraeft SK, Tirnauer JS, Schuyler SC, Chen LB, Hill DE, Pellman D, Bierer BE.; 1998 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27940

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THE BIOSYNTHESIS OF INSULIN AND A PROBABLE PRECURSOR OF INSULIN BY A HUMAN ISLET CELL ADENOMA. by Steiner DF, Oyer PE.; 1967 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=335530

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The Steroid Content of Adrenal Adenomas and Measurements of Aldosterone Production in Patients with Essential Hypertension and Primary Aldosteronism. by Kaplan NM.; 1967 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=297075

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Whole-gene APC deletions cause classical familial adenomatous polyposis, but not attenuated polyposis or "multiple" colorectal adenomas. by Sieber OM, Lamlum H, Crabtree MD, Rowan AJ, Barclay E, Lipton L, Hodgson S, Thomas HJ, Neale K, Phillips RK, Farrington SM, Dunlop MG, Mueller HJ, Bisgaard ML, Bulow S, Fidalgo P, Albuquerque C, Scarano MI, Bodmer W, Tomlinson IP, Heinimann K.; 2002 Mar 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=122454

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The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with adenoma, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “adenoma” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for adenoma (hyperlinks lead to article summaries): •

A basal cell adenoma of the sublingual gland. Author(s): Hiranuma T, Kagamiuchi H, Kitamura R. Source: International Journal of Oral and Maxillofacial Surgery. 2003 October; 32(5): 5667. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14759121

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A case of normoreninemic aldosterone-producing adenoma associated with chronic renal failure: case report and literature review. Author(s): Koshiyama H, Fujisawa T, Kuwamura N, Nakamura Y, Kanamori H, Oida E, Hara A, Suzuki T, Sasano H. Source: Endocrine. 2003 August; 21(3): 221-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14515005

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A large pleomorphic adenoma of soft palate causing sleep apnea syndrome--a case report. Author(s): Murthy SV, Murthy NC, Belagavi CS, Munishwara GB. Source: Indian J Pathol Microbiol. 2003 July; 46(3): 466-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15025309

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A pitfall of metaiodobenzylguanidine scan: paraganglioma in close proximity to adrenocortical adenoma. Author(s): Kekalainen P, Alhava E, Vanninen E, Niskanen L. Source: Experimental and Clinical Endocrinology & Diabetes : Official Journal, German Society of Endocrinology [and] German Diabetes Association. 2003 August; 111(5): 2947. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12951637

6 PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

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A prospective study of aspirin use and the risk for colorectal adenoma. Author(s): Chan AT, Giovannucci EL, Schernhammer ES, Colditz GA, Hunter DJ, Willett WC, Fuchs CS. Source: Annals of Internal Medicine. 2004 February 3; 140(3): 157-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14757613

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A serous oligocystic adenoma of the head of the pancreas successfully treated by dome resection and chemocautery: a new approach to serous oligocystic adenoma. Author(s): Sakata K, Maeda Y, Harada T, Nagashima J, Ueda M, Shimabukuro T, Sugano M, Nishizawa H, Fukuyama N, Kawashima M, Noguchi T, Iida Y, Yokota T. Source: Journal of Hepato-Biliary-Pancreatic Surgery. 2003; 10(6): 446-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14714166

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Accuracy of preoperative localization studies and intraoperative parathyroid hormone assay in patients with primary hyperparathyroidism and double adenoma. Author(s): Haciyanli M, Lal G, Morita E, Duh QY, Kebebew E, Clark OH. Source: Journal of the American College of Surgeons. 2003 November; 197(5): 739-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14585407

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Activation of nuclear hormone receptor peroxisome proliferator-activated receptordelta accelerates intestinal adenoma growth. Author(s): Gupta RA, Wang D, Katkuri S, Wang H, Dey SK, DuBois RN. Source: Nature Medicine. 2004 March; 10(3): 245-7. Epub 2004 February 01. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14758356

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Adenoma of the esophagus with intracytoplasmic mucoid bodies. Author(s): Lindboe CF, Matre J, Nesland JM. Source: Apmis : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica. 2004 January; 112(1): 29-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14961971

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Adenoma of the iris and ciliary body. Case report. Author(s): Romanowska-Dixon B, Orlowska-Heitzman J. Source: Pol J Pathol. 2003; 54(3): 187-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14703286

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Adenoma recurrences after resection of colorectal carcinoma: results from the Southwest Oncology Group 9041 calcium chemoprevention pilot study. Author(s): Chu DZ, Chansky K, Alberts DS, Meyskens FL Jr, Fenoglio-Preiser CM, Rivkin SE, Mills GM, Giguere JK, Goodman GE, Abbruzzese JL, Lippman SM. Source: Annals of Surgical Oncology : the Official Journal of the Society of Surgical Oncology. 2003 October; 10(8): 870-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14527904

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Adenoma versus carcinoid tumor of the middle ear: a study of 48 cases and review of the literature. Author(s): Torske KR, Thompson LD. Source: Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc. 2002 May; 15(5): 543-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12011260

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Adrenocortical adenoma and carcinoma: histopathological and molecular comparative analysis. Author(s): Stojadinovic A, Brennan MF, Hoos A, Omeroglu A, Leung DH, Dudas ME, Nissan A, Cordon-Cardo C, Ghossein RA. Source: Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc. 2003 August; 16(8): 742-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12920217

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Alveolar adenoma of the lung: computed tomography and magnetic resonance imaging findings. Author(s): Fujimoto K, Muller NL, Sadohara J, Harada H, Hayashi A, Hayabuchi N. Source: Journal of Thoracic Imaging. 2002 April; 17(2): 163-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11956369

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Alveolar adenoma of the lung--a report of two cases. Author(s): Papla B, Malinowski E. Source: Pol J Pathol. 2003; 54(2): 147-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14575424

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Ampullary adenoma: clinical manifestations, diagnosis, and treatment. Author(s): Martin JA, Haber GB. Source: Gastrointest Endosc Clin N Am. 2003 October; 13(4): 649-69. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14986792

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Amyloid (spheroid) deposits in pituitary adenoma presenting as Cushing disease--a case report. Author(s): Rane SR, Deshmukh SD, Bapat VM. Source: Indian J Pathol Microbiol. 2001 July; 44(3): 345-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12024930

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An unusual cause of facial pain: malignant change in a calcified pleomorphic adenoma in the deep lobe of the parotid gland. Author(s): Kesse W, Violaris N, Howlett DC. Source: Ear, Nose, & Throat Journal. 2003 August; 82(8): 623-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14503101

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Anastomotic recurrence of rectal adenoma after anterior resection. Author(s): Steele RJ, Campbell KL. Source: Surgical Endoscopy. 2003 November; 17(11): 1851. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14959739

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Atypical tentorial meningioma 30 years after radiotherapy for a pituitary adenoma. Author(s): Santoro A, Minniti G, Paolini S, Passacantilli E, Missori P, Frati A, Cantore GP. Source: Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2002 March; 22(6): 463-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11976979

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Basal cell adenoma in the parapharyngeal space: MR findings. Author(s): Jeong AK, Lee HK, Kim SY, Cho KJ. Source: Clinical Imaging. 2001 November-December; 25(6): 392-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11733151

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Basal cell adenoma of the sublingual gland. Author(s): Lin HC, Chien CY, Huang SC, Su CY. Source: The Annals of Otology, Rhinology, and Laryngology. 2003 December; 112(12): 1066-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14703112

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Basal cell adenoma-an unusual presentation. Author(s): Hemachandran M, Lal A, Vaiphei K. Source: Annals of Diagnostic Pathology. 2003 October; 7(5): 292-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14571431

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Baseline dietary fiber intake and colorectal adenoma recurrence in the wheat bran fiber randomized trial. Author(s): Jacobs ET, Giuliano AR, Roe DJ, Guillen-Rodriguez JM, Alberts DS, Martinez ME. Source: Journal of the National Cancer Institute. 2002 November 6; 94(21): 1620-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12419788

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Benign metastasizing pleomorphic adenoma of the parotid gland: a clinicopathologic puzzle. Author(s): Marioni G, Marino F, Stramare R, Marchese-Ragona R, Staffieri A. Source: Head & Neck. 2003 December; 25(12): 1071-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14648866

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Benign pituitary adenoma with multiple dural metastases: a case report. Author(s): Kumar K, Kelly M. Source: Surgical Neurology. 2000 November; 54(5): 380-3; Discussion 384. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11165617

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Beta-catenin expression in intramucosal neoplastic lesions of the stomach. Comparative analysis of adenoma/dysplasia, adenocarcinoma and signet-ring cell carcinoma. Author(s): Tsukashita S, Kushima R, Bamba M, Nakamura E, Mukaisho K, Sugihara H, Hattori T. Source: Oncology. 2003; 64(3): 251-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12697966

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Biallelic germline mutations in MYH predispose to multiple colorectal adenoma and somatic G:C-->T:A mutations. Author(s): Jones S, Emmerson P, Maynard J, Best JM, Jordan S, Williams GT, Sampson JR, Cheadle JP. Source: Human Molecular Genetics. 2002 November 1; 11(23): 2961-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12393807

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Bilateral asynchronous adrenal adenoma in a girl with an incomplete form of Beckwith-Wiedemann syndrome. Author(s): Beauloye V, Zain F, Malvaux P, Rahier J, Gosseye S, Honour JW, Maes M. Source: European Journal of Pediatrics. 2001 February; 160(2): 142-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11271390

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Bile duct adenoma: management by subtotal excision. Author(s): Ibrarullah M, Sreenivasa D. Source: Trop Gastroenterol. 2003 April-June; 24(2): 93-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14603832

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Black thyroid adenoma. Clinical, histochemical, and ultrastructural features. Author(s): Koren R, Bernheim J, Schachter P, Schwartz A, Siegal A, Gal R. Source: Applied Immunohistochemistry & Molecular Morphology : Aimm / Official Publication of the Society for Applied Immunohistochemistry. 2000 March; 8(1): 80-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10937053

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Bleeding hepatic adenoma: expectant treatment to limit the extent of liver resection. Author(s): Heeringa B, Sardi A. Source: The American Surgeon. 2001 October; 67(10): 927-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11603546

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Bottom-up histogenesis of colorectal adenomas: origin in the monocryptal adenoma and initial expansion by crypt fission. Author(s): Preston SL, Wong WM, Chan AO, Poulsom R, Jeffery R, Goodlad RA, Mandir N, Elia G, Novelli M, Bodmer WF, Tomlinson IP, Wright NA. Source: Cancer Research. 2003 July 1; 63(13): 3819-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12839979

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Bronchial adenoma presenting with chronic asthma and obstructive pneumonia: a case report. Author(s): Reechaipichitkul W, Saengsaard S, Puapairoj A, Boonsawat W. Source: Southeast Asian J Trop Med Public Health. 2002 March; 33(1): 164-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12118446

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Bronchial adenoma: an unusual cause of recurrent pneumonia in childhood. Author(s): Morini F, Quattrucci S, Cozzi DA, Tancredi G, Cicconi AM, Guidi R, Midulla F. Source: The Annals of Thoracic Surgery. 2003 December; 76(6): 2085-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14667652

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Brown tumor of the maxilla and mandible: progressive mandibular brown tumor after removal of parathyroid adenoma. Author(s): Yamazaki H, Ota Y, Aoki T, Karakida K. Source: Journal of Oral and Maxillofacial Surgery : Official Journal of the American Association of Oral and Maxillofacial Surgeons. 2003 June; 61(6): 719-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12796885

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Brown tumour of hyperparathyroidism in the mandible associated with parathyroid adenoma. Author(s): Kar DK, Agarwal G, Mishra SK. Source: The Journal of Laryngology and Otology. 2001 April; 115(4): 352-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11368025

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Brunner's adenoma, esophageal reflux and gastric ulcer. A case report. Author(s): Cavallaro G, Albanese V, Taranto F, Pustorino S, Baldari S. Source: Chir Ital. 2000 November-December; 52(6): 703-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11200007

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Brunner's gland adenoma with circumferential duodenal involvement. Author(s): Varma D, Prakash K, Augustine P, Mahadevan P, Ramesh H. Source: Indian J Gastroenterol. 2001 November-December; 20(6): 243-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11817781

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BsmI vitamin D receptor polymorphism and pathogenesis of parathyroid adenoma. Author(s): Pacheco D, Menarguez J, Cristobal E, Arribas B, Alcazar JA, Carrion R, Polo JR. Source: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 2000 July-August; 6(4): 658-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11208387

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Calcium, vitamin D, and risk of adenoma recurrence (United States). Author(s): Martinez ME, Marshall JR, Sampliner R, Wilkinson J, Alberts DS. Source: Cancer Causes & Control : Ccc. 2002 April; 13(3): 213-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12020102

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Canalicular adenoma of the parotid gland: a case report. Author(s): Rossiello R, Rossiello L, De Simone S, Apicella A, Lanza A, Colella G. Source: Anticancer Res. 2003 September-October; 23(5B): 4101-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14666608

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Carcinoembryonic antigen mRNA in blood: distinguishing follicular thyroid carcinoma from adenoma. Author(s): Sato T, Nakano S, Yamashita J. Source: Thyroid : Official Journal of the American Thyroid Association. 2003 September; 13(9): 891-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14588107

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Case of lacrimal gland carcinoma ex adenoma. Author(s): Kuroishikawa M, Kiyosawa M, Akashi T, Mochizuki M. Source: Japanese Journal of Ophthalmology. 2004 March-April; 48(2): 181-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15060804

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Cathepsin B and cathepsin D expression in the progression of colorectal adenoma to carcinoma. Author(s): Talieri M, Papadopoulou S, Scorilas A, Xynopoulos D, Arnogianaki N, Plataniotis G, Yotis J, Agnanti N. Source: Cancer Letters. 2004 March 8; 205(1): 97-106. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15036666

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Celiac disease and small intestinal tubulovillous adenoma: a role for push enteroscopy? Author(s): Bhala N, Hurlstone DP, Hadjivassiliou M, Dube AK, Sanders DS. Source: The American Journal of Gastroenterology. 2003 December; 98(12): 2814-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14687849

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Clinical features associated with lesions other than pituitary adenoma in patients with an optic chiasmal syndrome. Author(s): Mejico LJ, Miller NR, Dong LM. Source: American Journal of Ophthalmology. 2004 May; 137(5): 908-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15126157

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Clinicopathologic and endoscopic features of colorectal serrated adenoma: differences between polypoid and superficial types. Author(s): Oka S, Tanaka S, Hiyama T, Ito M, Kitadai Y, Yoshihara M, Haruma K, Chayama K. Source: Gastrointestinal Endoscopy. 2004 February; 59(2): 213-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14745394

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Coexistence of a parathyroid adenoma and parathyroid cyst causing primary hyperparathyroidism. Author(s): Ardito G, Fadda G, Danese D, Modugno P, Giordano A, Revelli L, Ardito F, Pontecorvi A. Source: J Endocrinol Invest. 2003 July; 26(7): 679-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14594122

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Coincidental diagnosis of an occult hilar steroid cell tumor of the ovary and a cortisolsecreting adrenal adenoma in a 49-year-old woman with severe hyperandrogenism. Author(s): Gorgojo JJ, Almodovar F, Lopez E, Vicente del Cerro J, Tejerina E, Donnay S. Source: Fertility and Sterility. 2003 December; 80(6): 1504-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14667891

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Colchicine effect in a colonic hyperplastic polyp. A lesion mimicking serrated adenoma. Author(s): Torbenson M, Montgomery EA, Iacobuzio-Donahue C, Yardley JH, Wu TT, Abraham SC. Source: Archives of Pathology & Laboratory Medicine. 2002 May; 126(5): 615-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11958673

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Colorectal adenoma characteristics as predictors of recurrence. Author(s): Bonithon-Kopp C, Piard F, Fenger C, Cabeza E, O'Morain C, Kronborg O, Faivre J; European Cancer Prevention Organisation Study Group. Source: Diseases of the Colon and Rectum. 2004 March; 47(3): 323-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14991494

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Colorectal proliferation and apoptosis in serrated versus conventional adenomacarcinoma pathway: growth, progression and survival. Author(s): Horkko TT, Makinen MJ. Source: Scandinavian Journal of Gastroenterology. 2003 December; 38(12): 1241-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14750644

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Common bile duct papillary adenoma causing obstructive jaundice: case report and review of the literature. Author(s): Fletcher ND, Wise PE, Sharp KW. Source: The American Surgeon. 2004 May; 70(5): 448-52. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15156955

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Comparative immunoprofile of polymorphous low-grade adenocarcinoma and canalicular adenoma. Author(s): Furuse C, Tucci R, Machado de Sousa SO, Rodarte Carvalho Y, Cavalcanti de Araujo V. Source: Annals of Diagnostic Pathology. 2003 October; 7(5): 278-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14571428

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Computed tomography-guided percutaneous acetic acid injection therapy for functioning adrenocortical adenoma. Author(s): Minowada S, Fujimura T, Takahashi N, Kishi H, Hasuo K, Minami M. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 December; 88(12): 5814-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14671174

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Contribution of the CHEK2 1100delC variant to risk of multiple colorectal adenoma and carcinoma. Author(s): Lipton L, Fleischmann C, Sieber OM, Thomas HJ, Hodgson SV, Tomlinson IP, Houlston RS. Source: Cancer Letters. 2003 October 28; 200(2): 149-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14568168

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Cosecretion of estrogen and inhibin B by a feminizing adrenocortical adenoma: impact on gonadotropin secretion. Author(s): Kuhn JM, Lefebvre H, Duparc C, Pellerin A, Luton JP, Strauch G. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 May; 87(5): 2367-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11994389

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Cushing's syndrome secondary to adrenal adenoma during pregnancy. Author(s): Lo CY, Lo CM, Lam KY. Source: Surgical Endoscopy. 2002 January; 16(1): 219-20. Epub 2001 October 13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11961658

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Cytologic characteristics of pulmonary papillary adenoma. A case report. Author(s): Minami Y, Morishita Y, Yamamoto T, Iijima T, Fukasawa M, Ishikawa S, Ichimura H, Noguchi M. Source: Acta Cytol. 2004 March-April; 48(2): 243-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15085761

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Daily soluble aspirin and prevention of colorectal adenoma recurrence: one-year results of the APACC trial. Author(s): Benamouzig R, Deyra J, Martin A, Girard B, Jullian E, Piednoir B, Couturier D, Coste T, Little J, Chaussade S. Source: Gastroenterology. 2003 August; 125(2): 328-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12891533

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Danazol-induced hepatocellular adenoma in patients with hereditary angio-oedema. Author(s): Bork K, Schneiders V. Source: Journal of Hepatology. 2002 May; 36(5): 707-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11983460

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Decreased expression of thyrotropin receptor gene suggests a high-risk subgroup for oncocytic adenoma. Author(s): Mirebeau-Prunier D, Guyetant S, Rodien P, Franc B, Baris O, Rohmer V, Reynier P, Tourmen Y, Malthiery Y, Savagner F. Source: European Journal of Endocrinology / European Federation of Endocrine Societies. 2004 March; 150(3): 269-76. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15012610

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Demonstration of enhanced potency of a chimeric somatostatin-dopamine molecule, BIM-23A387, in suppressing growth hormone and prolactin secretion from human pituitary somatotroph adenoma cells. Author(s): Saveanu A, Lavaque E, Gunz G, Barlier A, Kim S, Taylor JE, Culler MD, Enjalbert A, Jaquet P. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 December; 87(12): 5545-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12466351

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Detection of cancer clones in human gastric adenoma by increased DNA-instability and other biomarkers. Author(s): Sun A, Noriki S, Imamura Y, Fukuda M. Source: Eur J Histochem. 2003; 47(2): 111-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12777206

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81

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Determinant role of Tc-99m MIBI SPECT in the localization of a retrotracheal parathyroid adenoma successfully treated by radioguided surgery. Author(s): Rubello D, Casara D, Pagetta C, Piotto A, Pelizzo MR, Shapiro B. Source: Clinical Nuclear Medicine. 2002 October; 27(10): 711-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12352113

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Diagnostic applicability of dipeptidyl aminopeptidase IV activity in cytological samples for differentiating follicular thyroid carcinoma from follicular adenoma. Author(s): Maruta J, Hashimoto H, Yamashita H, Yamashita H, Noguchi S. Source: Archives of Surgery (Chicago, Ill. : 1960). 2004 January; 139(1): 83-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14718282

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Diet and colorectal adenoma in Japanese males and females. Author(s): Nagata C, Shimizu H, Kametani M, Takeyama N, Ohnuma T, Matsushita S. Source: Diseases of the Colon and Rectum. 2001 January; 44(1): 105-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11805576

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Difference in cytoplasmic localization pattern of neutral mucin among lobular endocervical glandular hyperplasia, adenoma malignum, and common adenocarcinoma of the uterine cervix. Author(s): Hayashi I, Tsuda H, Shimoda T, Maeshima A, Kasamatsu T, Yamada T, Tsunematsu R. Source: Virchows Archiv : an International Journal of Pathology. 2003 December; 443(6): 752-60. Epub 2003 October 11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14556072

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Differential expression of IGFBP-5 and two human ESTs in thyroid glands with goiter, adenoma and papillary or follicular carcinomas. Author(s): Stolf BS, Carvalho AF, Martins WK, Runza FB, Brun M, Hirata R Jr, Jordao Neves E, Soares FA, Postigo-Dias J, Kowalski LP, Reis LF. Source: Cancer Letters. 2003 March 10; 191(2): 193-202. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12618333

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Differential gene-expression profiles associated with gastric adenoma. Author(s): Takenawa H, Kurosaki M, Enomoto N, Miyasaka Y, Kanazawa N, Sakamoto N, Ikeda T, Izumi N, Sato C, Watanabe M. Source: British Journal of Cancer. 2004 January 12; 90(1): 216-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14710232

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Dinucleotide repeat in the insulin-like growth factor-I gene is not related to risk of colorectal adenoma. Author(s): Giovannucci E, Haiman CA, Platz EA, Hankinson SE, Pollak MN, Hunter DJ. Source: Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 2002 November; 11(11): 1509-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12433739

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Dissecting karyotypic patterns in colorectal tumors: two distinct but overlapping pathways in the adenoma-carcinoma transition. Author(s): Hoglund M, Gisselsson D, Hansen GB, Sall T, Mitelman F, Nilbert M. Source: Cancer Research. 2002 October 15; 62(20): 5939-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12384560

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DNA copy number changes in carcinoma in pleomorphic adenoma of the salivary gland: a comparative genomic hybridization study. Author(s): Morio T, Morimitsu Y, Hisaoka M, Makishima K, Hashimoto H. Source: Pathology International. 2002 August; 52(8): 501-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12366808

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DNA profiles and numeric histogram classifiers in nephrogenic adenoma. Author(s): Wiener HG, Remkes GW, Birner P, Pycha A, Schatzl G, Susani M, Breitenecker G. Source: Cancer. 2002 April 25; 96(2): 117-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11954029

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Does early polypoid colorectal cancer with depression have a pathway other than adenoma-carcinoma sequence? Author(s): Kanazawa T, Watanabe T, Nagawa H. Source: Tumori. 2003 July-August; 89(4): 408-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14606645

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Dopaminergic modulation of aldosterone secretions on changes of sodium intake in aldosterone-producing adenoma. Author(s): Wu KD, Chen YM, Chu TS, Chueh SC, Tsai GC, Tseng YZ, Hsieh BS. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 2002 July; 15(7 Pt 1): 609-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12118908

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Dose-response relationship for parathyroid adenoma after exposure to ionizing radiation in infancy. Author(s): Holmberg E, Wallgren A, Holm LE, Lundell M, Karlsson P. Source: Radiation Research. 2002 October; 158(4): 418-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12236809

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Down-regulated in adenoma mediates apical Cl-/HCO3- exchange in rabbit, rat, and human duodenum. Author(s): Jacob P, Rossmann H, Lamprecht G, Kretz A, Neff C, Lin-Wu E, Gregor M, Groneberg DA, Kere J, Seidler U. Source: Gastroenterology. 2002 March; 122(3): 709-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11875004

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Ductal adenoma of the breast with chondromyxoid change. Author(s): Kato N, Ohe S, Motoyama T. Source: Pathology International. 2002 March; 52(3): 239-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11972868

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Early change of thyroid hormone concentration after 131I treatment in patients with solitary toxic adenoma. Author(s): Pirnat E, Fidler V, Zaletel K, Gaberscek S, Hojker S. Source: Nuklearmedizin. 2002; 41(4): 178-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12224401

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Ectopic mediastinal parathyroid adenoma. Author(s): Caporale DM, Bobbio A, Accordino R, Ampollini L, Internullo E, Cattelani L, Carbognani P, Rusca M. Source: Acta Biomed Ateneo Parmense. 2003 December; 74(3): 157-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15055021

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Ectopic parathyroid adenoma initially suspected to be a thyroid lesion. Author(s): Pitsilos SA, Weber R, Baloch Z, LiVolsi VA. Source: Archives of Pathology & Laboratory Medicine. 2002 December; 126(12): 1541-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12456220

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Ectopic parathyroid adenoma localised with sestamibi SPECT and image-fused computed tomography. Author(s): Ng P, Lenzo NP, McCarthy MC, Thompson I, Leedman PJ. Source: The Medical Journal of Australia. 2003 November 3; 179(9): 485-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14583080

84

Adenoma

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Ectopic pituitary adenoma in the cavernous sinus causing oculomotor nerve paresis-case report. Author(s): Hata N, Inoue T, Katsuta T, Iwaki T. Source: Neurol Med Chir (Tokyo). 2003 August; 43(8): 399-403. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12968808

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Ectopic TSH-secreting pituitary adenoma of the vomerosphenoidal junction. Author(s): Pasquini E, Faustini-Fustini M, Sciarretta V, Saggese D, Roncaroli F, Serra D, Frank G. Source: European Journal of Endocrinology / European Federation of Endocrine Societies. 2003 February; 148(2): 253-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12590646

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Effect of fibre and calcium supplementation on adenoma recurrence and growth. Author(s): Faivre J, Bonithon-Kopp C. Source: Iarc Sci Publ. 2002; 156: 457-61. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12484234

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Endoscopic light-induced autofluorescence spectroscopy for the diagnosis of colorectal cancer and adenoma. Author(s): Mayinger B, Jordan M, Horner P, Gerlach C, Muehldorfer S, Bittorf BR, Matzel KE, Hohenberger W, Hahn EG, Guenther K. Source: Journal of Photochemistry and Photobiology. B, Biology. 2003 April; 70(1): 13-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12745242

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Endoscopic management of adenoma of the major duodenal papilla. Author(s): Catalano MF, Linder JD, Chak A, Sivak MV Jr, Raijman I, Geenen JE, Howell DA. Source: Gastrointestinal Endoscopy. 2004 February; 59(2): 225-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14745396

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Endoscopic mucosal resection for advanced non-polypoid colorectal adenoma and early stage carcinoma. Author(s): Bergmann U, Beger HG. Source: Surgical Endoscopy. 2003 March; 17(3): 475-9. Epub 2002 November 06. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12415335

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Endoscopic resection of a large Brunner's gland adenoma. Author(s): Jansen JM, Stuifbergen WN, van Milligen de Wit AW. Source: The Netherlands Journal of Medicine. 2002 July; 60(6): 253-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12365469

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Esophageal submucosal gland duct adenoma: characteristic EUS and histopathologic features. Author(s): Agawa H, Matsushita M, Kusumi F, Nishio A, Takakuwa H. Source: Gastrointestinal Endoscopy. 2003 June; 57(7): 983-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12776064

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Establishment of a colonic adenoma cell line (GEKI-2): spectral karyotype analysis and functional characterization. Author(s): Menzel T, Melcher R, Koehler S, Dusel G, Backhaus K, Ott G, Breithaupt W, Al-Taie O, Schauber J, Gostner A, Scheppach W, Luhrs H. Source: International Journal of Colorectal Disease. 2004 January; 19(1): 12-7. Epub 2003 May 24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14648095

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Exacerbation of ovarian hyperstimulation by leuprolide reveals a gonadotroph adenoma. Author(s): Castelbaum AJ, Bigdeli H, Post KD, Freedman MF, Snyder PJ. Source: Fertility and Sterility. 2002 December; 78(6): 1311-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12477530

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Expression and significance of PTEN, hypoxia-inducible factor-1 alpha in colorectal adenoma and adenocarcinoma. Author(s): Jiang YA, Fan LF, Jiang CQ, Zhang YY, Luo HS, Tang ZJ, Xia D, Wang M. Source: World Journal of Gastroenterology : Wjg. 2003 March; 9(3): 491-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12632503

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Expression of beta-catenin and E-cadherin in the adenoma-carcinoma sequence of the stomach. Author(s): Kim HS, Hong EK, Park SY, Kim WH, Lee HS. Source: Anticancer Res. 2003 May-June; 23(3C): 2863-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12926124

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Expression of estrogen receptor, progesterone receptor, and insulin-like growth factor receptor-1 and of MIB-1 in patients with recurrent pleomorphic adenoma of the parotid gland. Author(s): Glas AS, Hollema H, Nap RE, Plukker JT. Source: Cancer. 2002 April 15; 94(8): 2211-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12001119

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Expression of kinase genes in primary hyperparathyroidism: adenoma versus hyperplastic parathyroid tissue. Author(s): Schachter PP, Ayesh S, Schneider T, Laster M, Czerniak A, Hochberg A. Source: Surgery. 2002 December; 132(6): 1094-8; Discussion 1098-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12490860

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Extracerebral subdural manifestation of Chester-Erdheim disease associated with a giant adenoma of the pituitary. Author(s): Thorns V, Zajaczek J, Becker H, Walter GF, Hori A. Source: Clin Neuropathol. 2003 September-October; 22(5): 246-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14531550

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Extra-hepatic bile duct adenoma in a patient with a choledochal cyst. Author(s): Aggarwal S, Kumar S, Kumar A, Bhasin R, Garg PK, Bandhu S. Source: Journal of Gastroenterology and Hepatology. 2003 March; 18(3): 351-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12603542

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Faecal calprotectin and faecal occult blood tests in the diagnosis of colorectal carcinoma and adenoma. Author(s): Tibble J, Sigthorsson G, Foster R, Sherwood R, Fagerhol M, Bjarnason I. Source: Gut. 2001 September; 49(3): 402-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11511563

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Familial isolated parathyroid adenoma in a consanguineous family. Author(s): Bergwitz C, Bremer B, Soudah B, Mayr B, Brabant G. Source: J Endocrinol Invest. 2001 May; 24(5): 349-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11407655

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Fas ligand is up-regulated during the colorectal adenoma-carcinoma sequence. Author(s): Belluco C, Esposito G, Bertorelle R, Alaggio R, Giacomelli L, Bianchi LC, Nitti D, Lise M. Source: European Journal of Surgical Oncology : the Journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2002 March; 28(2): 120-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11884046

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Fatal hemorrhage from androgen-related hepatic adenoma after hematopoietic cell transplantation. Author(s): Kumar AR, Wagner JE, Auerbach AD, Coad JE, Dietz CA, Schwarzenberg SJ, MacMillan ML. Source: Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. 2004 January; 26(1): 16-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14707705

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Fate of a renal tubulopapillary adenoma transmitted by an organ donor. Author(s): Barrou B, Bitker MO, Delcourt A, Ourahma S, Richard F. Source: Transplantation. 2001 August 15; 72(3): 540-1. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11502993

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Fatty acid synthase is highly expressed in carcinoma, adenoma and in regenerative epithelium and intestinal metaplasia of the stomach. Author(s): Kusakabe T, Nashimoto A, Honma K, Suzuki T. Source: Histopathology. 2002 January; 40(1): 71-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11903600

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Features of gastritis predisposing to gastric adenoma and early gastric cancer. Author(s): Meining A, Riedl B, Stolte M. Source: Journal of Clinical Pathology. 2002 October; 55(10): 770-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12354805

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Fibrolamellar hepatocellular carcinoma occurring 5 years after hepatocellular adenoma in a 14-year-old girl: a case report with comparative genomic hybridization analysis. Author(s): Terracciano LM, Tornillo L, Avoledo P, Von Schweinitz D, Kuhne T, Bruder E. Source: Archives of Pathology & Laboratory Medicine. 2004 February; 128(2): 222-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14736278

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Fine needle aspiration diagnosis of malignant mixed tumor (carcinosarcoma) arising in pleomorphic adenoma of the salivary gland. A case report. Author(s): Kim T, Yoon GS, Kim O, Gong G. Source: Acta Cytol. 1998 July-August; 42(4): 1027-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9684598

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Fine-needle aspiration biopsy of a cystic pleomorphic adenoma with extensive adnexa-like differentiation: differential diagnostic pitfall with mucoepidermoid carcinoma. Author(s): Brachtel EF, Pilch BZ, Khettry U, Zembowicz A, Faquin WC. Source: Diagnostic Cytopathology. 2003 February; 28(2): 100-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12561031

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Flat adenoma: are western colonoscopists careful enough? Author(s): Kobayashi K, Sivak MV Jr. Source: Endoscopy. 1998 June; 30(5): 487-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9693899

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Fluorescence endoscopy using a fluorescein-labeled monoclonal antibody against carcinoembryonic antigen in patients with colorectal carcinoma and adenoma. Author(s): Keller R, Winde G, Terpe HJ, Foerster EC, Domschke W. Source: Endoscopy. 2002 October; 34(10): 801-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12244502

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Focal nodular hyperplasia and hepatocellular adenoma of the liver: differentiation with multiphasic helical CT. Author(s): Ruppert-Kohlmayr AJ, Uggowitzer MM, Kugler C, Zebedin D, Schaffler G, Ruppert GS. Source: Ajr. American Journal of Roentgenology. 2001 June; 176(6): 1493-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11373219

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Folate and colorectal neoplasia: relation between plasma and dietary markers of folate and adenoma recurrence. Author(s): Martinez ME, Henning SM, Alberts DS. Source: The American Journal of Clinical Nutrition. 2004 April; 79(4): 691-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15051616

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Follicular adenoma of the thyroid gland with extensive bone metaplasia. Author(s): Ardito G, Fadda G, Revelli L, Modugno P, Lucci C, Ardito F, Pontecorvi A, LiVolsi VA. Source: J Exp Clin Cancer Res. 2001 September; 20(3): 443-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11718227

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Follicular adenoma of thyroid associated with mediastinal malignant hemangioendothelioma, masquerading as malignant retrosternal goiter. Author(s): Mishra A, Mishra SK. Source: J Assoc Physicians India. 2001 July; 49: 730. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11573559

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Follicular adenoma with papillary architecture: a lesion mimicking papillary thyroid carcinoma. Author(s): Mai KT, Landry DC, Thomas J, Burns BF, Commons AS, Yazdi HM, Odell PF. Source: Histopathology. 2001 July; 39(1): 25-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11454041

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Food-dependent androgen and cortisol secretion by a gastric inhibitory polypeptidereceptor expressive adrenocortical adenoma leading to hirsutism and subclinical Cushing's syndrome: in vivo and in vitro studies. Author(s): Tsagarakis S, Tsigos C, Vassiliou V, Tsiotra P, Pratsinis H, Kletsas D, Trivizas P, Nikou A, Mavromatis T, Sotsiou F, Raptis S, Thalassinos N. Source: The Journal of Clinical Endocrinology and Metabolism. 2001 February; 86(2): 583-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11158012

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Frequency of proliferation, apoptosis, and their ratio during rat colon carcinogenesis and their characteristic pattern in the dimethylhydrazine-induced colon adenoma and carcinoma. Author(s): Melen-Mucha G, Niewiadomska H. Source: Cancer Investigation. 2002; 20(5-6): 700-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12197226

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Functioning adrenal black adenoma with pulmonary and cutaneous cryptococcosis: a case report and review of English literature. Author(s): Takahashi S, Iijima H, Moriwaki Y, Yamamoto T, Matsuoka S, Tsutsumi Z, Nojima M, Kubota A, Hada T. Source: J Endocrinol Invest. 2001 November; 24(10): 816-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11765053

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Gamma knife radiosurgery for pituitary adenoma. Author(s): Shin M. Source: Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie. 2002; 56 Suppl 1: 178S-181S. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12487277

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Gamma knife radiosurgery for pituitary adenoma: early results. Author(s): Petrovich Z, Yu C, Giannotta SL, Zee CS, Apuzzo ML. Source: Neurosurgery. 2003 July; 53(1): 51-9; Discussion 59-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12823873

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Gamma-probe localization of a parathyroid adenoma in the reoperative neck. Author(s): Damrose EJ, Hoh C, Calcaterra TC. Source: American Journal of Otolaryngology. 2000 November-December; 21(6): 394-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11115524

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Gastric outlet obstruction due to a large duodenal tubulovillous adenoma. Author(s): Felig DM, Geuder J. Source: Gastrointestinal Endoscopy. 2001 March; 53(3): 340-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11231397

90

Adenoma

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Gastrin and gastrin receptor activation: an early event in the adenoma-carcinoma sequence. Author(s): Smith AM, Watson SA. Source: Gut. 2000 December; 47(6): 820-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11076881

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Genetic alterations in adenoma-carcinoma sequencing of intraductal papillarymucinous neoplasm of the pancreas. Author(s): Nakata B, Yashiro M, Nishioka N, Aya M, Yamada S, Takenaka C, Ohira M, Ishikawa T, Nishino H, Wakasa K, Hirakawa K. Source: International Journal of Oncology. 2002 November; 21(5): 1067-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12370756

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Genetic alterations in gallbladder adenoma, dysplasia and carcinoma. Author(s): Kim YT, Kim J, Jang YH, Lee WJ, Ryu JK, Park YK, Kim SW, Kim WH, Yoon YB, Kim CY. Source: Cancer Letters. 2001 August 10; 169(1): 59-68. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11410326

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Genetic analysis of multiple synchronous lesions of the colon adenoma-carcinoma sequence. Author(s): Sedivy R, Wolf B, Kalipciyan M, Steger GG, Karner-Hanusch J, Mader RM. Source: British Journal of Cancer. 2000 April; 82(7): 1276-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10755401

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Genetic and epigenetic changes in the APC gene in sporadic colorectal carcinoma with synchronous adenoma. Author(s): Kim JC, Koo KH, Roh SA, Cho YK, Kim HC, Yu CS, Kim HJ, Kim JS, Cho MK. Source: International Journal of Colorectal Disease. 2003 May; 18(3): 203-9. Epub 2002 December 14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12673484

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Genetic basis of pituitary adenoma invasiveness: a review. Author(s): Suhardja A, Kovacs K, Rutka J. Source: Journal of Neuro-Oncology. 2001 May; 52(3): 195-204. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11519849

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Genomic events in the adenoma to carcinoma sequence. Author(s): Terdiman JP. Source: Semin Gastrointest Dis. 2000 October; 11(4): 194-206. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11057947

Studies

91

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Giant mediastinal parathyroid adenoma in a woman with hypercalcemia. Author(s): Batsakis C, Kalkana C, Ilias I, Panoutsopoulos G, Christakopoulou I. Source: Clinical Nuclear Medicine. 2001 November; 26(11): 950-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11595856

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Giant mediastinal parathyroid adenoma with hypercalcemia. Author(s): Dieter RA Jr, O'Brien T, Carpenter R. Source: Int Surg. 2002 October-December; 87(4): 217-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12575803

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Giant parotid pleomorphic adenoma involving the parapharyngeal space: report of a case. Author(s): Rodriguez-Ciurana J, Rodado C, Saez M, Bassas C. Source: Journal of Oral and Maxillofacial Surgery : Official Journal of the American Association of Oral and Maxillofacial Surgeons. 2000 October; 58(10): 1184-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11021720

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Giant pleomorphic adenoma of the parotid gland involving the parapharyngeal space treated by a totally extraoral transparotid approach. Author(s): Panoussopoulos D, Yotakis J, Pararas B, Theodoropoulos G, Papadimitriou K. Source: Journal of Surgical Oncology. 2002 November; 81(3): 155-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12407730

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Giant solitary parathyroid adenoma presenting with bone disease. Author(s): Prasad TR, Bhatnagar V. Source: Indian Pediatrics. 2002 November; 39(11): 1044-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12466576

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Gonadotropin releasing hormone analogue antiandrogen failure secondary to a pituitary adenoma. Author(s): Ogan K, Berger M, Ball R. Source: The Journal of Urology. 1998 August; 160(2): 497-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9679910

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Growth hormone-secreting pituitary adenoma associated with primary moyamoya disease--case report. Author(s): Uchida K, Arakawa Y, Ohyama K, Sirakawa M, Tsuji R, Yokoyama M, Imataka K, Sato M, Shimizu Y. Source: Neurol Med Chir (Tokyo). 2003 July; 43(7): 356-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12924597

92

Adenoma

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Growth hormone-secreting pituitary adenoma confined to the sphenoid sinus associated with a normal-sized empty sella. Author(s): Hori E, Akai T, Kurimoto M, Hirashima Y, Endo S. Source: Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia. 2002 March; 9(2): 196-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11922715

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Growth promoting effect of human plasma ultrafiltrate bioactive fraction (TBP) for human non-functioning pituitary adenoma cells in vitro. Author(s): Zarkovic N, Hayn M, Tatzber F, Reichel H, Kor ic M, Zarkovic K, Plav ic V, Breskovac LJ, Klingmuller M, Paladino J. Source: J Endocrinol Invest. 2000 December; 23(11): 737-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11194707

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Helicobacter pylori infection in patients with Brunner's gland adenoma. Author(s): Kovacevic I, Ljubicic N, Cupic H, Doko M, Zovak M, Troskot B, Kujundzic M, Banic M. Source: Acta Med Croatica. 2001; 55(4-5): 157-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12398018

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Hemoperitoneum from spontaneous rupture of a liver cell adenoma in a male with hyperthyroidism. Author(s): Adusumilli PS, Lee B, Parekh K, Dolgopolov S. Source: The American Surgeon. 2002 July; 68(7): 582-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12132736

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Hepatocellular adenoma and focal nodular hyperplasia: a series of 24 patients with clinicopathological and radiological correlation. Author(s): Ji Y, Zhu X, Sun H, Tan Y, Ma Z, Ye Q, Sujie A, Tang Z. Source: Chinese Medical Journal. 2000 September; 113(9): 852-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11776086

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Hepatocellular adenoma and polycystic ovary syndrome. Author(s): Toso C, Rubbia-Brandt L, Negro F, Morel P, Mentha G. Source: Liver International : Official Journal of the International Association for the Study of the Liver. 2003 February; 23(1): 35-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12640725

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Hepatocellular adenoma in type Ia glycogen storage disease. Author(s): Kudo M. Source: Journal of Gastroenterology. 2001; 36(1): 65-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11211215

Studies

93

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Hepatocellular adenoma presenting as a giant multicystic tumor of the liver. Author(s): Katsuramaki T, Nagayama M, Kimura Y, Meguro M, Furuhata T, Mukaiya M, Hirata K, Koito K, Hareyama M, Ikeda T, Satoh M. Source: Journal of Gastroenterology. 2003; 38(5): 516-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12768399

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Hepatocellular adenoma: diagnostic difficulties and novel imaging techniques. Author(s): Lim AK, Patel N, Gedroyc WM, Blomley MJ, Hamilton G, Taylor-Robinson SD. Source: The British Journal of Radiology. 2002 August; 75(896): 695-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12153946

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Hepatocellular carcinoma with solitary metastasis in pleomorphic adenoma of the submandibular gland. Author(s): Ichikawa T, Takagi H, Abe T, Ito H, Nagamine T, Mori M. Source: Histopathology. 2001 January; 38(1): 80-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11210852

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HERG K(+) currents in human prolactin-secreting adenoma cells. Author(s): Bauer CK, Wulfsen I, Schafer R, Glassmeier G, Wimmers S, Flitsch J, Ludecke DK, Schwarz JR. Source: Pflugers Archiv : European Journal of Physiology. 2003 February; 445(5): 589600. Epub 2002 December 06. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12634931

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High-grade dysplasia and invasive carcinoma in colorectal adenomas: a multivariate analysis of the impact of adenoma and patient characteristics. Author(s): Gschwantler M, Kriwanek S, Langner E, Goritzer B, Schrutka-Kolbl C, Brownstone E, Feichtinger H, Weiss W. Source: European Journal of Gastroenterology & Hepatology. 2002 February; 14(2): 1838. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11981343

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Histomorphological investigation regarding to malignant transformation of pleomorphic adenoma (so-called malignant mixed tumor) of the salivary gland origin: special reference to carcinosarcoma. Author(s): Harada H. Source: Kurume Med J. 2000; 47(4): 307-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11197153

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Adenoma

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Histopathology of pleomorphic adenoma in the parotid gland: a prospective unselected series of 100 cases. Author(s): Stennert E, Guntinas-Lichius O, Klussmann JP, Arnold G. Source: The Laryngoscope. 2001 December; 111(12): 2195-200. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11802025

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Holmium laser enucleation for prostate adenoma greater than 100 gm.: comparison to open prostatectomy. Author(s): Moody JA, Lingeman JE. Source: The Journal of Urology. 2001 February; 165(2): 459-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11176396

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Holmium laser enucleation for prostatic adenoma: analysis of learning curve over the course of 70 consecutive cases. Author(s): Seki N, Mochida O, Kinukawa N, Sagiyama K, Naito S. Source: The Journal of Urology. 2003 November; 170(5): 1847-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14532790

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How we do it: adrenal adenoma. Author(s): Horton KM. Source: Critical Reviews in Computed Tomography. 2002; 43(5): 317-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12425451

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Human telomerase reverse transcriptase, p53 and Ki-67 expression and apoptosis in colorectal serrated adenoma. Author(s): Oka S, Tanaka S, Hiyama T, Kitadai Y, Yoshihara M, Shimamoto F, Haruma K, Chayama K. Source: Scandinavian Journal of Gastroenterology. 2002 October; 37(10): 1194-200. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12408525

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Hypertension due to a giant aldosterone-secreting adenoma. Author(s): Felmeden DC, Gearty JG, Dawkins DM, Beevers G. Source: J Renin Angiotensin Aldosterone Syst. 2001 March; 2(1): 43-4. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11881068

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Hyponatremia after transspheniodal surgery of pituitary adenoma. Author(s): Wei T, Zuyuan R, Changbao S, Renzhi W, Yi Y, Wenbin M. Source: Chinese Medical Sciences Journal = Chung-Kuo I Hsueh K'o Hsueh Tsa Chih / Chinese Academy of Medical Sciences. 2003 June; 18(2): 120-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12903796

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95

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Hypophysopexy technique for radiosurgical treatment of cavernous sinus pituitary adenoma. Author(s): Couldwell WT, Rosenow JM, Rovit RL, Benzil DL. Source: Pituitary. 2002; 5(3): 169-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12812308

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Hypothyroid Hashimoto's thyroiditis with scintigraphic and echo-color Doppler features mimicking autonomous adenoma. Author(s): Boi F, Piga M, Loy M, Mariotti S. Source: J Endocrinol Invest. 2002 May; 25(5): 469-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12035946

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Identification of differentially expressed genes in colorectal adenoma compared to normal tissue by suppression subtractive hybridization. Author(s): Wentzensen N, Wilz B, Findeisen P, Wagner R, Dippold W, von Knebel Doeberitz M, Gebert J. Source: International Journal of Oncology. 2004 April; 24(4): 987-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15010839

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Ileal adenoma. Author(s): Ohwan T, Tada S, Ueno N, Gohda K, Uehara M, Suko H, Kamio T, Matsumoto T. Source: Gastrointestinal Endoscopy. 2003 January; 57(1): 98. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12518141

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Impact of proximal colon retroflexion on adenoma miss rates. Author(s): Harrison M, Singh N, Rex DK. Source: The American Journal of Gastroenterology. 2004 March; 99(3): 519-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15056095

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Increased membrane type 1 matrix metalloproteinase expression from adenoma to colon cancer: a possible mechanism of neoplastic progression. Author(s): Malhotra S, Newman E, Eisenberg D, Scholes J, Wieczorek R, Mignatti P, Shamamian P. Source: Diseases of the Colon and Rectum. 2002 April; 45(4): 537-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12006939

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Incremental diagnostic value of preoperative 99mTc-MIBI SPECT in patients with a parathyroid adenoma. Author(s): Lorberboym M, Minski I, Macadziob S, Nikolov G, Schachter P. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 2003 June; 44(6): 904-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12791817

