Basal Cell Carcinoma - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

BASAL CELL CARCINOMA 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., 1960Basal Cell Carcinoma: 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: 0-597-84350-3 1. Basal Cell Carcinoma-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 basal cell carcinoma. 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 BASAL CELL CARCINOMA ........................................................................ 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Basal Cell Carcinoma .................................................................... 4 E-Journals: PubMed Central ....................................................................................................... 41 The National Library of Medicine: PubMed ................................................................................ 42 CHAPTER 2. NUTRITION AND BASAL CELL CARCINOMA .............................................................. 87 Overview...................................................................................................................................... 87 Finding Nutrition Studies on Basal Cell Carcinoma................................................................... 87 Federal Resources on Nutrition ................................................................................................... 90 Additional Web Resources ........................................................................................................... 90 CHAPTER 3. ALTERNATIVE MEDICINE AND BASAL CELL CARCINOMA ........................................ 93 Overview...................................................................................................................................... 93 National Center for Complementary and Alternative Medicine.................................................. 93 Additional Web Resources ........................................................................................................... 98 General References ....................................................................................................................... 98 CHAPTER 4. CLINICAL TRIALS AND BASAL CELL CARCINOMA................................................... 101 Overview.................................................................................................................................... 101 Recent Trials on Basal Cell Carcinoma...................................................................................... 101 Keeping Current on Clinical Trials ........................................................................................... 103 CHAPTER 5. PATENTS ON BASAL CELL CARCINOMA ................................................................... 105 Overview.................................................................................................................................... 105 Patents on Basal Cell Carcinoma ............................................................................................... 105 Patent Applications on Basal Cell Carcinoma ........................................................................... 109 Keeping Current ........................................................................................................................ 115 CHAPTER 6. BOOKS ON BASAL CELL CARCINOMA ...................................................................... 117 Overview.................................................................................................................................... 117 Book Summaries: Online Booksellers......................................................................................... 117 Chapters on Basal Cell Carcinoma............................................................................................. 117 CHAPTER 7. PERIODICALS AND NEWS ON BASAL CELL CARCINOMA......................................... 121 Overview.................................................................................................................................... 121 News Services and Press Releases.............................................................................................. 121 Academic Periodicals covering Basal Cell Carcinoma ............................................................... 123 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 127 Overview.................................................................................................................................... 127 NIH Guidelines.......................................................................................................................... 127 NIH Databases........................................................................................................................... 129 Other Commercial Databases..................................................................................................... 131 The Genome Project and Basal Cell Carcinoma......................................................................... 131 APPENDIX B. PATIENT RESOURCES ............................................................................................... 135 Overview.................................................................................................................................... 135 Patient Guideline Sources.......................................................................................................... 135 Finding Associations.................................................................................................................. 142 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 145 Overview.................................................................................................................................... 145 Preparation................................................................................................................................. 145 Finding a Local Medical Library................................................................................................ 145 Medical Libraries in the U.S. and Canada ................................................................................. 145 ONLINE GLOSSARIES................................................................................................................ 151

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Online Dictionary Directories ................................................................................................... 152 BASAL CELL CARCINOMA DICTIONARY........................................................................... 153 INDEX .............................................................................................................................................. 209

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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 basal cell carcinoma 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 basal cell carcinoma, 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 basal cell carcinoma, 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 basal cell carcinoma. 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 basal cell carcinoma, 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 basal cell carcinoma. 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 BASAL CELL CARCINOMA Overview In this chapter, we will show you how to locate peer-reviewed references and studies on basal cell carcinoma.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and basal cell carcinoma, 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 “basal cell carcinoma” (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: •

Basal Cell Carcinoma: What Dentists Need to Know Source: JADA. Journal of the American Dental Association. 130(3): 375-380. March 1999. Summary: Basal cell carcinoma (BCC) is a malignant epithelial tumor of the skin, commonly seen in the head and neck. Because dentists routinely evaluate the head and neck, the authors of this article present three examples of BCC of the face and jaw to help clinicians recognize the condition. The authors also provide a literature review regarding the etiology, classification, treatment, and prevention of BCC. Sun exposure plays an important role in the development of BCC. The most susceptible people are those with minimal skin pigmentation. BCC is more frequently seen in men than in women. The most common form of BCC is the nodular type, which, if untreated, eventually ulcerates and may result in extensive local tissue destruction. The three cases