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Adenoma

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Inherited defects in the DNA glycosylase MYH cause multiple colorectal adenoma and carcinoma. Author(s): Cheadle JP, Dolwani S, Sampson JR. Source: Carcinogenesis. 2003 July; 24(7): 1281-2; Author Reply 1283. Epub 2003 May 09. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12807739

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Inhibition of growth hormone excess reduces insulin resistance and ovarian dysfunction in a lean case of polycystic ovary syndrome with a growth-hormoneproducing pituitary adenoma. Author(s): Hashimoto S, Yatabe J, Midorikawa S, Sanada H, Watanabe T. Source: Hormone Research. 2003; 59(3): 149-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12637795

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Initial transformed cells of colorectal adenoma: do they occur at the top of the crypt? Author(s): Fujimori T, Fujii S, Kitajima K, Nishi M, Sano Y. Source: Journal of Gastroenterology. 2002; 37(11): 982-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12483257

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Intake of supplemental and total fiber and risk of colorectal adenoma recurrence in the wheat bran fiber trial. Author(s): Jacobs ET, Giuliano AR, Roe DJ, Guillen-Rodriguez JM, Hess LM, Alberts DS, Martinez ME. Source: Cancer Epidemiol Biomarkers Prev. 2002 September;11(9):906-14. Erratum In: Cancer Epidemiol Biomarkers Prev. 2002 December;11(12):1699. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12223437

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Inter- and intratumoral variability in magnetic resonance imaging of pleomorphic adenoma: an attempt to interpret the variable magnetic resonance findings. Author(s): Motoori K, Yamamoto S, Ueda T, Nakano K, Muto T, Nagai Y, Ikeda M, Funatsu H, Ito H. Source: Journal of Computer Assisted Tomography. 2004 March-April; 28(2): 233-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15091129

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Interobserver variation in the diagnosis of adenoma malignum (minimal deviation adenocarcinoma) of the uterine cervix. Author(s): Tsuda H, Mikami Y, Kaku T, Akiyama F, Hasegawa T, Okada S, Hayashi I, Kasamatsu T. Source: Pathology International. 2003 July; 53(7): 440-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12828609

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Intraductal mucinous papillary tumor and pyloric gland adenoma of the pancreas. Author(s): Amaris J. Source: Gastrointestinal Endoscopy. 2002 September; 56(3): 441-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12196793

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Intraductal papillary-mucinous adenoma associated with unusual focal fibromatosis: a "postoperative" stromal nodule. Author(s): Sedivy R, Ba-Ssalamah A, Gnant M, Hammer J, Kloppel G. Source: Virchows Archiv : an International Journal of Pathology. 2002 September; 441(3): 308-11. Epub 2002 July 18. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12242530

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Intraductal tubular adenoma, pyloric type, of the pancreas: additional observations on a new type of pancreatic neoplasm. Author(s): Albores-Saavedra J, Sheahan K, O'Riain C, Shukla D. Source: The American Journal of Surgical Pathology. 2004 February; 28(2): 233-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15043313

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Intraosseous pleomorphic adenoma: case report and review of the literature. Author(s): Aver-De-Araujo LM, Chaves-Tarquinio SB, Neuzling-Gomes AP, Etges A. Source: Medicina Oral : Organo Oficial De La Sociedad Espanola De Medicina Oral Y De La Academia Iberoamericana De Patologia Y Medicina Bucal. 2002 May-June; 7(3): 16470. Review. English, Spanish. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11984497

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Intrathoracic parathyroid adenoma. Author(s): Shende MR, Pusca SV, Quinlan DP Jr, Bolanowski PJ, Donahoo JS. Source: The Annals of Thoracic Surgery. 2004 February; 77(2): 724. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14759477

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Intussusception of appendiceal adenoma mimicking invasive carcinoma. Author(s): Kawamura YJ, Toyama N, Kasamatsu T, Ota M, Konishi F. Source: Endoscopy. 2002 September; 34(9): 749. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12195340

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Invasive ductal carcinoma associated with tubular adenoma of the breast. Author(s): Domoto H, Tsuda H, Miyakawa K, Shinoda A, Nanasawa T. Source: Pathology International. 2002 March; 52(3): 244-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11972869

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Is atypical follicular adenoma of the thyroid a preinvasive malignancy? Author(s): Tzen CY, Huang YW, Fu YS. Source: Human Pathology. 2003 July; 34(7): 666-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12874762

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Is there a common cause of adenoma, focal nodular hyperplasia, and hemangioma of the liver? Author(s): Kondo F. Source: Journal of Gastroenterology and Hepatology. 2003 April; 18(4): 357-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12653881

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Juvenile intraoral pleomorphic adenoma: report of five cases and review of the literature. Author(s): Jorge J, Pires FR, Alves FA, Perez DE, Kowalski LP, Lopes MA, Almeila OP. Source: International Journal of Oral and Maxillofacial Surgery. 2002 June; 31(3): 273-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12190133

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Juxtaposition of an ectopic corticotroph adenoma of the sphenoid sinus with orthotopic intrasellar corticotroph hyperplasia in a patient with Cushing disease. Case report. Author(s): Al-Gahtany M, Bilbao J, Kovacs K, Horvath E, Smyth HS. Source: Journal of Neurosurgery. 2003 April; 98(4): 891-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12691418

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Ki-ras oncogene and p53 tumour suppressor gene mutations in colorectal carcinomas from the European Saar-Luxembourg region are less frequent than predicted by the classic adenoma-carcinoma sequence model. Author(s): Pauly M, Schmitz M, Kayser I, Tureci O, Lagoda P, Seitz G, Dicato M. Source: European Journal of Cancer (Oxford, England : 1990). 1997 November; 33(13): 2265-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9470817

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Lactating adenoma: a diagnosis of exclusion. Author(s): Baker TP, Lenert JT, Parker J, Kemp B, Kushwaha A, Evans G, Hunt KK. Source: The Breast Journal. 2001 September-October; 7(5): 354-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11906446

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Lactating adenoma--cytomorphologic study with review of literature. Author(s): Choudhury M, Singal MK. Source: Indian J Pathol Microbiol. 2001 October; 44(4): 445-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12035360

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99

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Laparoscopic adrenal-sparing surgery for primary hyperaldosteronism due to aldosterone-producing adenoma. Author(s): Kok KY, Yapp SK. Source: Surgical Endoscopy. 2002 January; 16(1): 108-11. Epub 2001 October 05. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11961617

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Laparoscopic resection for a left adrenal black adenoma. Author(s): Li W, Wang Y, Yang J. Source: Chinese Medical Journal. 2001 August; 114(8): 879-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11780373

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Large palatal mass. Carcinoma ex-pleomorphic adenoma. Author(s): Damm DD, Fantasia JE. Source: Gen Dent. 2001 November-December; 49(6): 574, 658. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12024743

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Large-needle aspiration biopsy for the preoperative selection of follicular adenoma diagnosed by fine-needle aspiration as a microfollicular nodule or suspected cancer. Author(s): Carpi A, Nicolini A, Sagripanti A, Menchini Fabris F, Righi C, Romani R, Di Coscio G. Source: American Journal of Clinical Oncology : the Official Publication of the American Radium Society. 2002 April; 25(2): 209-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11943905

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Late Lyme disease masking a non-functioning adenoma of the anterior lobe of the pituitary gland. Author(s): Mohrenschlager M, Kohn FM, Bauer M, Schaaf L, Hofmann H, Ring J. Source: Andrologia. 2002 June; 34(3): 162-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12059811

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Lipomatous pleomorphic adenoma of parotid gland. Author(s): Korkmaz H, Adsay NV, Jacobs JR, Lucas DR. Source: Histopathology. 2002 May; 40(5): 487-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12010373

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Liver adenoma and focal nodular hyperplasia associated with oral contraceptives. Author(s): Tajada M, Nerin J, Ruiz MM, Sanchez-Dehesa M, Fabre E. Source: The European Journal of Contraception & Reproductive Health Care : the Official Journal of the European Society of Contraception. 2001 December; 6(4): 227-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11848652

100

Adenoma

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Liver cell adenoma in a 26-year-old man. Author(s): Mamada Y, Onda M, Tajiri T, Akimaru K, Yoshida H, Taniai N, Mineta S, Hirakata A, Hirose Y. Source: Journal of Nippon Medical School = Nihon Ika Daigaku Zasshi. 2001 December; 68(6): 516-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11744932

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Liver cell adenoma with concomitant hepatocellular carcinoma: report of two cases. Author(s): Chuang WY, Chen TC, Hsu HL, Lee WC, Jeng LB, Huang SF. Source: J Formos Med Assoc. 2002 November; 101(11): 798-802. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12517062

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Liver cell adenoma with malignant transformation: a case report. Author(s): Ito M, Sasaki M, Wen CY, Nakashima M, Ueki T, Ishibashi H, Yano M, Kage M, Kojiro M. Source: World Journal of Gastroenterology : Wjg. 2003 October; 9(10): 2379-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14562419

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Long-term follow-up of contralateral lobe in patients hemithyroidectomized for solitary follicular adenoma. Author(s): Niepomniszcze H, Garcia A, Faure E, Castellanos A, del Carmen Zalazar M, Bur G, Elsner B. Source: Clinical Endocrinology. 2001 October; 55(4): 509-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11678834

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Long-term follow-up of intraductal papillary adenoma of the pancreas. Author(s): Kamisawa T, Fujiwara T, Tu Y, Egawa N, Tanaka T, Sakaki N, Funata N, Koike M. Source: Journal of Gastroenterology. 2002; 37(10): 868-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12424574

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Long-term follow-up of patients with tertiary hyperparathyroidism treated by resection of a single or double adenoma. Author(s): Nichol PF, Starling JR, Mack E, Klovning JJ, Becker BN, Chen H. Source: Annals of Surgery. 2002 May; 235(5): 673-8; Discussion 678-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11981213

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Long-term outcome of unilateral parathyroid exploration for primary hyperparathyroidism due to presumed solitary adenoma. Author(s): Sidhu S, Neill AK, Russell CF. Source: World Journal of Surgery. 2003 March; 27(3): 339-42. Epub 2003 February 27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12607063

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101

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Loss of heterozygosity in ampulla of Vater neoplasms during adenoma-carcinoma sequence. Author(s): Park S, Kim SW, Kim SH, Lee BL, Kim WH. Source: Anticancer Res. 2003 May-June; 23(3C): 2955-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12926143

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Loss of p21(WAF1) compartmentalisation in sebaceous carcinoma compared with sebaceous hyperplasia and sebaceous adenoma. Author(s): McBride SR, Leonard N, Reynolds NJ. Source: Journal of Clinical Pathology. 2002 October; 55(10): 763-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12354803

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Low-density pheochromocytoma on CT: a mimicker of adrenal adenoma. Author(s): Blake MA, Krishnamoorthy SK, Boland GW, Sweeney AT, Pitman MB, Harisinghani M, Mueller PR, Hahn PF. Source: Ajr. American Journal of Roentgenology. 2003 December; 181(6): 1663-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14627592

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Lymphocytic adenohypophysitis simulating a pituitary adenoma in a pregnant woman. Author(s): Vizner B, Talan-Hranilovic J, Gnjidic Z, Sekso M, Berkovic M, Altabas V, Rumboldt Z. Source: Coll Antropol. 2002 December; 26(2): 641-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12528294

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Magnetic resonance imaging of pleomorphic adenoma arising from the external auditory canal. Author(s): Masumura C, Horii A, Mishiro Y, Inohara H, Kitahara T, Takashima S, Kubo T. Source: The Journal of Laryngology and Otology. 2003 November; 117(11): 908-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14670158

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Malignant hypertension and hypertensive encephalopathy in primary aldosteronism caused by adrenal adenoma. Author(s): Bortolotto LA, Cesena FH, Jatene FB, Silva HB. Source: Arquivos Brasileiros De Cardiologia. 2003 July; 81(1): 97-100, 93-6. Epub 2003 July 31. English, Portuguese. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12908077

102

Adenoma

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Massive bleeding from an ectopic lingual thyroid follicular adenoma during pregnancy. Author(s): Chiu TT, Su CY, Hwang CF, Chien CY, Eng HL. Source: American Journal of Otolaryngology. 2002 May-June; 23(3): 185-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12019490

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Massive tumour arising from the hard palate after excision of a pleomorphic adenoma. Author(s): Sasaki T, Imai Y, Iwase H, Takimoto T. Source: The British Journal of Oral & Maxillofacial Surgery. 2003 October; 41(5): 360-2. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14581038

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Metanephric adenoma in a 59-year-old female: a case report. Author(s): Sato H, Miyazawa K, Ikeda R, Suzuki K. Source: Hinyokika Kiyo. 2004 January; 50(1): 41-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15032015

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Metanephric adenoma lacks the gains of chromosomes 7 and 17 and loss of Y that are typical of papillary renal cell carcinoma and papillary adenoma. Author(s): Brunelli M, Eble JN, Zhang S, Martignoni G, Cheng L. Source: Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc. 2003 October; 16(10): 1060-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14559991

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Metanephric adenoma of the kidney with massive hemorrhage and necrosis: immunohistochemical, ultrastructural, and flow cytometric studies. Author(s): Kato H, Suzuki M, Aizawa S, Hano H. Source: International Journal of Surgical Pathology. 2003 October; 11(4): 345-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14615836

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Metanephric adenoma of the kidney--a case report. Author(s): Mohanty SK, Arora R, Mandal AK, Kakkar N. Source: Indian J Pathol Microbiol. 2003 April; 46(2): 240-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15022926

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Metastatic foci of signet ring cell carcinoma in a tubular adenoma of the colon. Author(s): Bismar TA, Maluf H, Wang HL. Source: Archives of Pathology & Laboratory Medicine. 2003 November; 127(11): 1509-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14567750

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103

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Methionine synthase D919G polymorphism, folate metabolism, and colorectal adenoma risk. Author(s): Goode EL, Potter JD, Bigler J, Ulrich CM. Source: Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 2004 January; 13(1): 157-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14744749

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Microcystic papillary adenoma of the nose: a case report. Author(s): Sinha AK, Agarwal A, Lakhey M, Mishra A, Sah SP. Source: Indian J Pathol Microbiol. 2003 January; 46(1): 76-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15027732

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Minimally invasive pituitary surgery in a hemorrhagic necrosis of adenoma during pregnancy. Author(s): Gondim J, Ramos Junior F, Pinheiro I, Schops M, Tella Junior OI. Source: Minimally Invasive Neurosurgery : Min. 2003 June; 46(3): 173-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12872196

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Minor vestibular gland adenoma: a case report. Author(s): Punia RP, Bal A, Jain P, Mohan H. Source: The Australian & New Zealand Journal of Obstetrics & Gynaecology. 2003 August; 43(4): 322-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14714720

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Mucoepidermoid carcinoma expleomorphic adenoma of the submandibular gland. Author(s): To EW, Tsang WM, Tse GM. Source: American Journal of Otolaryngology. 2003 July-August; 24(4): 253-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12884219

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Myxolipomatous pleomorphic adenoma: an unusual oral presentation. Author(s): Ide F, Kusama K. Source: Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 2004 January; 33(1): 53-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14675141

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Neoplastic and antineoplastic effects of beta-carotene on colorectal adenoma recurrence: results of a randomized trial. Author(s): Baron JA, Cole BF, Mott L, Haile R, Grau M, Church TR, Beck GJ, Greenberg ER. Source: Journal of the National Cancer Institute. 2003 May 21; 95(10): 717-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12759389

104

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Nephrogenic adenoma of the bladder: two case reports and literature review. Author(s): Nakatani T, Kuratsukuri K, Uchida J, Sugimura K, Kuroki Y, Morikawa Y. Source: Hinyokika Kiyo. 2002 July; 48(7): 463-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12229190

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Nephrogenic adenoma of the prostatic urethra in a patient treated with ESWL for a lower ureteral stone. Author(s): Sakkas G, Simopoulou S, Zamparelou A, Moshos M. Source: International Urology and Nephrology. 2001; 33(2): 369-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12092658

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Nephrogenic adenoma of the urethra: an unusual cause of hematuria in the child. Author(s): de Buys Roessingh AS, Laurini RN, Meyrat BJ. Source: Journal of Pediatric Surgery. 2003 August; 38(8): E8-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12891515

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Nephrogenic adenoma of the urinary bladder--a case report and review of the literature. Author(s): Chosia M, Switala J, Domagala W. Source: Pol J Pathol. 2002; 53(2): 91-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12140873

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Neural adhesion molecule (N-CAM) in pleomorphic adenoma and carcinoma expleomorphic adenoma. Author(s): Saleh ER, Franca CM, Marques MM. Source: Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 2003 October; 32(9): 562-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12969231

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Neural transformation in a pituitary corticotroph adenoma. Author(s): Vidal S, Horvath E, Bonert V, Shahinian K, Kovacs K. Source: Acta Neuropathologica. 2002 October; 104(4): 435-40. Epub 2002 May 29. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12200632

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Neuroendocrine adenoma of the middle ear. Author(s): Aquino BF, Chandra RK, Haines GK, Micco AG. Source: Otolaryngology and Head and Neck Surgery. 2002 November; 127(5): 477-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12447249

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105

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Nipple adenoma: a differential diagnosis for Paget's disease. Author(s): Healy CE, Dijkstra B, Walsh M, Hill AD, Murphy J. Source: The Breast Journal. 2003 July-August; 9(4): 325-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12846871

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Normocalcemia and persistent elevated serum concentrations of 1-84 parathyroid hormone after operation for sporadic parathyroid adenoma: evidence of increased morbidity from cardiovascular disease. Author(s): Vestergaard H, OStergaard Kristensen L. Source: World Journal of Surgery. 2002 June; 26(6): 657-60. Epub 2002 March 01. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12053214

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Observations by G-banding and multicolor spectral karyotyping in a salivary gland basal cell adenoma. Author(s): Sjogren H, Dahlenfors R, Stenman G, Mark J. Source: Virchows Archiv : an International Journal of Pathology. 2003 January; 442(1): 86-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12596771

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Opposing effects of butyrate and bile acids on apoptosis of human colon adenoma cells: differential activation of PKC and MAP kinases. Author(s): McMillan L, Butcher SK, Pongracz J, Lord JM. Source: British Journal of Cancer. 2003 March 10; 88(5): 748-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12618885

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Oral and maxillofacial pathology case of the month. Canalicular adenoma. Author(s): McGuff HS, Alderson GL, Jones AC, Barr GS. Source: Tex Dent J. 2003 November; 120(11): 1088, 1092. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14685972

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Oral and maxillofacial pathology case of the month. Pleomorphic adenoma (PA). Author(s): Wright JM. Source: Tex Dent J. 2001 June; 118(6): 474, 479. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11484312

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Oral pathology quiz #28. Case 3. Pleomorphic adenoma. Author(s): Dolinsky H, Laifook M. Source: J N J Dent Assoc. 2000 Spring; 71(2): 16-7, 54-5. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11324059

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Oral pathology. Pleomorphic adenoma. Author(s): Houston GD. Source: J Okla Dent Assoc. 2003 Fall; 94(2): 31-3. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14619233

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Osteosarcoma and fibrosarcoma caused by postoperative radiotherapy for a pituitary adenoma. Case report. Author(s): Gnanalingham KK, Chakraborty A, Galloway M, Revesz T, Powell M. Source: Journal of Neurosurgery. 2002 May; 96(5): 960-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12005408

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Ovarian hyperstimulation caused by gonadotroph adenoma secreting folliclestimulating hormone in 28-year-old woman. Author(s): Valimaki MJ, Tiitinen A, Alfthan H, Paetau A, Poranen A, Sane T, Stenman UH. Source: The Journal of Clinical Endocrinology and Metabolism. 1999 November; 84(11): 4204-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10566673

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Ovarian hyperstimulation without elevated serum estradiol associated with pure follicle-stimulating hormone-secreting pituitary adenoma. Author(s): Shimon I, Rubinek T, Bar-Hava I, Nass D, Hadani M, Amsterdam A, Harel G. Source: The Journal of Clinical Endocrinology and Metabolism. 2001 August; 86(8): 3635-40. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11502789

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Overexpression of Reg IV in colorectal adenoma. Author(s): Zhang Y, Lai M, Lv B, Gu X, Wang H, Zhu Y, Zhu Y, Shao L, Wang G. Source: Cancer Letters. 2003 October 8; 200(1): 69-76. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14550954

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Parathyroid adenoma without hyperparathyroidism. Author(s): Sekine O, Hozumi Y, Takemoto N, Kiyozaki H, Yamada S, Konishi F. Source: Japanese Journal of Clinical Oncology. 2004 March; 34(3): 155-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15078912

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Pleomorphic adenoma (chondroid syringoma) on the face. Author(s): Chao PZ, Lee FP. Source: Otolaryngology and Head and Neck Surgery. 2004 April; 130(4): 499-500. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15100654

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Pleomorphic adenoma of lacrimal gland: diagnosis based on fine needle aspiration cytology. Author(s): Lakhey M, Thakur SK, Mishra A, Rani S. Source: Indian J Pathol Microbiol. 2001 July; 44(3): 333-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12024925

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Pleomorphic adenoma of the lacrimal gland with extensive calcification. Author(s): Stefko ST, DiBernardo C, Green WR, Merbs SL. Source: Archives of Ophthalmology. 2004 May; 122(5): 778-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15136329

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Pleomorphic adenoma of the lower lip: report of a case. Author(s): To EW, Tsang WM, Tse GM. Source: Journal of Oral and Maxillofacial Surgery : Official Journal of the American Association of Oral and Maxillofacial Surgeons. 2002 June; 60(6): 684-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12022109

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Pleomorphic adenoma of the nasal septum. Author(s): Mackle T, Zahirovic A, Walsh M. Source: The Annals of Otology, Rhinology, and Laryngology. 2004 March; 113(3 Pt 1): 210-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15053203

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Pleomorphic adenoma with extensive necrosis: report of two cases. Author(s): Chen YK, Lin CC, Lai S, Chen CH, Wang WC, Lin YR, Hsue SS, Lin LM. Source: Oral Diseases. 2004 January; 10(1): 54-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14996296

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Pol iota is a candidate for the mouse pulmonary adenoma resistance 2 locus, a major modifier of chemically induced lung neoplasia. Author(s): Wang M, Devereux TR, Vikis HG, McCulloch SD, Holliday W, Anna C, Wang Y, Bebenek K, Kunkel TA, Guan K, You M. Source: Cancer Research. 2004 March 15; 64(6): 1924-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15026325

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Predictive value of diminutive colonic adenoma trial: the PREDICT trial. Author(s): Schoenfeld P, Shad J, Ormseth E, Coyle W, Cash B, Butler J, Schindler W, Kikendall WJ, Furlong C, Sobin LH, Hobbs CM, Cruess D, Rex D; Military Colorectal Cancer Screening Trials Group. Source: Clin Gastroenterol Hepatol. 2003 May; 1(3): 195-201. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15017491

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Pyloric gland-type tubular adenoma superimposed on intraductal papillary mucinous tumor of the pancreas. Pyloric gland adenoma of the pancreas. Author(s): Kato N, Akiyama S, Motoyama T. Source: Virchows Archiv : an International Journal of Pathology. 2002 February; 440(2): 205-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11964052

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Quantitative comparison of alpha-fetoprotein and albumin mRNA levels in hepatocellular carcinoma/adenoma, non-tumor liver and blood: implications in cancer detection and monitoring. Author(s): Wong IH, Lau WY, Leung T, Johnson PJ. Source: Cancer Letters. 2000 August 11; 156(2): 141-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10880763

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Re: Pleomorphic adenoma of the human breast. Author(s): Muthuphei MN. Source: East Afr Med J. 2000 September; 77(9): 513. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12862146

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Recurrent pleomorphic adenoma of the parotid gland in pediatric and adult patients: value of multiple lesions as a diagnostic indicator. Author(s): Koral K, Sayre J, Bhuta S, Abemayor E, Lufkin R. Source: Ajr. American Journal of Roentgenology. 2003 April; 180(4): 1171-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12646477

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Recurrent pleomorphic adenoma of the parotid gland: a prospective histopathological and immunohistochemical study. Author(s): Stennert E, Wittekindt C, Klussmann JP, Arnold G, Guntinas-Lichius O. Source: The Laryngoscope. 2004 January; 114(1): 158-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14710014

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Reg IV, a differentially expressed gene in colorectal adenoma. Author(s): Zhang Y, Lai M, Gu X, Luo M, Shao L. Source: Chinese Medical Journal. 2003 June; 116(6): 918-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12877807

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Renal cell carcinoma metastatic to follicular adenoma of the thyroid gland. A case report. Author(s): Koo HL, Jang J, Hong SJ, Shong Y, Gong G. Source: Acta Cytol. 2004 January-February; 48(1): 64-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14969183

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Renal cortical adenoma incidentally found during living donor nephrectomy. Author(s): Jones JR, Woodside KJ, Early MG, Gugliuzza KK, Daller JA. Source: Progress in Transplantation (Aliso Viejo, Calif.). 2003 June; 13(2): 94-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12841514

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Reversible mental and behavioral disturbances due to giant mediastinal parathyroid adenoma-induced hypercalcemia. Author(s): Rotmensch HH, Kitzes I, Charach G, Weintraub M. Source: Isr Med Assoc J. 2002 December; 4(12): 1154-5. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12516916

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Risk of colorectal adenoma in liver transplant recipients compared to immunocompetent control population undergoing routine screening colonoscopy. Author(s): Atassi T, Thuluvath PJ. Source: Journal of Clinical Gastroenterology. 2003 July; 37(1): 72-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12811214

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Risk of duodenal adenoma in celiac disease. Author(s): Rampertab SD, Fleischauer A, Neugut AI, Green PH. Source: Scandinavian Journal of Gastroenterology. 2003 August; 38(8): 831-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12940435

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Role of inducible nitric oxide synthase expression in aberrant crypt foci-adenomacarcinoma sequence. Author(s): Xu MH, Deng CS, Zhu YQ, Lin J. Source: World Journal of Gastroenterology : Wjg. 2003 June; 9(6): 1246-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12800233

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Sarcomatous change after sellar irradiation in a growth hormone-secreting pituitary adenoma. Author(s): Prabhu SS, Aldape KD, Gagel RF, Benjamin RS, Trent JC, McCutcheon IE. Source: The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques. 2003 November; 30(4): 378-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14672272

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Serous oligocystic adenoma of the pancreas: a clinicopathological and immunohistochemical study of three cases with ultrastructural findings. Author(s): Santos LD, Chow C, Henderson CJ, Blomberg DN, Merrett ND, Kennerson AR, Killingsworth MC. Source: Pathology. 2002 April; 34(2): 148-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12009097

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Serous oligocystic and ill-demarcated adenoma of the pancreas. Author(s): Kruslin B, Zovak M, Doko M, Belicza M. Source: Virchows Archiv : an International Journal of Pathology. 2002 April; 440(4): 4412. Epub 2002 January 31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11956827

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Serum levels of angiogenic growth factors in patients with thyroid gland tumors and parathyroid adenoma. Author(s): Vesely D, Astl J, Matucha P, Sterzl I, Betka J. Source: Neuroendocrinol Lett. 2003 December; 24(6): 417-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15073567

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Signet-ring follicular adenoma of the thyroid diagnosed by fine needle aspiration. Report of a case with cytologic description. Author(s): el-Sahrigy D, Zhang XM, Elhosseiny A, Melamed MR. Source: Acta Cytol. 2004 January-February; 48(1): 87-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14969188

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Sporadic duodenal adenoma is associated with colorectal neoplasia. Author(s): Murray MA, Zimmerman MJ, Ee HC. Source: Gut. 2004 February; 53(2): 261-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14724161

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Stereotactic radiation for pituitary adenoma. Author(s): Mulroy L, Rheaume DE, Fleetwood I, Schella J, Robar J. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2004 February 3; 170(3): 320. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14757655

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Subcutaneous emphysema after associated colonoscopy and transanal excision of rectal adenoma. Author(s): Basso L, Pescatori M. Source: Surgical Endoscopy. 2003 October; 17(10): 1677. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14702972

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Successful management of persistent hyperparathyroidism without finding the adenoma. Author(s): Raza SN, Galindo J, Freeman JL. Source: The Journal of Otolaryngology. 2003 October; 32(5): 340-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14974868

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Synchronous serrated adenoma of the appendix and high-grade ovarian carcinoma: a case demonstrating different origin of the two neoplasms. Author(s): Rudzki Z, Zazula M, Bialas M, Klimek M, Stachura J. Source: Pol J Pathol. 2002; 53(1): 29-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12014223

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Telomerase activity in pituitary adenomas: significance of telomerase expression in predicting pituitary adenoma recurrence. Author(s): Yoshino A, Katayama Y, Fukushima T, Watanabe T, Komine C, Yokoyama T, Kusama K, Moro I. Source: Journal of Neuro-Oncology. 2003 June; 63(2): 155-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12825819

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Telomere shortening of epithelial cells characterises the adenoma-carcinoma transition of human colorectal cancer. Author(s): Plentz RR, Wiemann SU, Flemming P, Meier PN, Kubicka S, Kreipe H, Manns MP, Rudolph KL. Source: Gut. 2003 September; 52(9): 1304-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12912862

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Testing your diagnostic skills. Case no. 1. Pleomorphic adenoma. Author(s): Baughman R, Auletta A, Belanger L. Source: Todays Fda. 2003 August; 15(8): 18, 22. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=13677180

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The retinoblastoma protein interacts with Bag-1 in human colonic adenoma and carcinoma derived cell lines. Author(s): Arhel NJ, Packham G, Townsend PA, Collard TJ, H-Zadeh AM, Sharp A, Cutress RI, Malik K, Hague A, Paraskeva C, Williams AC. Source: International Journal of Cancer. Journal International Du Cancer. 2003 September 1; 106(3): 364-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12845674

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Three-millimeter apocrine adenoma in a man: a case report and review of the literature. Author(s): Pasquale-Styles MA, Milikowski C. Source: Archives of Pathology & Laboratory Medicine. 2003 November; 127(11): 1498500. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14567753

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Thrombotic thrombocytopenic purpura associated with a prolactin-producing pituitary adenoma. Author(s): Kovacs K, Garvey MB. Source: American Journal of Hematology. 2003 September; 74(1): 55-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12949891

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Transient rise in intact parathyroid hormone concentration after surgery for parathyroid adenoma. Author(s): Ferrer-Ramirez MJ, Arroyo Domingo M, Lopez-Molla C, Sola Izquierdo E, Garzon Pastor S, Morillas Arino C, Hernandez Mijares A. Source: Otolaryngology and Head and Neck Surgery. 2003 June; 128(6): 771-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12825025

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TTF-1 is useful in the diagnosis of pulmonary papillary adenoma. Author(s): Sheppard MN, Burke L, Kennedy M. Source: Histopathology. 2003 October; 43(4): 404-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14511264

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Tubular adenoma and intramucosal intestinal-type adenocarcinoma of the stomach: what are the pathobiological differences? Author(s): Kase S, Osaki M, Honjo S, Adachi H, Ito H. Source: Gastric Cancer : Official Journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association. 2003; 6(2): 71-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12861397

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Tubulovillous adenoma of the vulva. Author(s): Vitrey D, Frachon S, Balme B, Golfier F. Source: Obstetrics and Gynecology. 2003 November; 102(5 Pt 2): 1160-3. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14607042

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Uncontrolled insulin secretion from a childhood pancreatic beta-cell adenoma is not due to the functional loss of ATP-sensitive potassium channels. Author(s): Hussain K, Cosgrove KE, Shepherd RM, Chapman JC, Swift SM, Smith VV, Kassem SA, Glaser B, Lindley KJ, Aynsley-Green A, Dunne MJ. Source: Endocrine-Related Cancer. 2002 December; 9(4): 221-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12542400

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Unilateral lobectomy for Hurthle cell adenoma. Author(s): Wasvary H, Czako P, Poulik J, Lucas R. Source: The American Surgeon. 1998 August; 64(8): 729-32; Discussion 732-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9697901

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Unthreatened late pregnancy with a huge mucinous cyst adenoma of the left ovary: report of an unusual case. Author(s): Balat O, Kutlar I, Erkilic S, Sirikci A, Aksoy F, Aydin A. Source: Eur J Gynaecol Oncol. 2002; 23(1): 84-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11876402

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Unusual presentations of uncommon tumors: case 1. Benign metastasizing pleomorphic adenoma. Author(s): Raja V, China C, Masaki KH, Nakano G. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2002 May 1; 20(9): 2400-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11981014

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Uptake of radiolabelled alpha-fetoprotein by experimental mammary adenocarcinoma and adenoma: in vivo and in vitro studies. Author(s): Mirowski M, S'Witalska J, Wiercioch R, Byszewska E, Niewiadomska H, Michalska M. Source: Nuclear Medicine Communications. 2003 March; 24(3): 297-303. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12612471

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Urinary mutagenicity and colorectal adenoma risk. Author(s): Peters U, DeMarini DM, Sinha R, Brooks LR, Warren SH, Chatterjee N, Rothman N. Source: Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 2003 November; 12(11 Pt 1): 1253-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14652290

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Urolithiasis and primary parathyroid adenoma: report of one case. Author(s): Lee JS, Lau BH, Yeh ML, Lee CC. Source: Acta Paediatr Taiwan. 2003 November-December; 44(6): 372-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14983662

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Ursodeoxycholic acid therapy and the risk of colorectal adenoma in patients with primary biliary cirrhosis: an observational study. Author(s): Serfaty L, De Leusse A, Rosmorduc O, Desaint B, Flejou JF, Chazouilleres O, Poupon RE, Poupon R. Source: Hepatology (Baltimore, Md.). 2003 July; 38(1): 203-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12830003

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Usefulness of galectin-3 immunohistochemistry in differential diagnosis between thyroid follicular carcinoma and follicular adenoma. Author(s): Jakubiak-Wielganowicz M, Kubiak R, Sygut J, Pomorski L, Kordek R. Source: Pol J Pathol. 2003; 54(2): 111-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14575419

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Using technetium 99m tetrofosmin parathyroid imaging to detect parathyroid adenoma and its relation to P-glycoprotein expression. Author(s): Wu HS, Liu YC, Kao A, Wang JJ, Ho ST. Source: Surgery. 2002 September; 132(3): 456-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12324759

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Villous adenoma of common bile duct. Author(s): Jao YT, Tseng LJ, Wu CJ, Young TM, Mo LR, Wang CH, Wey KC. Source: Gastrointestinal Endoscopy. 2003 April; 57(4): 561-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12665769

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Villous adenoma of entire biliary tree. Author(s): Tseng LJ, Jao YT, Mo LR. Source: Gastrointestinal Endoscopy. 2003 January; 57(1): 95-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12518138

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Villous adenoma of the appendix. Diagnostic and therapeutic approach. Author(s): Fernandez Blanco CM, Fraguela JA, Gulias A, Sanchez Blas M, Freijoso C. Source: Rev Esp Enferm Dig. 2002 September; 94(9): 537-43. English, Spanish. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12587234

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Villous adenoma of the common bile duct transforming into a cholangiocarcinoma. Author(s): Ariche A, Shelef I, Hilzenrat N, Dreznik Z. Source: Isr Med Assoc J. 2002 December; 4(12): 1149-50. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12516913

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Villous adenoma of the extrahepatic biliary tract: a rare entity. Author(s): O'Shea M, Fletcher HS, Lara JF. Source: The American Surgeon. 2002 October; 68(10): 889-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12412717

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Villous adenoma of the urachus: a case with prostate specific antigen immunoreactivity. Author(s): Tzortzis V, Ioannou M, Melekos MD. Source: The Journal of Urology. 2003 October; 170(4 Pt 1): 1302-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14501748

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Villous adenoma of the urinary tract: a lesion frequently associated with malignancy. Author(s): Seibel JL, Prasad S, Weiss RE, Bancila E, Epstein JI. Source: Human Pathology. 2002 February; 33(2): 236-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11957151

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Villous adenoma of the urinary tract: a lesion frequently associated with malignancy. Author(s): Val-Bernal JF, Mayorga M, Garijo MF. Source: Human Pathology. 2002 November; 33(11): 1150. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12454823

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Virilizing adrenocortical adenoma with Cushing's syndrome, thyroid papillary carcinoma and hypergastrinemia in a middle-aged woman. Author(s): Fukushima A, Okada Y, Tanikawa T, Kawahara C, Misawa H, Kanda K, Morita E, Sasano H, Tanaka Y. Source: Endocrine Journal. 2003 April; 50(2): 179-87. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12803238

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Visceral cancer metastasis to pituitary adenoma: report of two cases. Author(s): Bret P, Jouvet A, Madarassy G, Guyotat J, Trouillas J. Source: Surgical Neurology. 2001 May; 55(5): 284-90. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11516470

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What is your diagnosis? Canalicular adenoma. Author(s): Pichardo RO, Lu D, Sangueza OP, Ball RA. Source: The American Journal of Dermatopathology. 2002 December; 24(6): 505-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12481772

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CHAPTER 2. NUTRITION AND ADENOMA Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and adenoma.

Finding Nutrition Studies on Adenoma The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail: [email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “adenoma” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

7 Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.

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The following information is typical of that found when using the “Full IBIDS Database” to search for “adenoma” (or a synonym): •

Absence of response to human parathyroid hormone in athymic mice grafted with human parathyroid adenoma, hyperplasia or parathyroid cells maintained in culture. Author(s): Unite 90 de l'INSERM and Departement de Nephrologie, Hopital Necker, Paris, France. [email protected] Source: Hory, B G Roussanne, M C Rostand, S Bourdeau, A Drueke, T B Gogusev, J JEndocrinol-Invest. 2000 May; 23(5): 273-9 0391-4097

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Adenoma of the papilla and ampulla--premalignant lesions? Author(s): Institute of Pathology, University of Leipzig, Germany. [email protected] Source: Wittekind, C Tannapfel, A Langenbecks-Arch-Surg. 2001 April; 386(3): 172-5 1435-2443

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AgNOR values are not helpful in the differential diagnosis of pituitary adenomas. Author(s): SSK Ankara Training and Research Hospital, Department of Pathology, Hosdere C. No. 164/3 06550 Y. Ayranci, Ankara, Turkey. [email protected] Source: Hucumenoglu, S Kaya, H Kotiloglu, E Erdem, G Demiray, E Ekicioglu, G ClinNeurol-Neurosurg. 2002 September; 104(4): 293-9 0303-8467

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APACC, a French prospective study on aspirin efficacy in reducing colorectal adenoma recurrence: design and baseline findings. Author(s): Service de gastro-enterologie, Hopital Avicenne, 125 rue de Stalingrad, 93009 Bobigny Cedex, France. [email protected] Source: Benamouzig, R Yoon, H Little, J Martin, A Couturier, D Deyra, J Coste, T Chaussade, S Eur-J-Cancer-Prevolume 2001 August; 10(4): 327-35 0959-8278

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Cellular characterization of pituitary adenoma cell line (AtT20 cell) transfected with insulin, glucose transporter type 2 (GLUT2) and glucokinase genes: insulin secretion in response to physiological concentrations of glucose. Author(s): Department of Metabolic Medicine, Kumamoto University School of Medicine, Japan. Source: Motoyoshi, S Shirotani, T Araki, E Sakai, K Kaneko, K Motoshima, H Yoshizato, K Shirakami, A Kishikawa, H Shichiri, M Diabetologia. 1998 December; 41(12): 1492-501 0012-186X

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Changes in the volume of residual pituitary adenomas in patients with adult-onset growth hormone deficiency during replacement therapy with the recombinant human growth hormone. Author(s): Department of Internal Medicine, University of Innsbruck, Austria. [email protected] Source: Finkenstedt, G Hofle, G Pallua, A Sailer, U Gasser, R W Wien-Klin-Wochenschr. 1999 November 12; 111(21): 887-90 0043-5325

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Characterization of autonomous thyroid adenoma: metabolism, gene expression, and pathology. Author(s): IRIBHN, Free University of Brussels, Brussels, Belgium. Source: Deleu, S Allory, Y Radulescu, A Pirson, I Carrasco, N Corvilain, B Salmon, I Franc, B Dumont, J E Van Sande, J Maenhaut, C Thyroid. 2000 February; 10(2): 131-40 1050-7256

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Cholecystectomy and the risk for developing colorectal cancer and distal colorectal adenomas. Author(s): Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115, USA. [email protected] Source: Schernhammer, E S Leitzmann, M F Michaud, D S Speizer, F E Giovannucci, E Colditz, G A Fuchs, C S Br-J-Cancer. 2003 January 13; 88(1): 79-83 0007-0920

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Combined primary aldosteronism and preclinical Cushing's syndrome: an unusual case presentation of adrenal adenoma. Author(s): Second Department of Internal Medicine, Gunma University School of Medicine, Maebashi, Japan. Source: Honda, T Nakamura, T Saito, Y Ohyama, Y Sumino, H Kurabayashi, M Hypertens-Res. 2001 November; 24(6): 723-6 0916-9636

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Current diet and colorectal adenomas: a case-control study including different sets of traditionally chosen control groups. Author(s): Medical Department, Rikshospitalet University Hospital, N-0027 Oslo, Norway. Source: Almendingen, K Hofstad, B Trygg, K Hoff, G Hussain, A Vatn, M Eur-J-CancerPrevolume 2001 October; 10(5): 395-406 0959-8278

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Development of hepatocellular adenomas and carcinomas associated with fibrosis in C57BL/6J male mice given a choline-deficient, L-amino acid-defined diet. Author(s): Department of Oncological Pathology, Cancer Center, Nara Medical University, Kashihara, Nara 634-8521, Japan. [email protected] Source: Denda, Ayumi Kitayama, Wakashi Kishida, Hideki Murata, Nao Tsutsumi, Masahiro Tsujiuchi, Toshifumi Nakae, Dai Konishi, Yoichi Jpn-J-Cancer-Res. 2002 February; 93(2): 125-32 0910-5050

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Dietary fibre for the prevention of colorectal adenomas and carcinomas. Author(s): General Surgery, University of Toronto, Mount Sinai Hospital, 600 University Avenue, Suite 449, Toronto, Ontario, Canada, M5G 1X5. [email protected] Source: Asano, T McLeod, R S Cochrane-Database-Syst-Revolume 2002; (2): CD003430 1469-493X

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Effectiveness of slow-release lanreotide in previously operated and untreated patients with GH-secreting pituitary macroadenoma. Author(s): Cattedra di Endocrinologia, University of Messina, Italy. [email protected] Source: Cannavo, S Squadrito, S Curto, L Almoto, B Trimarchi, F Horm-Metab-Res. 2001 October; 33(10): 618-24 0018-5043

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Gamma Knife radiosurgery as a primary surgical treatment for hypersecreting pituitary adenomas. Author(s): Department of Neurosurgery, Hua Shan Hospital & Shanghai Gamma Knife Hospital, Shanghai, China. [email protected] Source: Zhang, N Pan, L Dai, J Wang, B Wang, E Zhang, W Cai, P Stereotact-FunctNeurosurg. 2000; 75(2-3): 123-8 1011-6125

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Genetic polymorphisms in heterocyclic amine metabolism and risk of colorectal adenomas. Author(s): Genetic Epidemioly Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland 20892, USA. [email protected]

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Source: Ishibe, Naoko Sinha, Rashmi Hein, David W Kulldorff, Martin Strickland, Paul Fretland, Adrian J Chow, Wong Ho Kadlubar, Fred F Lang, Nicholas P Rothman, Nathaniel Pharmacogenetics. 2002 Mar; 12(2): 145-50 0960-314X •

Glutathione transferase GSTT1, broccoli, and prevalence of colorectal adenomas. Author(s): Division of Medical Genetics and Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, California 90502, USA. [email protected] Source: Lin, Henry J Zhou, Haiyan Dai, Aihua Huang, Hsiao Fen Lin, Jesse H Frankl, Harold D Lee, Eric R Haile, Robert W Pharmacogenetics. 2002 March; 12(2): 175-9 0960314X

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Grading dysplasia in colorectal adenomas by means of the quantitative binding pattern determination of Arachis hypogaea, Dolichos biflorus, Amaranthus caudatus, Maackia amurensis, and Sambucus nigra agglutinins. Author(s): Laboratory of Histology, Faculty of Medicine, Free University of Brussels, Belgium. Source: Bronckart, Y Nagy, N Decaestecker, C Bouckaert, Y Remmelink, M Gielen, I Hittelet, A Darro, F Pector, J C Yeaton, P Danguy, A Kiss, R Salmon, I Hum-Pathol. 1999 October; 30(10): 1178-91 0046-8177

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Hashimoto's thyroiditis presenting as a functioning adenoma. Author(s): Department of Internal Medicine, Groningen, The Netherlands. [email protected] Source: Hoogenberg, K van Tol, K M Thyroid. 2001 September; 11(9): 893 1050-7256

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Increased exocytosis of secretory granules in contrast to reduced serum hormone levels in pituitary adenomas of humans and rats treated with dopamine agonist. Author(s): Department of Pathology, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, Japan. [email protected] Source: Mori, H Saitoh, Y Maeda, T Okada, Y Hirano, H Tsuji, M Med-Electron-Microsc. 2001 June; 34(2): 123-33 0918-4287

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Minor tumour shrinkage in nonfunctioning pituitary adenomas by long-term treatment with the dopamine agonist cabergoline. Author(s): Department of Internal Medicine III, University of Leipzig, Germany. [email protected] Source: Lohmann, T Trantakis, C Biesold, M Prothmann, S Guenzel, S Schober, R Paschke, R Pituitary. 2001 August; 4(3): 173-8 1386-341X

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Pancreatic head cystadenoma: a case report. Author(s): Department of Surgery, Merkur University Hospital, Zagreb, Croatia. Source: Deskovic, S Bezjak, M Patrlj, L Martinac, M Makaruha, B Kocman, B Jadrijevic, S Hepatogastroenterology. 1999 Mar-April; 46(26): 872-4 0172-6390

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Phenotypes in canalicular adenoma of human minor salivary glands reflect the interplay of altered secretory product, absent neuro-effector relationships and the diversity of the microenvironment. Author(s): Oral Pathology Laboratory, Liverpool University Dental Hospital and School of Dentistry, Liverpool, UK. [email protected] Source: Triantafyllou, A Coulter, P Scott, J Histopathology. 1999 December; 35(6): 502-16 0309-0167

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Piroxicam and acarbose as chemopreventive agents for spontaneous intestinal adenomas in APC gene 1309 knockout mice. Author(s): Second Department of Surgery, Hamamatsu University School of Medicine, Shizuoka.

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Source: Quesada, C F Kimata, H Mori, M Nishimura, M Tsuneyoshi, T Baba, S Jpn-JCancer-Res. 1998 April; 89(4): 392-6 0910-5050 •

Prevention of urethane-induced lung adenomas by Withania somnifera (L.) Dunal in albino mice. Source: Singh, N. Singh, S.P. Nath, R. Singh, D.R. Gupta, M.L. Kohli, R.P. Bhargava, K.P. Int-J-Crude-Drug-Res. Lisse : Swets & Zeitlinger. June 1986. volume 24 (2) page 90-100. ill. 0167-7314

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Sarcoidosis within a pituitary adenoma. Author(s): Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. Source: Rubin, M R Bruce, J N Khandji, A G Freda, P U Pituitary. 2001 August; 4(3): 195202 1386-341X

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Small functional adrenal cortical adenoma: treatment with CT-guided percutaneous acetic acid injection--report of three cases. Author(s): Department of Radiology, Kaohsiung Veterans General Hospital, Taiwan, Republic of China. [email protected] Source: Liang, H L Pan, H B Lee, Y H Huang, J S Wu, T D Chang, C T Liang, H L Yang, T L Yang, C F Radiology. 1999 November; 213(2): 612-5 0033-8419

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Toxic thyroid adenoma and toxic multinodular goiter. Author(s): Franz-Volhard-Klinik, Humboldt University of Berlin, Berlin-Buch, Germany. [email protected] Source: Luft, F C J-Mol-Med. 2001; 78(12): 657-60 0946-2716

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Vitamin D receptor polymorphisms and risk of colorectal adenomas (United States). Author(s): Department of Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, USA. [email protected] Source: Ingles, S A Wang, J Coetzee, G A Lee, E R Frankl, H D Haile, R W CancerCauses-Control. 2001 September; 12(7): 607-14 0957-5243

Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •

healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0

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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov

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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov

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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/

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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/

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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/

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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/

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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/

Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats

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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html

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Google: http://directory.google.com/Top/Health/Nutrition/

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Healthnotes: http://www.healthnotes.com/

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Open Directory Project: http://dmoz.org/Health/Nutrition/

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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/

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WebMDHealth: http://my.webmd.com/nutrition

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

The following is a specific Web list relating to adenoma; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •

Vitamins Folic Acid Source: Healthnotes, Inc.; www.healthnotes.com Vitamin C Source: Prima Communications, Inc.www.personalhealthzone.com

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Minerals Calcium Source: Healthnotes, Inc.; www.healthnotes.com Calcium Source: Prima Communications, Inc.www.personalhealthzone.com Stinging Nettle Alternative names: Urtica dioica, Urtica urens, Nettle Source: Integrative Medicine Communications; www.drkoop.com

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Food and Diet High-Fiber Diet Source: Healthnotes, Inc.; www.healthnotes.com

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CHAPTER 3. ALTERNATIVE MEDICINE AND ADENOMA Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to adenoma. At the conclusion of this chapter, we will provide additional sources.

National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to adenoma and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “adenoma” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine that are related to adenoma: •

Accumulation and interactions of beta-carotene and alpha-tocopherol in patients with adenomatous polyps. Author(s): Simone F, Pappalardo G, Maiani G, Guadalaxara A, Bugianesi R, Conte AM, Azzini E, Mobarhan S. Source: European Journal of Clinical Nutrition. 2002 June; 56(6): 546-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12032655

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Acupuncture anaesthesia. Observations on its use for removal of thyroid adenomata and influence on recovery and morbidity in a Chinese hospital. Author(s): Kho HG, van Egmond J, Zhuang CF, Lin GF, Zhang GL. Source: Anaesthesia. 1990 June; 45(6): 480-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2382806

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Adenomas: preneoplastic events, growth and development in man and experimental systems. Author(s): Deschner EE. Source: Pathol Annu. 1983; 18 Pt 1: 205-19. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6348673

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Baseline dietary fiber intake and colorectal adenoma recurrence in the wheat bran fiber randomized trial. Author(s): Jacobs ET, Giuliano AR, Roe DJ, Guillen-Rodriguez JM, Alberts DS, Martinez ME. Source: Journal of the National Cancer Institute. 2002 November 6; 94(21): 1620-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12419788

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Bile acids reduce the apoptosis-inducing effects of sodium butyrate on human colon adenoma (AA/C1) cells: implications for colon carcinogenesis. Author(s): McMillan L, Butcher S, Wallis Y, Neoptolemos JP, Lord JM. Source: Biochemical and Biophysical Research Communications. 2000 June 24; 273(1): 45-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10873561

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Calcium and fibre supplementation in prevention of colorectal adenoma recurrence: a randomised intervention trial. European Cancer Prevention Organisation Study Group. Author(s): Bonithon-Kopp C, Kronborg O, Giacosa A, Rath U, Faivre J. Source: Lancet. 2000 October 14; 356(9238): 1300-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11073017

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Calcium supplementation decreases rectal epithelial cell proliferation in subjects with sporadic adenoma. Author(s): Wargovich MJ, Isbell G, Shabot M, Winn R, Lanza F, Hochman L, Larson E, Lynch P, Roubein L, Levin B. Source: Gastroenterology. 1992 July; 103(1): 92-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1612362

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Calcium supplements interact significantly with long-term diet while suppressing rectal epithelial proliferation of adenoma patients. Author(s): Rozen P, Lubin F, Papo N, Knaani J, Farbstein H, Farbstein M, Zajicek G. Source: Cancer. 2001 February 15; 91(4): 833-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11241253

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Calcium, vitamin D, and risk of adenoma recurrence (United States). Author(s): Martinez ME, Marshall JR, Sampliner R, Wilkinson J, Alberts DS.

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Source: Cancer Causes & Control : Ccc. 2002 April; 13(3): 213-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12020102 •

Changes in serum carotenoids in subjects with colorectal adenomas after 24 mo of beta-carotene supplementation. Australian Polyp Prevention Project Investigators. Author(s): Wahlqvist ML, Wattanapenpaiboon N, Macrae FA, Lambert JR, MacLennan R, Hsu-Hage BH. Source: The American Journal of Clinical Nutrition. 1994 December; 60(6): 936-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7985637

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Changes of the mucosal n3 and n6 fatty acid status occur early in the colorectal adenoma-carcinoma sequence. Author(s): Fernandez-Banares F, Esteve M, Navarro E, Cabre E, Boix J, Abad-Lacruz A, Klaassen J, Planas R, Humbert P, Pastor C, Gassull MA. Source: Gut. 1996 February; 38(2): 254-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8801207

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Chemoprevention of diethylnitrosamine-induced liver foci and hepatocellular adenomas in C3H mice. Author(s): Pereira MA. Source: Anticancer Res. 1995 September-October; 15(5B): 1953-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8572583

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Chemopreventive efficacy and pharmacokinetics of curcumin in the min/+ mouse, a model of familial adenomatous polyposis. Author(s): Perkins S, Verschoyle RD, Hill K, Parveen I, Threadgill MD, Sharma RA, Williams ML, Steward WP, Gescher AJ. Source: Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 2002 June; 11(6): 535-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12050094

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Colonic fermentation of dietary fibre to short chain fatty acids in patients with adenomatous polyps and colonic cancer. Author(s): Clausen MR, Bonnen H, Mortensen PB. Source: Gut. 1991 August; 32(8): 923-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1653178

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Colorectal adenoma-carcinoma sequence. Author(s): Khosraviani K. Source: Gut. 1996 August; 39(2): 342. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8991864

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Dermatomyositis in association with tubulovillous adenoma: resolution after resection of adenoma. Author(s): Badr AS, Saadeh CK, Yeary J, Hamous J, Khandheria B. Source: Southern Medical Journal. 1997 March; 90(3): 321-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9076305

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Dietary and supplemental calcium and the recurrence of colorectal adenomas. Author(s): Hyman J, Baron JA, Dain BJ, Sandler RS, Haile RW, Mandel JS, Mott LA, Greenberg ER. Source: Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 1998 April; 7(4): 291-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9568783

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Dietary calcium supplementation for preventing colorectal cancer and adenomatous polyps. Author(s): Weingarten MA, Zalmanovici A, Yaphe J. Source: Cochrane Database Syst Rev. 2004; (1): Cd003548. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14974021

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Dietary change in an intervention trial of wheat bran fiber and colorectal adenoma recurrence. Author(s): Jacobs ET, Giuliano AR, Roe DJ, Guillen-Rodriguez JM, Hartz VL, Whitacre RC, Alberts DS, Martinez ME. Source: Annals of Epidemiology. 2004 April; 14(4): 280-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15066608

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Dietary fibre for the prevention of colorectal adenomas and carcinomas. Author(s): Asano T, McLeod RS. Source: Cochrane Database Syst Rev. 2002; (2): Cd003430. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12076480

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Does a high-fiber dietary supplement of wheat bran reduce the recurrence rate of colorectal adenomas? Author(s): Vitanzo PC Jr, Hong ES. Source: The Journal of Family Practice. 2000 July; 49(7): 656. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10923579

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Duodenal papillary adenoma in a Jehovah's Witness. Author(s): Orr KB. Source: The Medical Journal of Australia. 1996 February 5; 164(3): 191. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8628152

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Effect of fibre and calcium supplementation on adenoma recurrence and growth. Author(s): Faivre J, Bonithon-Kopp C. Source: Iarc Sci Publ. 2002; 156: 457-61. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12484234

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Effect of folate supplementation on DNA methylation of rectal mucosa in patients with colonic adenomas: correlation with nutrient intake. Author(s): Cravo ML, Pinto AG, Chaves P, Cruz JA, Lage P, Nobre Leitao C, Costa Mira F. Source: Clinical Nutrition (Edinburgh, Lothian). 1998 April; 17(2): 45-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10205316

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Effect of longterm placebo controlled calcium supplementation on sigmoidal cell proliferation in patients with sporadic adenomatous polyps. Author(s): Weisgerber UM, Boeing H, Owen RW, Waldherr R, Raedsch R, Wahrendorf J. Source: Gut. 1996 March; 38(3): 396-402. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8675093

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Effect of red ginseng on natural killer cell activity in mice with lung adenoma induced by urethan and benzo(a)pyrene. Author(s): Yun YS, Moon HS, Oh YR, Jo SK, Kim YJ, Yun TK. Source: Cancer Detect Prev Suppl. 1987; 1: 301-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3480057

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Effect of vitamin A, C, and E supplementation on rectal cell proliferation in patients with colorectal adenomas. Author(s): Paganelli GM, Biasco G, Brandi G, Santucci R, Gizzi G, Villani V, Cianci M, Miglioli M, Barbara L. Source: Journal of the National Cancer Institute. 1992 January 1; 84(1): 47-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1738173

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Effect of wheat fiber and vitamins C and E on rectal polyps in patients with familial adenomatous polyposis. Author(s): DeCosse JJ, Miller HH, Lesser ML. Source: Journal of the National Cancer Institute. 1989 September 6; 81(17): 1290-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2549261

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Effects of different doses of fish oil on rectal cell proliferation in patients with sporadic colonic adenomas. Author(s): Anti M, Armelao F, Marra G, Percesepe A, Bartoli GM, Palozza P, Parrella P, Canetta C, Gentiloni N, De Vitis I, et al.

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Source: Gastroenterology. 1994 December; 107(6): 1709-18. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7958682 •

Effects of vitamin antioxidant supplementation on cell kinetics of patients with adenomatous polyps. Author(s): Cahill RJ, O'Sullivan KR, Mathias PM, Beattie S, Hamilton H, O'Morain C. Source: Gut. 1993 July; 34(7): 963-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8344584

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Electro-acupuncture anesthesia in pituitary adenoma extirpation. Author(s): Gao LD, He NQ, Jin DF, Zhou RX, Xue ZN, Yang SR. Source: Chinese Medical Journal. 1983 June; 96(6): 469-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6414783

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Electrochemical therapy (ECT) for thyroid adenoma during acupuncture anaesthesia: analysis of 46 patients. Author(s): Song LC, Liu CY, Zhang BP, Wang T, Song YQ, Li YW. Source: Eur J Surg Suppl. 1994; (574): 79-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7531029

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Faecal steroids and colorectal cancer: steroid profiles in subjects with adenomatous polyps of the large bowel. Author(s): Owen RW, Day DW, Thompson MH. Source: European Journal of Cancer Prevention : the Official Journal of the European Cancer Prevention Organisation (Ecp). 1992 February; 1(2): 105-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1463972

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Fecal ammonia in patients with adenomatous polyps and cancer of the colon. Author(s): Clausen MR, Mortensen PB. Source: Nutrition and Cancer. 1992; 18(2): 175-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1437654

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Feedback regulation of parathyroid hormone secretion in parathyroid adenoma. Author(s): Tajima K, Fukumoto Y, Yoshikawa H, Imai Y, Asami Y, Kawamura S, Mashita K, Nonaka K, Tarui S. Source: Hormone and Metabolic Research. Hormon- Und Stoffwechselforschung. Hormones Et Metabolisme. 1984 March; 16(3): 161-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6325318

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Folate supplementation and adenomatous colonic polyps. Author(s): Paspatis GA, Karamanolis DG.

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Source: Diseases of the Colon and Rectum. 1994 December; 37(12): 1340-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7995171 •

Folic acid reduces nuclear translocation of beta-catenin in rectal mucosal crypts of patients with colorectal adenomas. Author(s): Jaszewski R, Millar B, Hatfield JS, Nogothu K, Finkenauer R, Rishi AK, Naumoff JA, Kucuk O, Axelrod BN, Majumdar AP. Source: Cancer Letters. 2004 March 31; 206(1): 27-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15019156

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Fruits, vegetables, and adenomatous polyps: the Minnesota Cancer Prevention Research Unit case-control study. Author(s): Smith-Warner SA, Elmer PJ, Fosdick L, Randall B, Bostick RM, Grandits G, Grambsch P, Louis TA, Wood JR, Potter JD. Source: American Journal of Epidemiology. 2002 June 15; 155(12): 1104-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12048224

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Functional evidence for two types of parathyroid adenoma. Author(s): D'Amour P, Weisnagel J, Brossard JH, Ste-Marie LG, Rousseau L, Lepage R. Source: Clinical Endocrinology. 1998 May; 48(5): 593-601. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9666871

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Giant desmoid tumor of the abdominal wall associated with familial adenomatous polyposis. Author(s): Marone U, Amore A, Pezzullo L, Mozzillo N. Source: Tumori. 2003 May-June; 89(3): 331-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12908794

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High-fiber diet and colorectal adenomas. Author(s): Muller RJ. Source: The New England Journal of Medicine. 2000 September 7; 343(10): 737; Author Reply 737-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10979772

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High-fiber diet and colorectal adenomas. Author(s): Lowenfels A, Maisonneuve P. Source: The New England Journal of Medicine. 2000 September 7; 343(10): 737; Author Reply 737-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10979771

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High-fiber diet and colorectal adenomas. Author(s): Duprey PA.

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Source: The New England Journal of Medicine. 2000 September 7; 343(10): 737; Author Reply 737-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10979769 •

High-fiber diet and colorectal adenomas. Author(s): Davis BM. Source: The New England Journal of Medicine. 2000 September 7; 343(10): 736; Author Reply 737-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10979767

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Increased intake of n-3 polyunsaturated fatty acids elevates the level of apoptosis in the normal sigmoid colon of patients polypectomized for adenomas/tumors. Author(s): Cheng J, Ogawa K, Kuriki K, Yokoyama Y, Kamiya T, Seno K, Okuyama H, Wang J, Luo C, Fujii T, Ichikawa H, Shirai T, Tokudome S. Source: Cancer Letters. 2003 April 10; 193(1): 17-24. Erratum In: Cancer Lett. 2004 March 18; 205(2): 227. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12691819

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Intake of supplemental and total fiber and risk of colorectal adenoma recurrence in the wheat bran fiber trial. Author(s): Jacobs ET, Giuliano AR, Roe DJ, Guillen-Rodriguez JM, Hess LM, Alberts DS, Martinez ME. Source: Cancer Epidemiol Biomarkers Prev. 2002 September;11(9):906-14. Erratum In: Cancer Epidemiol Biomarkers Prev. 2002 December;11(12):1699. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12223437

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Lack of effect of a high-fiber cereal supplement on the recurrence of colorectal adenomas. Phoenix Colon Cancer Prevention Physicians' Network. Author(s): Alberts DS, Martinez ME, Roe DJ, Guillen-Rodriguez JM, Marshall JR, van Leeuwen JB, Reid ME, Ritenbaugh C, Vargas PA, Bhattacharyya AB, Earnest DL, Sampliner RE. Source: The New England Journal of Medicine. 2000 April 20; 342(16): 1156-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10770980

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Lack of effect of a low-fat, high-fiber diet on the recurrence of colorectal adenomas. Polyp Prevention Trial Study Group. Author(s): Schatzkin A, Lanza E, Corle D, Lance P, Iber F, Caan B, Shike M, Weissfeld J, Burt R, Cooper MR, Kikendall JW, Cahill J. Source: The New England Journal of Medicine. 2000 April 20; 342(16): 1149-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10770979

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Measurement of fecal pyruvate kinase type M2 (tumor M2-PK) concentrations in patients with gastric cancer, colorectal cancer, colorectal adenomas and controls. Author(s): Hardt PD, Toepler M, Ngoumou B, Rupp J, Kloer HU.

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Source: Anticancer Res. 2003 March-April; 23(2A): 851-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12820312 •

Nuclear DNA content of isolated crypts of background colonic mucosa from patients with familial adenomatous polyposis and sporadic colorectal cancer. Author(s): Nakamura S, Kino I, Baba S. Source: Gut. 1993 September; 34(9): 1240-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8406162

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Nucleolar organizer regions in pituitary adenomas. Author(s): Radhakrishnan VV, Radhakrishnan NS, Misra BK, Rout D. Source: Indian J Pathol Microbiol. 1995 January; 38(1): 25-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8919466

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Plasma enterolactone or intestinal Bifidobacterium levels do not explain adenoma formation in multiple intestinal neoplasia (Min) mice fed with two different types of rye-bran fractions. Author(s): Oikarinen S, Heinonen S, Karppinen S, Matto J, Adlercreutz H, Poutanen K, Mutanen M. Source: The British Journal of Nutrition. 2003 July; 90(1): 119-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12844383

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Prediagnostic serum selenium concentration and the risk of recurrent colorectal adenoma: a nested case-control study. Author(s): Wallace K, Byers T, Morris JS, Cole BF, Greenberg ER, Baron JA, Gudino A, Spate V, Karagas MR. Source: Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 2003 May; 12(5): 464-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12750244

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Protection against dimethylhydrazine-induced adenomatous tumors of the mouse colon by the dietary addition of an extract of soybeans containing the Bowman-Birk protease inhibitor. Author(s): Weed HG, McGandy RB, Kennedy AR. Source: Carcinogenesis. 1985 August; 6(8): 1239-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4040444

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Relation of vegetable, fruit, and grain consumption to colorectal adenomatous polyps. Author(s): Witte JS, Longnecker MP, Bird CL, Lee ER, Frankl HD, Haile RW. Source: American Journal of Epidemiology. 1996 December 1; 144(11): 1015-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8942431

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Relationship of diet to risk of colorectal adenoma in men. Author(s): Giovannucci E, Stampfer MJ, Colditz G, Rimm EB, Willett WC. Source: Journal of the National Cancer Institute. 1992 January 15; 84(2): 91-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1310511

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Relationship of visceral adipose tissue to recurrence of adenomatous polyps. Author(s): Sass DA, Schoen RE, Weissfeld JL, Weissfeld L, Thaete FL, Kuller LH, McAdams M, Lanza E, Schatzkin A. Source: The American Journal of Gastroenterology. 2004 April; 99(4): 687-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15089903

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Resveratrol inhibits intestinal tumorigenesis and modulates host-defense-related gene expression in an animal model of human familial adenomatous polyposis. Author(s): Schneider Y, Duranton B, Gosse F, Schleiffer R, Seiler N, Raul F. Source: Nutrition and Cancer. 2001; 39(1): 102-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11588890

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Selenium supplementation enhances low selenium levels and stimulates glutathione peroxidase activity in peripheral blood and distal colon mucosa in past and present carriers of colon adenomas. Author(s): Al-Taie OH, Seufert J, Karvar S, Adolph C, Mork H, Scheurlen M, Kohrle J, Jakob F. Source: Nutrition and Cancer. 2003; 46(2): 125-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14690787

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Sphingomyelin consumption suppresses aberrant colonic crypt foci and increases the proportion of adenomas versus adenocarcinomas in CF1 mice treated with 1,2dimethylhydrazine: implications for dietary sphingolipids and colon carcinogenesis. Author(s): Schmelz EM, Dillehay DL, Webb SK, Reiter A, Adams J, Merrill AH Jr. Source: Cancer Research. 1996 November 1; 56(21): 4936-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8895747

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Stereotactic radiosurgery XVI: a treatment for previously irradiated pituitary adenomas. Author(s): Swords FM, Allan CA, Plowman PN, Sibtain A, Evanson J, Chew SL, Grossman AB, Besser GM, Monson JP. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 November; 88(11): 5334-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14602770

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Successful treatment of a hyperprolactinemic infertile woman with a pituitary microadenoma using hachimijiogan. Author(s): Otani S, Usuki S, Iwasaki H, Inoue S, Yamashita K.

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Source: The American Journal of Chinese Medicine. 1991; 19(2): 145-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1816726 •

The effect of alpha-tocopherol and beta-carotene supplementation on colorectal adenomas in middle-aged male smokers. Author(s): Malila N, Virtamo J, Virtanen M, Albanes D, Tangrea JA, Huttunen JK. Source: Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 1999 June; 8(6): 489-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10385137

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The effect of prolactin on human aldosterone-producing adenomas in vitro. Author(s): Carroll JE, Campanile CP, Goodfriend TL. Source: The Journal of Clinical Endocrinology and Metabolism. 1982 April; 54(4): 689-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6277980

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The effect of wheat bran fiber and calcium supplementation on rectal mucosal proliferation rates in patients with resected adenomatous colorectal polyps. Author(s): Alberts DS, Einspahr J, Ritenbaugh C, Aickin M, Rees-McGee S, Atwood J, Emerson S, Mason-Liddil N, Bettinger L, Patel J, Bellapravalu S, Ramanujam PS, Phelps J, Clark L. Source: Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 1997 March; 6(3): 161-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9138658

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Three cases with familial adenomatous polyposis diagnosed as having malignant lesions in the course of a long-term trial using docosahexanoic acid (DHA)concentrated fish oil capsules. Author(s): Akedo I, Ishikawa H, Nakamura T, Kimura K, Takeyama I, Suzuki T, Kameyama M, Sato S, Nakamura T, Matsuzawa Y, Kakizoe T, Otani T. Source: Japanese Journal of Clinical Oncology. 1998 December; 28(12): 762-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9879296

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Three-dimensional configuration of crypts of different types of colorectal adenomas. Author(s): Araki K, Ogata T. Source: Scanning Microsc. 1995 March; 9(1): 149-56; Discussion 156-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8553013

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Tissue levels of fish fatty acids and risk of colorectal adenomas: a case-control study (Netherlands). Author(s): Busstra MC, Siezen CL, Grubben MJ, van Kranen HJ, Nagengast FM, van't Veer P.

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Source: Cancer Causes & Control : Ccc. 2003 April; 14(3): 269-76. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12814206 •

Two-site assay of intact parathyroid hormone in primary hyperparathyroidism: studies in basal conditions, following adenoma removal and during calcium and EDTA infusion. Author(s): Mazzuoli G, Minisola S, Scarnecchia L, Pacitti MT, Carnevale V, Romagnoli E, Bigi F, Bianchi G. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1990 October 15; 190(3): 239-48. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2123754

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Usefulness of medium-term bioassay determining formations of pulmonary adenoma in NIH(GP) mice for finding anticarcinogenic agents from natural products. Author(s): Yun TK. Source: J Toxicol Sci. 1991 February; 16 Suppl 1: 53-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1920544

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Vitamin and calcium supplement use is associated with decreased adenoma recurrence in patients with a previous history of neoplasia. Author(s): Whelan RL, Horvath KD, Gleason NR, Forde KA, Treat MD, Teitelbaum SL, Bertram A, Neugut AI. Source: Diseases of the Colon and Rectum. 1999 February; 42(2): 212-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10211498

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Vitamin D, calcium supplementation, and colorectal adenomas: results of a randomized trial. Author(s): Grau MV, Baron JA, Sandler RS, Haile RW, Beach ML, Church TR, Heber D. Source: Journal of the National Cancer Institute. 2003 December 3; 95(23): 1765-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14652238

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Wheat bran fiber and development of adenomatous polyps: evidence from randomized, controlled clinical trials. Author(s): Macrae F. Source: The American Journal of Medicine. 1999 January 25; 106(1A): 38S-42S. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10089114

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Zinc concentration in human prostatic fluid: normal, chronic prostatitis, adenoma and cancer. Author(s): Zaichick VY, Sviridova TV, Zaichick SV. Source: International Urology and Nephrology. 1996; 28(5): 687-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9061429

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Zn, Ca and Na levels in the prostatic secretion of patients with prostatic adenoma. Author(s): Romics I, Bach D. Source: International Urology and Nephrology. 1991; 23(1): 45-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1718918

Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •

Alternative Medicine Foundation, Inc.: http://www.herbmed.org/

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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats

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Chinese Medicine: http://www.newcenturynutrition.com/

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drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html

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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm

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Google: http://directory.google.com/Top/Health/Alternative/

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Healthnotes: http://www.healthnotes.com/

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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine

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Open Directory Project: http://dmoz.org/Health/Alternative/

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HealthGate: http://www.tnp.com/

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WebMDHealth: http://my.webmd.com/drugs_and_herbs

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/

The following is a specific Web list relating to adenoma; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •

General Overview Benign Prostatic Hyperplasia Alternative names: Prostate Enlargement Source: Prima Communications, Inc.www.personalhealthzone.com Cancer Prevention (Reducing the Risk) Source: Prima Communications, Inc.www.personalhealthzone.com Colon Cancer Source: Healthnotes, Inc.; www.healthnotes.com

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Colorectal Cancer Source: Integrative Medicine Communications; www.drkoop.com Constipation Source: Healthnotes, Inc.; www.healthnotes.com Systemic Lupus Erythematosus Source: Healthnotes, Inc.; www.healthnotes.com •

Herbs and Supplements Aristolochia Alternative names: Snakeroot, Guaco; Aristolochia sp Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Dehydroepiandrosterone (DHEA) Source: Healthnotes, Inc.; www.healthnotes.com Docosahexaenoic Acid Source: Healthnotes, Inc.; www.healthnotes.com Eleuthero Alternative names: Siberian Ginseng, Eleuthero; Acanthopanax/Eleutherococcus senticosus Rupr. & Maxim. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Fiber Source: Healthnotes, Inc.; www.healthnotes.com N-Acetyl Cysteine Source: Healthnotes, Inc.; www.healthnotes.com Nettle Source: Integrative Medicine Communications; www.drkoop.com Pygeum Alternative names: African Prune; Pygeum africanum Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Saw Palmetto Source: Prima Communications, Inc.www.personalhealthzone.com Symphytum Alternative names: Comfrey; Symphytum officinale L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Urtica Dioica Source: Integrative Medicine Communications; www.drkoop.com Urtica Urens Source: Integrative Medicine Communications; www.drkoop.com

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General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.

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CHAPTER 4. PATENTS ON ADENOMA Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.8 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “adenoma” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on adenoma, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Adenoma By performing a patent search focusing on adenoma, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We

8Adapted from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

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will tell you how to obtain this information later in the chapter. The following is an example of the type of information that you can expect to obtain from a patent search on adenoma: •

Assay methods involving ouabain Inventor(s): Blaustein; Mordecai P. (Baltimore, MD), DuCharme; Donald W. (Paw Paw, MI), Fisher; Jed F. (Three Rivers, MI), Hamlyn; John M. (Baltimore, MD), Harris; Douglas W. (Portage, MI), Ludens; James H. (Portage, MI), Mandel; Frederic (Vicksburg, MI), Mathews; William R. (Plainwell, MI) Assignee(s): University of Maryland at Baltimore (baltimore, Md) Patent Number: 5,164,296 Date filed: August 31, 1990 Abstract: Methods for diagnosing pre-hypertension, hypertension, congestive cardiomyopathy, renal failure, salt-sensitivity and adenomas and endocrine cell hyperplasias are disclosed. Also disclosed are methods for monitoring hypertension therapy, congestive cardiomyopathy therapy, renal failure therapy and adenoma and endocrine call hyperplasia therapy. These methods involve using an antibody having binding specificity to ouabain to immunologically measure the level of human ouabain in body fluid or tissue of a subject. Additionally, methods for treating a hypertensive subject by inducing passive or active immunity to human ouabain in the subject are disclosed, along with an antibody having binding specificity for ouabain. Excerpt(s): The development of the present invention was supported by the Upjohn Company and the University of Maryland at Baltimore. The present invention relates to methods for diagnosing pre-hypertension, hypertension, congestive cardiomyopathy, renal failure, salt-sensitivity and adenomas and endocrine cell hyperplasias. The present invention also relates to methods for monitoring hypertension therapy, congestive cardiomyopathy therapy, renal failure therapy and adenoma and endocrine cell hyperplasia therapy. These methods involve using an antibody having binding specificity to ouabain to immunologically measure the level of human ouabain in body fluid or tissue of a subject. Additionally, the present invention relates to methods for treating a hypertensive subject by inducing passive or active immunity to human ouabain in the subject, and to an antibody having binding specificity for ouabain. Endogenous factors include a group of factors found in animal and human body fluids and tissues. These factors appear to be associated with natriuresis, the excretion of sodium in the urine. Natriuresis arises as a result of inhibition of (Na.sup.+ +K.sup.+)ATPase (the biochemical equivalent of the sodium pump) by the endogenous factors. The sodium pump drives the transepithelial resorption of sodium in animal and human kidneys (De Wardener, H.E. et al, Clin. Sci., 63:415-420 (1982)). However, (Na.sup.+ +K.sup.+)ATPase is not limited to kidney tissue. That is, this enzyme can be found in virtually all animal and human cells. Web site: http://www.delphion.com/details?pn=US05164296__

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Colon mucosa gene having down regulated expression in colon adenomas and adenocarcinomas Inventor(s): Papas; Takis S. (Potomac, MD), Schweinfest; Clifford W. (Hampstead, MD) Assignee(s): The United States of America AS Represented by the Department of Health (washington, Dc) Patent Number: 5,569,755 Date filed: April 17, 1995 Abstract: A new down-regulated gene called DRA, for down regulated in adenoma, maps to chromosome 7 and is believed to encode a tumor suppressor. The DRA gene encodes a highly hydrophobic protein with charged clusters located primarily in the carboxyl terminus. Additionally, the expression of the mRNA product appears to be strictly limited to the mucosa of normal colon and it is down-regulated early in colon tumorigenesis. Absence of the DRA polypeptide in tissue that usually expresses it can be used as an indicator of tissue abnormality. The DRA gene and cDNA may also have therapeutic capabilities as well. Excerpt(s): Colorectal cancer is a significant cancer burden to the general population of many developed countries. In the United States alone, there are over 130,000 new cases of colorectal cancer per year, and over 65,000 deaths per year resulting from colorectal cancer. Colorectal cancer it is second only to lung cancer in cancer morbidity in the United States. The progression of colorectal cancer, or colorectal tumorigenesis, is a multi-step process involving the loss of function of so-called tumor suppressor genes, as well as the activation of oncogenes. Fearon et al., Cell 61: 759-67 (1990); Paraskeva et al., Anticancer Research 10: 1189-200 (1990). It is also marked by several phenotypically distinct stages during progression. These include normal, hyperplastic, benign, carcinoma and metastatic stages. These distinct stages make colorectal cancer an exceptionally useful paradigm for the studying the molecular genetic basis of cancer in general. Among the classical oncogenes implicated in cancer, the ras and myc genes have been found to be activated and/or show elevated expression in colorectal tumors. About half of large adenomas and at least half of carcinomas contain activated K-ras genes. Forrester et al., Nature 327:298-303 (1987); Bos et al., Nature 327: 293-97 (1987); Burmer et al., Proc. Nat'l Acad. Sci. USA 86: 2403-07 (1989). C-myc over expression and occasional gene amplification have also been demonstrated in colorectal tumors. Erisman et al., Mol. Cell. Biol. 5: 1969-76 (1985); Imaseki et al., Cancer 64: 704-09; Finley et al., Oncogene 4: 963-71 (1989). Furthermore, deregulated c-myc expression can be suppressed by microcell-mediated transfer of chromosome 5, which is the locus for the putative tumor-suppressor genes, APC (for adenomatous polyposis coli) and MCC (for mutated in colorectal carcinoma) discussed below. Rodriguez-Alfageme et al., Proc. Nat'l Acad. Sci. USA 89:1482-86 (1992). Although the importance of oncogenes in cancer development can not be ignored, it is the presently the tumor suppressor genes which have drawn the most interest for study of cancer development. Web site: http://www.delphion.com/details?pn=US05569755__

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Compound preparation for the treatment of hypogonadal men and men with hypophyseal diseases Inventor(s): Dittgen; Michael (Apolda, DE), Golbs; Siegfried (Leipzig, DE), Graser; Thomas (Erfurt, DE), Hubler; Doris (Schmieden, DE), Oettel; Michael (Jena, DE), Timpe; Carsten (Apolda, DE) Assignee(s): Jenapharm Gmbh & Co. KG (jena, De) Patent Number: 5,855,905 Date filed: April 30, 1997 Abstract: A compound preparation for the treatment of hypogonadal men and men with hypophyseal diseases. This invention relates to compound preparations containing biogenous or synthetic androgens and biogenous or synthetic estrogens that are used for the treatment of imbalances of the testosterone metabolism in old age, of hypogonadal men, and of men with hypophyseal diseases. These compound preparations are present in various galenic formulations such as ointments, gels, sprays, TTS systems, tablets, lozenges, capsules, and suppositories. These preparations are used to treat the fluctuations of the testosterone metabolism occurring in old age and with certain diseases such as hypophyseal diseases (adenoma), hypogonadism and/or metabolic syndrome, to maintain the balance between androgens and estrogens found in young and healthy men in ill and/or elderly men as well. The preparations for treating these imbalances are suitable for oral, parenteral, percutaneous, sublingual or rectal administration depending on their galenic form. Thus, unphysiological changes in steroid-converting enzymes such as aromatases and reductases are avoided, which considerably improves the outcome of the therapy. Excerpt(s): This invention relates to pharmaceutical compound preparations for oral, percutaneous, intranasal, rectal or parenteral application used in the treatment of hypogonadal men with or without metabolic syndrome and of men with hypophyseal diseases. Various endocrine functions undergo changes in the course of the aging process. The insulin-like growth factor (IGF-1) levels in the plasma diminishes in healthy persons as they get older (Rudman D(1985): Growth hormone, body composition, and aging. J Am Geriatr Soc 33: 800-807; Florini JR, Prinz PN, Vitiello MV, Hintz RL (1985): Somatomedin-C levels in healthy young and old men: Relationship to peak and 34-hour integrated levels of growth hormone. J. Gerontol 40: 2-7). The normal aging process in men is accompanied by a hypofunction of the testicles, in particular, by a decline in serum testosterone levels. At the same time, the levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in the plasma are increased (TienChun Chang, Chin-Chia Tung, Yung-Lien Hsiao (1994): Hormonal changes in elderly men with non-insulin-dependent diabetes mellitus and the hormonal relationships to abdominal adiposity. Gerontology 40: 260-267). The prevalence of specific diseases with or without a disturbed oral glucose tolerance increases parallel to these hormonal changes. Examples of this are the various forms of diabetes mellitus, high blood pressure, hypercholesterolaemia and other disorders of the lipid or lipoprotein metabolism, myocardial infarction, and Alzheimer's disease (Vermeulen A (1991): J. Clin Endocrinol Metab 73: 222). Quite frequently, the so-called metabolic syndrome is found in overweight elderly men which is accompanied by obesity, insulin or insulin receptor resistance, a testosterone deficit and a disproportionately high risk of cardiovascular diseases. There is a considerably increased mortality caused by cerebral or coronary ischaemia (McGovern PG et al. (1993): The role of stroke attack rate and case fatality in the decline of stroke mortality. The Minnesota Heart Survey. Ann Epidemiol. 3: 483-487;

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Hames CG et al. (1993): Black-white comparisons of 20-year coronary heart disease mortality in the Evans County Heart Study Cardiology 82: 122-136). Web site: http://www.delphion.com/details?pn=US05855905__ •

Condensed-ring thiophene derivatives, their production and use Inventor(s): Choh; Nobuo (Ibaraki, JP), Furuya; Shuichi (Ibaraki, JP), Hinuma; Shuji (Ibaraki, JP), Kato; Koichi (Ibaraki, JP) Assignee(s): Takeda Chemical Industries, Ltd. (osaka, Jp) Patent Number: 5,817,819 Date filed: June 16, 1995 Abstract: A gonadotropin-releasing hormone antagonistic composition, which comprises an optionally substituted condensed-bicyclic compound consisting of a homo or hetero 5 to 7 membered ring and a homo or hetero 5 to 7 membered ring is effective as a propylactic or therapeutic agent for the prevention or treatment of several hormone dependent diseases, for example, a sex hormone dependent cancer (e.g. prostatic cancer, cancer of uterine cervix, breast cancer, pituitary adenoma), benign prostatic hypertrophy, myoma of the uterus, endometriosis, precocious puberty, amenorrhea, premenstrual syndrome, polycystic ovary syndrome and acne vulgaris; is effective as a fertility controlling agent in both sexes (e.g. a pregnancy controlling agent and a menstrual cycle controlling agent); can be used as a contraceptive of male or female, as an ovulation-inducing agent of female; can be used as an infertility treating agent by using a rebound effect owing to a stoppage of administration thereof; is useful as modulating estrous cycles in animals in the field of animal husbandry, as an agent fro improving the quality of edible meat or promoting the growth of animals; is useful as an agent of spawning promotion in fish. Excerpt(s): The present invention relates to a pharmaceutical composition for antagonizing a gonadotropin-releasing hormone (GnRH) containing a condensedbycyclic compound consisting of a homo or hetero 5 to 7-membered ring group and a homo or hetero 5 to 7-membered ring group. The present invention also relates to novel condensed-ring hiophene derivatives and salts thereof. The present invention further relates to methods for manufacturing the novel condensed-ring thiophene derivatives and the salts thereof. Secretion of anterior pituitary hormone undergoes the control by peripheral hormone secreted from target organs for the respective hormones and by secretion-accelerating or -inhibiting hormone from hypothalamus, which is the upper central organ of anterior lobe of pituitary (in this specification, these hormones are collectively called "hypothalamic hormone"). At the present stage, as hypothalamic hormones, nine kinds of hormones including, for example, thyrotropin releasing hormone (TRH) or gonadotropin releasing hormone {GnRH: sometimes called as LHRH (luteinizing hormone releasing hormone)} are confirmed their existence (cf. Seirigaku 2, compiled by M. Iriku and K Toyama, published by Bunkohdo, p610-618, 1986). These hypothalamic hormones are assumed to show their actions via the receptor which is considered to exist in the anterior lobe of pituitary (cf. ibid), and observatinal studies of receptor genes specific to these hormones, including cases of human, have been developed (Receptor Kiso To Rinsho, compiled by H. Imura, et al., published by Asakura Shoten, p297-304, 1993). Accordingly, antagonists or agonists specifically and selectively acting on these receptors control the action of hypothalamic hormone and controlling the secretion of anterior pituitary hormone. As the results, they are expected to be useful for prophylactic and therapeutic agents of anterior pituitary hormone

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dependent diseases. Leuprorelin acetate ›Fujino et al., Biological and Biophysical Research Communications, Vol.60, 00.406-413, 1974); Oliver, R. T. D. et al., British Journal of Cancers, Vol.59, p.823, 1989; and Toguchi et al., Journal of International Medical Research, Vol.18, pp.35-41!, which is a highly potent derivative of gonadotropic hormone-releasing hormone, one of the hypothalamic hormones, (hereinafter sometimes abbreviated as GnRH) ›Schally A. V. et at., Journal of Biological Chemistry, Vol. 246, pp.7230-7236, 1971; and Burgus, R. et al., Proceeding of Natural Academic Science, USA, Vol.69, pp278-282, 1972!, by administration of multiple doses, lowers release,production of gonadotropic hormone in pituitary, causing lowering of reactivity on gonadotropic hormone is spermary and ovary to suppress secretion of testosterone and estrogen. Leuprorelin acetate has, therefore, been known to show antitumor activity on such hormone-dependent cancers as exemplified by prostate cancer, and has been widely used in the clinical field. Leuprorelin acetate has been widely used clinically also as a therapeutic agent of e.g. endometriosis and precocious puberty. The high antitumor activity of leuprorelin acetate is assumed to be due to its high resistance, as compared with natural GnRH, against protease,and to high affinity to GnRH receptor causing desensitization of GnRH due to decrease in number of receptors. However, as leuprorelin acetate is an ultra-agonist on GnRH receptor, it has been known that, immediately after the first administration, a transient aggravation accompanied with the rise of serum testosterone concentration due to pituitary-gonadotropic action (acute action) is observed. Circumstances being such as above, GnRH antagonistic drugs which are expected to have substantially the same therapeutic effects as described above but not to cause the above-mentioned transient pituitary-gonadotropic action (acute action) have been desired. As compounds having such GnRH antagonistic activity, a number of compounds including, for example, derivatives of GnRH such as straight-chain peptides, (U.S. Pat. No. 5140009, 5171835), cyclic hexapeptide derivatives ›JPA S61(1986)-191698! or bicyclic peptide derivatives ›Journal of medicinal chemistry, Vol.36, pp.3265-3273, 1993!. These compounds are, however, all peptides, which leave many problems including, for example, dosage forms, stability of drugs, durability of actions and stability on metabolism. For solving these problems, orally administrable GnRH antagonistic drugs, especially non-peptide ones, are strongly desired. At the present stage, however, no report on non-peptide GnRH antagonistic drugs has been made. Web site: http://www.delphion.com/details?pn=US05817819__ •

Method and kit for locating hyperactive parathyroid tissue or adenomatious tissue in a patient and for removal of such tissue Inventor(s): Norman, Jr.; James G. (Tampa, FL) Assignee(s): University of South Florida (tampa, Fl) Patent Number: 6,263,232 Date filed: November 17, 1998 Abstract: Disclosed herein are methods for locating hyperactive parathyroid tissue in a patient. The methods comprise providing a radiopharmaceutical which produces during a time window after administration of the radiopharmaceutical to the patient, a detectably greater radioactivity in the hyperactive parathyroid tissue than in adjacent thyroid tissue in the patient; administering the radiopharmaceutical to the patient; surgically opening an operative field in the proximity of the hyperactive parathyroid tissue; and introducing into the operative field during the time window, a probe, which detects the radioactivity produced by the hyperactive parathyroid tissue to determine

Patents 147

the location of the hyperactive parathyroid tissue upon moving the probe within the operative field. The method is particularly applicable to radioguided parathyroidectomy using a.sup.99m Tc Sestamibi and a hand-held gamma detection probe. The gamma detection probe is also used to verify ex vivo that the resected tissue is parathyroid adenoma. Also provided are kits comprising a probe capable of detecting the radioactivity emitted from the hyperactive parathyroid tissue packaged with an instruction manual for use of the probe in performing a parathyroidectomy using.sup.99m Tc Sestamibi. Excerpt(s): This invention relates generally to the labeling and detecting of tissues using radionuclides and, more particularly, to the intraoperative mapping of hyperactive parathyroid tissues using a radiopharmaceutical and a hand-held detector and the application of such in a method for performing a parathyroidectomy. Primary hyperparathyroidism results from a single parathyroid adenoma in 87-92 percent of all cases. Removal of this one gland produces a long-term cure. Nevertheless, most surgeons have performed a complete bilateral neck exploration in patients with primary hyperparathyroidism in order to examine and sometimes biopsy each gland in order to be certain that all hyperfunctional parathyroid tissues are found and resected, leaving behind only normal glands. This approach has been a consequence of the historical inability of preoperative testing to accurately distinguish those patients harboring a single diseased gland from the eight to thirteen percent of patients with multiple adenomas or four gland hyperplasia. This began to change in the early 1990's following the discovery that.sup.99m Tc Sestamibi, which had been used in cardiac imaging, preferentially concentrates in the parathyroid and can be used to localize parathyroid adenomas preoperatively (Taillefer et al., J. Nucl Med 33:1801-1807, 1992; Wei et al., Surgery 12:1111-1117, 1992). In the ensuing years, numerous surgeons have employed preoperative.sup.99m Tc Sestamibi in gamma surface mapping to identify and locate parathyroid adenomas (Denham et al., J Am Coll Surg 186:293-304, 1998). Web site: http://www.delphion.com/details?pn=US06263232__ •

Method for the prevention of colonic adenomas Inventor(s): Allen; Carroll Wayne (Chatham, NJ), Brasitus; Thomas Albert (Olympia Fields, IL), Earnest; David Lewis (Tuscon, AZ), Messerschmidt; Gerald Leigh (Mendham, NJ) Assignee(s): Novartis Corp. (new York City, Ny), University of Arizona (tucson, Az), University of Chicago (chicago, Il) Patent Number: 6,677,328 Date filed: October 18, 2000 Abstract: Method for the prevention of colonic adenomas in mammals at risk of developing them by administering to such mammals an effective colonic adenoma preventive amount of ursodiol or a pharmaceutically acceptable salt conjugation product thereof. Excerpt(s): The invention relates to the area of precancerous cell formation in the colon in those patients at risk for developing such precancerous cells. It also relates to preventing recurrence of such cell formation in those having been treated for cancer of the colon. Cancer of the colon is a common and deadly disease in the Western world. Genetic predisposition plays an important role, but exposure to substances that initiate and promote cancer is essential for a malignant tumor to develop. Bile acids have been

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implicated as important cancer-promoting agents. In the normal colon mucosa, epithelial cells line crypts along the mucosal wall. Those epithelial cells which line the colon exposed surface and approximately the upper 2/3 of the crypt are normally nonproliferating, while those lining the lower 1/3 of the crypts are proliferating. As the proliferating cells migrate toward the upper portion of the crypt they transform and lose their proliferative ability. Ultimately the oldest cells are shed from the colon surface in the normal functioning of the colon. However, when the proliferating epithelial cells are induced to retain their proliferative capacity after reaching the upper 1/3 of the crypt, the normal process may go awry and microadenomas form. The proliferating cell, now at the surface of the colon continues to proliferate and a polyp develops. Web site: http://www.delphion.com/details?pn=US06677328__ •

Portulaca oleracea and tumor cell growth Inventor(s): Ham; Seung Shi (Calgary, CA), Jun; Hee Sook (Calgary, CA), Yoon; Ji-Won (Calgary, CA) Assignee(s): Eastwood Biomedical Research, Inc. (ca) Patent Number: 5,869,060 Date filed: December 4, 1996 Abstract: Portulaca oleracea has been used throughout history for many different medicinal purposes. This invention is directed to the novel use of P. oleracea for the treatment of cancer. More specifically it is disclosed that P. oleracea has a specific and distinct effect on the inhibition and/or suppression of gastric tumor cell growth in vitro and in vivo. An aqueous extract of P. oleracea showed a tumoricidal activity against KATO III (human gastric carcinoma cell line) and COLO 320 HSR cells (human colon adenoma cell line) in a dose-dependent and time-dependent manner, but not against the non-tumorous cell lines, L929 (murine lung connective tissue) and W138 (human lung diploid cell) cells. Subcutaneous injection of six week old CD1 nude mice with COLO 320 HSR cells and subsequently Portulaca oleracea extract showed a clear inhibition of tumor growth as compared to the control nude mice which received only COLO 320 HSR cells. Excerpt(s): The present invention relates to the tumoricidal activity of Portulaca oleracea extracts. More specifically this invention relates to the suppression of tumor cell growth in vitro and in vivo. Full citations for references appear at the end of the examples section. Portulaca oleracea is found ubiquitously in habitats with warm climate (Habtemariam et al., 1993). It has been used as an edible plant by humans since the prehistoric age. In China, the Philippines, Southeast Asia, and Africa, this wild plant is still consumed as food in various ways (Herklots, 1972). P. oleracea is recognized as a quite nutritious vegetable. It includes carbohydrates, amino acids, omega-3 fatty acids (Simopoulos et al., 1992, Mohamed and Hussein, 1994), several vitamins and minerals and many others (Wattenbergs, 1993) (Table 1). Web site: http://www.delphion.com/details?pn=US05869060__

Patents 149

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Quinoline derivatives, their production and use Inventor(s): Choh; Nobuo (Tsukuba, JP), Furuya; Shuichi (Tsukuba, JP), Sasaki; Satoshi (Tsukuba, JP) Assignee(s): Takeda Chemical Industries Ltd. (osaka, Jp) Patent Number: 6,087,503 Date filed: September 14, 1998 Abstract: The present compounds are intermediates for the preparation of quinoline derivatives and compositions having gonadotropin-releasing hormone antagonistic activity useful as propylactics or therapeutic agent for the prevention or treatment of several hormone dependent diseases, for example, a sex hormone dependent cancer (e.g. prostatic cancer, uterine or cervical cancer, breast cancer, pituitary adenoma), benign prostatic hypertrophy, myoma of the uterus, endometriosis, precocious puberty, amenorrhea, premenstrual syndrome, polycystic ovary syndrome and acne vulgaris; are effective as a fertility controlling agent in both sexes (e.g. a pregnancy controlling agent and a menstrual cycle controlling agent); can be used as a male or female contraceptive, as an ovulation-inducing agent; can be used as an infertility treating agent by using a rebound effect owing to a stoppage of administration thereof; and are useful for modulating estrous cycles in animals in the field of animal husbandry, as agents for improving the quality of edible meat or promoting the growth of animals, and as agents for promoting spawning in fish. Excerpt(s): The present invention relates to novel quinoline derivatives and salts thereof. The present invention further relates to methods for manufacturing these quinoline derivatives and the salts thereof, and pharmaceutical compositions containing the quinoline derivatives. Secretion of anterior pituitary hormone is controlled by peripheral hormones secreted from target organs for the respective hormones and by secretion-accelerating or -inhibiting hormones from the hypothalamus, which is the upper central organ of the anterior lobe of the pituitary (in this specification, these hormones are collectively called "hypothalamic hormones"). At the present stage, nine kinds of hormones have been confirmed as hypothalamic hormones, including, for example, thyrotropin releasing hormone (TRH) or gonadotropin releasing hormone {GnRH: sometimes called LH-RH (luteinizing hormone releasing hormone)} (cf. Seirigaku 2, compiled by M. Iriku and K Toyama, published by Bunkohdo, pp.610-618, 1986). These hypothalamic hormones are assumed to show their actions via the receptor which is considered to exist in the anterior lobe of the pituitary (cf. ibid), and studies of receptor genes specific to these hormones, including those of humans, have been developed (Receptor Kiso To Rinsho, compiled by H. Imura, et al., published by Asakura Shoten, pp.297-304, 1993). Accordingly, antagonists or agonists specifically and selectively acting on these receptors control the action of hypothalamic hormone and the secretion of anterior pituitary hormone. As a result, they are expected to be useful as prophylactic and therapeutic agents of anterior pituitary hormone dependent diseases. As compounds having GnRH antagonistic activity, a number of compounds including, for example, derivatives of GnRH such as straight-chain peptides, (U.S. Pat. No. 5,140,009 and No. 5,171,835), cyclic hexapeptide derivatives [Japanese Patent Application Laid-open No. 61(1986)-191698) or bicyclic peptide derivatives [Journal of medicinal chemistry, Vol.36, pp.3265-3273, 1993] have been disclosed. Web site: http://www.delphion.com/details?pn=US06087503__

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Thienopyridine derivatives, their production and use Inventor(s): Furuya; Shuichi (Tsukuba, JP), Hayase; Yoji (Tsukuba, JP), Imada; Takashi (Tsukuba, JP), Matsumoto; Hirokazu (Tsukuba, JP), Suzuki; Nobuhiro (Tsukuba, JP) Assignee(s): Takeda Chemical Industries, Ltd. (osaka, Jp) Patent Number: 6,001,850 Date filed: August 14, 1997 Abstract: The present thienopyridine derivatives and composition having gonadotropinreleasing hormone antagonistic activity are useful as prophylactic or therapeutic agents for the prevention or treatment of several hormone dependent diseases, for example, a sex hormone dependent cancer (e.g. prostatic cancer, cancer of uterine cervix, breast cancer, pituitary adenoma), benign prostatic hypertrophy, myoma of the uterus, endometriosis, precocious puberty, amenorrhea, premenstrual syndrome, polycystic ovary syndrome and acne vulgaris; is effective as a fertility controlling agent in both sexes (e.g. a pregnancy controlling agent and a menstrual cycle controlling agent); is useful as a contraceptive of male or female, as an ovulation-inducing agent of female; is useful as an infertility treating agent by using a rebound effect owing to a stoppage of administration thereof; is useful as modulating estrous cycles in animals in the field of animal husbandry, as an agent for improving the quality of edible meat or promoting the growth of animals; is useful as an agent of spawning promotion in fish. Excerpt(s): The present invention relates to novel 4,7-dihydro-4-oxothieno[2,3b]pyridine derivatives and salts thereof. The present invention further relates to method for manufacturing these 4,7-dihydro-4-oxothieno[2,3-b]pyridine derivatives and salts thereof, and pharmaceutical composition containing these 4,7-dihydro-4-oxothieno[2,3b]pyridine derivatives and salts thereof. Secretion of anterior pituitary hormone undergoes the control by peripheral hormone secreted from target organs for the respective hormones and by secretion-accelerating or secretion-inhibiting hormone from hypothalamus, which is the upper central organ of anterior lobe of pituitary (in this specification, these hormones are collectively called "hypothalamic hormone"). At the present stage, as hypothalamic hormones, nine kinds of hormones including, for example, thyrotropin releasing hormone (TRH) or gonadotropin releasing hormone {GnRH: sometimes called as LH-RH (luteinizing hormone releasing hormone)} are confirmed their existence. These hypothalamic hormones are assumed to show their actions via the receptor which is considered to exist in the anterior lobe of pituitary, and observational studies of receptor genes specific to these hormones, including cases of human, have been developed. Accordingly, antagonists or agonists specifically and selectively control the action of hypothalamic hormone by acting on these receptors and control the secretion of anterior pituitary hormone. As the results, they are expected to be useful for prophylactic and therapeutic agents of anterior pituitary hormone dependent diseases. As compounds having such GnRH antagonistic activity, a number of compounds including, for example, derivatives of GnRH such as straight-chain peptides (U.S. Pat. No. 5,140,009, U.S. Pat. No. 5,171,835), cyclic hexapeptide derivatives (Japanese Patent Application Laid-open No.S61(1986)-191698) or bicyclic peptide derivatives (Journal of Medicinal Chemistry, Vol.36, pp.3265-3273, 1993). Furthermore, as non-peptide compounds having such GnRH antagonistic activity, compounds described in PCT International Publication No. WO 95/28405 are known. Web site: http://www.delphion.com/details?pn=US06001850__

Patents 151

Patent Applications on Adenoma As of December 2000, U.S. patent applications are open to public viewing.9 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to adenoma: •

CHELATED 8-HYDROXYQUINOLINE AND USE THEREOF IN A METHOD OF TREATING EPITHELIAL LESIONS Inventor(s): HANSON, CARL C.; (PARKER, CO), JORDAN, RUSSEL T.; (FORT COLLINS, CO), POTESTIO, FRANK S.; (PARKER, CO) Correspondence: Lathrop & Gage LC; 4845 Pearl East Circle; Suite 300; Boulder; CO; 80301; US Patent Application Number: 20040092496 Date filed: February 10, 1998 Abstract: Oxinates including 8-hydroxyquinoline and a heavy metal are topically applied to epidermal lesions for therapeutic effect. The zinc oxinate compositions are shown to be therapeutically effective against The therapeutic composition demonstrates selective toxicity with a therapeutic index of one-hundred percent on human lung cancer, breast cancer, melanoma, venereal warts, male veruoca warts, lesions produced by human papilloma virus, basal cell carcinoma, solar keratosis, and Kaposi's sarcoma. In veterinary applications where dogs, cats, and horses are the patients, the composition shows a one-hundred percent therapeutic index with selective toxicity against eye cancer, sarcoids, sarcoma, malignant melanoma, rectal adenoma, histiocytoma, and sebaceous adenoma. Excerpt(s): The present invention pertains to the field of oxinates and, particularly, to the therapeutic use of chelated metal 8-hydroxyquinolinates in the treatment of cancers, precancerous lesions, and other abnormal tissues. A preferred treatment modality for many cancers is surgical excision of the cancerous lesion. Surgical excision is not always desirable when surgery could sever nerves or produce scars that interfere with normal movements in tissues proximate the site of surgery. Chemicals have been developed to treat cancers. Rate-sensitive cytotoxic drugs have cytotoxic effects on all tissue types, but are particularly effective against certain cancers that function at a metabolic rate greater than the metabolic rate of normal cells. The increased metabolic rate of these cancers makes them more susceptible to the cytotoxicity of the drugs. In this manner it is possible to provide a dosage that is fatal to cancer cells, while that same dosage is not fatal to normal cells. By way of example, U.S. Pat. No. 5,684,169 teaches the formation of cyclodextrin complexes of taxol to improve the solubility of taxol in water. Taxol is a cytotoxic drug that is believed to attack and kill cancer cells with a rate-sensitive effect. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

9

This has been a common practice outside the United States prior to December 2000.