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Basal Cell Carcinoma

described in the article highlight the range of BCC severity. The authors stress that oral health care providers may play an important role in the recognition and diagnosis of BCC involving the head and neck. Early recognition and diagnosis may lead to management that results in improved cure rates, with reduced morbidity and reduced treatment costs. 6 figures. 1 table. 28 references. (AA-M). •

Odontogenic Keratocysts in a 5-Year-Old: Initial Manifestations of Nevoid Basal Cell Carcinoma Syndrome Source: Pediatric Dentistry. 22(1): 53-55. January-February 2000. Contact: Available from American Academy of Pediatric Dentistry. Publications Department, 211 East Chicago Avenue, Suite 700, Chicago, IL 60611-2616. Summary: This article reports the occurrence of odontogenic keratocysts in a young child. Odontogenic keratocysts are one of the principal features of nevoid basal cell carcinoma syndrome. Their occurrence in this syndrome is usually during the second or third decades of life. The authors describe the occurrence of odontogenic keratocysts in a 5 year old, which proved to be the initial presentation of nevoid basal cell carcinoma syndrome. The authors highlight the need to consider this syndrome as a possible diagnosis in all cases of odontogenic keratocysts. In children and adolescents, the cysts may cause displacement of the developing teeth, and delayed dental development has been reported. The importance of early diagnosis of nevoid basal cell carcinoma syndrome is that one can inform the patient and parents of the likely later development of multiple odontogenic keratocysts and multiple basal cell carcinomas. Careful dental follow up and treatment is required for the odontogenic keratocysts, which are continuous in their development and have a recurrence rate of 30 to 60 percent. Family members should also be investigated because the syndrome has autosomal dominant inheritance. 4 figures. 15 references.

Federally Funded Research on Basal Cell Carcinoma The U.S. Government supports a variety of research studies relating to basal cell carcinoma. 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 basal cell carcinoma. 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 basal cell carcinoma. The following is typical of the type of information found when searching the CRISP database for basal cell carcinoma:

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).

Studies

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Project Title: APPROACHES TO THE ISOLATION OF SKIN TUMOR MODIFIER GENES Principal Investigator & Institution: Balmain, Allan; Professor; Cancer Center; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 30-SEP-1999; Project End 31-MAR-2004 Summary: The purpose of this research is to develop the mouse skin carcinogenesis model as a paradigm for the study of tumor modifiers: their numbers and locations within the genome, their genetic interactions, biological functions and effects on the somatic genetic events of tumor development. Our ultimate goal is to clone tumor modifiers in the mouse for testing in human populations, with a view to improving the prospects for prediction of risk, prevention and therapy of human cancers. To achieve to broad aims set out in this proposal, we have set up an international consortium of groups and consultants with complementary expertise in the study of mouse tumor modifiers (P.Demant, Holland and T.Dragani, Italy), generation of novel models through germline manipulation, (T.Jacks, Boston;D.Hanahan and E.Epstein, San Francisco), physical induction of germline deletions for functional studies of modifier genes (T.Sato and M.Kusakabe, Japan) and the search for tumor modifiers in human populations (B.Ponder, UK). Our initial aim is to determine the number and chromosomal locations of skin tumor modifier loci in a variety of mouse strains, using a combination of genetic approaches including interspecific backcrosses between mus spretus and mus musculus. Since the detection of human modifiers of complex traits directly using human material involves approaches such as linkage disequilibrium with single nucleotide polymorphisms, we will pursue a parallel strategy in the mouse by investigating animals selected from a mixture of genetic backgrounds by virtue of sensitivity of resistance to skin carcinogenesis. This will be carried out using chemical carcinogenesis in skin as a method of tumor induction, and will provide us with information on the degree of overlap of these different approaches to the detection and analysis of tumor modifiers. A number of transgenic/knock out models for skin tumor induction will also be investigated. These include keratin promoter-driven ras or HPV transgenic mice, which develop multiple squamous carcinomas, and patched (Ptc) knock-out mice, which provide a model for the development of basal cell carcinomas after UV treatment. Modifiers of these transgene/knockout induced phenotypes will be analyzed using genetic mapping approaches in mus musculus and mus spretus crosses. In the same crosses, DNA repair capacity will be assessed (with J.Cleaver, San Francisco) in individual mice and the relationship between loci that control DNA repair and the tumor predisposition loci will be investigated. These studies may identify subsets of tumor modifiers which operate in skin independent of the mode of tumor induction, or which may be specific for a particular genetic insult or target cell within the skin. Together with Drs. Kusakabe and Sato in Japan, we will induce germline deletions in regions of the mouse genome that harbor potential tumor modifier or tumor suppressor genes as a prelude to functional studies in vivo. The relationship between these germline tumor modifiers and the somatic genetic alterations which take place during tumorigenesis will be investigated using microsatellite-based LOH, CGH and genomic arrays (with J.Gray, D.Pinkel and D.Albertson, San Francisco) to study patterns of gene loss or gain in tumors representing different stages of carcinogenesis. Finally, candidate modifiers identified using mouse approaches will be studied in humans to determine their relevance to the development of human skin or other tumor types. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Basal Cell Carcinoma