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CHIMERIC TOXINS FOR TARGETED THERAPY Inventor(s): LORBERBOUM-GALSKI, HAYA; (JERUSALEM, IL), MARIANOVSKY, IRINA; (JERUSALEM, IL), NECHUSHTAN, AMOTZ; (RAMAT HASHARON, IL), YARKONI, SHAI; (KFAR SABA, IL) Correspondence: Lowe Hauptman Gopstein; Gilman & Berner; 1700 Diagonal Road; Suite 310; Alexandria; VA; 22314 Patent Application Number: 20020028914 Date filed: March 1, 1999 Abstract: The present invention relates particularly to neoplastic cells targeted chimeric toxins comprising of cell targeting moieties and cell killing moieties for recognizing and for destroying the neoplastic cells, wherein the cell targeting moieties consist of gonadotropin releasing hormone homologues and the cell killing moieties consist of Pseudomonas Exotoxin A. The present invention further relates to pharmaceutical compositions containing as an active ingredient these neoplastic cells targeted chimeric toxins and to a method for the production of these chimeric toxins. The said invention also relates to a method for cancer therapy, treating malignant carcinoma cells and benign hyperplasia including uterine lyomyoma cells, extra uterian endometrial island cells, benign hyperplasia of prostate and breast and pituitary tumor adenoma cells, by the use of the above-mentioned chimeric toxins. Excerpt(s): The present invention relates generally to therapeutic agents useful particularly in cancer targeted therapy but also in treating malignant carcinomas such as breast, colon, hepatic, ovarian and renal carcinomas and treating benign tumors of the uterus, hyperplasia, endometriosis, BPH, polycystic disease of the breast and pituitary adenomas. More specifically the said invention relates to Pseudomonas Exotoxin based chimeric toxins aimed at those neoplastic cells bearing gonadotropin releasing hormone binding sites. The present invention further relates to pharmaceutical compositions comprising as an active ingredient the above mentioned neoplastic cell targeted chimeric toxins. Furthermore the present invention relates to a method for the production of said chimeric toxins. These chimeric proteins, according to the present invention, are comprised of cell targeting moieties which consist of gonadotropin releasing hormone homologues linked to cell killing moieties which consist, preferably, of the bacterial toxin Pseudomonas Exotoxin A, for recognizing and destroying neoplastic cells bearing gonadotropin releasing hormone binding sites. Targeting is a term for the selective delivery of chemotherapeutic agents to specific cell populations. It is possible to create chimeric molecules that possess cell targeting and cellular toxin domains. These chimeric molecules function as cell selective poisons by virtue of their abilities to target selective cells and then kill those cells via their toxin component. Pseudomonas Exotoxin A (hereinafter called PE), a bacterial toxin used in construction of such chimeric proteins, acts by irreversibly arresting protein synthesis in eukaryotic cells, resulting in cell death. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Patents 153

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Method of treating colonic adenomas Inventor(s): Evans, Jilly; (Brossard, CA), Kargman, Stacia; (Hampstead, CA), Simon, Thomas J.; (Berwyn, PA) Correspondence: Merck And CO Inc; P O Box 2000; Rahway; NJ; 070650907 Patent Application Number: 20020045605 Date filed: October 12, 2001 Abstract: This invention is directed to a method of retarding or preventing the transformation of a colonic adenoma to a colonic adenocarcinoma comprising the administration to a patient with FAP or a patient with one or more of said adenomas a non-toxic therapeutically effective amount of NSAID, said amount effective to inhibit the PGHS-2 in said adenoma. The preferred method comprises the administration of a specific PGHS-2 inhibiting agent as defined herein. Excerpt(s): This application is directed to a method of treating colonic adenomas by administration of a non-toxic therapeutically effective amount of an non-steroidal antiinflammatory agent (NSAID). In particular, this application is directed to a method of preventing or retarding the transformation of colonic adenomas to colonic adenocarcinomas by administration of a non-toxic therapeutically effective, specific PGHS-2 inhibitor. The enzyme prostaglandin G/H synthase (PGHS) is a key enzyme in the biosynthetic pathway leading to the formation of prostaglandins (Watkins, W. D., Peterson, M. B., and Fletcher, J. R. ed. Prostaglandins in Clinical Practice. New York: Raven, 1989 and Dewitt, D. L. Prostaglandin endoperoxide synthase: regulation and enzyme expression. Biochim. Biophys. Acta, 1083; 121-134, 1991). These prostanoids are potent biological mediators with diverse normal physiological effects and are also implicated in a variety of pathological conditions including inflammation and neoplastic transformation (Watkins, W. D., Peterson, M. B., and Fletcher, J. R. ed. Prostaglandins in Clinical Practice. New York: Raven, 1989 and Dewitt, D. L. Prostaglandin endoperoxide synthase: regulation and enzyme expression. Biochim. Biophys. Acta, 1083; 121-134, 1991 and Xie, W., Robertson, D. L., and Simmons, D. L. Mitogen-inducible prostaglandin G/H synthase: a new target for nonsteroidal anti-inflammatory drugs. Drug Dev. Res., 25; 249-265, 1992). Two isoforms of PGHS have been identified (Loll, P. J. and Garavito, R. M. The isoforms of cyclooxygenase: structure and function. Expert Opin. Invest. Drugs, 3; 1171-1180, 1994). PGHS-1 is constitutively expressed in most tissues and has been proposed to generate prostaglandins for normal physiological functions. The second isoform, PGHS-2, is characterized by a rapid induction by a variety of stimuli, including mitogens, hormones, cytokines and growth factors (Loll, P. J. and Garavito, R. M. The isoforms of cyclooxygenase: structure and function. Expert Opin. Invest. Drugs, 3; 1171-1180, 1994 and Battistini, B., Botting, R., and Bakhle, Y. S. COX-1 and COX-2: Toward the development of more selective NSAIDS. Drug News Perspectives, 7; 501512, 1994). In conditions such as inflammation, PGHS-2-derived prostaglandins may be the predominant effectors (Masferrer, J. L., Zweifel, B. S., Manning, P. T., Hauser, S. D., Leahy, K. M., Smith, W.G., Isakson, P. C., and Seibert, K. Selective inhibition of inducible cyclooxygenase 2 in vivo is anti-inflammatory and non-ulcerogenic. Proc. Natl. Acad. Sci. USA, 91; 3228-3232, 1994). Both PGHS-1 and PGHS-2 have been shown to be the target of nonsteroidal anti-inflammatory drugs (NSAIDs) (Battistini, B., Botting, R., and Bakhle, Y. S. COX-1 and COX-2: Toward the development of more selective NSAIDS. Drug News Perspectives, 7; 501-512, 1994 and O'Neill, G. P., Mancini, J. A., Kargman, S., Yergey, J., Kwan, M. Y., Falgueyret, J. -P., Abramovitz, M., Kennedy, B. P., Ouellet, M., Cromlish, W., Culp, S., Evans, J. F., Ford-Hutchinson, A. W. and Vickers, P. J. Overexpression of human prostaglandin G/H synthase-1 and -2 by recombinant

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vaccinia virus: inhibition by nonsteroidal anti-inflammatory drugs and biosynthesis of 15-hydroxyeicosatetraenoic acid. Mol. Pharmacol., 45; 245-254, 1994 and DeWitt, D. L., Meade, E. A., and Smith, W. L. PGH synthase isoenzyme selectivity: the potential for safer nonsteroidal anti-inflammatory drugs. Am. J. Med. (Suppl.), 95; 40S-44S, 1993). See also WO 94/14977, published July 7, 1994, which discloses a method of evaluating the potency of PGHS-2 inhibiting agents as well as the selectivity for PGHS-2 over PGHS- 1. Elevated levels of prostaglandins have been demonstrated in various cancers including lung and colon carcinomas (McLemore, T.L., Hubbard, W. C., Litterst, C. L., Liu, M. C., Miller, S., McMahon, N. A., Eggleston, J. C., and Boyd, M. R. Profiles of prostaglandin biosynthesis in normal lung and tumor tissue from lung cancer patients. Cancer Res., 48; 3140-3147, 1988 and Rigas, B., Goldman, I. S., and Levine, L. Altered eicosanoid levels in human colon cancer. J. Lab. Clin. Med., 122; 518-523, 1993). In particular, prostaglandin levels have been shown to be elevated in benign adenomatous polyps and further increased in cancerous colon tissue, as compared to histologically normal mucosa. Since prostanoids have been shown to be immunosuppressive, they may play a role in tumor development (Earnest, D. L., Hixson, L. J., and Alberts, D. S. Piroxicam and other cyclooxygenase inhibitors: potential for cancer chemoprevention. J. Cell. Biochem., 161 (Suppl.); 156-166, 1992). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method of treatment of prostatic adenoma Inventor(s): Goble, Nigel M.; (Berks, GB) Correspondence: Nixon & Vandehye P.C.; 8th Floor; 1100 North Glebe Road; Arlington; VA; 22201-4714; US Patent Application Number: 20010027317 Date filed: March 6, 2001 Abstract: A surgical technique for treating bladder outflow obstruction is disclosed in which access is gained to the treatment site via the bladder itself through one or more suprapubic conduits. The disclosed technique includes inserting at least a first conduit suprapubically into the bladder, inserting at least a surgical instrument along the first conduit, distending the bladder with an isotonic fluid, viewing the position of the instrument using remote visualisation means, direct visualisation means, or a combination of the two, and using the surgical instrument to create at least one hole in the prostate gland, thereby to debulk the adenoma. Preferably the procedure is performed using electrosurgery, which offers significant advantages in terms of minimally invasive surgery and patient recovery times in comparison to more conventional forms of surgery. Excerpt(s): The present invention relates to the treatment of benign growths in the prostate gland, known clinically as prostatic adenoma. A common complaint associated wit the prostate gland is benign prostatic hyperplasia, or an enlarging of the prostate, resulting in constriction of the urethra and a consequent difficult in urinating. Existing techniques for treating this condition include trans-urethral resectioning of the prostate (TURP for short), a procedure in which an instrument inserted along the urethra of the patient is used to remove the prostate tissue which obstructs the urethra. Typically this procedure is performed using an electrosurgical instrument which resects the prostate tissue, and involves removing the obstructing tissue in a series of thin strips. A disadvantage of this procedure is the consequent removal of virtually all of the urethra in the region of the prostate. In our U.S. Pat. No. 6,015,406 which relates inter alia to

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electrosurgical instruments and their operation for the purpose of debulking, cutting or coagulating tissue, we disclose the use of an electrosurgical instrument having a short, rigid brush electrode to debulk a tumour such as a prostate adenoma. Specifically, we disclose that prostatic adenoma can be treated by drilling a series of holes into the adenoma. The residual tissue bridges will shrink as part of the healing process. Whilst not removing the whole tumour, this technique is safer and quicker than removing the entire adenoma, when treatment is being performed for bladder outflow obstruction, and in addition results in significantly less destruction of the urethra. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Use of at least a fatty ester for preparing a composition designed to inhibit 5-$g(a)reductase activity, in pharmacology, in particular dematology, in cosmetics and as food additive Inventor(s): Legrand, Jacques; (Sur Eure, FR), Msika, Philippe; (Paris, FR), Piccirilli, Antoine; (Versailles, FR) Correspondence: Foley And Lardner; Suite 500; 3000 K Street NW; Washington; DC; 20007; US Patent Application Number: 20030129268 Date filed: August 29, 2002 Abstract: The invention concerns the use of at least a fatty ester for preparing a composition designed to inhibit 5.alpha.-reductase activity. Said use produces a remarkable inhibiting effect of 5.alpha.-reductase thereby providing a novel response for treating dermatological pathologies and/or disorders related to congenital or acquired exaggeration of 5.alpha.-reductase activity, in particular for treating prostatic hypertrophy, prostatic adenoma, acne, hyperseborrhea, alopecia and hirsutism. The invention also concerns cosmetic treatment methods, in particular for greasy skin, and the use of said fatty esters as additives in a food product for human and/or animal consumption. Excerpt(s): The present invention relates to the use of at least one fatty ester for preparing a composition designed to inhibit 5.alpha.-reductase activity, in particular for treating prostatic hypertrophy, prostatic adenoma, acne, hyperseborrhea, alopecia and hirsutism. The invention also relates to methods for cosmetic treatment, in particular of greasy skin, and the use of the fatty esters described as additives in a food product for human and/or animal consumption. 5.alpha.-Reductase is a NADPH-dependent microsomial enzyme which exists in the form of two isoenzymes synthesized from two different genes. The 5.alpha.-reductase type 1 isoenzyme is essentially found in the liver and the skin, more particularly in the sebaceous glands of nongenital skin and of the scalp, and appears at puberty. The type 2 isoenzyme is predominant in the prostate and in the skin of differentiated sexual areas: genital region, beard, and plays a role in sexual differentiation. The distribution of the 5.alpha.-reductase types 1 and 2 isoenzymes in the skin and cutaneous annexes in humans may be illustrated by the following table. A number of pathologies exist for which a congenital or acquired exaggeration of the 5.alpha.-reductase activity is completely or predominantly responsible for the disorders observed. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Vesicle membrane proteins Inventor(s): Hillman, Jennifer L.; (Santa Cruz, CA), Kaser, Matthew R.; (Castro Valley, CA), Lal, Preeti; (Santa Clara, CA), Yue, Henry; (Sunnyvale, CA) Correspondence: Incyte Corporation (formerly Known AS Incyte; Genomics, INC.); 3160 Porter Drive; Palo Alto; CA; 94304; US Patent Application Number: 20030175787 Date filed: March 19, 2003 Abstract: The invention provides mammalian cDNAs which encode mammalian vesicle membrane proteins. It also provides for the use of the cDNAs, fragments, complements, and variants thereof and of the encoded proteins, portions thereof and antibodies thereto for diagnosis and treatment of cell proliferative disorders, particularly cancers of the colon, breast, ovary, uterus, prostate, adrenal gland, and thyroid, and thyroid follicular adenoma and thyroid lymphocytic thyroiditis. The invention additionally provides expression vectors and host cells for the production of the proteins and transgenic model systems. Excerpt(s): This application is divisional application of U.S. Ser. No. 09/718,996 filed Nov. 22, 2000, which is a continuation-in-part of U.S. Ser. No. 08/959,004, filed Oct. 28, 1997, now U.S. Pat. No. 6,197,543. This invention relates to mammalian cDNAs which encode vesicle membrane proteins and to the use of the cDNAs and the encoded protein in the diagnosis and treatment of cell proliferative disorders, particularly cancers of the colon, breast, ovary, uterus, prostate, adrenal gland, and thyroid, and thyroid follicular adenoma and thyroid lymphocytic thyroiditis. Phylogenetic relationships among organisms have been demonstrated many times, and studies from a diversity of prokaryotic and eukaryotic organisms suggest a more or less gradual evolution of molecules, biochemical and physiological mechanisms, and metabolic pathways. Despite different evolutionary pressures, the proteins of nematode, fly, rat, and man have common chemical and structural features and generally perform the same cellular function. Comparisons of the nucleic acid and protein sequences from organisms where structure and/or function are known accelerate the investigation of human sequences and allow the development of model systems for testing diagnostic and therapeutic agents for human conditions, diseases, and disorders. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Keeping Current In order to stay informed about patents and patent applications dealing with adenoma, you can access the U.S. Patent Office archive via the Internet at the following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “adenoma” (or synonyms) into the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on adenoma. You can also use this procedure to view pending patent applications concerning adenoma. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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CHAPTER 5. BOOKS ON ADENOMA Overview This chapter provides bibliographic book references relating to adenoma. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on adenoma include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.

Chapters on Adenoma In order to find chapters that specifically relate to adenoma, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and adenoma using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” Type “adenoma” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on adenoma: •

Cushing's Disease and Syndrome Source: in Graham, S.D., Jr., et al., eds. Glenn's Urologic Surgery. 5th ed. Philadelphia, PA: Lippincott Williams and Wilkins. 1998. p. 3-7. Contact: Available from Lippincott Williams and Wilkins. P.O. Box 1600, Hagerstown, MD 21741. (800) 638-3030 or (301) 714-2300. Fax (301) 824-7390. Website: lww.com. PRICE: $199.00 plus shipping and handling. ISBN: 0397587376. Summary: Cushing's disease and syndrome are characterized by the association of pituitary lesions in patients with hirsutism, proximal muscle weakness, round plethoric faces, increased supraclavicular and infrascapular fat pads, thin skin, and other less frequent signs such as acne, purple abdominal striae, and psychiatric symptoms. This chapter on Cushing's disease and syndrome is from an exhaustive textbook on urologic surgery. There are numerous etiologies of Cushing's syndrome, most involving the production of excessive ACTH from pituitary adenomas or from ectopic sources, benign adrenal tumors, and adrenal hyperplasia (overgrowth). The criteria for a diagnosis of

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Cushing's syndrome is excessive ACTH. The diagnosis may also be based on an abnormality of the plasma or urinary cortisol. Indications for surgery of the adrenal gland in patients with Cushing's syndrome include adrenal adenoma, adrenal hyperplasia, and adrenal carcinoma. The author then describes the posterior approach to the adrenal glands. Surgical complications following adrenal surgery for Cushing's syndrome include not only those that pertain to routine retroperitoneal surgery (e.g., blood loss and infection) but also those complications specific to patients with hormonal imbalances. Postoperative wound healing may be impaired, and the infection rate has been described to be between 4 and 21 percent. 6 figures. 6 references. •

Interstitial Laser Therapy of Benign Prostatic Hyperplasia Source: in Graham, S.D., Jr., et al., eds. Glenn's Urologic Surgery. 5th ed. Philadelphia, PA: Lippincott Williams and Wilkins. 1998. p. 1111-1117. Contact: Available from Lippincott Williams and Wilkins. P.O. Box 1600, Hagerstown, MD 21741. (800) 638-3030 or (301) 714-2300. Fax (301) 824-7390. Website: lww.com. PRICE: $199.00 plus shipping and handling. ISBN: 0397587376. Summary: Interstitial laser coagulation (ILC) of benign prostatic hyperplasia (BPH) is used to decrease urethral obstruction and both obstructive and irritative symptoms. In this technique, coagulation necrosis (tissue death) is generated well inside the adenoma, rather than at its urethral surface. This chapter on ILC is from an exhaustive textbook on urologic surgery. Candidates for ILC are all patients with moderate and severe voiding symptoms due to mechanical obstruction of the bladder outlet due to BPH who are otherwise candidates for surgical intervention, either transurethral or open. Because ILC has essentially no major morbidity and can be performed with local anesthesia, even high risk patients who are not candidates for transurethral resection of the prostate (TURP) can be considered for ILC treatment. Recurrent or residual BPH after previous prostate surgery, laser treatment, or microwave treatment can also be treated by ILC. The author details the surgical techniques used and the anticipated outcomes. ILC uses Nd:YAG or diode lasers, as they offer relatively deep penetration in water, efficient volumetric heating (permitting necrotic temperatures deep into tissues) and the ability to be delivered with flexible optical fibers. ILC can be performed using the transurethral approach or the percutaneous (perineal) approach. Complications include retrograde ejaculation (0 to 12 percent incidence), the need for repeat BPH treatment, transient irritative symptoms, urethral strictures, and uncomplicated urinary tract infections; no study reported any occurrence of impotence (erectile dysfunction) or sustained urinary incontinence. 8 figures. 5 tables. 15 references.

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Open Prostatectomy Source: in Graham, S.D., Jr., et al., eds. Glenn's Urologic Surgery. 5th ed. Philadelphia, PA: Lippincott Williams and Wilkins. 1998. p. 255-268. Contact: Available from Lippincott Williams and Wilkins. P.O. Box 1600, Hagerstown, MD 21741. (800) 638-3030 or (301) 714-2300. Fax (301) 824-7390. Website: lww.com. PRICE: $199.00 plus shipping and handling. ISBN: 0397587376. Summary: Open prostatectomy is the enucleation of the hyperplastic adenomatous growth of the prostate. This procedure does not involve total removal of the prostate. A tissue plane exists between the adenoma and the compressed true prostate, which is left intact. This chapter on open prostatectomy is from an exhaustive textbook on urologic surgery. The indications for prostatectomy include the following symptoms or findings secondary to prostatic obstruction: acute urinary retention; recurrent or persistent

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urinary tract infections; recurrent gross hematuria (blood in the urine); documented significant residual urine (in the bladder) after voiding, with or without overflow incontinence; pathophysiological changes of the kidneys, ureters, or bladder; abnormally low urinary flow rate; and normal flow rate with abnormally high intravesical voiding pressure and intractable symptoms such as nocturia, frequency, and urgency. The author describes three surgical approaches to the prostate: suprapubic, retropubic, and perineal. Complications can include hemorrhage, infections, incontinence of urine (uncommon), and urinary fistulas. The author concludes that enucleation of the enlarged prostatic adenoma by an open procedure is applicable in 5 to 10 percent of patients presenting with significant bladder outlet obstruction. The operative mortality and morbidity are minimal. 27 figures. 14 references. •

Endocrine Conditions Source: in Scully, C. and Cawson, R.A. Medical Problems in Dentistry. 4th ed. Woburn, MA: Butterworth-Heinemann. 1998. p. 263-297. Contact: Available from Butterworth-Heinemann. 225 Wildwood Avenue, Woburn, MA 01801-2041. (800) 366-2665 or (781) 904-2500. Fax (800) 446-6520 or (781) 933-6333. E-mail: [email protected]. Website: www.bh.com. PRICE: $110.00. ISBN: 0723610568. Summary: The endocrine system is a widespread system consisting of glands that exert their effects, usually at some distance, by means of chemicals (hormones) secreted into the circulation. Endocrine and nervous system mechanisms thus normally maintain homeostasis. This chapter on endocrine conditions is from a text that covers the general medical and surgical conditions relevant to the oral health care sciences. Topics include the hypothalamus and pituitary, posterior pituitary hypofunction, anterior pituitary hypo and hyperfunction, adrenocortical hypofunction, systemic corticosteroid therapy, acute adrenal insufficiency, adrenocortical hyperfunction (including Cushing's syndrome), hyperaldosteronism, pheochromocytoma, the thyroid, goiter, lingual thyroid, hypo and hyperthyroidism, the parathyroids, hypo and hyperparathyroidism, the pancreas, diabetes mellitus, hormone-secreting pancreatic tumors, the gonads, oral contraceptives, pregnancy, lactation, prematurity, menopause, hormone replacement therapy, multiple endocrine adenoma (MEA), and endocrine and metabolic manifestations of cancer and other diseases. For each condition, the authors discuss general aspects, diagnosis and management issues, dental aspects, and patient care strategies. The chapter includes a summary of the points covered. 1 appendix. 5 figures. 23 tables. 53 references.

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Diseases of the External Auditory Canal Source: in Canalis, R.F. and Lambert, P.R., eds. Ear: Comprehensive Otology. Philadelphia, PA: Lippincott Williams and Wilkins. 2000. p. 341-357. Contact: Available from Lippincott Williams and Wilkins. P.O. Box 1600, Hagerstown, MD 21741. (800) 638-3030. Fax (301) 223-2300. Website: www.lww.com. PRICE: $179.00 plus shipping and handling. ISBN: 078171558X. Summary: The external auditory canal (EAC) allows sound to reach the tympanic membrane and middle ear and protects those delicate structures. This chapter on diseases of the external auditory canal is from a textbook that offers complete coverage of the field of clinical otology (study of the ear). The book is oriented to serve both the otolaryngology resident as a practical learning tool and the practicing otolaryngologist as an updated reference source of clinical and basic information. This chapter covers the anatomy and physiology of the external auditory canal; hyperceruminosis (production

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of too much earwax, or cerumen); foreign bodies in the ear canal; dermatologic diseases, including essential pruritis and dermatitis; infectious diseases, including bacteria otitis externa, chronic stenosing external otitis (medial canal fibrosis), otomycosis, malignant external otitis, and furunculosis (acute localized otitis externa); trauma; acquired stenosis; tumor like lesions of the external auditory canal, including herniated temporomandibular joint soft tissue, inflammatory polyp, keratosis obturans, and cholesteatoma of the external auditory canal; benign tumors of the external auditory canal, including skin lesions, seborrheic keratosis, osteoma, exostosis, hemangioma, angiolymphoid hyperplasia with eosinophilia, and ceruminal gland adenoma; and malignant tumors of the external auditory canal, including basal cell carcinoma, squamous cell carcinoma, adenoidcystic carcinoma, and ceruminal gland adenocarcinoma. 24 figures. 1 table. 45 references. •

Cancer Prevention Strategies in Inflammatory Bowel Disease Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 257-261. Contact: Available from B.C. Decker Inc. 20 Hughson Street South, P.O. Box 620, L.C.D. 1 Hamilton, Ontario L8N 3K7. (905) 522-7017 or (800) 568-7281. Fax (905) 522-7839. Email: [email protected]. Website: www.bcdecker.com. PRICE: $129.00 plus shipping and handling. ISBN: 1550091220. Summary: This chapter on cancer prevention strategies in inflammatory bowel disease (IBD) is from the second edition of a book devoted to the details of medical, surgical, and supportive management of patients with Crohn's disease (CD) and ulcerative colitis (UC), together known as inflamatory bowel disease (IBD). Ulcerative colitis is associated with an increased risk of developing colorectal cancer (CRC). The risk of CRC is approximately 7 to 14 percent at 25 years of disease. Crohn's disease has a similar ageadjusted increased risk of developing CRC. The risks of developing CRC inUC correlate with increased disease duration and increased disease extent. Neoplasia (new tissue, which can include dysplasia, polyps, or cancer) usually is first evident after approximately 8 years of disease and is more likely to occur among patients with pancolitis than those with left-sided colitis. When cancer occurs in UC, it is more commonly found in the rectosigmoid. For CD, the increased risk is associated with disease duration and extent of 'at risk mucosa' as well. Patients with limited cecal disease are at limited risk for developing CRC and isolated ileal disease does not appear to increase the risk of CRC. The author reviews the pitfalls and benefits of dysplasia surveillance and offers suggestions for the clinical approach to patient counseling, surveillance timing, biopsy site and number, adenoma like masses, and the presence of pseudopolyps. Preventing or removing CRC at an early stage in UC patients is as advantageous as diagnosing early CRC in the general population. 2 figures. 12 references.

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Diseases of the Ampulla of Vater and Pancreas Source: in Sherlock, S.; Dooley, J. Diseases of the Liver and Biliary System. Malden, MA: Blackwell Science, Inc. 2002. p.639-646. Contact: Available from Blackwell Science, Inc. 350 Main Street, Commerce Place, Malden, MA 02148. (800) 215-1000 or (617) 388-8250. Fax (617) 388-8270. E-mail: [email protected]. Website: www.blackwell-science.com. PRICE: $178.95. ISBN: 0632055820.

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Summary: This chapter on diseases of the ampulla of Vater (the opening formed by the junction of the pancreatic and bile ducts as they open into the duodenum) and the pancreas is from a textbook that presents a comprehensive and up-to-date account of diseases of the liver and biliary system. Topics include peri-ampullary carcinoma (cancer), including benign villous adenoma of the ampulla of Vater, cystic tumors of the pancreas, and endocrine tumors of the pancreas; chronic pancreatitis; obstruction of the common bile duct by enlarged lymph glands; and other causes of extrinsic pressure on the common bile duct. 5 figures. 54 references. •

Hepatic Tumors Source: in Friedman, L.S. and Keeffe, E.B., eds. Handbook of Liver Disease. Philadelphia, PA: Churchill-Livingstone. 1998. p. 361-371. Contact: Available from W.B. Saunders Company. Book Order Fulfillment Department, 6277 Sea Harbor Drive, Orlando, FL 32887-4430. (800) 545-2522. Fax (800) 874-6418. Email: [email protected]. PRICE: $73.00 plus shipping and handling. ISBN: 0443055203. Summary: This chapter on hepatic tumors (benign and malignant) is from a comprehensive handbook in outline format that offers easy access to information on the full range of liver disorders and covers symptoms, signs, differential diagnoses, and treatments. Hemangioma of the liver is found in up to 1 percent of the normal population and is rarely of clinical consequence. Other benign tumors of the liver, including hepatic adenoma, are rare. Hepatic adenoma usually requires surgical resection because of the risks of rupture and the development of malignancy. In the presence of cirrhosis, hepatocellular carcinoma (HCC) accounts for approximately 75 percent of all liver tumors. The most important risk factors for development of HCC are cirrhosis and chronic hepatitis B virus, and hepatitis C virus infection. Although surgical resection or liver transplantation offers the best chance of curing HCC, few patients are suitable for surgery. Cholangiocarcinoma (CCC) is not usually associated with cirrhosis; CCC of the central type is often associated with primary sclerosing cholangitis and has a poor prognosis. 3 figures. 4 tables. 10 references. (AA-M).

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Salivary Gland Neoplasms Source: in Marx, R.E.; Stern, D. Oral and Maxillofacial Pathology: A Rationale for Diagnosis and Treatment. Chicago, IL: Quintessence Publishing Co, Inc. 2003. p.527-572. Contact: Available from Quintessence Publishing Co, Inc. 551 Kimberly Drive, Carol Stream, IL 60188-9981. (800) 621-0387 or (630) 682-3223. Fax (630) 682-3288. E-mail: [email protected]. Website: www.quintpub.com. PRICE: $ 399.00 plus shipping and handling. ISBN: 0867153903. Summary: This chapter on salivary gland neoplasms is from a clinically oriented guide for oral and maxillofacial surgeons and other advanced dental and medical specialists who deal with pathologies in the oral cavity, midface, and neck. Topics include pleomorphic adenoma, myoepithelioma, Warthin tumor, basal cell adenoma, canalicular andenoma, oncocytoma, inverted ductal papilloma, intraductal papilloma, sialadenoma papilliferum, sebaceous adenoma and sebaceous lymphadenoma, mucoepidermoid carcinoma, central mucoepidermoid carcinoma, adenoid cystic carcinoma, polymorphous low-grade adenocarcinoma, acinic cell carcinoma, and pleomorphic adenoma. For each condition, the authors discuss clinical presentation and pathogenesis, differential diagnosis, diagnostic work-up, histopathology, treatment, and

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prognosis. The authors also describe transoral minor salivary gland tumor surgery and surgeries of the parotid gland. Full-color photographs illustrate the chapter. 54 figures. •

Kidney Source: in MacLennan, G.T.; Resnick, M.I.; Bostwick, D.G. Pathology for Urologists. New York, NY: Elsevier Science, Inc. 2003. p. 1-32. Contact: Available from Elsevier Science, Inc. Journal Information Center, 655 Avenue of the Americas, New York, NY 10010. (212) 633-3750. Fax (212) 633-3764. Website: www.elsevier.com. PRICE: $149.00. ISBN: 721600913. Summary: This chapter on the kidney is from a pathology textbook that explores the full range of urology, including congenital, hereditary, inflammatory, degenerative, and benign and malignant neoplastic disorders found in the adrenal glands, kidney, renal pelvis, ureter, bladder, prostate, seminal vesicles, urethra, spermatic cord, testis, testicular adnexal, penis, and scrotum. The chapter includes full-color photographs of gross and microscopic pathologic specimens, representing virtually all of the common and rare entities seen in practice. Specific disorders covered are unilateral renal (kidney) agenesis, bilateral renal agenesis, hypoplasia, supernumerary kidney, simple ectopic kidney, crossed ectopic kidney, superior ectopic kidney, horseshoe kidney, hereditary cystic kidney diseases, acute pyelonephritis, chronic pyelonephritis, papillary necrosis, xanthogranulomatous pyelonephritis, malacoplakia, tuberculosis, renal adenoma, renal oncocytoma, metanephric adenoma, cystic nephroma, renal cell carcinoma (cancer), carcinoid tumor, small cell carcinoma, benign soft tissue neoplasms of kidney, renal sarcoma, lymphoma, tumors metastatic to the kidney, nephroblastoma (Wilms' tumor), cystic partially differentiated nephroblastoma, mesoblastic nephroma, clear cell sarcoma of kidney, and rhabdoid tumor of kidney. Each photograph is accompanied by a descriptive text section. The text also includes explanations of the most current neoplasm classification and staging systems. 82 figures. 1 table.

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Chapter 84: Tumors of Skin Appendages Source: in Freedberg, I.M., et al., eds. Fitzpatrick's Dermatology in General Medicine. 5th ed., Vol. 1. New York, NY: McGraw-Hill. 1999. p. 890-914. Contact: Available from McGraw-Hill Customer Services. P.O. Box 548, Blacklick, OH 43004-0548. (800) 262-4729 or (877) 833-5524. Fax (614) 759-3749 or (614) 759-3641. E-mail: [email protected]. PRICE: $395.00 plus shipping and handling. ISBN: 0070219435. Summary: This chapter provides health professionals with information on benign and malignant tumors of skin appendages. Many benign tumors of the skin are classified as skin appendage tumors because they display certain structural similarities to the eccrine or apocrine glands, the hair follicle, the sebaceous gland, or the epidermis. Benign tumors with eccrine differentiation include eccrine nevus, syringoma, eccrine hidrocystoma, eccrine poroma, eccrine spiradenoma, clear cell hidradenoma, chondroid syringoma, and syringocystadenoma papilliferum. Benign tumors with apocrine differentiation include apocrine nevus, apocrine hidrocystoma, Moll's gland cyst, hidradenoma papilliferum, and cylindroma. Benign tumors with hair differentiation include pigmented hairy nevus, trichofolliculoma, multiple trichoepithelioma, solitary trichoepithelioma, desmoplastic trichoepithelioma, pilomatricoma, steatocystoma multiplex, trichilemmal cyst, proliferating trichilemmal tumor or cyst, and trichilemmoma. Benign tumors with sebaceous differentiation include nevus sebaceous, senile sebaceous hyperplasia and Fordyce's disease, sebaceous adenoma, and sebaceous

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epithelioma. Benign tumors with epidermal differentiation include epidermal or epidermoid cyst, milium, and dermoid cyst. Malignant tumors with eccrine differentiation include malignant eccrine poroma, malignant eccrine spiradenoma, and malignant clear cell hidradenoma. Other malignant appendage tumors include carcinoma of eccrine, apocrine, and sebaceous glands. The chapter describes the features of these benign and malignant tumors and provides histopathological information on many of them. 39 figures, 5 tables, and 129 references. •

Gastric Polyps Source: in Snape, W.J., ed. Consultations in Gastroenterology. Philadelphia, PA: W.B. Saunders Company. 1996. p. 300-304. Contact: Available from W.B. Saunders Company. Order Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887. (800) 545-2522. Fax (800) 874-6418 or (407) 352-3445. PRICE: $125.00. ISBN: 0721646700. Summary: This chapter, from a gastroenterology yearbook, covers gastric polyps, focusing on polyps of epithelial origin, i.e., hyperplastic and adenomatous polyps. Topics include incidence, pathology, clinical presentation, relation to carcinoma, diagnosis, management, therapy, deciding which polyps to remove, and patient followup of gastric polyps removed and not removed. The author notes that large polyps (greater than 2 cm) are at risk for development of gastric carcinoma. The larger the polyp, the greater the risk of dysplasia, a precancerous state. Although hyperplastic polyps carry a very low risk for cancer, malignancy can occur in a polyp as it enlarges and transforms to an adenoma. Adenomatous polyps are premalignant and tend to increase in size, which carries an increased risk of cancer. Additionally, cancer may also develop in nonadenomatous gastric tissue. Endoscopic followup of both hyperplastic and adenomatous polyps is important. Age greater than 50 years appears to be a risk factor for the development of dysplasia and carcinoma in polyps. One section of the chapter presents a discussion of endoscopic polypectomy. 21 references. (AA-M).

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Diseases of the External Ear Source: in Ballenger, J.J.; Snow, J.B., Jr., eds. Otorhinolaryngology: Head and Neck Surgery. 15th ed. Baltimore, MD: Williams and Wilkins. 1996. p. 974-988. Contact: Available from Williams and Wilkins. P.O. Box 64686, Baltimore, MD 212644786. (800) 638-0672; Fax (800) 447-8438. PRICE: $179.00 plus shipping and handling. ISBN: 0683003151. Summary: This chapter, from a medical textbook on otorhinolaryngology, summarizes diseases of the external ear. Topics covered include problems of the auricle, including trauma, frostbite, and perichondritis; tumors of the external ear; benign tumors of the auricle, including angiomas, cysts, fibroma, papilloma, and Winkler's disease; the external auditory canal, including cerumen (earwax), foreign bodies, external otitis, malignant external otitis, chronic stenosing external otitis, and keratosis obliterans; benign tumors of the external auditory canal, including exostosis and adenoma; benign tumors of the middle ear, including glomus jugulare tumor; and malignant tumors of the ear, including carcinoma, ceruminoma, cystic adenoid carcinoma (Brooke's tumor), and malignant melanoma. 17 figures. 19 references.

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Neoplastic Cell Growth Source: in Miller, R.L., et al. General and Oral Pathology for the Dental Hygienist. St. Louis, MO: Mosby-Year Book, Inc. 1995. p. 87-105. Contact: Available from Mosby-Year Book, Inc. 11830 Westline Industrial Drive, St. Louis, MO 63146-9934. (800) 426-4545 or (314) 872-8370; Fax (800) 535-9935 or (314) 4321380; E-mail: [email protected]; http://www.mosby.com. PRICE: $43.00 plus shipping and handling. ISBN: 0801670241. Stock Number 07024. Summary: This chapter, from a textbook on pathology for dental hygiene students, covers neoplastic cell growth. Topics covered include the role of repressors and accelerators in regulating cell growth; the differences between neoplasm, carcinoma, sarcoma, cancer, adenoma, and tumor; the properties of benign and malignant neoplasms, including the clinical manifestations of both, the histopathologic changes of malignant tissues, and the significance of these changes; the etiology of neoplasia, including chemicals, viruses, radiation, other environmental factors, genetic predisposition, hormonal factors, immune system factors, nutritional factors, and aging; theories of the pathogenesis of neoplasia; the course of malignancy; the prognosis of cancer based on stage, histologic features, and tissue of origin; treatment options for malignancy; and the common routes of metastasis for cancers. The chapter includes a list of learning objectives; illustrative case studies; and recommended readings. 2 figures. 2 tables.

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Benign Tumors Source: in Bork, K., et al. Diseases of the Oral Mucosa and the Lips. Orlando, FL: W.B. Saunders Company. 1993. p. 293-320. Contact: Available from W.B. Saunders Company. Order Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887-4430. (800) 545-2522 (individuals) or (800) 782-4479 (schools); Fax (800) 874-6418 or (407) 352-3445; http://www.wbsaunders.com. PRICE: $99.00 plus shipping and handling. ISBN: 0721640397. Summary: This lengthy chapter, from a textbook on diseases of the oral mucosa and the lips, discusses benign tumors. Topics include epulis, pyogenic granuloma, epulis gravidarum, peripheral fibromas, peripheral giant cell granuloma, congenital gingival granular cell tumor (congenital epulis), traumatic fibroma, oral squamous papilloa, oral papillomatosis, atypical fibrous histiocytoma, keloid and hypertrophic scar, fibromatosis, lipomas, juvenile xanthogranuloma, verruciform xanthoma, myxomas, chondromas and osteomas, hemangiomas, glomus tumor, other vascular tumors, lymphangiomas, myomas (leiomyoma and rhabdomyoma), neural tumors, granular cell tumor, pigmented lesions (labial and oral melanotic macules, melanocystic nevi or moles, Spitz nevus, blue nevus, combined nevus, nevus of Ota, melanotic neuroectodermal tumor of infancy), keratoacanthoma, epidermal nevus, malanoacanthoma, warty dyskeratoma, benign adnexal tumors, chondroid syringoma, sebaceous adenoma, and salivary gland neoplasms. For each topic, the authors describe the clinical features and present brief therapeutic recommendations. Full-color photographs illustrate the chapter; references are provided for most sections. 52 figures. 73 references.

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Liver Tumors Source: in Beckingham, I.J., ed. ABC of Liver, Pancreas and Gallbladder. London, UK: BMJ Publishing Group. 2001. p.25-28.

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Contact: Available from BMJ Publishing Group. BMA Books, BMA House, Tavistock Square, London WCIH 9JR. Fax 44 (0)20 7383 6402. E-mail: [email protected]. Website: www.bmjbooks.com. PRICE: Contact publisher for price. ISBN: 0727915312. Summary: Tumors of the liver may be cystic or solid, benign (harmless) or malignant (cancerous). Most are asymptomatic, with patients having normal liver function, and they are increasingly discovered incidentally during ultrasound or computed tomography (CT scan). This chapter on liver tumors is from an atlas of the liver, pancreas and gallbladder. Topics include cystic liver lesions; benign tumors, including hemangiomas, liver cell adenoma and focal nodular hyperplasia; malignant tumors, including hepatocellular carcinoma (HCC), metastatic tumors, and colorectal liver metastases; and liver resection. The authors conclude that modern imaging, combined with recent technical advances in liver surgery, can now offer many patients safe and potentially curative resections for malignant, as well as benign, conditions affecting the liver. The chapter concludes with summary points of the concepts discussed. 8 figures. 1 table. 3 references. •

Approach to the Patient with a Liver Mass Source: in Textbook of Gastroenterology. 4th ed. [2-volume set]. Hagerstown, MD: Lippincott Williams and Wilkins. 2003. p. 973-982. Contact: Available from Lippincott Williams and Wilkins. P.O. Box 1600, Hagerstown, MD 21741. (800) 638-6423. Fax: (301) 223-2400. Website: www.lww.com. PRICE: $289.00. ISBN: 781728614. Summary: With increasing use of imaging modalities for evaluation of various abdominal conditions, more liver masses are being recognized. These lesions may be small or large and may or may not be the cause of the patient's symptoms. Although most of the incidentally noted masses are benign, a definitive diagnosis has to be established to reassure the patient and also to be certain that a radiologically observed lesion is not malignant. This chapter is devoted to the most common liver masses found in clinical practice and the advantages and disadvantages of the various diagnostic modalities. The chapter is from a lengthy, two-volume textbook that integrates the various demands of science, technology, expanding information, good judgment, and common sense into the diagnosis and management of gastrointestinal patients. Topics include cavernosa hemangioma, focal nodular hyperplasia, nodular regenerative hyperplasia, hepatic adenoma, cystic lesions, hemangioendothelioma, angiomyolipomas, focal fatty infiltrate, inflammatory pseudotumor, laparoscopy, and recommended clinical approach. 6 figures. 2 tables. 98 references.

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CHAPTER 6. PERIODICALS AND NEWS ON ADENOMA Overview In this chapter, we suggest a number of news sources and present various periodicals that cover adenoma.

News Services and Press Releases One of the simplest ways of tracking press releases on adenoma is to search the news wires. In the following sample of sources, we will briefly describe how to access each service. These services only post recent news intended for public viewing. PR Newswire To access the PR Newswire archive, simply go to http://www.prnewswire.com/. Select your country. Type “adenoma” (or synonyms) into the search box. You will automatically receive information on relevant news releases posted within the last 30 days. The search results are shown by order of relevance. Reuters Health The Reuters’ Medical News and Health eLine databases can be very useful in exploring news archives relating to adenoma. While some of the listed articles are free to view, others are available for purchase for a nominal fee. To access this archive, go to http://www.reutershealth.com/en/index.html and search by “adenoma” (or synonyms). The following was recently listed in this archive for adenoma: •

UK study shows big variation in adenoma detection rates Source: Reuters Medical News Date: May 18, 2004

•

ODC polymorphism and aspirin use tied to reduced risk of adenoma recurrence Source: Reuters Medical News Date: June 16, 2003

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•

Beta-carotene use may promote adenoma recurrence in smokers or drinkers Source: Reuters Medical News Date: May 20, 2003

•

PPAR-gamma ligands inhibit pituitary adenoma growth Source: Reuters Industry Breifing Date: May 12, 2003

•

Aspirin prevents colorectal adenomas in patients with previous neoplasia Source: Reuters Industry Breifing Date: March 05, 2003

•

Multiple colorectal adenomas often linked to biallelic MYH mutation Source: Reuters Medical News Date: February 27, 2003

•

Fiber intake does not protect against adenoma recurrence Source: Reuters Medical News Date: November 05, 2002

•

Nephrogenic adenomas in renal-transplant recipients derived from donor renal tubular cells Source: Reuters Medical News Date: August 29, 2002

•

Large or multiple adenomas at first colonoscopy linked with recurrence Source: Reuters Medical News Date: July 29, 2002

•

Low-dose aspirin reduces risk of recurrent large bowel adenomas Source: Reuters Industry Breifing Date: April 08, 2002

•

Sulindac does not prevent adenomas in familial adenomatous polyposis Source: Reuters Medical News Date: April 03, 2002

•

Long-term sulindac therapy effective in familial adenomatous polyposis Source: Reuters Medical News Date: March 26, 2002

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Alcoholism increases risk of high-risk adenomas and colon cancer Source: Reuters Medical News Date: January 07, 2002

•

Risk factors for recurrence of advanced colonic adenomas identified Source: Reuters Medical News Date: April 20, 2001

•

Holmium laser enucleation safe and effective for large prostatic adenomas Source: Reuters Medical News Date: February 12, 2001

•

Physicians lax in screening patients with family history of adenomatous polyps Source: Reuters Medical News Date: May 22, 2000

•

Slow-release lanreotide suppresses thyrotropin secretion by pituitary adenomas Source: Reuters Medical News Date: April 21, 2000

Periodicals and News

•

Sigmoidoscopic screening for colorectal adenomas in elderly not highly effective Source: Reuters Medical News Date: December 27, 1999

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Medical management a feasible option for aldosterone-producing adenomas Source: Reuters Medical News Date: July 23, 1999

•

Follow-up of distal colonic tubular adenoma should not be based on adenoma size Source: Reuters Medical News Date: May 06, 1999

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Adenomatous polyposis coli mutation increases cancer risk in Ashkenazi Jews Source: Reuters Medical News Date: March 09, 1999

•

Features of pituitary adenoma headache described Source: Reuters Medical News Date: February 10, 1999

•

Surgery improves headache in most patients with pituitary adenomas Source: Reuters Medical News Date: January 15, 1999

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Calcium supplementation reduces risk of recurrent colorectal adenomas Source: Reuters Medical News Date: January 14, 1999

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Aberrant crypt foci: precursors of adenomas and colon cancers Source: Reuters Medical News Date: October 29, 1998

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Small, single adenomas seen on sigmoidoscopy not an indication for colonoscopy Source: Reuters Medical News Date: August 17, 1998

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Colonic colonization by E. coli found in patients with adenoma and carcinoma Source: Reuters Medical News Date: August 10, 1998

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First-degree relative with colorectal adenoma: high risk for colon cancer Source: Reuters Medical News Date: June 01, 1998

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Aspirin Prevents Spontaneous Intestinal Adenomas In Mice Source: Reuters Medical News Date: May 06, 1998

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Mechanism Of Transition From Adenoma To Carcinoma Described Source: Reuters Medical News Date: March 12, 1998

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Colonoscopy Recommended For Patients With Diminutive Or Small Rectosigmoid Adenomas Source: Reuters Medical News Date: January 02, 1997

•

Adenoma Risk High After Curative Resection Of Colorectal Cancer Source: Reuters Medical News Date: October 24, 1996

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Flat Adenomas Possible Precursor Of Colon Cancer in Patients With HNPCC Source: Reuters Medical News Date: February 29, 1996

•

Exercise Protects Against Colorectal Adenomas Source: Reuters Medical News Date: November 13, 1995 The NIH

Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “adenoma” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “adenoma” (or synonyms). If you know the name of a company that is relevant to adenoma, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/.

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BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “adenoma” (or synonyms).

Academic Periodicals covering Adenoma Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to adenoma. In addition to these sources, you can search for articles covering adenoma that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

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CHAPTER 7. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.

U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for adenoma. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a nonprofit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI Advice for the Patient can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with adenoma. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The

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following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to adenoma: Celecoxib •

Systemic - U.S. Brands: Celebrex http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203736.html

Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.

Mosby’s Drug Consult Mosby’s Drug Consult database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee.

Researching Orphan Drugs Although the list of orphan drugs is revised on a daily basis, you can quickly research orphan drugs that might be applicable to adenoma by using the database managed by the National Organization for Rare Disorders, Inc. (NORD), at http://www.rarediseases.org/. Scroll down the page, and on the left toolbar, click on “Orphan Drug Designation Database.” On this page (http://www.rarediseases.org/search/noddsearch.html), type “adenoma” (or synonyms) into the search box, and click “Submit Query.” When you receive your results, note that not all of the drugs may be relevant, as some may have been withdrawn from orphan status. Write down or print out the name of each drug and the relevant contact information. From there, visit the Pharmacopeia Web site and type the name of each orphan

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drug into the search box at http://www.nlm.nih.gov/medlineplus/druginformation.html. You may need to contact the sponsor or NORD for further information. NORD conducts “early access programs for investigational new drugs (IND) under the Food and Drug Administration’s (FDA’s) approval ‘Treatment INDs’ programs which allow for a limited number of individuals to receive investigational drugs before FDA marketing approval.” If the orphan product about which you are seeking information is approved for marketing, information on side effects can be found on the product’s label. If the product is not approved, you may need to contact the sponsor. The following is a list of orphan drugs currently listed in the NORD Orphan Drug Designation Database for adenoma: •

FGN-1 http://www.rarediseases.org/nord/search/nodd_full?code=487

If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.

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APPENDICES

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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.

NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute10: •

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

•

National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/

•

National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html

•

National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25

•

National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm

•

National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm

•

National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375

•

National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/

10

These publications are typically written by one or more of the various NIH Institutes.

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•

National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm

•

National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/

•

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm

•

National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm

•

National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/

•

National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/

•

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm

•

National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html

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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm

•

National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm

•

National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm

•

National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html

•

National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm

•

Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp

•

National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/

•

National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp

•

Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html

•

Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm

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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.11 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:12 •

Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html

•

HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html

•

NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html

•

Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/

•

Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html

•

Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html

•

Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/

•

Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html

•

Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html

•

Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html

•

MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html

11 Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 12 See http://www.nlm.nih.gov/databases/databases.html.

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•

Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html

•

Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html

The NLM Gateway13 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.14 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “adenoma” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category. Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total

Items Found 67798 219 474 4 305 68800

HSTAT15 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.16 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.17 Simply search by “adenoma” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

13

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.

14

The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 15 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 16 17

The HSTAT URL is http://hstat.nlm.nih.gov/.

Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.

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Coffee Break: Tutorials for Biologists18 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.19 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.20 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •

CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.

•

Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.

18 Adapted 19

from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 20 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.

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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on adenoma can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.

Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to adenoma. Due to space limitations, these sources are listed in a concise manner. Do not hesitate to consult the following sources by either using the Internet hyperlink provided, or, in cases where the contact information is provided, contacting the publisher or author directly. The National Institutes of Health The NIH gateway to patients is located at http://health.nih.gov/. From this site, you can search across various sources and institutes, a number of which are summarized below. Topic Pages: MEDLINEplus The National Library of Medicine has created a vast and patient-oriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages” which list links to available materials relevant to adenoma. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html. From there you can either search using the alphabetical index or browse by broad topic areas. Recently, MEDLINEplus listed the following when searched for “adenoma”:

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Adrenal Gland Disorders http://www.nlm.nih.gov/medlineplus/adrenalglanddisorders.html Brain Cancer http://www.nlm.nih.gov/medlineplus/braincancer.html Colonic Polyps http://www.nlm.nih.gov/medlineplus/colonicpolyps.html Colorectal Cancer http://www.nlm.nih.gov/medlineplus/colorectalcancer.html Pituitary Disorders http://www.nlm.nih.gov/medlineplus/pituitarydisorders.html You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The National Guideline Clearinghouse™ The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search this site located at http://www.guideline.gov/ by using the keyword “adenoma” (or synonyms). The following was recently posted: •

American Cancer Society guidelines on screening and surveillance for the early detection of adenomatous polyps and colorectal cancer-update 2003. In: American Cancer Society guidelines for the early detection of cancer, 2003 Source: American Cancer Society - Disease Specific Society; 2001 (revised 2003 Jan-Feb); 17 pages http://www.guideline.gov/summary/summary.aspx?doc_id=4006&nbr=3135&a mp;string=adenoma

•

Management of colonic polyps and adenomas Source: Society for Surgery of the Alimentary Tract, Inc - Medical Specialty Society; 1996 (revised 2000); 4 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2176&nbr=1402&a mp;string=adenoma The NIH Search Utility

The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate

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in some way to adenoma. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats

•

Family Village: http://www.familyvillage.wisc.edu/specific.htm

•

Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/

•

Med Help International: http://www.medhelp.org/HealthTopics/A.html

•

Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/

•

Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/

•

WebMDHealth: http://my.webmd.com/health_topics

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to adenoma. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with adenoma. The National Health Information Center (NHIC) The National Health Information Center (NHIC) offers a free referral service to help people find organizations that provide information about adenoma. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine.

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To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “adenoma” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information. The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “adenoma”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” Type “adenoma” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “adenoma” (or a synonym) into the search box, and click “Submit Query.”

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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.

Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.21

Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.

Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of

21

Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.

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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)22: •

Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/

•

Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)

•

Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm

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California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html

•

California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html

•

California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/

•

California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp

•

California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html

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California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/

•

California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/

•

California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/

•

California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html

•

California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/

•

Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/

•

Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/

•

Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/

22

Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.

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•

Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml

•

Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm

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Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html

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Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm

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Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp

•

Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/

•

Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm

•

Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html

•

Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/

•

Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm

•

Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/

•

Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/

•

Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/

•

Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm

•

Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html

•

Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm

•

Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/

•

Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/

•

Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10

•

Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/

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•

Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html

•

Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp

•

Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp

•

Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/

•

Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html

•

Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm

•

Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp

•

Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/

•

Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html

•

Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/

•

Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm

•

Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/

•

Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html

•

Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm

•

Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330

•

Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)

•

National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html

•

National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/

•

National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/

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Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm

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New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/

•

New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm

•

New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm

•

New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/

•

New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html

•

New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/

•

New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html

•

New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/

•

Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm

•

Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp

•

Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/

•

Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/

•

Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml

•

Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html

•

Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html

•

Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml

•

Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp

•

Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm

•

Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/

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South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp

•

Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/

•

Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/

•

Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72

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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •

ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html

•

MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp

•

Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/

•

Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html

•

On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/

•

Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp

•

Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm

Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a).

Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

•

MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

•

Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

•

Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

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ADENOMA DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 1,2-Dimethylhydrazine: A DNA alkylating agent that has been shown to be a potent carcinogen and is widely used to induce colon tumors in experimental animals. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Ablation: The removal of an organ by surgery. [NIH] Accommodation: Adjustment, especially that of the eye for various distances. [EU] Acetaldehyde: A colorless, flammable liquid used in the manufacture of acetic acid, perfumes, and flavors. It is also an intermediate in the metabolism of alcohol. It has a general narcotic action and also causes irritation of mucous membranes. Large doses may cause death from respiratory paralysis. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acidosis: A pathologic condition resulting from accumulation of acid or depletion of the alkaline reserve (bicarbonate content) in the blood and body tissues, and characterized by an increase in hydrogen ion concentration. [EU] Acne: A disorder of the skin marked by inflammation of oil glands and hair glands. [NIH] Acne Vulgaris: A chronic disorder of the pilosebaceous apparatus associated with an increase in sebum secretion. It is characterized by open comedones (blackheads), closed comedones (whiteheads), and pustular nodules. The cause is unknown, but heredity and age are predisposing factors. [NIH] Actin: Essential component of the cell skeleton. [NIH] Acupuncture Anesthesia: Insertion of acupuncture needles at specific points in the body to block the afferent nerve impulses from reaching the brain, thus producing the loss of sensation of pain. The technique is used in performing surgery. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [NIH] Adenoma: A benign epithelial tumor with a glandular organization. [NIH] Adenoma, Chromophobe: A benign tumor of the anterior pituitary in which the cells do not stain with acidic or basic dyes. [NIH] Adenomatous Polyposis Coli: An autosomal dominant polyposis syndrome in which the colon contains few to thousands of adenomatous polyps, often occurring by age 15 to 25.

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[NIH]

Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenovirus: A group of viruses that cause respiratory tract and eye infections. Adenoviruses used in gene therapy are altered to carry a specific tumor-fighting gene. [NIH] Adipocytes: Fat-storing cells found mostly in the abdominal cavity and subcutaneous tissue. Fat is usually stored in the form of tryglycerides. [NIH] Adipose Tissue: Connective tissue composed of fat cells lodged in the meshes of areolar tissue. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adnexa: The appendages of the eye, as the lacrimal apparatus, the eyelids, and the extraocular muscles. [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal Glands: Paired glands situated in the retroperitoneal tissues at the superior pole of each kidney. [NIH] Adrenal insufficiency: The reduced secretion of adrenal glands. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]

Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]

Age of Onset: The age or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual. [NIH]

Dictionary 199

Age-Adjusted: Summary measures of rates of morbidity or mortality in a population using statistical procedures to remove the effect of age differences in populations that are being compared. Age is probably the most important and the most common variable in determining the risk of morbidity and mortality. [NIH] Agenesis: Lack of complete or normal development; congenital absence of an organ or part. [NIH]

Agglutinins: Substances, usually of biological origin, that cause cells or other organic particles to aggregate and stick to each other. They also include those antibodies which cause aggregation or agglutination of a particulate or insoluble antigen. [NIH] Aggravation: An increasing in seriousness or severity; an act or circumstance that intensifies, or makes worse. [EU] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Alcohol Dehydrogenase: An enzyme that catalyzes reversibly the final step of alcoholic fermentation by reducing an aldehyde to an alcohol. In the case of ethanol, acetaldehyde is reduced to ethanol in the presence of NADH and hydrogen. The enzyme is a zinc protein which acts on primary and secondary alcohols or hemiacetals. EC 1.1.1.1. [NIH] Aldosterone: (11 beta)-11,21-Dihydroxy-3,20-dioxopregn-4-en-18-al. A hormone secreted by the adrenal cortex that functions in the regulation of electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. [NIH] Alertness: A state of readiness to detect and respond to certain specified small changes occurring at random intervals in the environment. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkylating Agents: Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. They have also been used as components in poison gases. [NIH]

Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allelic Imbalance: A situation where one member (allele) of a gene pair is lost (loss of heterozygosity) or amplified. [NIH]

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Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Allergic Rhinitis: Inflammation of the nasal mucous membrane associated with hay fever; fits may be provoked by substances in the working environment. [NIH] Allylamine: Possesses an unusual and selective cytotoxicity for vascular smooth muscle cells in dogs and rats. Useful for experiments dealing with arterial injury, myocardial fibrosis or cardiac decompensation. [NIH] Alopecia: Absence of hair from areas where it is normally present. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alpha-1: A protein with the property of inactivating proteolytic enzymes such as leucocyte collagenase and elastase. [NIH] Alpha-fetoprotein: AFP. A protein normally produced by a developing fetus. AFP levels are usually undetectable in the blood of healthy nonpregnant adults. An elevated level of AFP suggests the presence of either a primary liver cancer or germ cell tumor. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Alveolar Process: The thickest and spongiest part of the maxilla and mandible hollowed out into deep cavities for the teeth. [NIH] Amenorrhea: Absence of menstruation. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Ampulla: A sac-like enlargement of a canal or duct. [NIH] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH]

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Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Androgens: A class of sex hormones associated with the development and maintenance of the secondary male sex characteristics, sperm induction, and sexual differentiation. In addition to increasing virility and libido, they also increase nitrogen and water retention and stimulate skeletal growth. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anemic: Hypoxia due to reduction of the oxygen-carrying capacity of the blood as a result of a decrease in the total hemoglobin or an alteration of the hemoglobin constituents. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Angiolymphoid Hyperplasia with Eosinophilia: Solitary or multiple benign cutaneous nodules comprised of immature and mature vascular structures intermingled with endothelial cells and a varied infiltrate of eosinophils, histiocytes, lymphocytes, and mast cells. [NIH] Animal Husbandry: The science of breeding, feeding, and care of domestic animals; includes housing and nutrition. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Anovulation: Suspension or cessation of ovulation in animals and humans. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Anterior chamber: The space in front of the iris and behind the cornea. [NIH] Anthropometry: The technique that deals with the measurement of the size, weight, and proportions of the human or other primate body. [NIH] Antiallergic: Counteracting allergy or allergic conditions. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH]

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Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticarcinogenic: Pertaining to something that prevents or delays the development of cancer. [NIH] Anticarcinogenic Agents: Agents that reduce the frequency or rate of spontaneous or induced tumors independently of the mechanism involved. They differ from antineoplastic agents in that they prevent neoplasms from forming. The anticarcinogenic substances can be divided into three categories. The first consists of compounds that prevent the formation of carcinogens from precursor substances. The second group consists of "blocking agents" which inhibit carcinogenesis by preventing carcinogenic agents from reaching or reacting with critical target sites in the tissues. The third group is the "suppressor agents" which act by suppression of expression of neoplasia in cells previously exposed to carcinogens that would otherwise cause neoplasms. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Antidiuretic: Suppressing the rate of urine formation. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [NIH] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antineoplastic Agents: Substances that inhibit or prevent the proliferation of neoplasms. [NIH]

Antipruritic: Relieving or preventing itching. [EU] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Apnea: A transient absence of spontaneous respiration. [NIH] Apocrine Glands: Large, branched, specialized sweat glands that empty into the upper portion of a hair follicle instead of directly onto the skin. [NIH]

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Apolipoproteins: The protein components of lipoproteins which remain after the lipids to which the proteins are bound have been removed. They play an important role in lipid transport and metabolism. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [NIH] Aqueous: Having to do with water. [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Asbestos: Fibrous incombustible mineral composed of magnesium and calcium silicates with or without other elements. It is relatively inert chemically and used in thermal insulation and fireproofing. Inhalation of dust causes asbestosis and later lung and gastrointestinal neoplasms. [NIH] Ascites: Accumulation or retention of free fluid within the peritoneal cavity. [NIH] Aspiration: The act of inhaling. [NIH] Aspirin: A drug that reduces pain, fever, inflammation, and blood clotting. Aspirin belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is also being studied in cancer prevention. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Asymptomatic: Having no signs or symptoms of disease. [NIH] Attenuated: Strain with weakened or reduced virulence. [NIH] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Auditory: Pertaining to the sense of hearing. [EU] Autodigestion: Autolysis; a condition found in disease of the stomach: the stomach wall is digested by the gastric juice. [NIH] Azoxymethane: A potent carcinogen and neurotoxic compound. It is particularly effective in inducing colon carcinomas. [NIH]

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Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial toxin: A toxic substance, made by bacteria, that can be modified to kill specific tumor cells without harming normal cells. [NIH] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Bacteriuria: The presence of bacteria in the urine with or without consequent urinary tract infection. Since bacteriuria is a clinical entity, the term does not preclude the use of urine/microbiology for technical discussions on the isolation and segregation of bacteria in the urine. [NIH] Basal cell carcinoma: A type of skin cancer that arises from the basal cells, small round cells found in the lower part (or base) of the epidermis, the outer layer of the skin. [NIH] Basal cells: Small, round cells found in the lower part (or base) of the epidermis, the outer layer of the skin. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Basophil: A type of white blood cell. Basophils are granulocytes. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Benign prostatic hyperplasia: A benign (noncancerous) condition in which an overgrowth of prostate tissue pushes against the urethra and the bladder, blocking the flow of urine. Also called benign prostatic hypertrophy or BPH. [NIH] Benign tumor: A noncancerous growth that does not invade nearby tissue or spread to other parts of the body. [NIH] Benzo(a)pyrene: A potent mutagen and carcinogen. It is a public health concern because of its possible effects on industrial workers, as an environmental pollutant, an as a component of tobacco smoke. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones. [NIH] Bile duct: A tube through which bile passes in and out of the liver. [NIH] Bile Pigments: Pigments that give a characteristic color to bile including: bilirubin,

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biliverdine, and bilicyanin. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Biliary Tract: The gallbladder and its ducts. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Bioassay: Determination of the relative effective strength of a substance (as a vitamin, hormone, or drug) by comparing its effect on a test organism with that of a standard preparation. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biological Transport: The movement of materials (including biochemical substances and drugs) across cell membranes and epithelial layers, usually by passive diffusion. [NIH] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biopsy specimen: Tissue removed from the body and examined under a microscope to determine whether disease is present. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alteration may be either nonsynthetic (oxidation-reduction, hydrolysis) or synthetic (glucuronide formation, sulfate conjugation, acetylation, methylation). This also includes metabolic detoxication and clearance. [NIH] Bladder: The organ that stores urine. [NIH] Blastocyst: The mammalian embryo in the post-morula stage in which a fluid-filled cavity, enclosed primarily by trophoblast, contains an inner cell mass which becomes the embryonic disc. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in

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an insoluble fibrin clot. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Body Composition: The relative amounts of various components in the body, such as percent body fat. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Body Mass Index: One of the anthropometric measures of body mass; it has the highest correlation with skinfold thickness or body density. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Boron: A trace element with the atomic symbol B, atomic number 5, and atomic weight 10.81. Boron-10, an isotope of boron, is used as a neutron absorber in boron neutron capture therapy. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Brain Ischemia: Localized reduction of blood flow to brain tissue due to arterial obtruction or systemic hypoperfusion. This frequently occurs in conjuction with brain hypoxia. Prolonged ischemia is associated with brain infarction. [NIH] Breeding: The science or art of changing the constitution of a population of plants or animals through sexual reproduction. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bronchoalveolar Lavage: Washing out of the lungs with saline or mucolytic agents for diagnostic or therapeutic purposes. It is very useful in the diagnosis of diffuse pulmonary infiltrates in immunosuppressed patients. [NIH] Budesonide: A glucocorticoid used in the management of asthma, the treatment of various skin disorders, and allergic rhinitis. [NIH] Butyric Acid: A four carbon acid, CH3CH2CH2COOH, with an unpleasant odor that occurs in butter and animal fat as the glycerol ester. [NIH]

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Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. [NIH] Calcification: Deposits of calcium in the tissues of the breast. Calcification in the breast can be seen on a mammogram, but cannot be detected by touch. There are two types of breast calcification, macrocalcification and microcalcification. Macrocalcifications are large deposits and are usually not related to cancer. Microcalcifications are specks of calcium that may be found in an area of rapidly dividing cells. Many microcalcifications clustered together may be a sign of cancer. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calcium Carbonate: Carbonic acid calcium salt (CaCO3). An odorless, tasteless powder or crystal that occurs in nature. It is used therapeutically as a phosphate buffer in hemodialysis patients and as a calcium supplement. [NIH] Calcium Oxalate: The calcium salt of oxalic acid, occurring in the urine as crystals and in certain calculi. [NIH] Callus: A callosity or hard, thick skin; the bone-like reparative substance that is formed round the edges and fragments of broken bone. [NIH] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carboxy: Cannabinoid. [NIH] Carboxy-terminal: The end of any polypeptide or protein that bears a free carboxyl group. [NIH]

Carcinoembryonic Antigen: A glycoprotein that is secreted into the luminal surface of the epithelia in the gastrointestinal tract. It is found in the feces and pancreaticobiliary secretions and is used to monitor the respone to colon cancer treatment. [NIH] Carcinogen: Any substance that causes cancer. [NIH] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinoid: A type of tumor usually found in the gastrointestinal system (most often in the appendix), and sometimes in the lungs or other sites. Carcinoid tumors are usually benign. [NIH]

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Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]

Carcinoma in Situ: A malignant tumor that has not yet invaded the basement membrane of the epithelial cell of origin and has not spread to other tissues. [NIH] Carcinosarcoma: A malignant tumor that is a mixture of carcinoma (cancer of epithelial tissue, which is skin and tissue that lines or covers the internal organs) and sarcoma (cancer of connective tissue, such as bone, cartilage, and fat). [NIH] Cardiac: Having to do with the heart. [NIH] Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often of obscure or unknown etiology. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Carotene: The general name for a group of pigments found in green, yellow, and leafy vegetables, and yellow fruits. The pigments are fat-soluble, unsaturated aliphatic hydrocarbons functioning as provitamins and are converted to vitamin A through enzymatic processes in the intestinal wall. [NIH] Carotenoids: Substance found in yellow and orange fruits and vegetables and in dark green, leafy vegetables. May reduce the risk of developing cancer. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case-Control Studies: Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group. [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Causal: Pertaining to a cause; directed against a cause. [EU] Cavernous Sinus: An irregularly shaped venous space in the dura mater at either side of the sphenoid bone. [NIH] Cecum: The beginning of the large intestine. The cecum is connected to the lower part of the small intestine, called the ileum. [NIH] Celecoxib: A drug that reduces pain. Celecoxib belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is being studied for cancer prevention. [NIH] Celiac Disease: A disease characterized by intestinal malabsorption and precipitated by gluten-containing foods. The intestinal mucosa shows loss of villous structure. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH]

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Cell Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells. [NIH] Cell Cycle Proteins: Proteins that control the cell division cycle. This family of proteins includes a wide variety of classes, including cyclin-dependent kinases, mitogen-activated kinases, cyclins, and phosphoprotein phosphatases (phosphoprotein phosphatase) as well as their putative substrates such as chromatin-associated proteins, cytoskeletal proteins, and transcription factors. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell Extracts: Preparations of cell constituents or subcellular materials, isolates, or substances. [NIH] Cell Lineage: The developmental history of cells as traced from the first division of the original cell or cells in the embryo. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Cell Transplantation: Transference of cells within an individual, between individuals of the same species, or between individuals of different species. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH]

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Cerumen: The yellow or brown waxy secretions produced by vestigial apocrine sweat glands in the external ear canal. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Chemoprevention: The use of drugs, vitamins, or other agents to try to reduce the risk of, or delay the development or recurrence of, cancer. [NIH] Chemopreventive: Natural or synthetic compound used to intervene in the early precancerous stages of carcinogenesis. [NIH] Chemoprotective: A quality of some drugs used in cancer treatment. Chemoprotective agents protect healthy tissue from the toxic effects of anticancer drugs. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotherapeutic agent: A drug used to treat cancer. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chenodeoxycholic Acid: A bile acid, usually conjugated with either glycine or taurine. It acts as a detergent to solubilize fats for intestinal absorption and is reabsorbed by the small intestine. It is used as cholagogue, a choleretic laxative, and to prevent or dissolve gallstones. [NIH] Chimeric Proteins: Proteins in individuals that are derived from genetically different zygotes. [NIH] Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [NIH] Choledochal Cyst: A congenital cystic dilatation of the common bile duct; this condition may be asymptomatic, or cause vomiting, fever, jaundice, or pain in the right upper quadrant. [NIH] Choleretic: A choleretic agent. [EU] Cholesteatoma: A non-neoplastic keratinizing mass with stratified squamous epithelium, frequently occurring in the meninges, central nervous system, bones of the skull, and most commonly in the middle ear and mastoid region. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Cholesterol Esters: Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis. [NIH] Choline: A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes,

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and in lipid metabolism. [NIH] Chondrocytes: Polymorphic cells that form cartilage. [NIH] Chromaffin System: The cells of the body which stain with chromium salts. They occur along the sympathetic nerves, in the adrenal gland, and in various other organs. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chronic prostatitis: Inflammation of the prostate gland, developing slowly and lasting a long time. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from the small intestines to the tissues. [NIH] Cicatrix: The formation of new tissue in the process of wound healing. [NIH] Cicatrix, Hypertrophic: An elevated scar, resembling a keloid, but which does not spread into surrounding tissues. It is formed by enlargement and overgrowth of cicatricial tissue and regresses spontaneously. [NIH] Ciliary: Inflammation or infection of the glands of the margins of the eyelids. [NIH] Ciliary Body: A ring of tissue extending from the scleral spur to the ora serrata of the retina. It consists of the uveal portion and the epithelial portion. The ciliary muscle is in the uveal portion and the ciliary processes are in the epithelial portion. [NIH] Ciliary processes: The extensions or projections of the ciliary body that secrete aqueous humor. [NIH] Circulatory system: The system that contains the heart and the blood vessels and moves blood throughout the body. This system helps tissues get enough oxygen and nutrients, and it helps them get rid of waste products. The lymph system, which connects with the blood system, is often considered part of the circulatory system. [NIH] Cirrhosis: A type of chronic, progressive liver disease. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Clathrin: The main structural coat protein of coated vesicles which play a key role in the intracellular transport between membranous organelles. Clathrin also interacts with cytoskeletal proteins. [NIH] Claviceps: A genus of ascomycetous fungi, family Clavicipitaceae, order Hypocreales, parasitic on various grasses. The sclerotia contain several toxic alkaloids. Claviceps purpurea on rye causes ergotism. [NIH] Clavicle: A long bone of the shoulder girdle. [NIH] Clear cell carcinoma: A rare type of tumor of the female genital tract in which the inside of

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the cells looks clear when viewed under a microscope. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]

Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Cluster Analysis: A set of statistical methods used to group variables or observations into strongly inter-related subgroups. In epidemiology, it may be used to analyze a closely grouped series of events or cases of disease or other health-related phenomenon with welldefined distribution patterns in relation to time or place or both. [NIH] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Coated Vesicles: Vesicles formed when cell-membrane coated pits invaginate and pinch off. The outer surface of these vesicles are covered with a lattice-like network of coat proteins, such as clathrin, coat protein complex proteins, or caveolins. [NIH] Codon: A set of three nucleotides in a protein coding sequence that specifies individual amino acids or a termination signal (codon, terminator). Most codons are universal, but some organisms do not produce the transfer RNAs (RNA, transfer) complementary to all codons. These codons are referred to as unassigned codons (codons, nonsense). [NIH] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics. [NIH] Colectomy: An operation to remove the colon. An open colectomy is the removal of the colon through a surgical incision made in the wall of the abdomen. Laparoscopic-assisted colectomy uses a thin, lighted tube attached to a video camera. It allows the surgeon to remove the colon without a large incision. [NIH] Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH]

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Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colloidal: Of the nature of a colloid. [EU] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] Colon Polyps: Small, fleshy, mushroom-shaped growths in the colon. [NIH] Colonic Polyps: Pedunculated or sessile growths arising from the mucous membrane of the colon. [NIH] Colonoscopy: Endoscopic examination, therapy or surgery of the luminal surface of the colon. [NIH] Colorectal: Having to do with the colon or the rectum. [NIH] Colorectal Cancer: Cancer that occurs in the colon (large intestine) or the rectum (the end of the large intestine). A number of digestive diseases may increase a person's risk of colorectal cancer, including polyposis and Zollinger-Ellison Syndrome. [NIH] Colorectal Neoplasms: Tumors or cancer of the either the colon or rectum or both. The most frequent malignant tumor in the United States. Etiological factors which increase the risk of colorectal cancer include chronic ulcerative colitis, familial polyposis of the colon, exposure to asbestos, irradiation of the cervix. [NIH] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH] Common Bile Duct: The largest biliary duct. It is formed by the junction of the cystic duct and the hepatic duct. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements,

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megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [NIH] Compliance: Distensibility measure of a chamber such as the lungs (lung compliance) or bladder. Compliance is expressed as a change in volume per unit change in pressure. [NIH] Compress: A plug used to occludate an orifice in the control of bleeding, or to mop up secretions; an absorbent pad. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Confounding: Extraneous variables resulting in outcome effects that obscure or exaggerate the "true" effect of an intervention. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjugation: 1. The act of joining together or the state of being conjugated. 2. A sexual process seen in bacteria, ciliate protozoa, and certain fungi in which nuclear material is exchanged during the temporary fusion of two cells (conjugants). In bacterial genetics a form of sexual reproduction in which a donor bacterium (male) contributes some, or all, of its DNA (in the form of a replicated set) to a recipient (female) which then incorporates differing genetic information into its own chromosome by recombination and passes the recombined set on to its progeny by replication. In ciliate protozoa, two conjugants of separate mating types exchange micronuclear material and then separate, each now being a fertilized cell. In certain fungi, the process involves fusion of two gametes, resulting in union of their nuclei and formation of a zygote. 3. In chemistry, the joining together of two

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compounds to produce another compound, such as the combination of a toxic product with some substance in the body to form a detoxified product, which is then eliminated. [EU] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue Cells: A group of cells that includes fibroblasts, cartilage cells, adipocytes, smooth muscle cells, and bone cells. [NIH] Constriction: The act of constricting. [NIH] Consultation: A deliberation between two or more physicians concerning the diagnosis and the proper method of treatment in a case. [NIH] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Contraceptive: An agent that diminishes the likelihood of or prevents conception. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Contralateral: Having to do with the opposite side of the body. [NIH] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all. [NIH] Cor: The muscular organ that maintains the circulation of the blood. c. adiposum a heart that has undergone fatty degeneration or that has an accumulation of fat around it; called also fat or fatty, heart. c. arteriosum the left side of the heart, so called because it contains oxygenated (arterial) blood. c. biloculare a congenital anomaly characterized by failure of formation of the atrial and ventricular septums, the heart having only two chambers, a single atrium and a single ventricle, and a common atrioventricular valve. c. bovinum (L. 'ox heart') a greatly enlarged heart due to a hypertrophied left ventricle; called also c. taurinum and bucardia. c. dextrum (L. 'right heart') the right atrium and ventricle. c. hirsutum, c. villosum. c. mobile (obs.) an abnormally movable heart. c. pendulum a heart so movable that it seems to be hanging by the great blood vessels. c. pseudotriloculare biatriatum a congenital cardiac anomaly in which the heart functions as a three-chambered heart because of tricuspid atresia, the right ventricle being extremely small or rudimentary and the right atrium greatly dilated. Blood passes from the right to the left atrium and thence disease due to pulmonary hypertension secondary to disease of the lung, or its blood vessels, with hypertrophy of the right ventricle. [EU] Corneum: The superficial layer of the epidermis containing keratinized cells. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH]

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Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Corpus: The body of the uterus. [NIH] Corpus Luteum: The yellow glandular mass formed in the ovary by an ovarian follicle that has ruptured and discharged its ovum. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to angiotensin II. They are divided, according to their predominant biological activity, into three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance; and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees, and others exert only one type of effect. The corticosteroids are used clinically for hormonal replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [EU] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cowpox: A mild, eruptive skin disease of milk cows caused by cowpox virus, with lesions occurring principally on the udder and teats. Human infection may occur while milking an infected animal. [NIH] Cowpox Virus: A species of orthopoxvirus that is the etiologic agent of cowpox. It is closely related to but antigenically different from vaccina virus. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Cranial Nerves: Twelve pairs of nerves that carry general afferent, visceral afferent, special afferent, somatic efferent, and autonomic efferent fibers. [NIH] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Cross-Sectional Studies: Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a representative sample at one particular time. This contrasts with longitudinal studies which are followed over a period of time. [NIH] Crowding: Behavior with respect to an excessive number of individuals, human or animal, in relation to available space. [NIH] Cryotherapy: Any method that uses cold temperature to treat disease. [NIH] Cryptococcosis: Infection with a fungus of the species Cryptococcus neoformans. [NIH] Culture Media: Any liquid or solid preparation made specifically for the growth, storage, or transport of microorganisms or other types of cells. The variety of media that exist allow for

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the culturing of specific microorganisms and cell types, such as differential media, selective media, test media, and defined media. Solid media consist of liquid media that have been solidified with an agent such as agar or gelatin. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Curcumin: A dye obtained from tumeric, the powdered root of Curcuma longa Linn. It is used in the preparation of curcuma paper and the detection of boron. Curcumin appears to possess a spectrum of pharmacological properties, due primarily to its inhibitory effects on metabolic enzymes. [NIH] Cutaneous: Having to do with the skin. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclin: Molecule that regulates the cell cycle. [NIH] Cyclin-Dependent Kinases: Protein kinases that control cell cycle progression in all eukaryotes and require physical association with cyclins to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events. [NIH]

Cyclooxygenase Inhibitors: Compounds or agents that combine with cyclooxygenase (prostaglandin-endoperoxide synthase) and thereby prevent its substrate-enzyme combination with arachidonic acid and the formation of eicosanoids, prostaglandins, and thromboxanes. [NIH] Cyproheptadine: A serotonin antagonist and a histamine H1 blocker used as antipruritic, appetite stimulant, antiallergic, and for the post-gastrectomy dumping syndrome, etc. [NIH] Cyst: A sac or capsule filled with fluid. [NIH] Cystic Duct: The tube that carries bile from the gallbladder into the common bile duct and the small intestine. [NIH] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytoskeletal Proteins: Major constituent of the cytoskeleton found in the cytoplasm of eukaryotic cells. They form a flexible framework for the cell, provide attachment points for organelles and formed bodies, and make communication between parts of the cell possible. [NIH]

Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH]

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Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Dairy Products: Raw and processed or manufactured milk and milk-derived products. These are usually from cows (bovine) but are also from goats, sheep, reindeer, and water buffalo. [NIH] Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices. The process is usually preliminary to statistical analysis of the data. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Decidua: The epithelial lining of the endometrium that is formed before the fertilized ovum reaches the uterus. The fertilized ovum embeds in the decidua. If the ovum is not fertilized, the decidua is shed during menstruation. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Dental Care: The total of dental diagnostic, preventive, and restorative services provided to meet the needs of a patient (from Illustrated Dictionary of Dentistry, 1982). [NIH] Deoxycholic Acid: A bile acid formed by bacterial action from cholate. It is usually conjugated with glycine or taurine. Deoxycholic acid acts as a detergent to solubilize fats for intestinal absorption, is reabsorbed itself, and is used as a choleretic and detergent. [NIH] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Dermatitis: Any inflammation of the skin. [NIH] Dermis: A layer of vascular connective tissue underneath the epidermis. The surface of the dermis contains sensitive papillae. Embedded in or beneath the dermis are sweat glands, hair follicles, and sebaceous glands. [NIH] Dermoid: A benign mixed tumor, usually congenital, containing teeth, hairs, skin glands, fibrous tissue, and other skin elements, rarely found in the limbal region of the eye and orbit. [NIH] Dermoid Cyst: A benign mixed tumor, usually congenital, containing teeth, hairs, skin glands, fibrous tissue, and other skin elements, rarely found in the limbal region of the eye and orbit. [NIH] DES: Diethylstilbestrol. A synthetic hormone that was prescribed from the early 1940s until 1971 to help women with complications of pregnancy. DES has been linked to an increased risk of clear cell carcinoma of the vagina in daughters of women who used DES. DES may also increase the risk of breast cancer in women who used DES. [NIH] Desensitization: The prevention or reduction of immediate hypersensitivity reactions by administration of graded doses of allergen; called also hyposensitization and immunotherapy. [EU] Desmoid tumor: A tumor of the tissue that surrounds muscles, usually in the abdomen. Desmoid tumors rarely metastasize. [NIH] Detoxification: Treatment designed to free an addict from his drug habit. [EU]

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Developed Countries: Countries that have reached a level of economic achievement through an increase of production, per capita income and consumption, and utilization of natural and human resources. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diaphragm: The musculofibrous partition that separates the thoracic cavity from the abdominal cavity. Contraction of the diaphragm increases the volume of the thoracic cavity aiding inspiration. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diastolic blood pressure: The minimum pressure that remains within the artery when the heart is at rest. [NIH] Dietary Fiber: The remnants of plant cell walls that are resistant to digestion by the alimentary enzymes of man. It comprises various polysaccharides and lignins. [NIH] Diethylnitrosamine: A nitrosamine derivative with alkylating, carcinogenic, and mutagenic properties. [NIH] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Digitalis: A genus of toxic herbaceous Eurasian plants of the Scrophulaceae which yield cardiotonic glycosides. The most useful are Digitalis lanata and D. purpurea. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrete: Made up of separate parts or characterized by lesions which do not become blended; not running together; separate. [NIH] Dissection: Cutting up of an organism for study. [NIH] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU]

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Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Diuresis: Increased excretion of urine. [EU] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Dosage Forms: Completed forms of the pharmaceutical preparation in which prescribed doses of medication are included. They are designed to resist action by gastric fluids, prevent vomiting and nausea, reduce or alleviate the undesirable taste and smells associated with oral administration, achieve a high concentration of drug at target site, or produce a delayed or long-acting drug effect. They include capsules, liniments, ointments, pharmaceutical solutions, powders, tablets, etc. [NIH] Dose-dependent: Refers to the effects of treatment with a drug. If the effects change when the dose of the drug is changed, the effects are said to be dose dependent. [NIH] Dosimetry: All the methods either of measuring directly, or of measuring indirectly and computing, absorbed dose, absorbed dose rate, exposure, exposure rate, dose equivalent, and the science associated with these methods. [NIH] Double-blind: Pertaining to a clinical trial or other experiment in which neither the subject nor the person administering treatment knows which treatment any particular subject is receiving. [EU] Doxycycline: A synthetic tetracycline derivative with a range of antimicrobial activity and mode of action similar to that of tetracycline, but more effective against many species. Animal studies suggest that it may cause less tooth staining than other tetracyclines. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duct: A tube through which body fluids pass. [NIH] Ductal carcinoma in situ: DCIS. Abnormal cells that involve only the lining of a duct. The cells have not spread outside the duct to other tissues in the breast. Also called intraductal carcinoma. [NIH] Dumping Syndrome: Gastrointestinal nonfunctioning pylorus. [NIH]

symptoms

resulting

from

an

absent

or

Duodenum: The first part of the small intestine. [NIH] Dura mater: The outermost, toughest, and most fibrous of the three membranes (meninges) covering the brain and spinal cord; called also pachymeninx. [EU]

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Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Ectopic: Pertaining to or characterized by ectopia. [EU] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Eicosanoids: A class of oxygenated, endogenous, unsaturated fatty acids derived from arachidonic acid. They include prostaglandins, leukotrienes, thromboxanes, and hydroxyeicosatetraenoic acid compounds (HETE). They are hormone-like substances that act near the site of synthesis without altering functions throughout the body. [NIH] Ejaculation: The release of semen through the penis during orgasm. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electrocoagulation: Electrosurgical procedures used to treat hemorrhage (e.g., bleeding ulcers) and to ablate tumors, mucosal lesions, and refractory arrhythmias. [NIH] Electrode: Component of the pacing system which is at the distal end of the lead. It is the interface with living cardiac tissue across which the stimulus is transmitted. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]

Emboli: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Emesis: Vomiting; an act of vomiting. Also used as a word termination, as in haematemesis. [EU]

Emollient: Softening or soothing; called also malactic. [EU] Emphysema: A pathological accumulation of air in tissues or organs. [NIH] Emulsions: Colloids of two immiscible liquids where either phase may be either fatty or aqueous; lipid-in-water emulsions are usually liquid, like milk or lotion and water-in-lipid emulsions tend to be creams. [NIH]

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Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endocrine Glands: Ductless glands that secrete substances which are released directly into the circulation and which influence metabolism and other body functions. [NIH] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endoderm: The inner of the three germ layers of the embryo. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endometrial: Having to do with the endometrium (the layer of tissue that lines the uterus). [NIH]

Endometriosis: A condition in which tissue more or less perfectly resembling the uterine mucous membrane (the endometrium) and containing typical endometrial granular and stromal elements occurs aberrantly in various locations in the pelvic cavity. [NIH] Endometrium: The layer of tissue that lines the uterus. [NIH] Endorphins: One of the three major groups of endogenous opioid peptides. They are large peptides derived from the pro-opiomelanocortin precursor. The known members of this group are alpha-, beta-, and gamma-endorphin. The term endorphin is also sometimes used to refer to all opioid peptides, but the narrower sense is used here; opioid peptides is used for the broader group. [NIH] Endoscope: A thin, lighted tube used to look at tissues inside the body. [NIH] Endoscopic: A technique where a lateral-view endoscope is passed orally to the duodenum for visualization of the ampulla of Vater. [NIH] Endoscopy: Endoscopic examination, therapy or surgery performed on interior parts of the body. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxins: Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Energy balance: Energy is the capacity of a body or a physical system for doing work. Energy balance is the state in which the total energy intake equals total energy needs. [NIH] Enkephalin: A natural opiate painkiller, in the hypothalamus. [NIH] Enterohepatic: Of or involving the intestine and liver. [EU] Enterohepatic Circulation: Recycling through liver by excretion in bile, reabsorption from intestines into portal circulation, passage back into liver, and re-excretion in bile. [NIH] Enteroscopy: An examination of the small intestine with an endoscope. The endoscope is

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inserted through the mouth and stomach into the small intestine. [NIH] Enucleation: Removal of the nucleus from an eucaryiotic cell. [NIH] Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Eosinophils: Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiologic Factors: Events, characteristics, or other definable entities that have the potential to bring about a change in a health condition or other defined outcome. [NIH] Epidemiologic Studies: Studies designed to examine associations, commonly, hypothesized causal relations. They are usually concerned with identifying or measuring the effects of risk factors or exposures. The common types of analytic study are case-control studies, cohort studies, and cross-sectional studies. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermal Growth Factor: A 6 kD polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and epithelial cells. [NIH] Epidermal growth factor receptor: EGFR. The protein found on the surface of some cells and to which epidermal growth factor binds, causing the cells to divide. It is found at abnormally high levels on the surface of many types of cancer cells, so these cells may divide excessively in the presence of epidermal growth factor. Also known as ErbB1 or HER1. [NIH] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epidermoid carcinoma: A type of cancer in which the cells are flat and look like fish scales. Also called squamous cell carcinoma. [NIH] Epigastric: Having to do with the upper middle area of the abdomen. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH]

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Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelioma: A neoplasm of epithelial origin, ranging from benign (adenoma and papilloma) to malignant (carcinoma). [EU] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Erectile: The inability to get or maintain an erection for satisfactory sexual intercourse. Also called impotence. [NIH] Erection: The condition of being made rigid and elevated; as erectile tissue when filled with blood. [EU] Ergot: Cataract due to ergot poisoning caused by eating of rye cereals contaminated by a fungus. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Erythropoiesis: The production of erythrocytes. [EU] Esophageal: Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Estradiol: The most potent mammalian estrogenic hormone. It is produced in the ovary, placenta, testis, and possibly the adrenal cortex. [NIH] Estrogen: One of the two female sex hormones. [NIH] Estrogen receptor: ER. Protein found on some cancer cells to which estrogen will attach. [NIH]