Project Title: ARSENIC INDUCED MIOTIC ARREST ASSOCIATED APOPTOSIS Principal Investigator & Institution: States, J Christopher.; Associate Professor; Pharmacology and Toxicology; University of Louisville University of Louisville Louisville, Ky 40292 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 30-APR-2008 Summary: (provided by applicant): Arsenic is a natural contaminant of drinking water in many parts of the world, is a known human carcinogen and is #1 on the EPA list of hazardous chemicals. Cancers most often associated with chronic arsenism are squamous and basal cell carcinomas of the skin. How arsenic causes cancer is unknown. However, the National Research Council Report on Arsenic in Drinking Water concluded that the most likely mode of action is induction of numerical and structural chromosomal abnormalities. Arsenite, the carcinogenic form of arsenic found in drinking water, disrupts mitosis causing an anaphase delay and induces aneuploidy in normal diploid human fibroblasts and peripheral blood lymphocytes, and mitotic arrest associated apoptosis (MAAA) in p53 deficient human fibroblasts. The sensitivity of p53 deficient human cells to arsenite induced MAAA suggests that the mechanism of arsenite carcinogenesis is different than sunlight induced skin carcinogenesis in which p53 mutation is an early and common event. The hypothesis to be investigated is that p53 relieves the arsenite-induced anaphase block by activation of the G2 checkpoint response which inactivates cyclin B/cdc2 and derepresses the mitotic exit network and allow the cells to escape arsenite induced MAAA. It is the prevention of apoptosis in arsenic intoxicated cells that allows genetic instability (aneuploidy) after mitotic disruption. Identification of the cellular factors that interact with p53 or the p53 regulated genes to prevent mitotic arrest associated apoptosis and to allow cells to proceed through mitosis with a delay will provide valuable information regarding the mode of action of arsenite. The specific aims proposed are: 1.) Determine activation of the G2 checkpoint pathway in p53(+) and p53(-) cells arrested by arsenite in mitosis; 2.) Test by overexpression and targeted knockdown of G2 checkpoint proteins the role of G2 checkpoint activation in the escape from arsenite induced anaphase block; 3.) Test whether arsenic associated skin tumors are p53 wild type or mutant. The results of these studies will identify players mediating release from arsenite induced mitotic arrest, and will provide valuable information on the mechanism of arsenic induced carcinogenesis, clues to the usefulness of arsenite as a chemotherapeutic agent and valuable information on the mode of action of mitosis disrupting drugs in killing human cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BASAL CELL CARCINOMA CHEMOPREVENTION IN BCNS PATIENTS Principal Investigator & Institution: Epstein, Ervin H.; Research Professor; Dermatology; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 21-JUL-1999; Project End 30-JUN-2004 Summary: (Applicant's Description) Basal Cell Carcinomas (BCCs) are the commonest human cancer and are of increasing incidence, due in part to increased recreational sunlight exposure. During the past two years, the fundamental molecular defect apparently underlying the aberrant behavior of these tumor cells has been uncovered; all BCCs have abnormal regulation of the hedgehog signaling pathway. Patients with the basal cell nevus syndrome (BCNS) are susceptible to developing multiple basal cell carcinomas because they inherit one defective allele of the PTC gene, which encodes a protein that hampers hedgehog signaling. Mice hemizygous for a functioning ptc gene,