Estrogen Replacement Therapy: The use of hormonal agents with estrogen-like activity in postmenopausal or other estrogen-deficient women to alleviate effects of hormone deficiency, such as vasomotor symptoms, dyspareunia, and progressive development of osteoporosis. This may also include the use of progestational agents in combination therapy. [NIH]

Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Ethionine: 2-Amino-4-(ethylthio)butyric acid. An antimetabolite and methionine antagonist that interferes with amino acid incorporation into proteins and with cellular ATP utilization. It also produces liver neoplasms. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Excrete: To get rid of waste from the body. [NIH] Exisulind: A drug that is being studied in the treatment and prevention of cancer. It has been shown to cause apoptosis (cell death) in cancerous and precancerous cells by acting through a group of cellular enzymes called cGMP phosphodiesterases. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exocytosis: Cellular release of material within membrane-limited vesicles by fusion of the

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vesicles with the cell membrane. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exon: The part of the DNA that encodes the information for the actual amino acid sequence of the protein. In many eucaryotic genes, the coding sequences consist of a series of exons alternating with intron sequences. [NIH] External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Extraction: The process or act of pulling or drawing out. [EU] Extraocular: External to or outside of the eye. [NIH] Extrapyramidal: Outside of the pyramidal tracts. [EU] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH] Facial: Of or pertaining to the face. [EU] Facial Nerve: The 7th cranial nerve. The facial nerve has two parts, the larger motor root which may be called the facial nerve proper, and the smaller intermediate or sensory root. Together they provide efferent innervation to the muscles of facial expression and to the lacrimal and salivary glands, and convey afferent information for taste from the anterior two-thirds of the tongue and for touch from the external ear. [NIH] Facial Pain: Pain in the facial region including orofacial pain and craniofacial pain. Associated conditions include local inflammatory and neoplastic disorders and neuralgic syndromes involving the trigeminal, facial, and glossopharyngeal nerves. Conditions which feature recurrent or persistent facial pain as the primary manifestation of disease are referred to as facial pain syndromes. [NIH] Faecal: Pertaining to or of the nature of feces. [EU] Familial polyposis: An inherited condition in which numerous polyps (tissue masses) develop on the inside walls of the colon and rectum. It increases the risk for colon cancer. [NIH]

Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Farnesyl: Enzyme which adds 15 carbon atoms to the Ras precursor protein. [NIH]

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Fat: Total lipids including phospholipids. [NIH] Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Fermentation: An enzyme-induced chemical change in organic compounds that takes place in the absence of oxygen. The change usually results in the production of ethanol or lactic acid, and the production of energy. [NIH] Fetoprotein: Transabdominal aspiration of fluid from the amniotic sac with a view to detecting increases of alpha-fetoprotein in maternal blood during pregnancy, as this is an important indicator of open neural tube defects in the fetus. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibroblast Growth Factor: Peptide isolated from the pituitary gland and from the brain. It is a potent mitogen which stimulates growth of a variety of mesodermal cells including chondrocytes, granulosa, and endothelial cells. The peptide may be active in wound healing and animal limb regeneration. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibroid: A benign smooth muscle tumor, usually in the uterus or gastrointestinal tract. Also called leiomyoma. [NIH] Fibroma: A benign tumor of fibrous or fully developed connective tissue. [NIH] Fibrosarcoma: A type of soft tissue sarcoma that begins in fibrous tissue, which holds bones, muscles, and other organs in place. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fine-needle aspiration: The removal of tissue or fluid with a needle for examination under a microscope. Also called needle biopsy. [NIH] Fistula: Abnormal communication most commonly seen between two internal organs, or between an internal organ and the surface of the body. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluorouracil: A pyrimidine analog that acts as an antineoplastic antimetabolite and also has immunosuppressant. It interferes with DNA synthesis by blocking the thymidylate synthetase conversion of deoxyuridylic acid to thymidylic acid. [NIH] Foam Cells: Lipid-laden macrophages originating from monocytes or from smooth muscle cells. [NIH] Focus Groups: A method of data collection and a qualitative research tool in which a small group of individuals are brought together and allowed to interact in a discussion of their opinions about topics, issues, or questions. [NIH] Folate: A B-complex vitamin that is being studied as a cancer prevention agent. Also called folic acid. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Folic

Acid:

N-(4-(((2-Amino-1,4-dihydro-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-L-

Dictionary 227

glutamic acid. A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses. Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia. [NIH] Follicles: Shafts through which hair grows. [NIH] Foramen: A natural hole of perforation, especially one in a bone. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Frostbite: Damage to tissues as the result of low environmental temperatures. [NIH] Fungus: A general term used to denote a group of eukaryotic protists, including mushrooms, yeasts, rusts, moulds, smuts, etc., which are characterized by the absence of chlorophyll and by the presence of a rigid cell wall composed of chitin, mannans, and sometimes cellulose. They are usually of simple morphological form or show some reversible cellular specialization, such as the formation of pseudoparenchymatous tissue in the fruiting body of a mushroom. The dimorphic fungi grow, according to environmental conditions, as moulds or yeasts. [EU] Furunculosis: An infection where furuncles are present over a period of weeks to months. Species of Staphylococcus are usually the causative agents. [NIH] Gallate: Antioxidant present in tea. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gamma Rays: Very powerful and penetrating, high-energy electromagnetic radiation of shorter wavelength than that of x-rays. They are emitted by a decaying nucleus, usually between 0.01 and 10 MeV. They are also called nuclear x-rays. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Ganglion: 1. A knot, or knotlike mass. 2. A general term for a group of nerve cell bodies located outside the central nervous system; occasionally applied to certain nuclear groups within the brain or spinal cord, e.g. basal ganglia. 3. A benign cystic tumour occurring on a aponeurosis or tendon, as in the wrist or dorsum of the foot; it consists of a thin fibrous capsule enclosing a clear mucinous fluid. [EU] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gastrectomy: An operation to remove all or part of the stomach. [NIH] Gastric: Having to do with the stomach. [NIH] Gastric Inhibitory Polypeptide: A gastrointestinal hormone consisting of a 43-amino acid polypeptide (molecular weight 5105). It inhibits gastric secretion and motility and stimulates release of insulin. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastritis: Inflammation of the stomach. [EU] Gastroenterology: A subspecialty of internal medicine concerned with the study of the physiology and diseases of the digestive system and related structures (esophagus, liver, gallbladder, and pancreas). [NIH] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH]

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Gels: Colloids with a solid continuous phase and liquid as the dispersed phase; gels may be unstable when, due to temperature or other cause, the solid phase liquifies; the resulting colloid is called a sol. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Amplification: A selective increase in the number of copies of a gene coding for a specific protein without a proportional increase in other genes. It occurs naturally via the excision of a copy of the repeating sequence from the chromosome and its extrachromosomal replication in a plasmid, or via the production of an RNA transcript of the entire repeating sequence of ribosomal RNA followed by the reverse transcription of the molecule to produce an additional copy of the original DNA sequence. Laboratory techniques have been introduced for inducing disproportional replication by unequal crossing over, uptake of DNA from lysed cells, or generation of extrachromosomal sequences from rolling circle replication. [NIH] Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Targeting: The integration of exogenous DNA into the genome of an organism at sites where its expression can be suitably controlled. This integration occurs as a result of homologous recombination. [NIH] Gene Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic Markers: A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genital: Pertaining to the genitalia. [EU] Genomics: The systematic study of the complete DNA sequences (genome) of organisms. [NIH]

Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Germline mutation: A gene change in the body's reproductive cells (egg or sperm) that becomes incorporated into the DNA of every cell in the body of offspring; germline mutations are passed on from parents to offspring. Also called hereditary mutation. [NIH]

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Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Ginseng: An araliaceous genus of plants that contains a number of pharmacologically active agents used as stimulants, sedatives, and tonics, especially in traditional medicine. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]

Glomeruli: Plural of glomerulus. [NIH] Glossopharyngeal Nerve: The 9th cranial nerve. The glossopharyngeal nerve is a mixed motor and sensory nerve; it conveys somatic and autonomic efferents as well as general, special, and visceral afferents. Among the connections are motor fibers to the stylopharyngeus muscle, parasympathetic fibers to the parotid glands, general and taste afferents from the posterior third of the tongue, the nasopharynx, and the palate, and afferents from baroreceptors and chemoreceptors of the carotid sinus. [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Glucokinase: A group of enzymes that catalyzes the conversion of ATP and D-glucose to ADP and D-glucose 6-phosphate. They are found in invertebrates and microorganisms and are highly specific for glucose. (Enzyme Nomenclature, 1992) EC 2.7.1.2. [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] Glucose tolerance: The power of the normal liver to absorb and store large quantities of glucose and the effectiveness of intestinal absorption of glucose. The glucose tolerance test is a metabolic test of carbohydrate tolerance that measures active insulin, a hepatic function based on the ability of the liver to absorb glucose. The test consists of ingesting 100 grams of glucose into a fasting stomach; blood sugar should return to normal in 2 to 21 hours after ingestion. [NIH] Glucose Tolerance Test: Determination of whole blood or plasma sugar in a fasting state before and at prescribed intervals (usually 1/2 hr, 1 hr, 3 hr, 4 hr) after taking a specified amount (usually 100 gm orally) of glucose. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]

Glutathione Peroxidase: An enzyme catalyzing the oxidation of 2 moles of glutathione in the presence of hydrogen peroxide to yield oxidized glutathione and water. EC 1.11.1.9. [NIH]

Gluten: The protein of wheat and other grains which gives to the dough its tough elastic character. [EU]

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Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycogen: A sugar stored in the liver and muscles. It releases glucose into the blood when cells need it for energy. Glycogen is the chief source of stored fuel in the body. [NIH] Glycogen Storage Disease: A group of inherited metabolic disorders involving the enzymes responsible for the synthesis and degradation of glycogen. In some patients, prominent liver involvement is presented. In others, more generalized storage of glycogen occurs, sometimes with prominent cardiac involvement. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycoside: Any compound that contains a carbohydrate molecule (sugar), particularly any such natural product in plants, convertible, by hydrolytic cleavage, into sugar and a nonsugar component (aglycone), and named specifically for the sugar contained, as glucoside (glucose), pentoside (pentose), fructoside (fructose) etc. [EU] Glycosidic: Formed by elimination of water between the anomeric hydroxyl of one sugar and a hydroxyl of another sugar molecule. [NIH] Goats: Any of numerous agile, hollow-horned ruminants of the genus Capra, closely related to the sheep. [NIH] Goblet Cells: Cells of the epithelial lining that produce and secrete mucins. [NIH] Goiter: Enlargement of the thyroid gland. [NIH] Gonadal: Pertaining to a gonad. [EU] Gonadorelin: A decapeptide hormone released by the hypothalamus. It stimulates the synthesis and secretion of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary gland. [NIH] Gonadotropic: Stimulating the gonads; applied to hormones of the anterior pituitary which influence the gonads. [EU] Gonadotropin: The water-soluble follicle stimulating substance, by some believed to originate in chorionic tissue, obtained from the serum of pregnant mares. It is used to supplement the action of estrogens. [NIH] Gonads: The gamete-producing glands, ovary or testis. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Grading: A system for classifying cancer cells in terms of how abnormal they appear when examined under a microscope. The objective of a grading system is to provide information about the probable growth rate of the tumor and its tendency to spread. The systems used to grade tumors vary with each type of cancer. Grading plays a role in treatment decisions. [NIH]

Granular Cell Tumor: Unusual tumor affecting any site of the body, but most often encountered in the head and neck. Considerable debate has surrounded the histogenesis of this neoplasm; however, it is considered to be a myoblastoma of, usually, a benign nature. It affects women more often than men. When it develops beneath the epidermis or mucous membrane, it can lead to proliferation of the squamous cells and mimic squamous cell carcinoma. [NIH] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into

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three groups: neutrophils, eosinophils, and basophils. [NIH] Granuloma: A relatively small nodular inflammatory lesion containing grouped mononuclear phagocytes, caused by infectious and noninfectious agents. [NIH] Granulosa Cells: Cells of the membrana granulosa lining the vesicular ovarian follicle which become luteal cells after ovulation. [NIH] Grasses: A large family, Gramineae, of narrow-leaved herbaceous monocots. Many grasses produce highly allergenic pollens and are hosts to cattle parasites and toxic fungi. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Guanine: One of the four DNA bases. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [NIH] Haplotypes: The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the major histocompatibility complex. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Headache Disorders: Common conditions characterized by persistent or recurrent headaches. Headache syndrome classification systems may be based on etiology (e.g., vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache, paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [NIH] Health Status: The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Hematogenous: Originating in the blood or spread through the bloodstream. [NIH] Hematuria: Presence of blood in the urine. [NIH] Hemianopsia: Partial or complete loss of vision in one half of the visual field(s) of one or both eyes. Subtypes include altitudinal hemianopsia, characterized by a visual defect above or below the horizontal meridian of the visual field. Homonymous hemianopsia refers to a visual defect that affects both eyes equally, and occurs either to the left or right of the midline of the visual field. Binasal hemianopsia consists of loss of vision in the nasal hemifields of both eyes. Bitemporal hemianopsia is the bilateral loss of vision in the temporal fields. Quadrantanopsia refers to loss of vision in one quarter of the visual field in one or both eyes. [NIH]

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Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoglobin C: A commonly occurring abnormal hemoglobin in which lysine replaces a glutamic acid residue at the sixth position of the beta chains. It results in reduced plasticity of erythrocytes. [NIH] Hemolytic: A disease that affects the blood and blood vessels. It destroys red blood cells, cells that cause the blood to clot, and the lining of blood vessels. HUS is often caused by the Escherichia coli bacterium in contaminated food. People with HUS may develop acute renal failure. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]

Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocellular: Pertaining to or affecting liver cells. [EU] Hepatocellular carcinoma: A type of adenocarcinoma, the most common type of liver tumor. [NIH] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Hereditary mutation: A gene change in the body's reproductive cells (egg or sperm) that becomes incorporated into the DNA of every cell in the body of offspring; hereditary mutations are passed on from parents to offspring. Also called germline mutation. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Herniated: Protrusion of a degenerated or fragmented intervertebral disc into the intervertebral foramen compressing the nerve root. [NIH] Heterodimers: Zippered pair of nonidentical proteins. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

Heterozygotes: Having unlike alleles at one or more corresponding loci on homologous chromosomes. [NIH]

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Hirsutism: Excess hair in females and children with an adult male pattern of distribution. The concept does not include hypertrichosis, which is localized or generalized excess hair. [NIH]

Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Histones: Small chromosomal proteins (approx 12-20 kD) possessing an open, unfolded structure and attached to the DNA in cell nuclei by ionic linkages. Classification into the various types (designated histone I, histone II, etc.) is based on the relative amounts of arginine and lysine in each. [NIH] Homeobox: Distinctive sequence of DNA bases. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Homozygotes: An individual having a homozygous gene pair. [NIH] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormonal therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called hormone therapy or endocrine therapy. [NIH] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hormone Replacement Therapy: Therapeutic use of hormones to alleviate the effects of hormone deficiency. [NIH] Horny layer: The superficial layer of the epidermis containing keratinized cells. [NIH] Human growth hormone: A protein hormone, secreted by the anterior lobe of the pituitary, which promotes growth of the whole body by stimulating protein synthesis. The human gene has already been cloned and successfully expressed in bacteria. [NIH] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU]

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Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hyperaldosteronism: Aldosteronism. [EU] Hyperandrogenism: A state characterized or caused by an excessive secretion of androgens by the adrenal cortex, ovaries, or testes. The clinical significance in males is negligible, so the term is used most commonly with reference to the female. The common manifestations in women are hirsutism and virilism. It is often caused by ovarian disease (particularly the polycystic ovary syndrome) and by adrenal diseases (particularly adrenal gland hyperfunction). [NIH] Hyperbilirubinemia: Pathologic process consisting of an abnormal increase in the amount of bilirubin in the circulating blood, which may result in jaundice. [NIH] Hypercalcemia: Abnormally high level of calcium in the blood. [NIH] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hyperstimulation: Excessive stimulation. [EU] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypertensive Encephalopathy: Brain dysfunction or damage resulting from malignant hypertension, usually associated with a diastolic blood pressure in excess of 125 mmHg. Clinical manifestations include headache, nausea, emesis, seizures, altered mental status (in some cases progressing to coma), papilledema, and retinal hemorrhage. Focal neurologic signs may develop. Pathologically, this condition may be associated with the formation of ischemic lesions in the brain (brain ischemia). [NIH] Hyperthyroidism: Excessive functional activity of the thyroid gland. [NIH] Hypertrichosis: Localized or generalized excess hair. The concept does not include hirsutism, which is excess hair in females and children with an adult male pattern of distribution. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hypogonadism: Condition resulting from or characterized by abnormally decreased functional activity of the gonads, with retardation of growth and sexual development. [NIH] Hypophyseal: Hypophysial. [EU] Hypophysis: A remnant of the entodermal pouch of Rathke beneath the mucous membrane of the pharynx, which shows pituitary tissue. [NIH] Hypopituitarism: Diminution or cessation of secretion of one or more hormones from the anterior pituitary gland (including LH; FSH; somatotropin; and corticotropin). This may result from surgical or radiation ablation, non-secretory pituitary neoplasms, metastatic tumors, infarction, pituitary apoplexy, infiltrative or granulomatous processes, and other conditions. [NIH] Hypoplasia: Incomplete development or underdevelopment of an organ or tissue. [EU] Hypothalamic: Of or involving the hypothalamus. [EU]

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Hypothalamic Hormones: Hormones isolated from the hypothalamus which exercise control over other organs, primarily the pituitary gland. Well-known members include certain pituitary hormone-releasing hormones and pituitary hormone release inhibiting hormones. Vasopressin and oxytocin which are found in the posterior pituitary may also be secreted by the hypothalamus but are not grouped here (pituitary hormones, posterior). [NIH]

Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Hypoxic: Having too little oxygen. [NIH] Ibuprofen: A nonsteroidal anti-inflammatory agent with analgesic properties used in the therapy of rheumatism and arthritis. [NIH] Ileal: Related to the ileum, the lowest end of the small intestine. [NIH] Ileum: The lower end of the small intestine. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by antigen injection or infection with microorganisms containing the antigen. [NIH] Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]

effects

of

foreign

Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunodiffusion: Technique involving the diffusion of antigen or antibody through a semisolid medium, usually agar or agarose gel, with the result being a precipitin reaction. [NIH]

Immunoelectrophoresis: A technique that combines protein electrophoresis and double immunodiffusion. In this procedure proteins are first separated by gel electrophoresis (usually agarose), then made visible by immunodiffusion of specific antibodies. A distinct elliptical precipitin arc results for each protein detectable by the antisera. [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunosuppressant: An agent capable of suppressing immune responses. [EU] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It

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includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] Impotence: The inability to perform sexual intercourse. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH] Infiltrating cancer: Cancer that has spread beyond the layer of tissue in which it developed and is growing into surrounding, healthy tissues. Also called invasive cancer. [NIH] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Inflammatory bowel disease: A general term that refers to the inflammation of the colon and rectum. Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. [NIH]

Informed Consent: Voluntary authorization, given to the physician by the patient, with full comprehension of the risks involved, for diagnostic or investigative procedures and medical and surgical treatment. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called

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intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Inhibin: Glyceroprotein hormone produced in the seminiferous tubules by the Sertoli cells in the male and by the granulosa cells in the female follicles. The hormone inhibits FSH and LH synthesis and secretion by the pituitary cells thereby affecting sexual maturation and fertility. [NIH] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inositol: An isomer of glucose that has traditionally been considered to be a B vitamin although it has an uncertain status as a vitamin and a deficiency syndrome has not been identified in man. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1379) Inositol phospholipids are important in signal transduction. [NIH] Inotropic: Affecting the force or energy of muscular contractions. [EU] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insomnia: Difficulty in going to sleep or getting enough sleep. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Insulin-like: Muscular growth factor. [NIH] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Interindividual: Occurring between two or more individuals. [EU] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intervertebral: Situated between two contiguous vertebrae. [EU] Intestinal: Having to do with the intestines. [NIH] Intestinal Mucosa: The surface lining of the intestines where the cells absorb nutrients. [NIH] Intestinal Neoplasms: Tumors or cancer of the intestines. [NIH]

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Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intracellular: Inside a cell. [NIH] Intracellular Membranes: Membranes of subcellular structures. [NIH] Intraductal carcinoma: Abnormal cells that involve only the lining of a duct. The cells have not spread outside the duct to other tissues in the breast. Also called ductal carcinoma in situ. [NIH] Intraductal Papilloma: A benign epithelial neoplasm which may arise from the skin, mucous membranes or glandular ducts. [NIH] Intraepithelial: Within the layer of cells that form the surface or lining of an organ. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intravenous: IV. Into a vein. [NIH] Intravesical: Within the bladder. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Invasive cancer: Cancer that has spread beyond the layer of tissue in which it developed and is growing into surrounding, healthy tissues. Also called infiltrating cancer. [NIH] Invertebrates: Animals that have no spinal column. [NIH] Ionization: 1. Any process by which a neutral atom gains or loses electrons, thus acquiring a net charge, as the dissociation of a substance in solution into ions or ion production by the passage of radioactive particles. 2. Iontophoresis. [EU] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Iris: The most anterior portion of the uveal layer, separating the anterior chamber from the posterior. It consists of two layers - the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented epithelium. [NIH] Irradiation: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Isoenzyme: Different forms of an enzyme, usually occurring in different tissues. The isoenzymes of a particular enzyme catalyze the same reaction but they differ in some of their properties. [NIH]

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Isothiocyanates: Organic compounds with the general formula R-NCS. [NIH] Isotonic: A biological term denoting a solution in which body cells can be bathed without a net flow of water across the semipermeable cell membrane. Also, denoting a solution having the same tonicity as some other solution with which it is compared, such as physiologic salt solution and the blood serum. [EU] Isotretinoin: A topical dermatologic agent that is used in the treatment of acne vulgaris and several other skin diseases. The drug has teratogenic and other adverse effects. [NIH] Isozymes: The multiple forms of a single enzyme. [NIH] Jaundice: A clinical manifestation of hyperbilirubinemia, consisting of deposition of bile pigments in the skin, resulting in a yellowish staining of the skin and mucous membranes. [NIH]

Karyotype: The characteristic chromosome complement of an individual, race, or species as defined by their number, size, shape, etc. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Keloid: A sharply elevated, irregularly shaped, progressively enlarging scar resulting from formation of excessive amounts of collagen in the dermis during connective tissue repair. It is differentiated from a hypertrophic scar (cicatrix, hypertrophic) in that the former does not spread to surrounding tissues. [NIH] Keratoacanthoma: A benign, non-neoplastic, usually self-limiting epithelial lesion closely resembling squamous cell carcinoma clinically and histopathologically. It occurs in solitary, multiple, and eruptive forms. The solitary and multiple forms occur on sunlight exposed areas and are identical histologically; they affect primarily white males. The eruptive form usually involves both sexes and appears as a generalized papular eruption. [NIH] Keratosis: Any horny growth such as a wart or callus. [NIH] Ketoprofen: An ibuprofen-type anti-inflammatory analgesic and antipyretic. It is used in the treatment of rheumatoid arthritis and osteoarthritis. [NIH] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kidney stone: A stone that develops from crystals that form in urine and build up on the inner surfaces of the kidney, in the renal pelvis, or in the ureters. [NIH] Kinetic: Pertaining to or producing motion. [EU] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Lacrimal: Pertaining to the tears. [EU] Lacrimal Apparatus: The tear-forming and tear-conducting system which includes the lacrimal glands, eyelid margins, conjunctival sac, and the tear drainage system. [NIH] Lacrimal gland: The small almond-shaped structure that produces tears; located just above the outer corner of the eye. [NIH] Lactation: The period of the secretion of milk. [EU] Laminin: Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion. [NIH] Laparoscopy: Examination, therapy or surgery of the abdomen's interior by means of a

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laparoscope. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Laser Coagulation: The coagulation of tissues using lasers. These lasers produce light in the visible green wavelength that is selectively absorbed by hemoglobin, and thus it is possible to seal bleeding blood vessels. [NIH] Laser therapy: The use of an intensely powerful beam of light to kill cancer cells. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative. [EU]

Lectin: A complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants. [NIH] Leiomyoma: A benign tumor derived from smooth muscle tissue, also known as a fibroid tumor. They rarely occur outside of the uterus and the gastrointestinal tract but can occur in the skin and subcutaneous tissues, probably arising from the smooth muscle of small blood vessels in these tissues. [NIH] Leptin: A 16-kD peptide hormone secreted from white adipocytes and implicated in the regulation of food intake and energy balance. Leptin provides the key afferent signal from fat cells in the feedback system that controls body fat stores. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Leucocyte: All the white cells of the blood and their precursors (myeloid cell series, lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. [NIH]

Leukotrienes: A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system. [NIH] Leuprolide: A potent and long acting analog of naturally occurring gonadotropin-releasing hormone (gonadorelin). Its action is similar to gonadorelin, which regulates the synthesis and release of pituitary gonadotropins. [NIH] Libido: The psychic drive or energy associated with sexual instinct in the broad sense (pleasure and love-object seeking). It may also connote the psychic energy associated with instincts in general that motivate behavior. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH] Ligase: An enzyme that repairs single stranded discontinuities in double-stranded DNA molecules in the cell. Purified DNA ligase is used in gene cloning to join DNA molecules together. [NIH]

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Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lip: Either of the two fleshy, full-blooded margins of the mouth. [NIH] Lipid: Fat. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Liquor: 1. A liquid, especially an aqueous solution containing a medicinal substance. 2. A general term used in anatomical nomenclature for certain fluids of the body. [EU] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver cancer: A disease in which malignant (cancer) cells are found in the tissues of the liver. [NIH]

Liver metastases: Cancer that has spread from the original (primary) tumor to the liver. [NIH]

Liver Neoplasms: Tumors or cancer of the liver. [NIH] Liver Transplantation: The transference of a part of or an entire liver from one human or animal to another. [NIH] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [NIH] Lobectomy: The removal of a lobe. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] Loss of Heterozygosity: The loss of one allele at a specific locus, caused by a deletion mutation; or loss of a chromosome from a chromosome pair. It is detected when heterozygous markers for a locus appear monomorphic because one of the alleles was deleted. When this occurs at a tumor suppressor gene locus where one of the alleles is already abnormal, it can result in neoplastic transformation. [NIH] Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] Lucida: An instrument, invented by Wollaton, consisting essentially of a prism or a mirror through which an object can be viewed so as to appear on a plane surface seen in direct view and on which the outline of the object may be traced. [NIH] Luciferase: Any one of several enzymes that catalyze the bioluminescent reaction in certain marine crustaceans, fish, bacteria, and insects. The enzyme is a flavoprotein; it oxidizes luciferins to an electronically excited compound that emits energy in the form of light. The

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color of light emitted varies with the organism. The firefly enzyme is a valuable reagent for measurement of ATP concentration. (Dorland, 27th ed) EC 1.13.12.-. [NIH] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Lung metastases: Cancer that has spread from the original (primary) tumor to the lung. [NIH]

Lutein Cells: The cells of the corpus luteum which are derived from the granulosa cells and the theca cells of the Graafian follicle. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphocytes: White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each); those with characteristics of neither major class are called null cells. [NIH] Lymphocytic: Referring to lymphocytes, a type of white blood cell. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Major Histocompatibility Complex: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) transplantation antigens, genes which control the structure of the immune responseassociated (Ia) antigens, the immune response (Ir) genes which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malacoplakia: The formation of soft patches on the mucous membrane of a hollow organ, such as the urogenital tract or digestive tract. [NIH] Malformation: A morphologic developmental process. [EU]

defect

resulting

from

an

intrinsically

abnormal

Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and

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spread to other parts of the body. [NIH] Malignant tumor: A tumor capable of metastasizing. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

Mammary: Pertaining to the mamma, or breast. [EU] Mammogram: An x-ray of the breast. [NIH] Mandible: The largest and strongest bone of the face constituting the lower jaw. It supports the lower teeth. [NIH] Matrilysin: The smallest member of the matrix metalloproteinases. It plays a role in tumor progression. EC 3.4.24.23. [NIH] Matrix metalloproteinase: A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues (i.e., extracellular matrix proteins). Because these enzymes need zinc or calcium atoms to work properly, they are called metalloproteinases. Matrix metalloproteinases are involved in wound healing, angiogenesis, and tumor cell metastasis. [NIH] Maxillary: Pertaining to the maxilla : the irregularly shaped bone that with its fellow forms the upper jaw. [EU] Meat: The edible portions of any animal used for food including domestic mammals (the major ones being cattle, swine, and sheep) along with poultry, fish, shellfish, and game. [NIH]

Meatus: A canal running from the internal auditory foramen through the petrous portion of the temporal bone. It gives passage to the facial and auditory nerves together with the auditory branch of the basilar artery and the internal auditory veins. [NIH] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical oncologist: A doctor who specializes in diagnosing and treating cancer using chemotherapy, hormonal therapy, and biological therapy. A medical oncologist often serves as the main caretaker of someone who has cancer and coordinates treatment provided by other specialists. [NIH] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Megaloblastic: A large abnormal red blood cell appearing in the blood in pernicious anaemia. [EU] Melanin: The substance that gives the skin its color. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH]

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Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells. [NIH] Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Meningioma: A type of tumor that occurs in the meninges, the membranes that cover and protect the brain and spinal cord. Meningiomas usually grow slowly. [NIH] Menopause: Permanent cessation of menstruation. [NIH] Menstrual Cycle: The period of the regularly recurring physiologic changes in the endometrium occurring during the reproductive period in human females and some primates and culminating in partial sloughing of the endometrium (menstruation). [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Health: The state wherein the person is well adjusted. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Mesoderm: The middle germ layer of the embryo. [NIH] Metabolic acidosis: (met-ah-BOL-ik as-id-O-sis): A condition in which the blood is too acidic. It may be caused by severe illness or sepsis (bacteria in the bloodstream). [NIH] Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metaplasia: A condition in which there is a change of one adult cell type to another similar adult cell type. [NIH] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastasize: To spread from one part of the body to another. When cancer cells metastasize and form secondary tumors, the cells in the metastatic tumor are like those in the original (primary) tumor. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] Methylcholanthrene: A carcinogen that is often used in experimental cancer studies. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microcalcifications: Tiny deposits of calcium in the breast that cannot be felt but can be detected on a mammogram. A cluster of these very small specks of calcium may indicate that cancer is present. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH]

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Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein tubulin. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Millimeter: A measure of length. A millimeter is approximately 26-times smaller than an inch. [NIH] Mineralocorticoids: A group of corticosteroids primarily associated with the regulation of water and electrolyte balance. This is accomplished through the effect on ion transport in renal tubules, resulting in retention of sodium and loss of potassium. Mineralocorticoid secretion is itself regulated by plasma volume, serum potassium, and angiotensin II. [NIH] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Mononuclear: A cell with one nucleus. [NIH] Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motility: The ability to move spontaneously. [EU] Motor nerve: An efferent nerve conveying an impulse that excites muscular contraction. [NIH]

Mucinous: Containing or resembling mucin, the main compound in mucus. [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucolytic: Destroying or dissolving mucin; an agent that so acts : a mucopolysaccharide or

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glycoprotein, the chief constituent of mucus. [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Multivariate Analysis: A set of techniques used when variation in several variables has to be studied simultaneously. In statistics, multivariate analysis is interpreted as any analytic method that allows simultaneous study of two or more dependent variables. [NIH] Mutagen: Any agent, such as X-rays, gamma rays, mustard gas, TCDD, that can cause abnormal mutation in living cells; having the power to cause mutations. [NIH] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagenic: Inducing genetic mutation. [EU] Mutagenicity: Ability to damage DNA, the genetic material; the power to cause mutations. [NIH]

Myelin: The fatty substance that covers and protects nerves. [NIH] Myelin Sheath: The lipid-rich sheath investing many axons in both the central and peripheral nervous systems. The myelin sheath is an electrical insulator and allows faster and more energetically efficient conduction of impulses. The sheath is formed by the cell membranes of glial cells (Schwann cells in the peripheral and oligodendroglia in the central nervous system). Deterioration of the sheath in demyelinating diseases is a serious clinical problem. [NIH] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myoepithelioma: A benign tumor made up of myoepithelial cells. [NIH] Nasal Cavity: The proximal portion of the respiratory passages on either side of the nasal septum, lined with ciliated mucosa, extending from the nares to the pharynx. [NIH] Nasal Septum: The partition separating the two nasal cavities in the midplane, composed of cartilaginous, membranous and bony parts. [NIH] Natriuresis: The excretion of abnormal amounts of sodium in the urine. [EU] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Needle biopsy: The removal of tissue or fluid with a needle for examination under a microscope. Also called fine-needle aspiration. [NIH]

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Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Nephrectomy: Surgery to remove a kidney. Radical nephrectomy removes the kidney, the adrenal gland, nearby lymph nodes, and other surrounding tissue. Simple nephrectomy removes only the kidney. Partial nephrectomy removes the tumor but not the entire kidney. [NIH]

Nephroblastoma: A malignant kidney tumor made up of three cell types: blastemal, stromal, and epithelial, but not all present in every case. [NIH] Nephrogenic: Constant thirst and frequent urination because the kidney tubules cannot respond to antidiuretic hormone. The result is an increase in urine formation and excessive urine flow. [NIH] Nephropathy: Disease of the kidneys. [EU] Nerve Compression Syndromes: Mechanical compression of nerves or nerve roots from internal or external causes. These may result in a conduction block to nerve impulses (due to myelin sheath dysfunction) or axonal loss. The nerve and nerve sheath injuries may be caused by ischemia; inflammation; or a direct mechanical effect. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neuroectodermal tumor: A tumor of the central or peripheral nervous system. [NIH] Neuroendocrine: Having to do with the interactions between the nervous system and the endocrine system. Describes certain cells that release hormones into the blood in response to stimulation of the nervous system. [NIH] Neurogenic: Loss of bladder control caused by damage to the nerves controlling the bladder. [NIH] Neurologic: Having to do with nerves or the nervous system. [NIH] Neurosecretory Systems: A system of neurons that has the specialized function to produce and secrete hormones, and that constitutes, in whole or in part, an endocrine organ or system. [NIH] Neurosyphilis: A late form of syphilis that affects the brain and may lead to dementia and death. [NIH] Neurotoxic: Poisonous or destructive to nerve tissue. [EU] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH]

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Nevus: A benign growth on the skin, such as a mole. A mole is a cluster of melanocytes and surrounding supportive tissue that usually appears as a tan, brown, or flesh-colored spot on the skin. The plural of nevus is nevi (NEE-vye). [NIH] Nevus, Blue: Usually a benign tumor, that commonly presents as a solitary blue nodule with spindled melanocytes covered by smooth skin. Several variants have been identified, one variant being malignant. The blue color is caused by large, densely packed melanocytes deep in the dermis of the nevus. In children, they usually occur on the buttocks and lumbar area. Malignant blue nevi are more commonly found on the scalp. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]

Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with nucleoproteins which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH] Nucleoproteins: Proteins conjugated with nucleic acids. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Observational study: An epidemiologic study that does not involve any intervention, experimental or otherwise. Such a study may be one in which nature is allowed to take its course, with changes in one characteristic being studied in relation to changes in other characteristics. Analytical epidemiologic methods, such as case-control and cohort study designs, are properly called observational epidemiology because the investigator is observing without intervention other than to record, classify, count, and statistically analyze

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results. [NIH] Occult: Obscure; concealed from observation, difficult to understand. [EU] Occult Blood: Chemical, spectroscopic, or microscopic detection of extremely small amounts of blood. [NIH] Oculomotor: Cranial nerve III. It originate from the lower ventral surface of the midbrain and is classified as a motor nerve. [NIH] Oculomotor Nerve: The 3d cranial nerve. The oculomotor nerve sends motor fibers to the levator muscles of the eyelid and to the superior rectus, inferior rectus, and inferior oblique muscles of the eye. It also sends parasympathetic efferents (via the ciliary ganglion) to the muscles controlling pupillary constriction and accommodation. The motor fibers originate in the oculomotor nuclei of the midbrain. [NIH] Odds Ratio: The ratio of two odds. The exposure-odds ratio for case control data is the ratio of the odds in favor of exposure among cases to the odds in favor of exposure among noncases. The disease-odds ratio for a cohort or cross section is the ratio of the odds in favor of disease among the exposed to the odds in favor of disease among the unexposed. The prevalence-odds ratio refers to an odds ratio derived cross-sectionally from studies of prevalent cases. [NIH] Oedema: The presence of abnormally large amounts of fluid in the intercellular tissue spaces of the body; usually applied to demonstrable accumulation of excessive fluid in the subcutaneous tissues. Edema may be localized, due to venous or lymphatic obstruction or to increased vascular permeability, or it may be systemic due to heart failure or renal disease. Collections of edema fluid are designated according to the site, e.g. ascites (peritoneal cavity), hydrothorax (pleural cavity), and hydropericardium (pericardial sac). Massive generalized edema is called anasarca. [EU] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Oligomenorrhea: Abnormally infrequent menstruation. [NIH] Oligosaccharides: Carbohydrates consisting of between two and ten monosaccharides connected by either an alpha- or beta-glycosidic link. They are found throughout nature in both the free and bound form. [NIH] Omega-3 fatty acid: A type of fat obtained in the diet and involved in immunity. [NIH] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH] Oncologist: A doctor who specializes in treating cancer. Some oncologists specialize in a particular type of cancer treatment. For example, a radiation oncologist specializes in treating cancer with radiation. [NIH] Optic Chiasm: The X-shaped structure formed by the meeting of the two optic nerves. At the optic chiasm the fibers from the medial part of each retina cross to project to the other side of the brain while the lateral retinal fibers continue on the same side. As a result each half of the brain receives information about the contralateral visual field from both eyes. [NIH]

Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the

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lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [NIH] Orbit: One of the two cavities in the skull which contains an eyeball. Each eye is located in a bony socket or orbit. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Organogenesis: Clonal propagation which involves culturing explants from roots, leaves, or stems to form undifferentiated callus tissue; after the cells form shoots, they are separated and rooted. Alternatively, if the callus is put in liquid culture, somatic embryos form. [NIH] Orgasm: The crisis of sexual excitement in either humans or animals. [NIH] Ornithine: An amino acid produced in the urea cycle by the splitting off of urea from arginine. [NIH] Ornithine Decarboxylase: A pyridoxal-phosphate protein, believed to be the rate-limiting compound in the biosynthesis of polyamines. It catalyzes the decarboxylation of ornithine to form putrescine, which is then linked to a propylamine moiety of decarboxylated Sadenosylmethionine to form spermidine. EC 4.1.1.17. [NIH] Orofacial: Of or relating to the mouth and face. [EU] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Osteoarthritis: A progressive, degenerative joint disease, the most common form of arthritis, especially in older persons. The disease is thought to result not from the aging process but from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans. [NIH] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Otitis: Inflammation of the ear, which may be marked by pain, fever, abnormalities of hearing, hearing loss, tinnitus, and vertigo. [EU] Otolaryngologist: A doctor who specializes in treating diseases of the ear, nose, and throat. Also called an ENT doctor. [NIH] Otolaryngology: A surgical specialty concerned with the study and treatment of disorders of the ear, nose, and throat. [NIH] Otology: The branch of medicine which deals with the diagnosis and treatment of the disorders and diseases of the ear. [NIH] Otorhinolaryngology: That branch of medicine concerned with medical and surgical treatment of the head and neck, including the ears, nose and throat. [EU] Ouabain: A cardioactive glycoside consisting of rhamnose and ouabagenin, obtained from the seeds of Strophanthus gratus and other plants of the Apocynaceae; used like digitalis. It is commonly used in cell biological studies as an inhibitor of the NA(+)-K(+)-exchanging atpase. [NIH]

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Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Overweight: An excess of body weight but not necessarily body fat; a body mass index of 25 to 29.9 kg/m2. [NIH] Ovulation: The discharge of a secondary oocyte from a ruptured graafian follicle. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxalate: A chemical that combines with calcium in urine to form the most common type of kidney stone (calcium oxalate stone). [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Oxytocin: A nonapeptide posterior pituitary hormone that causes uterine contractions and stimulates lactation. [NIH] P53 gene: A tumor suppressor gene that normally inhibits the growth of tumors. This gene is altered in many types of cancer. [NIH] Palate: The structure that forms the roof of the mouth. It consists of the anterior hard palate and the posterior soft palate. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic cancer: Cancer of the pancreas, a salivary gland of the abdomen. [NIH] Pancreatic Juice: The fluid containing digestive enzymes secreted by the pancreas in response to food in the duodenum. [NIH] Pancreatitis: Acute or chronic inflammation of the pancreas, which may be asymptomatic or symptomatic, and which is due to autodigestion of a pancreatic tissue by its own enzymes. It is caused most often by alcoholism or biliary tract disease; less commonly it may be associated with hyperlipaemia, hyperparathyroidism, abdominal trauma (accidental or operative injury), vasculitis, or uraemia. [EU] Papilla: A small nipple-shaped elevation. [NIH] Papillary: Pertaining to or resembling papilla, or nipple. [EU] Papillary tumor: A tumor shaped like a small mushroom, with its stem attached to the epithelial layer (inner lining) of an organ. [NIH] Papilledema: Swelling around the optic disk. [NIH] Papilloma: A benign epithelial neoplasm which may arise from the skin, mucous membranes or glandular ducts. [NIH] Paraffin: A mixture of solid hydrocarbons obtained from petroleum. It has a wide range of uses including as a stiffening agent in ointments, as a lubricant, and as a topical anti-

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inflammatory. It is also commonly used as an embedding material in histology. [NIH] Paraffin Embedding: The infiltrating of tissue specimens with paraffin, as a supporting substance, to prepare for sectioning with a microtome. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] Paranasal Sinuses: Air-filled extensions of the respiratory part of the nasal cavity into the frontal, ethmoid, sphenoid, and maxillary cranial bones. They vary in size and form in different individuals and are lined by the ciliated mucous membranes of the nasal cavity. [NIH]

Paraparesis: Mild to moderate loss of bilateral lower extremity motor function, which may be a manifestation of spinal cord diseases; peripheral nervous system diseases; muscular diseases; intracranial hypertension; parasagittal brain lesions; and other conditions. [NIH] Parathyroid: 1. Situated beside the thyroid gland. 2. One of the parathyroid glands. 3. A sterile preparation of the water-soluble principle(s) of the parathyroid glands, ad-ministered parenterally as an antihypocalcaemic, especially in the treatment of acute hypoparathyroidism with tetany. [EU] Parathyroid Glands: Two small paired endocrine glands in the region of the thyroid gland. They secrete parathyroid hormone and are concerned with the metabolism of calcium and phosphorus. [NIH] Parathyroid hormone: A substance made by the parathyroid gland that helps the body store and use calcium. Also called parathormone, parathyrin, or PTH. [NIH] Parathyroidectomy: Excision of one or both of the parathyroid glands. [NIH] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Paresis: A general term referring to a mild to moderate degree of muscular weakness, occasionally used as a synonym for paralysis (severe or complete loss of motor function). In the older literature, paresis often referred specifically to paretic neurosyphilis. "General paresis" and "general paralysis" may still carry that connotation. Bilateral lower extremity paresis is referred to as paraparesis. [NIH] Parietal: 1. Of or pertaining to the walls of a cavity. 2. Pertaining to or located near the parietal bone, as the parietal lobe. [EU] Parotid: The space that contains the parotid gland, the facial nerve, the external carotid artery, and the retromandibular vein. [NIH] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Parturition: The act or process of given birth to a child. [EU] Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathologies: The study of abnormality, especially the study of diseases. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Satisfaction: The degree to which the individual regards the health care service or product or the manner in which it is delivered by the provider as useful, effective, or beneficial. [NIH]

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Pelvic: Pertaining to the pelvis. [EU] Pelvis: The lower part of the abdomen, located between the hip bones. [NIH] Penis: The external reproductive organ of males. It is composed of a mass of erectile tissue enclosed in three cylindrical fibrous compartments. Two of the three compartments, the corpus cavernosa, are placed side-by-side along the upper part of the organ. The third compartment below, the corpus spongiosum, houses the urethra. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] Perforation: 1. The act of boring or piercing through a part. 2. A hole made through a part or substance. [EU] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Perinatal: Pertaining to or occurring in the period shortly before and after birth; variously defined as beginning with completion of the twentieth to twenty-eighth week of gestation and ending 7 to 28 days after birth. [EU] Perineal: Pertaining to the perineum. [EU] Perineum: The area between the anus and the sex organs. [NIH] Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] Petroleum: Naturally occurring complex liquid hydrocarbons which, after distillation, yield combustible fuels, petrochemicals, and lubricants. [NIH] Pharmaceutical Solutions: Homogeneous liquid preparations that contain one or more chemical substances dissolved, i.e., molecularly dispersed, in a suitable solvent or mixture of mutually miscible solvents. For reasons of their ingredients, method of preparation, or use, they do not fall into another group of products. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer

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phenotype, characteristic of yeasts. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphoprotein Phosphatase: A group of enzymes removing the serine- or threoninebound phosphate groups from a wide range of phosphoproteins, including a number of enzymes which have been phosphorylated under the action of a kinase. (Enzyme Nomenclature, 1992) EC 3.1.3.16. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Photocoagulation: Using a special strong beam of light (laser) to seal off bleeding blood vessels such as in the eye. The laser can also burn away blood vessels that should not have grown in the eye. This is the main treatment for diabetic retinopathy. [NIH] Photodynamic therapy: Treatment with drugs that become active when exposed to light. These drugs kill cancer cells. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pilot Projects: Small-scale tests of methods and procedures to be used on a larger scale if the pilot study demonstrates that these methods and procedures can work. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Pituitary Apoplexy: Sudden hemorrhage or ischemic necrosis involving the pituitary gland which may be associated with acute visual loss, severe headache, meningeal signs, cranial nerve palsies, panhypopituitarism, and rarely coma. The most common cause is hemorrhage (intracranial hemorrhages) related to a pituitary adenoma. Ischemia, meningitis, intracranial hypertension, and other disorders may be associated with this condition. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Pituitary Hormone Release Inhibiting Hormones: Polypeptide hormones produced in the hypothalamus which inhibit the release of pituitary hormones. Used for PHRIH in general or for which there is no specific heading. [NIH] Pituitary Hormone-Releasing Hormones: Hormones released by one structure (e.g., the hypothalamus or the thyroid gland) that effect the secretion of hormones from the pituitary gland. [NIH] Pituitary Hormones: Hormones secreted by the anterior and posterior lobes of the pituitary

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gland and the pars intermedia, an ill-defined region between the two. Their secretion is regulated by the hypothalamus. [NIH] Pituitary Neoplasms: Neoplasms which arise from or metastasize to the pituitary gland. The majority of pituitary neoplasms are adenomas, which are divided into non-secreting and secreting forms. Hormone producing forms are further classified by the type of hormone they secrete. Pituitary adenomas may also be characterized by their staining properties (adenoma, basophil; adenoma, acidophil; and adenoma, chromophobe). Pituitary tumors may compress adjacent structures, including the hypothalamus, several cranial nerves, and the optic chiasm. Chiasmal compression may result in bitemporal hemianopsia. [NIH]

Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Plant Oils: Oils derived from plants or plant products. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] Plasmid: An autonomously replicating, extra-chromosomal DNA molecule found in many bacteria. Plasmids are widely used as carriers of cloned genes. [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Pleomorphic: Occurring in various distinct forms. In terms of cells, having variation in the size and shape of cells or their nuclei. [NIH] Pleura: The thin serous membrane enveloping the lungs and lining the thoracic cavity. [NIH] Pleural: A circumscribed area of hyaline whorled fibrous tissue which appears on the surface of the parietal pleura, on the fibrous part of the diaphragm or on the pleura in the interlobar fissures. [NIH] Pleural cavity: A space enclosed by the pleura (thin tissue covering the lungs and lining the interior wall of the chest cavity). It is bound by thin membranes. [NIH] Pneumonia: Inflammation of the lungs. [NIH]

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Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair. [NIH] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH] Polycystic Ovary Syndrome: Clinical symptom complex characterized by oligomenorrhea or amenorrhea, anovulation, and regularly associated with bilateral polycystic ovaries. [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polyp: A growth that protrudes from a mucous membrane. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polyposis: The development of numerous polyps (growths that protrude from a mucous membrane). [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Polyunsaturated fat: An unsaturated fat found in greatest amounts in foods derived from plants, including safflower, sunflower, corn, and soybean oils. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postoperative: After surgery. [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potassium Channels: Cell membrane glycoproteins selective for potassium ions. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precancerous: A term used to describe a condition that may (or is likely to) become cancer. Also called premalignant. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU]

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Predictive factor: A situation or condition that may increase a person's risk of developing a certain disease or disorder. [NIH] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Premalignant: A term used to describe a condition that may (or is likely to) become cancer. Also called precancerous. [NIH] Premenstrual Syndrome: A syndrome occurring most often during the last week of the menstrual cycle and ending soon after the onset of menses. Some of the symptoms are emotional instability, insomnia, headache, nausea, vomiting, abdominal distension, and painful breasts. [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Preoperative: Preceding an operation. [EU] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Primary Biliary Cirrhosis: A chronic liver disease. Slowly destroys the bile ducts in the liver. This prevents release of bile. Long-term irritation of the liver may cause scarring and cirrhosis in later stages of the disease. [NIH] Primary Sclerosing Cholangitis: Irritation, scarring, and narrowing of the bile ducts inside and outside the liver. Bile builds up in the liver and may damage its cells. Many people with this condition also have ulcerative colitis. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Progeny: The offspring produced in any generation. [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Prolactin: Pituitary lactogenic hormone. A polypeptide hormone with a molecular weight of about 23,000. It is essential in the induction of lactation in mammals at parturition and is synergistic with estrogen. The hormone also brings about the release of progesterone from lutein cells, which renders the uterine mucosa suited for the embedding of the ovum should fertilization occur. [NIH] Prolactinoma: A pituitary adenoma which secretes prolactin, leading to hyperprolactinemia. Clinical manifestations include amenorrhea; galactorrhea; impotence; headache; visual disturbances; and cerebrospinal fluid rhinorrhea. [NIH] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prone: Having the front portion of the body downwards. [NIH] Pro-Opiomelanocortin: A precursor protein, MW 30,000, synthesized mainly in the anterior pituitary gland but also found in the hypothalamus, brain, and several peripheral tissues. It

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incorporates the amino acid sequences of ACTH and beta-lipotropin. These two hormones, in turn, contain the biologically active peptides MSH, corticotropin-like intermediate lobe peptide, alpha-lipotropin, endorphins, and methionine enkephalin. [NIH] Prospective Studies: Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostaglandin Endoperoxides: Precursors in the biosynthesis of prostaglandins and thromboxanes from arachidonic acid. They are physiologically active compounds, having effect on vascular and airway smooth muscles, platelet aggregation, etc. [NIH] Prostaglandin-Endoperoxide Synthase: An enzyme complex that catalyzes the formation of prostaglandins from the appropriate unsaturated fatty acid, molecular oxygen, and a reduced acceptor. EC 1.14.99.1. [NIH] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] Prostaglandins F: (9 alpha,11 alpha,13E,15S)-9,11,15-Trihydroxyprost-13-en-1-oic acid (PGF(1 alpha)); (5Z,9 alpha,11,alpha,13E,15S)-9,11,15-trihydroxyprosta-5,13-dien-1-oic acid (PGF(2 alpha)); (5Z,9 alpha,11 alpha,13E,15S,17Z)-9,11,15-trihydroxyprosta-5,13,17-trien-1oic acid (PGF(3 alpha)). A family of prostaglandins that includes three of the six naturally occurring prostaglandins. All naturally occurring PGF have an alpha configuration at the 9carbon position. They stimulate uterine and bronchial smooth muscle and are often used as oxytocics. [NIH] Prostaglandins H: A group of physiologically active prostaglandin endoperoxides. They are precursors in the biosynthesis of prostaglandins and thromboxanes. The most frequently encountered member of this group is the prostaglandin H2. [NIH]

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Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Prostate gland: A gland in the male reproductive system just below the bladder. It surrounds part of the urethra, the canal that empties the bladder, and produces a fluid that forms part of semen. [NIH] Prostatectomy: Complete or partial surgical removal of the prostate. Three primary approaches are commonly employed: suprapubic - removal through an incision above the pubis and through the urinary bladder; retropubic - as for suprapubic but without entering the urinary bladder; and transurethral (transurethral resection of prostate). [NIH] Prostatic Hyperplasia: Enlargement or overgrowth of the prostate gland as a result of an increase in the number of its constituent cells. [NIH] Prostatitis: Inflammation of the prostate. [EU] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein. EC 2.7.1.37. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteoglycans: Glycoproteins which have a very high polysaccharide content. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Proteome: The protein complement of an organism coded for by its genome. [NIH] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU]

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Psychogenic: Produced or caused by psychic or mental factors rather than organic factors. [EU]

Puberty: The period during which the secondary sex characteristics begin to develop and the capability of sexual reproduction is attained. [EU] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Purpura: Purplish or brownish red discoloration, easily visible through the epidermis, caused by hemorrhage into the tissues. [NIH] Pustular: Pertaining to or of the nature of a pustule; consisting of pustules (= a visible collection of pus within or beneath the epidermis). [EU] Putrescine: A toxic diamine formed by putrefaction from the decarboxylation of arginine and ornithine. [NIH] Pyelonephritis: Inflammation of the kidney and its pelvis, beginning in the interstitium and rapidly extending to involve the tubules, glomeruli, and blood vessels; due to bacterial infection. [EU] Pyogenic: Producing pus; pyopoietic (= liquid inflammation product made up of cells and a thin fluid called liquor puris). [EU] Pyridoxal: 3-Hydroxy-5-(hydroxymethyl)-2-methyl-4- pyridinecarboxaldehyde. [NIH] Pyrimidines: A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (cytosine, thymine, and uracil) and form the basic structure of the barbiturates. [NIH] Pyruvate Kinase: ATP:pyruvate 2-O-phosphotransferase. A phosphotransferase that catalyzes reversibly the phosphorylation of pyruvate to phosphoenolpyruvate in the presence of ATP. It has four isozymes (L, R, M1, and M2). Deficiency of the enzyme results in hemolytic anemia. EC 2.7.1.40. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the

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waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH] Radioactivity: The quality of emitting or the emission of corpuscular or electromagnetic radiations consequent to nuclear disintegration, a natural property of all chemical elements of atomic number above 83, and possible of induction in all other known elements. [EU] Radioimmunotherapy: Radiotherapy where cytotoxic radionuclides are linked to antibodies in order to deliver toxins directly to tumor targets. Therapy with targeted radiation rather than antibody-targeted toxins (immunotoxins) has the advantage that adjacent tumor cells, which lack the appropriate antigenic determinants, can be destroyed by radiation cross-fire. Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (radiotherapy). [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease. [NIH] Radiopharmaceutical: Any medicinal product which, when ready for use, contains one or more radionuclides (radioactive isotopes) included for a medicinal purpose. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NIH] Ras gene: A gene that has been found to cause cancer when it is altered (mutated). Agents that block its activity may stop the growth of cancer. A ras peptide is a protein fragment produced by the ras gene. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Rebound effect: The characteristic of a drug to produce reverse effects when either the effect of the drug has passed, or when the patient no longer responds to the drug. [EU] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and

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causes a specific physiologic effect in the cell. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Rectal: By or having to do with the rectum. The rectum is the last 8 to 10 inches of the large intestine and ends at the anus. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflux: The term used when liquid backs up into the esophagus from the stomach. [NIH] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Relative risk: The ratio of the incidence rate of a disease among individuals exposed to a specific risk factor to the incidence rate among unexposed individuals; synonymous with risk ratio. Alternatively, the ratio of the cumulative incidence rate in the exposed to the cumulative incidence rate in the unexposed (cumulative incidence ratio). The term relative risk has also been used synonymously with odds ratio. This is because the odds ratio and relative risk approach each other if the disease is rare ( 5 percent of population) and the number of subjects is large. [NIH] Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal agenesis: The absence or severe malformation of one or both kidneys. [NIH] Renal cell carcinoma: A type of kidney cancer. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Renal pelvis: The area at the center of the kidney. Urine collects here and is funneled into the ureter, the tube that connects the kidney to the bladder. [NIH] Renal tubular: A defect in the kidneys that hinders their normal excretion of acids. Failure to excrete acids can lead to weak bones, kidney stones, and poor growth in children. [NIH] Reproductive cells: Egg and sperm cells. Each mature reproductive cell carries a single set of 23 chromosomes. [NIH] Reproductive system: In women, this system includes the ovaries, the fallopian tubes, the uterus (womb), the cervix, and the vagina (birth canal). The reproductive system in men includes the prostate, the testes, and the penis. [NIH] Resected: Surgical removal of part of an organ. [NIH] Resection: Removal of tissue or part or all of an organ by surgery. [NIH] Resorption: The loss of substance through physiologic or pathologic means, such as loss of

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dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinal Hemorrhage: Bleeding from the vessels of the retina. [NIH] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retinoblastoma Protein: Product of the retinoblastoma tumor suppressor gene. It is a nuclear phosphoprotein hypothesized to normally act as an inhibitor of cell proliferation. Rb protein is absent in retinoblastoma cell lines. It also has been shown to form complexes with the adenovirus E1A protein, the SV40 T antigen, and the human papilloma virus E7 protein. [NIH]

Retinoids: Derivatives of vitamin A. Used clinically in the treatment of severe cystic acne, psoriasis, and other disorders of keratinization. Their possible use in the prophylaxis and treatment of cancer is being actively explored. [NIH] Retrograde: 1. Moving backward or against the usual direction of flow. 2. Degenerating, deteriorating, or catabolic. [EU] Retroperitoneal: Having to do with the area outside or behind the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Retropubic: A potential space between the urinary bladder and the symphisis and body of the pubis. [NIH] Retrosternal: Situated or occurring behind the sternum. [EU] Rhabdoid tumor: A malignant tumor of either the central nervous system (CNS) or the kidney. Malignant rhabdoid tumors of the CNS often have an abnormality of chromosome 22. These tumors usually occur in children younger than 2 years. [NIH] Rhamnose: A methylpentose whose L- isomer is found naturally in many plant glycosides and some gram-negative bacterial lipopolysaccharides. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Rhinorrhea: The free discharge of a thin nasal mucus. [EU]

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Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Risk patient: Patient who is at risk, because of his/her behaviour or because of the type of person he/she is. [EU] Rye: A hardy grain crop, Secale cereale, grown in northern climates. It is the most frequent host to ergot (claviceps), the toxic fungus. Its hybrid with wheat is triticale, another grain. [NIH]

Saline: A solution of salt and water. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary Gland Neoplasms: Tumors or cancer of the salivary glands. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] Sarcoma: A connective tissue neoplasm formed by proliferation of mesodermal cells; it is usually highly malignant. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Scrotum: In males, the external sac that contains the testicles. [NIH] Sebaceous: Gland that secretes sebum. [NIH] Sebaceous gland: Gland that secretes sebum. [NIH] Sebum: The oily substance secreted by sebaceous glands. It is composed of keratin, fat, and cellular debris. [NIH] Secondary tumor: Cancer that has spread from the organ in which it first appeared to another organ. For example, breast cancer cells may spread (metastasize) to the lungs and cause the growth of a new tumor. When this happens, the disease is called metastatic breast cancer, and the tumor in the lungs is called a secondary tumor. Also called secondary cancer. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Sediment: A precipitate, especially one that is formed spontaneously. [EU] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to

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as epilepsy or "seizure disorder." [NIH] Selenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of glutathione peroxidase. [NIH] Sella: A deep depression in the shape of a Turkish saddle in the upper surface of the body of the sphenoid bone in the deepest part of which is lodged the hypophysis cerebri. [NIH] Sella Turcica: A bony prominence situated on the upper surface of the body of the sphenoid bone. It houses the pituitary gland. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Seminal vesicles: Glands that help produce semen. [NIH] Seminiferous tubule: Tube used to transport sperm made in the testes. [NIH] Senescence: The bodily and mental state associated with advancing age. [NIH] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sensibility: The ability to receive, feel and appreciate sensations and impressions; the quality of being sensitive; the extend to which a method gives results that are free from false negatives. [NIH] Sensor: A device designed to respond to physical stimuli such as temperature, light, magnetism or movement and transmit resulting impulses for interpretation, recording, movement, or operating control. [NIH] Sepsis: The presence of bacteria in the bloodstream. [NIH] Sequence Analysis: A multistage process that includes the determination of a sequence (protein, carbohydrate, etc.), its fragmentation and analysis, and the interpretation of the resulting sequence information. [NIH] Sequence Homology: The degree of similarity between sequences. Studies of amino acid and nucleotide sequences provide useful information about the genetic relatedness of certain species. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serrata: The serrated anterior border of the retina located approximately 8.5 mm from the limbus and adjacent to the pars plana of the ciliary body. [NIH] Serrated: Having notches or teeth on the edge as a saw has. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins

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have been removed. [NIH] Sessile: Attached directly by the base, denoting a tumor without penduncle or stalk; in zoology, attached so that it is not possible to move about. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Sigmoid: 1. Shaped like the letter S or the letter C. 2. The sigmoid colon. [EU] Sigmoid Colon: The lower part of the colon that empties into the rectum. [NIH] Sigmoidal: S-shaped; shaped like the letter sigma. [NIH] Sigmoidoscopy: Endoscopic examination, therapy or surgery of the sigmoid flexure. [NIH] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signet ring cell carcinoma: A highly malignant type of cancer typically found in glandular cells that line the digestive organs. The cells resemble signet rings when examined under a microscope. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Sleep apnea: A serious, potentially life-threatening breathing disorder characterized by repeated cessation of breathing due to either collapse of the upper airway during sleep or absence of respiratory effort. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH]

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Smallpox: A generalized virus infection with a vesicular rash. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Social Support: Support systems that provide assistance and encouragement to individuals with physical or emotional disabilities in order that they may better cope. Informal social support is usually provided by friends, relatives, or peers, while formal assistance is provided by churches, groups, etc. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Soft Tissue Neoplasms: Neoplasms of whatever cell type or origin, occurring in the extraskeletal connective tissue framework of the body including the organs of locomotion and their various component structures, such as nerves, blood vessels, lymphatics, etc. [NIH] Soft tissue sarcoma: A sarcoma that begins in the muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Somatomedins: Insulin-like polypeptides made by the liver and some fibroblasts and released into the blood when stimulated by somatotropin. They cause sulfate incorporation into collagen, RNA, and DNA synthesis, which are prerequisites to cell division and growth of the organism. [NIH] Somatotropin: A small peptide hormone released by the anterior pituitary under hypothalamic control. Somatotropin, or growth hormone, stimulates mitosis, cell growth, and, for some cell types, differentiation in many tissues of the body. It has profound effects on many aspects of gene expression and metabolism. [NIH] Soybean Oil: Oil from soybean or soybean plant. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectroscopic: The recognition of elements through their emission spectra. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by

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refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Spermidine: A polyamine formed from putrescine. It is found in almost all tissues in association with nucleic acids. It is found as a cation at all pH values, and is thought to help stabilize some membranes and nucleic acid structures. It is a precursor of spermine. [NIH] Sphenoid: An unpaired cranial bone with a body containing the sphenoid sinus and forming the posterior part of the medial walls of the orbits. [NIH] Sphenoid Sinus: One of the paired paranasal sinuses, located in the body of the sphenoid bone and communicating with the highest meatus of the nasal cavity on the same side. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinous: Like a spine or thorn in shape; having spines. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Squamous: Scaly, or platelike. [EU] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cells: Flat cells that look like fish scales under a microscope. These cells cover internal and external surfaces of the body. [NIH] Squamous Epithelium: Tissue in an organ such as the esophagus. Consists of layers of flat, scaly cells. [NIH] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]

Stenosis: Narrowing or stricture of a duct or canal. [EU] Sterile: Unable to produce children. [NIH] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] Sternum: Breast bone. [NIH] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]

Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other

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excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stricture: The abnormal narrowing of a body opening. Also called stenosis. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stroma: The middle, thickest layer of tissue in the cornea. [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Sublingual: Located beneath the tongue. [EU] Submandibular: Four to six lymph glands, located between the lower jaw and the submandibular salivary gland. [NIH] Submaxillary: Four to six lymph glands, located between the lower jaw and the submandibular salivary gland. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Substrate: A substance upon which an enzyme acts. [EU] Sulindac: A sulfinylindene derivative whose sulfinyl moiety is converted in vivo to an active anti-inflammatory analgesic that undergoes enterohepatic circulation to maintain constant blood levels without causing gastrointestinal side effects. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suppressive: Tending to suppress : effecting suppression; specifically : serving to suppress activity, function, symptoms. [EU] Supraclavicular: The depression above the clavicle and lateral to the sternomastoid muscle. [NIH]

Sweat: The fluid excreted by the sweat glands. It consists of water containing sodium chloride, phosphate, urea, ammonia, and other waste products. [NIH] Sweat Glands: Sweat-producing structures that are embedded in the dermis. Each gland

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consists of a single tube, a coiled body, and a superficial duct. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Syringoma: Adenoma of the sweat glands. [NIH] Systemic: Affecting the entire body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Taurine: 2-Aminoethanesulfonic acid. A conditionally essential nutrient, important during mammalian development. It is present in milk but is isolated mostly from ox bile and strongly conjugates bile acids. [NIH] Technetium: The first artificially produced element and a radioactive fission product of uranium. The stablest isotope has a mass number 99 and is used diagnostically as a radioactive imaging agent. Technetium has the atomic symbol Tc, atomic number 43, and atomic weight 98.91. [NIH] Telomerase: Essential ribonucleoprotein reverse transcriptase that adds telomeric DNA to the ends of eukaryotic chromosomes. Telomerase appears to be repressed in normal human somatic tissues but reactivated in cancer, and thus may be necessary for malignant transformation. EC 2.7.7.-. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [EU] Terminator: A DNA sequence sited at the end of a transcriptional unit that signals the end of transcription. [NIH] Testicles: The two egg-shaped glands found inside the scrotum. They produce sperm and male hormones. Also called testes. [NIH] Testicular: Pertaining to a testis. [EU] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Tetany: 1. Hyperexcitability of nerves and muscles due to decrease in concentration of extracellular ionized calcium, which may be associated with such conditions as parathyroid hypofunction, vitamin D deficiency, and alkalosis or result from ingestion of alkaline salts; it is characterized by carpopedal spasm, muscular twitching and cramps, laryngospasm with inspiratory stridor, hyperreflexia and choreiform movements. 2. Tetanus. [EU]

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Tetracycline: An antibiotic originally produced by Streptomyces viridifaciens, but used mostly in synthetic form. It is an inhibitor of aminoacyl-tRNA binding during protein synthesis. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Third Ventricle: A narrow cleft inferior to the corpus callosum, within the diencephalon, between the paired thalami. Its floor is formed by the hypothalamus, its anterior wall by the lamina terminalis, and its roof by ependyma. It communicates with the fourth ventricle by the cerebral aqueduct, and with the lateral ventricles by the interventricular foramina. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]

Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase. [NIH] Thymidine: A chemical compound found in DNA. Also used as treatment for mucositis. [NIH]

Thymidylate Synthase: An enzyme of the transferase class that catalyzes the reaction 5,10methylenetetrahydrofolate and dUMP to dihydrofolate and dTMP in the synthesis of thymidine triphosphate. (From Dorland, 27th ed) EC 2.1.1.45. [NIH] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyroid Hormones: Hormones secreted by the thyroid gland. [NIH] Thyroiditis: Inflammation of the thyroid gland. [NIH] Thyrotropin: A peptide hormone secreted by the anterior pituitary. It promotes the growth of the thyroid gland and stimulates the synthesis of thyroid hormones and the release of thyroxine by the thyroid gland. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tinnitus: Sounds that are perceived in the absence of any external noise source which may take the form of buzzing, ringing, clicking, pulsations, and other noises. Objective tinnitus

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refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of cochlear diseases; vestibulocochlear nerve diseases; intracranial hypertension; craniocerebral trauma; and other conditions. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tone: 1. The normal degree of vigour and tension; in muscle, the resistance to passive elongation or stretch; tonus. 2. A particular quality of sound or of voice. 3. To make permanent, or to change, the colour of silver stain by chemical treatment, usually with a heavy metal. [EU] Tonicity: The normal state of muscular tension. [NIH] Topical: On the surface of the body. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicokinetics: Study of the absorption, distribution, metabolism, and excretion of test substances. [NIH] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Transcriptase: An enzyme which catalyses the synthesis of a complementary mRNA molecule from a DNA template in the presence of a mixture of the four ribonucleotides (ATP, UTP, GTP and CTP). [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer

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both local and systemic cellular immunity to nonimmune recipients. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Transurethral: Performed through the urethra. [EU] Transurethral resection: Surgery performed with a special instrument inserted through the urethra. Also called TUR. [NIH] Transurethral Resection of Prostate: Resection of the prostate using a cystoscope passed through the urethra. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Trigeminal: Cranial nerve V. It is sensory for the eyeball, the conjunctiva, the eyebrow, the skin of face and scalp, the teeth, the mucous membranes in the mouth and nose, and is motor to the muscles of mastication. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tuberculosis, Renal: Infection of the kidney with species of Mycobacterium. [NIH] Tubulin: A microtubule subunit protein found in large quantities in mammalian brain. It has also been isolated from sperm flagella, cilia, and other sources. Structurally, the protein is a dimer with a molecular weight of approximately 120,000 and a sedimentation coefficient of 5.8S. It binds to colchicine, vincristine, and vinblastine. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumor model: A type of animal model which can be used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Tumor suppressor gene: Genes in the body that can suppress or block the development of cancer. [NIH] Tumorigenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH]

Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU]

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Tunica: A rather vague term to denote the lining coat of hollow organs, tubes, or cavities. [NIH]

Tympanic membrane: A thin, tense membrane forming the greater part of the outer wall of the tympanic cavity and separating it from the external auditory meatus; it constitutes the boundary between the external and middle ear. [NIH] Type 2 diabetes: Usually characterized by a gradual onset with minimal or no symptoms of metabolic disturbance and no requirement for exogenous insulin. The peak age of onset is 50 to 60 years. Obesity and possibly a genetic factor are usually present. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ulceration: 1. The formation or development of an ulcer. 2. An ulcer. [EU] Ulcerative colitis: Chronic inflammation of the colon that produces ulcers in its lining. This condition is marked by abdominal pain, cramps, and loose discharges of pus, blood, and mucus from the bowel. [NIH] Ulcerogenic: Causing ulceration; leading to the production of ulcers. [EU] Urachus: The urinary canal of the fetus; postnatally it is usually a fibrous cord but occasionally persists as a vesicoumbilical fistula. [NIH] Uracil: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH] Uraemia: 1. An excess in the blood of urea, creatinine, and other nitrogenous end products of protein and amino acids metabolism; more correctly referred to as azotemia. 2. In current usage the entire constellation of signs and symptoms of chronic renal failure, including nausea, vomiting anorexia, a metallic taste in the mouth, a uraemic odour of the breath, pruritus, uraemic frost on the skin, neuromuscular disorders, pain and twitching in the muscles, hypertension, edema, mental confusion, and acid-base and electrolyte imbalances. [EU]

Uranium: A radioactive element of the actinide series of metals. It has an atomic symbol U, atomic number 92, and atomic weight 238.03. U-235 is used as the fissionable fuel in nuclear weapons and as fuel in nuclear power reactors. [NIH] Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. [NIH] Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [NIH] Ureters: Tubes that carry urine from the kidneys to the bladder. [NIH] Urethane: Antineoplastic agent that is also used as a veterinary anesthetic. It has also been used as an intermediate in organic synthesis. Urethane is suspected to be a carcinogen. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Urethral Obstruction: Obstruction anywhere along the urethra. [NIH] Urinalysis: Examination of urine by chemical, physical, or microscopic means. Routine urinalysis usually includes performing chemical screening tests, determining specific gravity, observing any unusual color or odor, screening for bacteriuria, and examining the sediment microscopically. [NIH] Urinary: Having to do with urine or the organs of the body that produce and get rid of

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urine. [NIH] Urinary Fistula: An abnormal passage in any organ of the urinary tract or between urinary organs and other organs. [NIH] Urinary Retention: Inability to urinate. The etiology of this disorder includes obstructive, neurogenic, pharmacologic, and psychogenic causes. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [NIH] Urinary tract infection: An illness caused by harmful bacteria growing in the urinary tract. [NIH]

Urinate: To release urine from the bladder to the outside. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Urogenital: Pertaining to the urinary and genital apparatus; genitourinary. [EU] Ursodeoxycholic Acid: An epimer of chenodeoxycholic acid. It is a mammalian bile acid found first in the bear and is apparently either a precursor or a product of chenodeoxycholate. Its administration changes the composition of bile and may dissolve gallstones. It is used as a cholagogue and choleretic. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Vaccination: Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vaccinia: The cutaneous and occasional systemic reactions associated with vaccination using smallpox (variola) vaccine. [NIH] Vaccinia Virus: The type species of Orthopoxvirus, related to cowpox virus, but whose true origin is unknown. It has been used as a live vaccine against smallpox. It is also used as a vector for inserting foreign DNA into animals. Rabbitpox virus is a subspecies of vaccinia virus. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginal: Of or having to do with the vagina, the birth canal. [NIH] Variola: A generalized virus infection with a vesicular rash. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vascular endothelial growth factor: VEGF. A substance made by cells that stimulates new blood vessel formation. [NIH] Vasculitis: Inflammation of a blood vessel. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vasomotor: 1. Affecting the calibre of a vessel, especially of a blood vessel. 2. Any element or agent that effects the calibre of a blood vessel. [EU] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venereal: Pertaining or related to or transmitted by sexual contact. [EU]

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Venous: Of or pertaining to the veins. [EU] Ventral: 1. Pertaining to the belly or to any venter. 2. Denoting a position more toward the belly surface than some other object of reference; same as anterior in human anatomy. [EU] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vertigo: An illusion of movement; a sensation as if the external world were revolving around the patient (objective vertigo) or as if he himself were revolving in space (subjective vertigo). The term is sometimes erroneously used to mean any form of dizziness. [EU] Vestibular: Pertaining to or toward a vestibule. In dental anatomy, used to refer to the tooth surface directed toward the vestibule of the mouth. [EU] Vestibule: A small, oval, bony chamber of the labyrinth. The vestibule contains the utricle and saccule, organs which are part of the balancing apparatus of the ear. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Villi: The tiny, fingerlike projections on the surface of the small intestine. Villi help absorb nutrients. [NIH] Villous: Of a surface, covered with villi. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral vector: A type of virus used in cancer therapy. The virus is changed in the laboratory and cannot cause disease. Viral vectors produce tumor antigens (proteins found on a tumor cell) and can stimulate an antitumor immune response in the body. Viral vectors may also be used to carry genes that can change cancer cells back to normal cells. [NIH] Virilism: Development of masculine traits in the female. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Visual field: The entire area that can be seen when the eye is forward, including peripheral vision. [NIH] Vitamin A: A substance used in cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Vitelline Membrane: The plasma membrane of the egg. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH]

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Vulva: The external female genital organs, including the clitoris, vaginal lips, and the opening to the vagina. [NIH] Wart: A raised growth on the surface of the skin or other organ. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Womb: A hollow, thick-walled, muscular organ in which the impregnated ovum is developed into a child. [NIH] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xanthoma: A tumour composed of lipid-laden foam cells, which are histiocytes containing cytoplasmic lipid material. Called also xanthelasma. [EU] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] X-ray therapy: The use of high-energy radiation from x-rays to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. X-ray therapy is also called radiation therapy, radiotherapy, and irradiation. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Yolk Sac: An embryonic membrane formed from endoderm and mesoderm. In reptiles and birds it incorporates the yolk into the digestive tract for nourishing the embryo. In placental mammals its nutritional function is vestigial; however, it is the source of most of the intestinal mucosa and the site of formation of the germ cells. It is sometimes called the vitelline sac, which should not be confused with the vitelline membrane of the egg. [NIH] Zebrafish: A species of North American fishes of the family Cyprinidae. They are used in embryological studies and to study the effects of certain chemicals on development. [NIH] Zygote: The fertilized ovum. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]

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INDEX 1 1,2-Dimethylhydrazine, 55, 134, 197 A Abdomen, 42, 197, 206, 212, 218, 223, 238, 239, 241, 251, 253, 263, 269, 276 Abdominal, 131, 144, 157, 165, 197, 198, 219, 251, 253, 257, 263, 274 Abdominal Pain, 197, 274 Aberrant, 6, 26, 30, 35, 45, 60, 109, 134, 169, 197 Ablation, 25, 41, 64, 197, 234 Accommodation, 197, 249 Acetaldehyde, 197, 199 Acetylcholine, 197, 210, 247, 248 Acidosis, 197 Acne, 145, 149, 150, 155, 157, 197, 239, 263 Acne Vulgaris, 145, 149, 150, 197, 239 Actin, 60, 197 Acupuncture Anesthesia, 130, 197 Adaptability, 197, 209 Adenocarcinoma, 40, 42, 45, 62, 75, 79, 81, 85, 96, 112, 113, 153, 160, 161, 197, 232 Adenoma, Chromophobe, 197, 255 Adenomatous Polyposis Coli, 9, 32, 35, 48, 67, 68, 69, 70, 143, 197 Adenosine, 198, 207, 254 Adenovirus, 65, 198, 263 Adipocytes, 198, 215, 240 Adipose Tissue, 134, 198 Adjuvant, 55, 198 Adnexa, 87, 198 Adrenal Cortex, 198, 199, 216, 224, 234, 257 Adrenal Glands, 158, 162, 198 Adrenal insufficiency, 5, 159, 198 Adrenergic, 198, 220, 223, 270 Adverse Effect, 198, 239, 266 Aerobic, 198, 245 Aerosol, 12, 198 Afferent, 197, 198, 216, 225, 240 Affinity, 16, 146, 198, 199, 267 Agar, 44, 198, 217, 235 Age of Onset, 198, 274 Age-Adjusted, 160, 199 Agenesis, 162, 199 Agglutinins, 120, 199 Aggravation, 146, 199 Agonist, 10, 43, 120, 146, 199, 220

Airway, 199, 258, 266 Albumin, 108, 199, 255 Alcohol Dehydrogenase, 27, 31, 199 Aldosterone, 70, 71, 82, 94, 99, 135, 169, 199 Alertness, 199, 207 Algorithms, 57, 199, 205 Alimentary, 186, 199, 219, 252 Alkaline, 197, 199, 200, 207, 270 Alkylating Agents, 199, 274 Alleles, 5, 47, 199, 232, 241 Allelic Imbalance, 47, 199 Allergen, 200, 218 Allergic Rhinitis, 200, 206 Allylamine, 200 Alopecia, 155, 200 Alpha Particles, 200, 261 Alpha-1, 70, 200 Alpha-fetoprotein, 108, 113, 200, 226 Alternative medicine, 170, 200 Alveolar Process, 200, 263 Amenorrhea, 145, 149, 150, 200, 256, 257 Amine, 18, 119, 200, 233 Amino Acid Sequence, 200, 201, 225, 228, 258 Amino Acids, 148, 200, 212, 228, 253, 256, 259, 264, 265, 273, 274 Ammonia, 130, 200, 269, 274 Ampulla, 101, 118, 160, 161, 200, 222 Anaesthesia, 125, 130, 200, 236 Anal, 19, 200, 223, 246 Analgesic, 201, 235, 239, 269 Analog, 201, 226, 240 Analogous, 201, 272 Anaphylatoxins, 201, 213 Androgens, 144, 198, 201, 216, 234 Anemia, 36, 201, 227, 260 Anemic, 36, 201 Anesthesia, 158, 199, 201 Angiolymphoid Hyperplasia with Eosinophilia, 160, 201 Animal Husbandry, 145, 149, 150, 201 Animal model, 9, 25, 26, 40, 134, 201, 273 Anions, 199, 201, 238 Anovulation, 201, 256 Antagonism, 201, 207 Anterior chamber, 201, 238 Anthropometry, 40, 201

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Antiallergic, 201, 216, 217 Antibiotic, 66, 201, 268, 271 Antibodies, 8, 14, 39, 156, 199, 201, 202, 231, 235, 255, 261 Antibody, 88, 142, 198, 202, 213, 231, 233, 235, 236, 238, 243, 245, 261, 267, 277 Anticarcinogenic, 27, 136, 202 Anticarcinogenic Agents, 136, 202 Anticoagulant, 202, 259 Antidiuretic, 202, 247 Antigen, 77, 114, 198, 199, 201, 202, 213, 233, 234, 235, 236, 243, 263 Antigen-Antibody Complex, 202, 213 Anti-inflammatory, 10, 28, 153, 202, 203, 208, 216, 229, 235, 239, 252, 269 Anti-Inflammatory Agents, 202, 203, 208, 216 Antimetabolite, 202, 224, 226 Antimicrobial, 202, 220 Antineoplastic, 103, 199, 202, 216, 226, 274 Antineoplastic Agents, 199, 202 Antipruritic, 202, 217 Antipyretic, 202, 239 Anus, 200, 202, 206, 213, 253, 262 Anxiety, 12, 202 Apnea, 202 Apocrine Glands, 162, 202 Apolipoproteins, 203, 241 Apoptosis, 9, 11, 14, 20, 22, 24, 29, 30, 40, 48, 61, 62, 66, 68, 79, 89, 94, 105, 126, 132, 203, 224 Applicability, 81, 203 Aqueous, 148, 203, 204, 211, 217, 221, 233, 241 Arachidonic Acid, 32, 203, 217, 221, 240, 258 Arginine, 201, 203, 233, 248, 250, 260 Arterial, 200, 203, 206, 210, 215, 234, 259, 270 Arteries, 203, 206, 215, 241, 246, 271 Arterioles, 203, 206 Artery, 203, 216, 219, 221, 243, 252, 260 Asbestos, 203, 213 Ascites, 203, 249 Aspiration, 87, 99, 107, 110, 203, 226 Aspirin, 28, 54, 57, 70, 72, 80, 118, 167, 168, 169, 203 Assay, 12, 15, 16, 19, 29, 42, 55, 72, 136, 142, 203 Asymptomatic, 165, 203, 210, 251 Attenuated, 9, 70, 203 Attenuation, 36, 203

Atypical, 47, 74, 98, 164, 203 Auditory, 101, 159, 163, 203, 243, 274 Autodigestion, 203, 251 Azoxymethane, 66, 203 B Bacterial toxin, 152, 204 Bacterium, 204, 214, 232 Bacteriuria, 204, 274 Basal cell carcinoma, 151, 160, 204 Basal cells, 204 Base, 8, 51, 204, 228, 239, 256, 266, 270, 274 Basement Membrane, 34, 204, 208, 225, 239 Basophil, 204, 255 Benign prostatic hyperplasia, 154, 158, 204 Benign tumor, 152, 160, 161, 162, 163, 164, 165, 197, 204, 226, 240, 246, 248 Benzo(a)pyrene, 11, 129, 204 Bilateral, 75, 147, 162, 204, 231, 252, 256 Bile, 45, 46, 53, 75, 79, 86, 105, 126, 147, 161, 204, 205, 210, 217, 218, 222, 227, 239, 241, 257, 268, 270, 275 Bile Acids, 46, 105, 204, 268, 270 Bile Acids and Salts, 204 Bile duct, 75, 79, 86, 161, 204, 205, 257 Bile Pigments, 204, 239 Biliary, 72, 114, 160, 161, 205, 213, 251 Biliary Tract, 114, 205, 251 Bilirubin, 199, 204, 205, 234 Binding Sites, 152, 205 Bioassay, 136, 205 Biochemical, 8, 29, 30, 43, 59, 60, 62, 126, 142, 156, 199, 202, 205, 240, 250, 265 Biological response modifier, 205, 237 Biological therapy, 205, 231, 243 Biological Transport, 205, 219 Biomarkers, 10, 11, 12, 14, 20, 27, 34, 51, 80, 82, 96, 103, 113, 127, 128, 132, 133, 135, 205 Biopsy, 15, 87, 99, 147, 160, 205, 253 Biopsy specimen, 15, 205 Biosynthesis, 28, 154, 203, 205, 250, 258, 265 Biotechnology, 67, 71, 170, 181, 205 Biotransformation, 205 Bladder, 11, 57, 104, 154, 155, 158, 159, 162, 204, 205, 214, 236, 238, 247, 259, 262, 263, 274, 275 Blastocyst, 205, 214, 255 Blood Coagulation, 205, 207, 271 Blood Glucose, 206, 232, 237 Blood pressure, 144, 206, 208, 234, 245, 267

281

Body Composition, 144, 206 Body Fluids, 142, 205, 206, 220, 267, 273 Body Mass Index, 206, 251 Bone Marrow, 206, 228, 235, 242, 267, 269 Boron, 206, 217 Bowel, 9, 130, 160, 168, 200, 206, 219, 236, 238, 240, 253, 269, 274 Bowel Movement, 206, 219, 269 Brachytherapy, 206, 237, 238, 261, 277 Bradykinin, 206, 248, 255 Brain Ischemia, 206, 234 Breeding, 201, 206 Bronchial, 76, 206, 233, 258 Bronchoalveolar Lavage, 10, 206 Budesonide, 10, 11, 42, 206 Butyric Acid, 206, 224 C Caffeine, 18, 207, 260 Calcification, 107, 207 Calcium Carbonate, 9, 207 Calcium Oxalate, 207, 251 Callus, 207, 239, 250 Capsules, 135, 144, 207, 220 Carbohydrate, 60, 207, 216, 229, 230, 256, 265 Carbon Dioxide, 207, 218, 255, 263 Carboxy, 61, 207 Carboxy-terminal, 61, 207 Carcinoembryonic Antigen, 88, 207 Carcinogen, 6, 12, 18, 26, 197, 203, 204, 207, 244, 274 Carcinogenesis, 9, 10, 18, 22, 23, 24, 27, 31, 32, 40, 43, 48, 55, 57, 58, 59, 62, 66, 89, 96, 126, 133, 134, 202, 207, 210 Carcinogenic, 27, 34, 199, 202, 207, 219, 237, 249, 257, 268, 273 Carcinoid, 73, 162, 207 Carcinoma in Situ, 208 Carcinosarcoma, 87, 93, 208 Cardiac, 147, 200, 207, 208, 215, 221, 223, 230, 246, 268 Cardiomyopathy, 142, 208 Cardiovascular, 14, 105, 144, 208, 240, 265 Cardiovascular disease, 14, 105, 144, 208 Carotene, 103, 125, 127, 135, 168, 208, 263 Carotenoids, 127, 208 Case-Control Studies, 28, 31, 62, 208, 223 Catecholamine, 208, 220 Cations, 208, 238 Caudal, 208, 235, 256 Causal, 208, 223 Cavernous Sinus, 84, 95, 208

Cecum, 40, 208, 240 Celecoxib, 20, 48, 53, 174, 208 Celiac Disease, 109, 208 Cell Cycle, 7, 26, 29, 30, 39, 43, 45, 58, 65, 66, 209, 217 Cell Cycle Proteins, 43, 209 Cell Death, 62, 152, 203, 209, 224, 246 Cell Differentiation, 209, 266 Cell Division, 204, 209, 231, 245, 255, 264, 267 Cell Extracts, 16, 209 Cell Lineage, 44, 47, 61, 209 Cell membrane, 61, 205, 209, 218, 225, 239, 246, 254, 256 Cell proliferation, 11, 37, 44, 65, 126, 129, 209, 263, 266 Cell Respiration, 209, 245, 263 Cell Survival, 30, 209, 231 Cell Transplantation, 86, 209 Central Nervous System, 65, 197, 207, 209, 210, 227, 229, 231, 240, 246, 250, 263, 265 Central Nervous System Infections, 209, 231 Cerebral, 144, 209, 223, 271 Cerebrospinal, 209, 257 Cerebrospinal fluid, 209, 257 Cerebrovascular, 208, 209 Cerebrum, 209 Cerumen, 160, 163, 210 Cervical, 149, 210 Cervix, 81, 96, 145, 150, 210, 213, 262 Character, 210, 218, 229 Chemoprevention, 6, 10, 11, 13, 17, 21, 35, 42, 52, 58, 72, 127, 154, 210 Chemopreventive, 6, 11, 15, 34, 42, 43, 53, 57, 62, 67, 120, 127, 210 Chemoprotective, 6, 210 Chemotactic Factors, 210, 213 Chemotherapeutic agent, 152, 210 Chemotherapy, 55, 210, 243 Chenodeoxycholic Acid, 210, 275 Chimeric Proteins, 152, 210 Chin, 144, 210, 244 Choledochal Cyst, 86, 210 Choleretic, 210, 218, 275 Cholesteatoma, 160, 210 Cholesterol, 204, 210, 211, 215, 241, 268 Cholesterol Esters, 210, 241 Choline, 24, 119, 210 Chondrocytes, 211, 226 Chromaffin System, 211, 222 Chromatin, 48, 203, 209, 211, 223, 242

282

Adenoma

Chromosomal, 44, 48, 55, 67, 69, 211, 233, 255 Chromosome, 8, 33, 49, 55, 143, 211, 214, 228, 231, 239, 241, 263, 264 Chronic Disease, 27, 36, 211 Chronic prostatitis, 136, 211 Chronic renal, 71, 211, 256, 274 Chylomicrons, 211, 241 Cicatrix, 211, 239 Cicatrix, Hypertrophic, 211, 239 Ciliary, 72, 211, 249, 265 Ciliary Body, 72, 211, 265 Ciliary processes, 211 Circulatory system, 211, 222 Cirrhosis, 161, 211, 257 CIS, 23, 32, 47, 59, 211, 263 Clathrin, 60, 211, 212 Claviceps, 211, 264 Clavicle, 211, 269 Clear cell carcinoma, 211, 218 Clinical Medicine, 212, 256 Clinical study, 212, 215 Clinical trial, 5, 12, 26, 42, 62, 64, 181, 212, 215, 220, 259, 261 Cloning, 23, 55, 69, 205, 212, 240 Cluster Analysis, 64, 212 Coagulation, 51, 158, 205, 212, 232, 240, 255 Coated Vesicles, 211, 212 Codon, 32, 212, 228 Cofactor, 212, 259, 271 Cohort Studies, 26, 27, 57, 212, 223 Colectomy, 9, 212 Colitis, 160, 212 Collagen, 34, 204, 212, 225, 226, 239, 243, 255, 257, 267 Collapse, 213, 266 Colloidal, 199, 213, 221 Colon Polyps, 32, 213 Colonic Polyps, 32, 52, 130, 186, 213 Colonoscopy, 12, 22, 28, 29, 40, 61, 109, 110, 168, 169, 213 Colorectal Neoplasms, 16, 21, 26, 213 Combination Therapy, 52, 213, 224 Common Bile Duct, 114, 161, 210, 213, 217 Complement, 28, 52, 201, 213, 214, 228, 239, 242, 255 Complementary and alternative medicine, 125, 139, 213 Complementary medicine, 125, 214 Complete remission, 214, 262 Compliance, 52, 56, 214

Compress, 214, 255 Computational Biology, 181, 214 Computed tomography, 73, 79, 83, 165, 214 Computerized axial tomography, 214 Computerized tomography, 214 Conception, 214, 215, 226, 268 Concomitant, 70, 100, 214 Conduction, 214, 246, 247 Confounding, 18, 214 Conjugated, 204, 210, 214, 217, 218, 248 Conjugation, 147, 205, 214 Connective Tissue, 57, 148, 206, 208, 212, 215, 218, 226, 227, 239, 242, 244, 264, 267 Connective Tissue Cells, 215 Constriction, 154, 215, 238, 249 Consultation, 15, 215 Contamination, 41, 215 Contraceptive, 145, 149, 150, 215 Contraindications, ii, 215 Contralateral, 100, 215, 249 Control group, 119, 215 Controlled clinical trial, 136, 215 Cor, 215, 234, 258 Corneum, 215, 223 Coronary, 144, 208, 215, 216, 246 Coronary heart disease, 145, 208, 215 Coronary Thrombosis, 216, 246 Corpus, 216, 242, 253, 257, 271 Corpus Luteum, 216, 242, 257 Cortex, 216 Cortical, 109, 121, 216, 264 Corticosteroid, 159, 216 Cortisol, 44, 78, 89, 158, 199, 216 Cowpox, 216, 275 Cowpox Virus, 216, 275 Cranial, 37, 216, 225, 229, 231, 249, 252, 253, 254, 255, 268, 273 Cranial Nerves, 216, 255 Craniocerebral Trauma, 216, 231, 272 Crossing-over, 216, 262 Cross-Sectional Studies, 216, 223 Crowding, 57, 216 Cryotherapy, 4, 216 Cryptococcosis, 89, 216 Culture Media, 198, 216 Curative, 165, 169, 217, 271 Curcumin, 127, 217 Cutaneous, 89, 155, 201, 217, 275 Cyclic, 146, 149, 150, 207, 217, 231, 248, 258 Cyclin, 58, 209, 217

283

Cyclin-Dependent Kinases, 58, 209, 217 Cyclooxygenase Inhibitors, 154, 217 Cyproheptadine, 68, 217 Cyst, 78, 113, 162, 217 Cystic Duct, 213, 217 Cytochrome, 21, 27, 35, 217 Cytokine, 59, 217 Cytoplasm, 61, 203, 209, 217, 222, 223, 230, 242, 264 Cytoskeletal Proteins, 209, 211, 217 Cytoskeleton, 60, 217, 245 Cytotoxic, 151, 218, 261, 266 Cytotoxicity, 151, 200, 218 D Dairy Products, 62, 218 Data Collection, 218, 226 Decarboxylation, 218, 233, 250, 260 Decidua, 218, 255 Degenerative, 162, 218, 232, 250 Deletion, 39, 59, 68, 203, 218, 241 Dental Care, 4, 218 Deoxycholic Acid, 53, 218 Depolarization, 218, 266 Dermatitis, 160, 218 Dermis, 218, 239, 248, 269 Dermoid, 163, 218 Dermoid Cyst, 163, 218 DES, 7, 201, 218 Desensitization, 146, 218 Desmoid tumor, 131, 218 Detoxification, 19, 218 Developed Countries, 143, 219 Diabetes Mellitus, 144, 159, 219, 229, 232 Diagnostic procedure, 141, 170, 219 Diaphragm, 219, 255 Diarrhea, 23, 38, 219 Diastolic, 219, 234 Diastolic blood pressure, 219, 234 Dietary Fiber, 74, 126, 219 Diethylnitrosamine, 127, 219 Diffusion, 53, 205, 219, 235 Digestion, 199, 204, 206, 219, 238, 241, 269 Digestive system, 219, 227 Digestive tract, 219, 242, 266, 268, 277 Digitalis, 219, 250 Dihydrotestosterone, 219, 262 Diploid, 148, 219, 255 Direct, iii, 12, 25, 36, 39, 40, 42, 45, 63, 66, 68, 154, 173, 212, 219, 220, 241, 247, 262 Discrete, 62, 219 Dissection, 49, 219 Dissociation, 198, 219, 238

Distal, 27, 30, 49, 55, 68, 119, 134, 169, 220, 221, 259 Diuresis, 207, 220 Dopamine, 68, 80, 120, 220, 247 Dorsal, 220, 256 Dosage Forms, 146, 220 Dose-dependent, 148, 220 Dosimetry, 51, 220 Double-blind, 52, 53, 220 Doxycycline, 66, 220 Drug Interactions, 174, 220 Drug Tolerance, 220, 272 Duct, 85, 161, 200, 213, 220, 224, 238, 264, 268, 270 Ductal carcinoma in situ, 47, 220, 238 Dumping Syndrome, 217, 220 Duodenum, 83, 161, 204, 220, 222, 251, 269 Dura mater, 208, 220 Dyes, 14, 197, 221 Dysplasia, 13, 34, 45, 57, 75, 90, 93, 120, 160, 163, 221 E Ectopic, 83, 84, 98, 102, 157, 162, 221 Edema, 221, 249, 274 Effector, 32, 120, 197, 213, 221 Efficacy, 12, 35, 42, 52, 56, 67, 118, 127, 221 Eicosanoids, 217, 221 Ejaculation, 158, 221, 265 Elastin, 212, 221, 225 Elective, 221 Electrocoagulation, 212, 221 Electrode, 155, 221 Electrolyte, 60, 199, 216, 221, 245, 256, 267, 274 Electrons, 204, 221, 238, 251, 261 Electrophoresis, 7, 67, 221, 235 Emboli, 60, 221 Embryo, 25, 43, 205, 209, 221, 222, 236, 244, 277 Emesis, 221, 234 Emollient, 221, 249 Emphysema, 110, 221 Emulsions, 198, 221 Endemic, 222, 268 Endocrine Glands, 222, 252 Endocrine System, 159, 222, 247 Endoderm, 222, 277 Endogenous, 38, 142, 220, 221, 222, 272 Endometrial, 152, 222 Endometriosis, 145, 146, 149, 150, 152, 222 Endometrium, 218, 222, 244 Endorphins, 222, 247, 258

284

Adenoma

Endoscope, 222 Endoscopic, 4, 12, 35, 57, 78, 84, 163, 213, 222, 266 Endoscopy, 4, 18, 74, 78, 79, 84, 85, 87, 88, 89, 95, 97, 99, 110, 114, 222 Endothelial cell, 39, 201, 222, 226, 271 Endothelium, 222, 248 Endothelium-derived, 222, 248 Endotoxins, 213, 222 End-stage renal, 211, 222, 256 Energy balance, 222, 240 Enkephalin, 222, 258 Enterohepatic, 222, 269 Enterohepatic Circulation, 222, 269 Enteroscopy, 77, 222 Enucleation, 94, 158, 168, 223 Environmental Exposure, 31, 223, 249 Environmental Health, 180, 182, 223 Enzymatic, 26, 207, 208, 213, 217, 223, 233, 263 Eosinophils, 201, 223, 231 Epidemic, 223, 268 Epidemiologic Factors, 21, 223 Epidemiologic Studies, 22, 26, 28, 62, 223 Epidemiological, 9, 223 Epidermal, 69, 151, 163, 164, 223, 243 Epidermal Growth Factor, 69, 223 Epidermal growth factor receptor, 69, 223 Epidermis, 162, 204, 215, 218, 223, 230, 233, 260 Epidermoid carcinoma, 223, 268 Epigastric, 223, 251 Epinephrine, 198, 220, 223, 247, 248, 274 Epithelial Cells, 6, 17, 25, 32, 34, 42, 45, 58, 60, 66, 111, 148, 223, 224, 232, 239 Epithelioma, 163, 224 Epithelium, 6, 12, 17, 22, 26, 34, 39, 43, 45, 50, 58, 69, 87, 204, 222, 224, 238 Erectile, 158, 224, 253 Erection, 224 Ergot, 224, 264 Erythrocytes, 201, 206, 224, 232 Erythropoiesis, 36, 224 Esophageal, 76, 85, 224 Esophagus, 57, 72, 219, 224, 227, 262, 268, 269 Estradiol, 106, 224 Estrogen, 6, 44, 79, 85, 146, 224, 257 Estrogen receptor, 6, 85, 224 Estrogen Replacement Therapy, 6, 224 Ethanol, 199, 224, 226 Ethionine, 103, 224

Eukaryotic Cells, 152, 217, 224, 236, 250 Excitation, 57, 224, 247 Excrete, 224, 262 Exisulind, 9, 224 Exocrine, 224, 251 Exocytosis, 53, 60, 120, 224 Exogenous, 37, 205, 222, 225, 228, 274 Exon, 59, 225 External-beam radiation, 225, 238, 261, 277 Extracellular, 8, 42, 53, 61, 215, 225, 226, 243, 267, 270 Extracellular Matrix, 215, 225, 226, 243 Extracellular Matrix Proteins, 225, 243 Extraction, 17, 225 Extraocular, 198, 225 Extrapyramidal, 220, 225 Extremity, 225, 252 Eye Infections, 198, 225 F Facial, 73, 225, 243, 252 Facial Nerve, 225, 252 Facial Pain, 73, 225 Faecal, 86, 130, 225 Familial polyposis, 213, 225 Family Planning, 181, 225 Farnesyl, 11, 225 Fatty acids, 127, 135, 199, 221, 226, 258 Feces, 207, 225, 226, 269 Fermentation, 127, 199, 226 Fetoprotein, 226 Fetus, 200, 226, 255, 257, 274, 275 Fibroblast Growth Factor, 69, 226 Fibroblasts, 215, 226, 267 Fibroid, 226, 240 Fibroma, 163, 164, 226 Fibrosarcoma, 106, 226 Fibrosis, 119, 160, 200, 226 Fine-needle aspiration, 87, 99, 226, 246 Fistula, 226, 274 Fluorescence, 57, 59, 88, 226 Fluorouracil, 55, 226 Foam Cells, 226, 277 Focus Groups, 56, 226 Folate, 16, 18, 20, 24, 26, 27, 31, 46, 57, 88, 103, 129, 130, 226, 227 Fold, 53, 226 Folic Acid, 26, 57, 122, 226 Follicles, 218, 227, 237 Foramen, 210, 227, 232, 243, 253 Forearm, 206, 227 Frostbite, 163, 227

285

Fungus, 216, 224, 227, 264 Furunculosis, 160, 227 G Gallate, 43, 227 Gallbladder, 90, 164, 165, 197, 205, 217, 219, 227 Gamma Rays, 227, 246, 261 Ganglia, 197, 227, 247, 253 Ganglion, 227, 249 Gas, 200, 207, 219, 227, 233, 246, 248 Gastrectomy, 217, 227 Gastric, 55, 66, 76, 80, 81, 87, 89, 112, 132, 148, 163, 203, 220, 223, 227, 233 Gastric Inhibitory Polypeptide, 89, 227 Gastrin, 90, 227, 233 Gastritis, 87, 227 Gastrointestinal tract, 48, 58, 207, 224, 226, 227, 240, 265, 273 Gels, 144, 228 Gene, 7, 9, 14, 15, 16, 18, 19, 21, 23, 25, 26, 27, 28, 29, 30, 32, 33, 35, 37, 38, 39, 41, 42, 43, 44, 45, 46, 48, 49, 51, 55, 58, 59, 60, 64, 66, 67, 68, 69, 70, 80, 81, 82, 90, 98, 108, 118, 120, 134, 143, 198, 199, 205, 228, 232, 233, 240, 249, 251, 261, 264, 267 Gene Amplification, 143, 228 Gene Expression, 15, 23, 25, 26, 29, 30, 33, 37, 42, 43, 51, 58, 59, 64, 66, 118, 134, 228, 267 Gene Targeting, 25, 228 Gene Therapy, 198, 228 Genetic Code, 228, 248 Genetic Engineering, 5, 205, 212, 228 Genetic Markers, 18, 228 Genetics, 5, 6, 8, 18, 28, 33, 48, 75, 119, 120, 214, 228 Genital, 155, 211, 228, 275, 277 Genomics, 10, 228 Genotype, 18, 20, 31, 33, 50, 54, 57, 228, 253 Germ Cells, 228, 251, 267, 270, 277 Germline mutation, 7, 29, 75, 228, 232 Gestation, 229, 253, 255 Ginseng, 129, 138, 229 Glomerular, 229, 262 Glomeruli, 229, 260 Glossopharyngeal Nerve, 225, 229 Glucocorticoid, 10, 43, 206, 229 Glucokinase, 118, 229 Glucose, 40, 118, 144, 206, 219, 229, 230, 232, 237, 264 Glucose Intolerance, 219, 229

Glucose tolerance, 40, 144, 229 Glucose Tolerance Test, 40, 229 Glutamic Acid, 227, 229, 232, 247, 257 Glutathione Peroxidase, 134, 229, 265 Gluten, 208, 229 Glycine, 204, 210, 218, 230, 247, 265 Glycogen, 92, 230 Glycogen Storage Disease, 92, 230 Glycoprotein, 114, 207, 230, 239, 246, 271 Glycoside, 230, 250, 264 Glycosidic, 230, 249 Goats, 218, 230 Goblet Cells, 45, 230 Goiter, 81, 88, 121, 159, 230 Gonadal, 230, 268 Gonadorelin, 230, 240 Gonadotropic, 146, 230 Gonadotropin, 5, 34, 79, 91, 145, 149, 150, 152, 230, 240 Gonads, 159, 230, 234 Governing Board, 230, 256 Grade, 13, 51, 79, 93, 111, 161, 230 Grading, 44, 120, 230 Granular Cell Tumor, 164, 230 Granulocytes, 204, 230, 240, 266, 277 Granuloma, 164, 231 Granulosa Cells, 231, 237, 242 Grasses, 211, 227, 231 Growth factors, 23, 39, 54, 110, 153, 231 Guanine, 70, 231, 260 Guanylate Cyclase, 231, 248 H Haploid, 65, 231, 255 Haplotypes, 18, 231 Haptens, 198, 231 Headache, 169, 207, 231, 234, 254, 257 Headache Disorders, 231 Health Status, 54, 231 Heart attack, 208, 231 Heart failure, 231, 249 Hematogenous, 61, 231 Hematuria, 104, 159, 231 Hemianopsia, 231, 255 Hemodialysis, 207, 232 Hemoglobin, 57, 201, 224, 232, 240 Hemoglobin C, 201, 232 Hemolytic, 232, 260 Hemorrhage, 4, 86, 102, 159, 216, 221, 231, 232, 254, 260, 269 Hemostasis, 35, 232, 265 Hepatic, 15, 36, 75, 86, 152, 161, 165, 199, 213, 229, 232

286

Adenoma

Hepatitis, 161, 232 Hepatocellular, 24, 67, 80, 87, 88, 92, 93, 100, 108, 119, 127, 161, 165, 232 Hepatocellular carcinoma, 24, 87, 93, 100, 108, 161, 165, 232 Hepatocytes, 232 Hereditary, 7, 30, 31, 42, 80, 162, 228, 232, 263 Hereditary mutation, 228, 232 Heredity, 197, 228, 232 Herniated, 160, 232 Heterodimers, 23, 232 Heterogeneity, 14, 198, 232 Heterozygotes, 27, 232 Hirsutism, 19, 89, 155, 157, 233, 234 Histamine, 201, 217, 233 Histology, 45, 49, 120, 233, 252 Histones, 211, 233 Homeobox, 5, 233 Homeostasis, 8, 36, 159, 233 Homologous, 25, 27, 199, 216, 228, 232, 233, 264, 270 Homozygotes, 5, 27, 233 Hormonal, 44, 144, 158, 164, 216, 224, 233, 243 Hormonal therapy, 233, 243 Hormone Replacement Therapy, 159, 233 Horny layer, 223, 233 Human growth hormone, 118, 233 Hybrid, 38, 233, 264 Hybridization, 45, 82, 87, 95, 233 Hydrogen, 197, 199, 200, 204, 207, 225, 229, 233, 245, 247, 248, 251, 259 Hydrogen Peroxide, 229, 233 Hydrolysis, 205, 233, 254, 256, 259 Hydrophobic, 19, 143, 233, 241 Hydroxylysine, 212, 234 Hydroxyproline, 212, 234 Hyperaldosteronism, 99, 159, 234 Hyperandrogenism, 78, 234 Hyperbilirubinemia, 234, 239 Hypercalcemia, 8, 91, 109, 234 Hyperplasia, 19, 44, 47, 50, 68, 81, 88, 92, 98, 99, 101, 118, 142, 147, 152, 157, 162, 165, 234 Hypersensitivity, 25, 200, 218, 234, 240, 263 Hyperstimulation, 85, 106, 234 Hypertension, 70, 82, 94, 101, 142, 208, 215, 231, 234, 252, 254, 272, 274 Hypertensive Encephalopathy, 101, 234 Hyperthyroidism, 92, 159, 234

Hypertrichosis, 233, 234 Hypertrophy, 145, 149, 150, 155, 204, 215, 234 Hypogonadism, 5, 144, 234 Hypophyseal, 144, 234 Hypophysis, 234, 265 Hypopituitarism, 38, 234 Hypoplasia, 162, 234 Hypothalamic, 145, 149, 150, 234, 235, 267 Hypothalamic Hormones, 145, 149, 150, 235 Hypothalamus, 145, 149, 150, 159, 222, 230, 234, 235, 254, 255, 257, 271 Hypoxia, 32, 85, 201, 206, 235 Hypoxic, 31, 235 I Ibuprofen, 235, 239 Ileal, 95, 160, 235 Ileum, 208, 235 Immune response, 198, 202, 216, 231, 235, 242, 269, 275, 276 Immune Sera, 235 Immune system, 164, 205, 235, 240, 275, 277 Immunity, 142, 235, 249, 273 Immunization, 9, 235, 236 Immunodiffusion, 198, 235 Immunoelectrophoresis, 198, 235 Immunohistochemistry, 10, 48, 75, 114, 235 Immunologic, 210, 235, 261 Immunology, 48, 198, 235 Immunosuppressant, 199, 226, 235 Immunosuppressive, 154, 229, 235, 236 Immunotherapy, 205, 218, 235 Implant radiation, 236, 237, 238, 261, 277 Impotence, 158, 224, 236, 257 In situ, 25, 26, 36, 44, 236 In Situ Hybridization, 25, 26, 36, 236 In vivo, 6, 23, 25, 35, 39, 44, 45, 46, 50, 57, 67, 89, 113, 148, 153, 228, 236, 269, 271 Incision, 212, 236, 238, 259 Incontinence, 158, 159, 236 Induction, 23, 31, 42, 57, 66, 153, 201, 236, 257, 261 Infancy, 83, 164, 236 Infarction, 206, 234, 236 Infertility, 145, 149, 150, 236 Infiltrating cancer, 236, 238 Inflammatory bowel disease, 36, 160, 236 Informed Consent, 17, 236 Infusion, 136, 236

287

Ingestion, 229, 237, 270 Inhalation, 198, 203, 237 Inhibin, 79, 237 Initiation, 42, 49, 237, 272 Inositol, 32, 42, 237 Inotropic, 220, 237 Insight, 8, 10, 16, 29, 44, 65, 237 Insomnia, 237, 257 Insulin, 22, 39, 40, 57, 82, 85, 96, 112, 118, 144, 227, 229, 237, 267, 274 Insulin-dependent diabetes mellitus, 144, 237 Insulin-like, 22, 39, 40, 57, 82, 85, 144, 237, 267 Interferon, 58, 59, 237 Interferon-alpha, 237 Interindividual, 28, 237 Internal Medicine, 4, 12, 34, 65, 72, 118, 119, 120, 227, 237 Internal radiation, 237, 238, 261, 277 Interstitial, 53, 158, 206, 237, 238, 262, 277 Intervertebral, 232, 237 Intestinal Mucosa, 60, 208, 237, 277 Intestinal Neoplasms, 28, 66, 237 Intestine, 23, 25, 45, 59, 204, 206, 213, 222, 223, 238, 240 Intracellular, 37, 43, 207, 211, 236, 238, 244, 248, 256, 258, 265, 266 Intracellular Membranes, 238, 244 Intraductal carcinoma, 220, 238 Intraductal Papilloma, 161, 238 Intraepithelial, 32, 238 Intramuscular, 238, 252 Intravenous, 40, 237, 238, 252 Intravesical, 159, 238 Intrinsic, 53, 57, 198, 204, 238 Invasive, 12, 23, 41, 47, 93, 97, 103, 154, 235, 236, 238, 242 Invasive cancer, 23, 47, 236, 238 Invertebrates, 229, 238 Ionization, 7, 238 Ionizing, 83, 200, 223, 238, 261 Ions, 45, 53, 204, 219, 221, 233, 238, 256 Iris, 72, 201, 238 Irradiation, 109, 213, 238, 277 Ischemia, 206, 238, 247, 254 Isoenzyme, 154, 155, 238 Isothiocyanates, 20, 239 Isotonic, 154, 239, 245 Isotretinoin, 12, 239 Isozymes, 35, 239, 260

J Jaundice, 79, 210, 234, 239 K Karyotype, 69, 85, 239 Kb, 23, 180, 239 Keloid, 164, 211, 239 Keratoacanthoma, 164, 239 Keratosis, 151, 160, 163, 239 Ketoprofen, 11, 239 Kidney Disease, 162, 180, 239 Kidney stone, 65, 239, 251, 262 Kinetic, 238, 239 L Labile, 213, 239 Lacrimal, 77, 107, 198, 225, 239 Lacrimal Apparatus, 198, 239 Lacrimal gland, 77, 107, 239 Lactation, 159, 239, 251, 257 Laminin, 34, 204, 225, 239 Laparoscopy, 165, 239 Large Intestine, 22, 49, 56, 208, 213, 219, 238, 240, 262, 266 Laser Coagulation, 158, 240 Laser therapy, 4, 240 Latent, 240, 257 Laxative, 198, 210, 240 Lectin, 240, 244 Leiomyoma, 164, 226, 240 Leptin, 65, 240 Lesion, 3, 4, 45, 47, 62, 78, 83, 88, 115, 151, 165, 231, 239, 240, 241, 274 Lethal, 25, 240 Leucocyte, 200, 240 Leukotrienes, 203, 221, 240 Leuprolide, 85, 240 Libido, 201, 240 Ligament, 240, 259 Ligands, 23, 25, 30, 61, 70, 168, 240 Ligase, 29, 240 Linkage, 228, 241 Lip, 107, 241 Lipid, 41, 60, 144, 203, 211, 221, 226, 237, 241, 246, 277 Lipoprotein, 144, 241 Liquor, 241, 260 Liver cancer, 200, 241 Liver metastases, 165, 241 Liver Neoplasms, 224, 241 Liver Transplantation, 161, 241 Lobe, 5, 73, 99, 100, 145, 149, 150, 233, 241, 252, 258 Lobectomy, 112, 241

288

Adenoma

Localization, 44, 45, 61, 64, 72, 81, 89, 235, 241 Localized, 61, 160, 206, 233, 234, 236, 239, 241, 249, 255, 274 Locomotion, 241, 255, 267 Loop, 25, 241 Loss of Heterozygosity, 49, 199, 241 Low-density lipoprotein, 241 Lucida, 239, 241 Luciferase, 25, 47, 241 Lumbar, 242, 248 Lung metastases, 30, 242 Lutein Cells, 242, 257 Lymph, 161, 210, 211, 222, 242, 247, 269 Lymph node, 210, 242, 247 Lymphatic, 222, 236, 242, 244, 249, 267, 271 Lymphatic system, 242, 267, 271 Lymphocytes, 16, 27, 201, 202, 235, 240, 242, 271, 277 Lymphocytic, 101, 156, 242 Lymphoid, 37, 201, 240, 242 Lymphoma, 162, 242 M Magnetic Resonance Imaging, 41, 73, 96, 242 Major Histocompatibility Complex, 231, 242 Malabsorption, 208, 242 Malacoplakia, 162, 242 Malformation, 242, 262 Malignancy, 39, 47, 49, 98, 115, 161, 163, 164, 242 Malignant tumor, 50, 51, 147, 160, 162, 163, 165, 208, 213, 243, 263 Malnutrition, 199, 243 Mammary, 113, 243 Mammogram, 207, 243, 244 Mandible, 33, 76, 200, 210, 243, 263 Matrilysin, 42, 243 Matrix metalloproteinase, 42, 95, 243 Maxillary, 33, 243, 252 Meat, 18, 31, 62, 145, 149, 150, 243 Meatus, 243, 268, 274 Medial, 160, 243, 249, 268 Mediate, 6, 32, 34, 43, 220, 243 Mediator, 36, 243, 265 Medical oncologist, 43, 243 MEDLINE, 181, 243 Megaloblastic, 227, 243 Melanin, 238, 243, 274 Melanocytes, 243, 248

Melanoma, 151, 163, 243 Membrane, 34, 38, 60, 69, 95, 156, 200, 209, 212, 213, 218, 222, 224, 230, 234, 239, 242, 243, 244, 246, 250, 254, 255, 256, 263, 266, 273, 274, 276, 277 Membrane Glycoproteins, 244 Membrane Proteins, 156, 244 Meninges, 209, 210, 216, 220, 244 Meningioma, 74, 244 Menopause, 159, 244, 256 Menstrual Cycle, 145, 149, 150, 244, 257 Menstruation, 200, 218, 244, 249 Mental, iv, 5, 109, 180, 182, 210, 219, 234, 244, 259, 260, 265, 274 Mental Health, iv, 5, 180, 182, 244, 260 Mesenchymal, 223, 244 Mesoderm, 244, 277 Metabolic acidosis, 60, 244 Metabolic disorder, 230, 244 Metabolite, 19, 205, 244 Metaplasia, 87, 88, 244 Metastasis, 25, 29, 35, 42, 60, 63, 93, 115, 164, 243, 244 Metastasize, 218, 244, 255, 264 Metastatic, 26, 30, 36, 102, 108, 143, 162, 165, 234, 244, 264 Methylcholanthrene, 10, 244 Microbe, 244, 272 Microbiology, 48, 203, 204, 244 Microcalcifications, 207, 244 Microorganism, 212, 244, 276 Microscopy, 14, 22, 204, 245 Microtubules, 70, 245 Migration, 62, 245 Millimeter, 111, 245 Mineralocorticoids, 198, 216, 245 Mitochondria, 57, 245, 250 Mitochondrial Swelling, 245, 246 Mitosis, 203, 245, 267 Modeling, 13, 50, 63, 64, 245 Modification, 13, 27, 46, 63, 228, 245 Monitor, 9, 50, 77, 207, 245, 248 Monoclonal, 37, 44, 65, 88, 238, 245, 261, 277 Mononuclear, 231, 245 Morphological, 25, 47, 221, 227, 243, 245 Morphology, 17, 45, 46, 51, 75, 245 Motility, 4, 25, 227, 245, 265 Motor nerve, 245, 249 Mucinous, 51, 90, 97, 108, 113, 227, 245 Mucins, 230, 245, 264 Mucolytic, 206, 245

289

Mucus, 245, 246, 263, 274 Multivariate Analysis, 93, 246 Mutagen, 204, 246 Mutagenesis, 46, 246 Mutagenic, 199, 219, 246 Mutagenicity, 113, 246 Myelin, 246, 247 Myelin Sheath, 246, 247 Myocardial infarction, 144, 216, 246 Myocardium, 246 Myoepithelioma, 161, 246 N Nasal Cavity, 246, 252, 268 Nasal Septum, 107, 246 Natriuresis, 142, 246 Nausea, 220, 234, 246, 257, 274 NCI, 1, 10, 26, 27, 63, 179, 211, 246 Necrosis, 15, 102, 103, 107, 158, 162, 203, 236, 246, 254 Needle biopsy, 226, 246 Neoplasm, 34, 90, 97, 162, 164, 224, 230, 238, 247, 251, 264, 273 Nephrectomy, 109, 247 Nephroblastoma, 162, 247 Nephrogenic, 82, 104, 168, 247 Nephropathy, 239, 247 Nerve Compression Syndromes, 37, 247 Nervous System, 159, 198, 209, 243, 247, 253, 270 Networks, 32, 54, 247 Neural, 104, 164, 198, 226, 247 Neuroectodermal tumor, 164, 247 Neuroendocrine, 65, 104, 247 Neurogenic, 247, 275 Neurologic, 37, 234, 247 Neurosecretory Systems, 222, 247 Neurosyphilis, 247, 252 Neurotoxic, 203, 247 Neurotransmitter, 197, 198, 206, 220, 229, 230, 233, 247, 248, 266, 269 Neutrons, 200, 238, 247, 261 Nevus, 162, 164, 248 Nevus, Blue, 164, 248 Nitric Oxide, 109, 248 Nitrogen, 200, 201, 225, 248, 273 Norepinephrine, 198, 220, 247, 248 Nuclear Proteins, 23, 248 Nuclei, 59, 200, 214, 221, 228, 233, 242, 245, 247, 248, 249, 250, 255, 259 Nucleic acid, 156, 228, 233, 236, 248, 260, 268 Nucleic Acid Hybridization, 233, 248

Nucleoproteins, 59, 248 Nucleus, 61, 203, 211, 217, 223, 224, 227, 242, 245, 247, 248, 259 O Observational study, 12, 113, 248 Occult, 78, 86, 249 Occult Blood, 86, 249 Oculomotor, 84, 249 Oculomotor Nerve, 84, 249 Odds Ratio, 249, 262 Oedema, 80, 249 Ointments, 144, 220, 249, 251 Oligomenorrhea, 249, 256 Oligosaccharides, 19, 249 Omega-3 fatty acid, 148, 249 Oncogene, 18, 23, 67, 98, 143, 249 Oncogenic, 69, 249 Oncologist, 243, 249 Optic Chiasm, 78, 235, 249, 255 Optic Nerve, 249, 263 Oral Health, 159, 250 Orbit, 218, 250 Organelles, 211, 217, 243, 250 Organogenesis, 5, 250 Orgasm, 221, 250 Ornithine, 32, 70, 250, 260 Ornithine Decarboxylase, 32, 70, 250 Orofacial, 225, 250 Osmotic, 199, 245, 250 Osteoarthritis, 239, 250 Osteoporosis, 224, 250 Otitis, 160, 163, 250 Otolaryngologist, 159, 250 Otolaryngology, 89, 102, 103, 104, 106, 110, 112, 159, 250 Otology, 74, 76, 101, 107, 159, 250 Otorhinolaryngology, 163, 250 Ouabain, 142, 250 Ovaries, 234, 251, 256, 262, 266 Ovary, 78, 113, 146, 156, 216, 224, 230, 251 Overweight, 121, 144, 251 Ovulation, 34, 145, 149, 150, 201, 231, 251 Ovum, 216, 218, 229, 251, 257, 277 Oxalate, 38, 251 Oxidation, 205, 217, 229, 251 Oxytocin, 235, 251 P P53 gene, 29, 251 Palate, 71, 102, 229, 251 Palliative, 251, 271 Pancreatic, 15, 72, 97, 112, 120, 159, 161, 251

290

Adenoma

Pancreatic cancer, 15, 251 Pancreatic Juice, 15, 251 Pancreatitis, 161, 251 Papilla, 10, 84, 118, 251 Papillary, 49, 79, 80, 81, 88, 90, 97, 100, 102, 103, 108, 112, 115, 128, 162, 251 Papillary tumor, 97, 251 Papilledema, 234, 251 Papilloma, 151, 161, 163, 224, 251, 263 Paraffin, 15, 251, 252 Paraffin Embedding, 15, 252 Paralysis, 197, 252 Paranasal Sinuses, 252, 268 Paraparesis, 252 Parathyroid Glands, 33, 252 Parathyroid hormone, 53, 69, 72, 105, 112, 118, 130, 136, 252 Parathyroidectomy, 147, 252 Parenteral, 144, 252 Paresis, 84, 252 Parietal, 252, 253, 255 Parotid, 3, 73, 74, 77, 85, 91, 94, 99, 108, 162, 229, 252 Partial remission, 252, 262 Parturition, 252, 257 Pathologic, 15, 21, 23, 35, 36, 162, 197, 203, 205, 215, 234, 252, 262 Pathologic Processes, 203, 252 Pathologies, 7, 155, 161, 252 Pathophysiology, 36, 52, 252 Patient Satisfaction, 12, 252 Pelvic, 222, 253, 259 Pelvis, 197, 242, 251, 253, 260, 275 Penis, 162, 221, 253, 262 Peptide, 7, 36, 146, 149, 150, 226, 240, 253, 256, 258, 259, 261, 267, 271 Percutaneous, 79, 121, 144, 158, 253 Perforation, 4, 227, 253 Perfusion, 14, 235, 253 Perinatal, 25, 253 Perineal, 158, 159, 253 Perineum, 253 Peripheral blood, 27, 134, 237, 253 Peripheral Nervous System, 246, 247, 252, 253, 269 Peritoneal, 203, 249, 253 Peritoneal Cavity, 203, 249, 253 Peritoneum, 253, 263 Petroleum, 251, 253 Pharmaceutical Solutions, 220, 253 Pharmacokinetic, 253 Pharmacologic, 201, 253, 272, 275

Phenotype, 5, 6, 18, 21, 25, 28, 33, 37, 39, 48, 49, 58, 66, 253 Phospholipases, 254, 266 Phospholipids, 226, 237, 241, 254 Phosphoprotein Phosphatase, 209, 254 Phosphorus, 207, 252, 254 Phosphorylation, 61, 217, 254, 260 Photocoagulation, 212, 254 Photodynamic therapy, 4, 254 Physiologic, 25, 39, 199, 205, 239, 244, 254, 258, 262 Physiology, 38, 53, 93, 159, 227, 254 Pigment, 205, 243, 254 Pilot Projects, 64, 254 Pilot study, 9, 12, 20, 41, 72, 254 Pituitary Apoplexy, 234, 254 Pituitary Gland, 5, 99, 216, 226, 230, 234, 235, 254, 255, 257, 265 Pituitary Hormone Release Inhibiting Hormones, 235, 254 Pituitary Hormone-Releasing Hormones, 235, 254 Pituitary Hormones, 235, 254 Pituitary Neoplasms, 37, 234, 255 Placenta, 25, 224, 255, 257 Plant Oils, 249, 255 Plants, 206, 207, 210, 219, 229, 230, 240, 245, 248, 250, 255, 256, 264, 272 Plasma cells, 201, 255 Plasma protein, 199, 255 Plasmid, 228, 255, 275 Platelet Activation, 255, 266 Platelet Aggregation, 201, 248, 255, 258, 271 Platelets, 248, 255, 265 Pleura, 255 Pleural, 10, 249, 255 Pleural cavity, 249, 255 Pneumonia, 76, 215, 255 Point Mutation, 29, 256 Polycystic, 92, 96, 145, 149, 150, 152, 234, 256 Polycystic Ovary Syndrome, 92, 96, 145, 149, 150, 234, 256 Polymorphic, 19, 31, 211, 256 Polymorphism, 21, 27, 29, 32, 49, 68, 70, 77, 103, 167, 256 Polyp, 10, 32, 49, 52, 53, 54, 56, 78, 127, 132, 148, 160, 163, 256 Polypeptide, 143, 200, 207, 212, 223, 227, 233, 254, 256, 257, 277 Polysaccharide, 55, 202, 256, 259

291

Polyunsaturated fat, 132, 256, 271 Posterior, 158, 159, 200, 220, 229, 235, 238, 251, 254, 256, 268 Postmenopausal, 6, 224, 250, 256 Postoperative, 97, 106, 158, 256 Postsynaptic, 256, 266 Potassium, 112, 199, 245, 256 Potassium Channels, 112, 256 Potentiation, 256, 266 Practice Guidelines, 12, 182, 186, 256 Precancerous, 11, 147, 151, 163, 210, 224, 256, 257 Preclinical, 10, 53, 119, 256 Precursor, 15, 22, 31, 32, 52, 62, 170, 202, 203, 210, 220, 221, 222, 223, 225, 248, 256, 257, 268, 273, 274, 275 Predictive factor, 32, 257 Predisposition, 7, 21, 34, 147, 164, 257 Premalignant, 32, 45, 47, 118, 163, 256, 257 Premenstrual Syndrome, 145, 149, 150, 257 Prenatal, 221, 257 Preoperative, 72, 95, 99, 147, 257 Prevalence, 28, 120, 144, 249, 257 Primary Biliary Cirrhosis, 113, 257 Primary Sclerosing Cholangitis, 161, 257 Probe, 89, 146, 257 Progeny, 214, 257 Progesterone, 85, 257, 268 Progressive, 30, 76, 209, 211, 220, 224, 246, 250, 255, 257, 262, 273 Prolactin, 5, 38, 80, 93, 112, 135, 257 Prolactinoma, 52, 257 Proline, 212, 234, 257 Promoter, 23, 25, 26, 32, 44, 45, 59, 257 Prone, 34, 257 Pro-Opiomelanocortin, 44, 222, 257 Prospective Studies, 39, 258 Prospective study, 24, 72, 118, 258 Prostaglandin, 28, 52, 54, 153, 217, 258, 271 Prostaglandin Endoperoxides, 258, 271 Prostaglandin-Endoperoxide Synthase, 217, 258 Prostaglandins A, 258 Prostaglandins F, 153, 258 Prostaglandins H, 154, 258 Prostate, 43, 94, 114, 137, 146, 152, 154, 155, 156, 158, 162, 204, 205, 211, 259, 262, 273 Prostate gland, 154, 211, 259 Prostatectomy, 94, 158, 259

Prostatic Hyperplasia, 137, 158, 259 Prostatitis, 259 Protease, 42, 133, 146, 213, 259 Protein C, 41, 199, 200, 203, 212, 241, 259, 274 Protein Kinases, 30, 259 Protein S, 7, 152, 156, 205, 228, 233, 259, 264, 271 Proteoglycans, 204, 225, 259 Proteolytic, 36, 42, 65, 200, 213, 259 Proteome, 7, 259 Protocol, 4, 10, 38, 259 Protons, 200, 233, 238, 259, 261 Protozoa, 214, 244, 259 Proximal, 4, 30, 59, 95, 157, 220, 246, 259 Psychiatric, 157, 259 Psychiatry, 259 Psychic, 240, 244, 259, 260, 264 Psychogenic, 260, 275 Puberty, 5, 145, 146, 149, 150, 155, 260 Public Health, 13, 16, 26, 27, 39, 62, 76, 182, 204, 260 Public Policy, 181, 260 Publishing, 67, 161, 164, 165, 260 Pulmonary, 12, 55, 80, 89, 107, 112, 136, 206, 215, 240, 260, 276 Pulmonary Artery, 206, 260, 276 Pulse, 41, 245, 260 Purines, 260, 265 Purpura, 112, 260 Pustular, 197, 260 Putrescine, 250, 260, 268 Pyelonephritis, 162, 260 Pyogenic, 164, 260 Pyridoxal, 16, 250, 260 Pyrimidines, 260, 265 Pyruvate Kinase, 132, 260 R Race, 18, 239, 245, 260 Radiation, 51, 70, 83, 110, 164, 223, 225, 226, 227, 234, 237, 238, 249, 260, 261, 277 Radiation therapy, 51, 225, 237, 238, 261, 277 Radioactive, 233, 236, 237, 238, 248, 249, 261, 270, 273, 274, 277 Radioactivity, 146, 261 Radioimmunotherapy, 261 Radiolabeled, 238, 261, 277 Radiological, 92, 253, 261 Radiology, 93, 121, 261 Radiopharmaceutical, 146, 147, 261 Radiotherapy, 74, 106, 206, 238, 261, 277

292

Adenoma

Randomized, 9, 10, 13, 20, 27, 35, 52, 56, 57, 61, 74, 103, 126, 136, 221, 261 Randomized clinical trial, 27, 261 Ras gene, 143, 261 Reagent, 242, 261 Rebound effect, 145, 149, 150, 261 Recombinant, 65, 118, 153, 262, 275 Recombination, 25, 50, 214, 228, 262 Rectal, 4, 9, 20, 22, 48, 63, 74, 110, 126, 129, 131, 135, 144, 151, 262 Rectum, 4, 40, 78, 81, 95, 131, 136, 202, 206, 213, 219, 225, 227, 236, 240, 259, 262, 266 Reductase, 21, 27, 29, 57, 155, 262 Refer, 1, 213, 222, 241, 247, 261, 262, 272, 276 Reflux, 76, 262 Regeneration, 226, 262 Regimen, 10, 221, 262 Relapse, 35, 262 Relative risk, 10, 262 Remission, 36, 262 Renal agenesis, 162, 262 Renal cell carcinoma, 102, 108, 162, 262 Renal failure, 142, 232, 262 Renal pelvis, 162, 239, 262 Renal tubular, 168, 262 Reproductive cells, 228, 232, 262 Reproductive system, 259, 262 Resected, 30, 53, 135, 147, 262 Resection, 15, 38, 72, 74, 75, 84, 99, 100, 128, 161, 165, 169, 262, 273 Resorption, 142, 262 Respiration, 202, 207, 245, 263 Retina, 211, 249, 263, 265 Retinal, 234, 249, 263 Retinal Hemorrhage, 234, 263 Retinoblastoma, 111, 263 Retinoblastoma Protein, 111, 263 Retinoids, 263, 276 Retrograde, 158, 263 Retroperitoneal, 158, 198, 263 Retropubic, 159, 259, 263 Retrosternal, 88, 263 Rhabdoid tumor, 162, 263 Rhamnose, 250, 263 Rheumatoid, 36, 239, 263 Rheumatoid arthritis, 36, 239, 263 Rhinorrhea, 257, 263 Ribosome, 264, 273 Risk factor, 13, 22, 39, 46, 53, 56, 62, 63, 64, 65, 161, 163, 168, 223, 258, 262, 264 Risk patient, 158, 264

Rye, 133, 211, 224, 264 S Saline, 206, 264 Saliva, 264 Salivary, 3, 70, 82, 87, 93, 105, 120, 161, 164, 219, 225, 251, 264, 269 Salivary Gland Neoplasms, 161, 164, 264 Salivary glands, 3, 120, 219, 225, 264 Saponins, 264, 268 Sarcoma, 151, 162, 164, 208, 264, 267 Screening, 4, 13, 19, 31, 38, 40, 54, 56, 61, 107, 109, 168, 169, 186, 212, 264, 274 Scrotum, 162, 264, 270 Sebaceous, 70, 101, 151, 155, 161, 162, 164, 218, 264 Sebaceous gland, 155, 162, 218, 264 Sebum, 197, 264 Secondary tumor, 244, 264 Secretory, 49, 53, 120, 234, 264 Sediment, 264, 274 Segregation, 204, 262, 264 Seizures, 234, 264 Selenium, 20, 48, 53, 62, 133, 134, 265 Sella, 92, 254, 265 Sella Turcica, 254, 265 Semen, 221, 259, 265 Seminal vesicles, 162, 265 Seminiferous tubule, 237, 265 Senescence, 39, 265 Senile, 162, 250, 265 Sensibility, 200, 265 Sensor, 19, 265 Sepsis, 244, 265 Sequence Analysis, 6, 26, 49, 265 Sequence Homology, 38, 265 Sequencing, 7, 18, 48, 54, 90, 265 Serine, 37, 254, 265 Serotonin, 217, 247, 265, 273 Serous, 51, 72, 109, 110, 222, 255, 265 Serrata, 211, 265 Serrated, 78, 79, 94, 111, 265 Sessile, 213, 266 Sex Characteristics, 201, 260, 266, 270 Shock, 266, 273 Side effect, 42, 52, 173, 175, 198, 205, 266, 269, 272 Sigmoid, 4, 132, 266 Sigmoid Colon, 132, 266 Sigmoidal, 129, 266 Sigmoidoscopy, 28, 169, 266 Signal Transduction, 30, 42, 50, 53, 237, 266

293

Signet ring cell carcinoma, 102, 266 Signs and Symptoms, 262, 266, 274 Skeletal, 33, 201, 266 Skeleton, 197, 258, 266 Skull, 210, 216, 250, 266, 270 Sleep apnea, 71, 266 Small intestine, 208, 210, 211, 217, 220, 222, 233, 235, 238, 266, 276 Smallpox, 267, 275 Smooth muscle, 200, 201, 207, 215, 226, 233, 240, 258, 267, 269 Social Support, 20, 267 Sodium, 23, 46, 82, 126, 142, 199, 245, 246, 267, 269 Soft tissue, 160, 162, 206, 226, 266, 267 Soft Tissue Neoplasms, 162, 267 Soft tissue sarcoma, 226, 267 Solid tumor, 39, 267 Soma, 267 Somatic, 37, 50, 75, 216, 229, 245, 250, 253, 267, 270 Somatomedins, 52, 267 Somatotropin, 234, 267 Soybean Oil, 256, 267 Specialist, 187, 267 Species, 209, 216, 220, 223, 227, 233, 239, 245, 260, 265, 267, 269, 273, 275, 276, 277 Specificity, 12, 49, 59, 142, 198, 267 Spectroscopic, 42, 57, 249, 267 Spectrum, 217, 267 Sperm, 201, 211, 228, 232, 262, 265, 268, 270, 273 Spermidine, 250, 268 Sphenoid, 92, 98, 208, 252, 265, 268 Sphenoid Sinus, 92, 98, 268 Spinal cord, 209, 210, 220, 227, 244, 247, 252, 253, 268 Spinous, 223, 268 Sporadic, 7, 17, 29, 30, 48, 90, 105, 110, 126, 129, 133, 263, 268 Squamous, 70, 160, 164, 210, 223, 230, 239, 268 Squamous cell carcinoma, 70, 160, 223, 230, 239, 268 Squamous cells, 230, 268 Squamous Epithelium, 210, 268 Staging, 162, 268 Stenosis, 160, 268, 269 Sterile, 252, 268 Sterility, 78, 85, 236, 268 Sternum, 263, 268 Steroid, 70, 78, 130, 144, 204, 216, 264, 268

Stimulant, 207, 217, 233, 268 Stimulus, 221, 224, 268, 271 Stomach, 75, 85, 87, 112, 197, 203, 219, 223, 224, 227, 229, 233, 246, 253, 262, 266, 269 Stool, 12, 15, 35, 213, 236, 240, 269 Stress, 3, 60, 208, 216, 246, 257, 263, 269 Stricture, 268, 269 Stroke, 144, 180, 208, 269 Stroma, 238, 269 Stromal, 97, 222, 247, 269 Subacute, 236, 269 Subarachnoid, 231, 269 Subclinical, 89, 236, 264, 269 Subcutaneous, 110, 148, 198, 221, 240, 249, 252, 269 Sublingual, 71, 74, 144, 269 Submandibular, 68, 93, 103, 269 Submaxillary, 223, 269 Subspecies, 267, 269, 275 Substance P, 244, 264, 269 Substrate, 217, 269 Sulindac, 11, 52, 168, 269 Supplementation, 9, 27, 57, 84, 126, 127, 128, 129, 130, 134, 135, 136, 169, 269 Suppression, 29, 39, 43, 45, 66, 95, 148, 202, 216, 269 Suppressive, 66, 269 Supraclavicular, 157, 269 Sweat, 202, 210, 218, 269, 270 Sweat Glands, 202, 210, 218, 269, 270 Sympathomimetic, 220, 223, 248, 270 Symphysis, 210, 259, 270 Symptomatic, 251, 270 Synaptic, 247, 266, 270 Synergistic, 257, 270 Syringoma, 106, 162, 164, 270 Systemic, 138, 159, 174, 206, 223, 236, 238, 249, 261, 270, 273, 275, 277 Systolic, 234, 270 T Taurine, 204, 210, 218, 270 Technetium, 114, 270 Telomerase, 49, 94, 111, 270 Temporal, 36, 231, 243, 270 Teratogenic, 199, 239, 270 Terminator, 212, 270 Testicles, 144, 264, 270 Testicular, 162, 270 Testis, 162, 224, 230, 270 Testosterone, 144, 146, 262, 270 Tetany, 252, 270 Tetracycline, 45, 220, 271

294

Adenoma

Therapeutics, 174, 271 Thermal, 41, 51, 203, 219, 247, 271 Third Ventricle, 235, 271 Threonine, 37, 254, 265, 271 Threshold, 234, 271 Thrombin, 255, 259, 271 Thrombomodulin, 259, 271 Thrombosis, 259, 269, 271 Thromboxanes, 203, 217, 221, 258, 271 Thymidine, 271 Thymidylate Synthase, 31, 271 Thymus, 43, 235, 242, 271 Thyroid Gland, 81, 88, 108, 110, 230, 234, 252, 254, 271 Thyroid Hormones, 271, 274 Thyroiditis, 95, 120, 156, 271 Thyrotropin, 68, 80, 145, 149, 150, 168, 271 Thyroxine, 199, 271 Tinnitus, 250, 271 Tolerance, 25, 40, 197, 229, 272 Tomography, 94, 96, 272 Tone, 251, 272 Tonicity, 239, 272 Topical, 224, 233, 239, 251, 272 Toxic, iv, 43, 83, 121, 153, 199, 204, 210, 211, 215, 218, 219, 223, 231, 235, 260, 264, 265, 272 Toxicity, 10, 52, 151, 220, 272 Toxicokinetics, 272 Toxicology, 27, 182, 272 Toxin, 152, 272 Trace element, 62, 206, 272 Trachea, 271, 272 Transcriptase, 94, 270, 272 Transcription Factors, 6, 23, 43, 44, 59, 209, 272 Transduction, 266, 272 Transfection, 25, 205, 228, 272 Transfer Factor, 235, 272 Translation, 61, 63, 273 Translational, 6, 16, 32, 63, 273 Translocation, 131, 273 Transmitter, 197, 220, 243, 248, 273 Transplantation, 87, 109, 211, 235, 242, 273 Transurethral, 158, 259, 273 Transurethral resection, 158, 259, 273 Transurethral Resection of Prostate, 259, 273 Trauma, 160, 163, 246, 251, 273 Trigeminal, 225, 273 Tryptophan, 212, 265, 273 Tuberculosis, 162, 273

Tuberculosis, Renal, 162, 273 Tubulin, 245, 273 Tumor marker, 21, 205, 273 Tumor model, 35, 55, 273 Tumor suppressor gene, 11, 18, 26, 29, 32, 33, 47, 48, 55, 58, 66, 143, 241, 251, 263, 273 Tumorigenic, 6, 26, 46, 273 Tumour, 76, 98, 102, 120, 155, 227, 273, 277 Tunica, 246, 274 Tympanic membrane, 159, 274 Type 2 diabetes, 40, 274 Tyrosine, 220, 274 U Ulcer, 76, 274 Ulceration, 274 Ulcerative colitis, 160, 213, 236, 257, 274 Ulcerogenic, 153, 274 Urachus, 114, 274 Uracil, 16, 27, 260, 274 Uraemia, 251, 274 Uranium, 270, 274 Urea, 250, 269, 274 Uremia, 262, 274 Ureters, 159, 239, 274, 275 Urethane, 121, 274 Urethra, 104, 154, 162, 204, 253, 259, 273, 274, 275 Urethral Obstruction, 158, 274 Urinalysis, 10, 274 Urinary, 11, 20, 57, 104, 113, 115, 158, 204, 236, 259, 263, 274, 275 Urinary Fistula, 159, 275 Urinary Retention, 158, 275 Urinary tract, 115, 158, 159, 204, 275 Urinary tract infection, 158, 159, 204, 275 Urinate, 275 Urine, 19, 142, 159, 202, 204, 205, 207, 220, 223, 231, 236, 239, 246, 247, 251, 262, 274, 275 Urogenital, 242, 275 Ursodeoxycholic Acid, 19, 20, 53, 275 Uterus, 145, 149, 150, 152, 156, 210, 216, 218, 222, 226, 240, 244, 251, 257, 262, 275 V Vaccination, 275 Vaccine, 198, 259, 275 Vaccinia, 154, 275 Vaccinia Virus, 154, 275 Vagina, 210, 218, 244, 262, 275, 277 Vaginal, 275, 277 Variola, 275

295

Vascular, 14, 39, 164, 200, 201, 218, 222, 231, 236, 248, 249, 255, 258, 271, 275 Vascular endothelial growth factor, 39, 275 Vasculitis, 251, 275 Vasodilator, 206, 220, 233, 275 Vasomotor, 224, 275 Vector, 272, 275 Vein, 238, 248, 252, 275 Venereal, 151, 275 Venous, 208, 249, 259, 276 Ventral, 235, 249, 276 Ventricle, 215, 260, 270, 271, 276 Venules, 206, 276 Vertigo, 250, 276 Vestibular, 103, 276 Vestibule, 276 Veterinary Medicine, 181, 276 Villi, 276 Villous, 4, 13, 114, 115, 161, 208, 276 Viral, 66, 249, 272, 273, 276 Viral vector, 66, 276 Virilism, 234, 276 Virulence, 203, 272, 276 Virus, 151, 161, 209, 216, 228, 237, 263, 267, 272, 275, 276 Viscera, 267, 276 Visceral, 115, 134, 216, 229, 253, 276

Visual field, 231, 249, 276 Vitamin A, 130, 237, 276 Vitelline Membrane, 276, 277 Vitro, 6, 7, 12, 23, 24, 25, 28, 36, 37, 39, 44, 46, 53, 59, 63, 65, 68, 89, 92, 113, 135, 148, 228, 236, 276 Vivo, 25, 36, 67, 147, 276 Vulva, 112, 277 W Wart, 239, 277 White blood cell, 202, 204, 242, 246, 255, 277 Windpipe, 271, 277 Womb, 262, 275, 277 Wound Healing, 14, 158, 211, 226, 243, 277 X Xanthoma, 164, 277 Xenograft, 201, 273, 277 X-ray, 214, 226, 227, 238, 243, 246, 248, 261, 277 X-ray therapy, 238, 277 Y Yeasts, 227, 254, 277 Yolk Sac, 25, 277 Z Zebrafish, 44, 277 Zygote, 214, 277 Zymogen, 259, 277

296

Adenoma