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like BCNS patients with the same genotype, are highly susceptible to the development of BCCs, and these are induced by the relevant environmental insult-ultraviolet light. This project will utilize the growing knowledge of HCC signaling aberrations, the murine BCC model, and the chemopreventive effects of tea extracts to develop agents efficacious in preventing BCC carcinogenesis in mice and man and will investigate the mechanisms underlying such efficacy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BASAL CELL CARCINOMA:MOLECULAR PATHOGENESIS & PREVENTION Principal Investigator & Institution: Bickers, David R.; Carl Truman Nelson Professor/Chair; Dermatology; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 23-JUL-2002; Project End 30-JUN-2007 Summary: (provided by applicant): Non-melanoma skin cancer (NMSC) includes basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), which together are the most common type of human malignancy. More than one million Americans develop one or more of these tumors annually and BCCs represent more than 75% of NMSC. Thus BCCs are a major public health problem and a major cause of morbidity and escalating health care costs in this country. Environmental exposure to solar ultraviolet B (UVB) is the major risk factor for the induction of BCCs. The molecular basis underlying the development of these tumors is now known to relate to mutations in the hedgehog signaling pathway including patched (PTCH). sonic hedgehog (SHH) and smoothened (SMO). In addition, an animal model for BCCs. the patched heterozygous knockout mouse, has been developed which provides a system with which to explore the molecular pathogenesis of UVB-induced BCCs. It is known that skin exposure to UVB drives a proliferative stimulus to epidermal keratinocytes and that induction of the enzyme ornithine decarhoxylase (ODC') is a major contributor to the augmented growth and clonal expansion of initiated cells. UVB exposure also enhances oxidant stress in the skin. which is accompanied by increased generation of reactive oxygen species (ROS) that can induce ODC and augment keratinocyte proliferation. In this proposal we will test the hypothesis that factors which enhance cell proliferation such as increased ODC expression and oxidant stress are crucial for UVB induction of BCCs. We have developed a novel modification of patch +/- heterozygous mice in which ODC is overexpressed (ptch +I-/ODC TgN). These mice have accelerated spontaneous development of microscopic BCCs like tumors by the age of 20 weeks and with UVB exposure visible BCCs within 30 weeks. We will utilize this animal model to probe the pathogenesis of IJVB-induced BCCs by assessing the role of over-expression of ODC, by evaluating the effects of altered cell cycle regulation and by measuring oxidant stress. The result of these studies will be used to devise innovative pharmacogenetic approaches to the chemoprevention of UVB-induced BCCs. It is likely that novel anticarcinogenic agents potentially suitable for testing in the human population could be identified as a result of the studies in this proposal. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BIOLOGIC APPROACH TO THERAPY OF AGGRESSIVE SKIN CANCER Principal Investigator & Institution: Lippman, Scottm; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030

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Timing: Fiscal Year 2002 Summary: Standard local treatment of aggressive squamous cell carcinomas (SCC) of the skin continues to be plaqued with primary disease recurrence and second primary tumors in most patients afflicted with these cancers. In addition to substantial mortality rates, cosmetic, psychologic and functional impairment are frequent and devastating sequelae of aggressive skin cancers and the required definitive local therapy. Using our prospective skin cancer database, four clinical-histologic criteria (depth of invasion, perineural invasion, lesion size, regional metastases) define a population of patients at greater than 70% risk of local, and/or regional recurrence after definitive local/regional therapy. Second primary tumors (SPTs) occur at a rate approximating 6% per year. Single-agent therapy with retinoic acid or alpha-interferon have limited activity in the therapy of advanced solid tumors. However, both of these agents are known to possess antiproliferative, differentiative, anti-angiogenic and immunomodulatory properties; probably exerting these effects through separate molecular mechanisms. Ongoing mechanistic studies have indicated some potentially important anticancer interaction sof retinoid-interferon combinations. In vitro studies of retinoid-interferon-alpha combinations indicate a synergistic interaction in the induction of interferon-stimulated gene factor and several interferon inducible enzymes (e.g., 2'-5' oligoadenylate synthetase) and programmed-cell death. In vivo studies have found synergistic inhibition of experimental tumor induced angiogenesis. Clinical studies include two recent phase II trials of 13-cis retinoic acid (13-cRA) in combination with alphainterferon which have reported major responses rates of 50% and 68% in advanced skin SCC. Based on the substantial preclinical and clinical experience, we now propose an adjuvant chemoprevention study using these agents for six months in patients with aggressive squamous carcinoma of the skin treated with standard surgery and radiation therapy. This chemopreventive and therapeutic approach is designed to decrease the development of primary disease recurrence (local, regional and distant) as well as SPTs, in a controlled, randomized trial. A number of correlative laboratory and mechanistic studies aimed at understanding several major aspects of the mechanisms of action of retinoids and interferon are included within this clinical trial. In addition, we will obtain, through self-administered questionnaires, outcome information on these SCC patients relative to emotional well-being, quality of life, cognitive functioning, and pain in order to develop longitudinal profiles of these outcome parameters. A total of 90 patients, meeting these high risk criteria, will be required for the study with a minimum follow-up of three years. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CELL CARCINOGENES

CYCLE

REGULATORY

PROTEINS

IN

UVB-SKIN

Principal Investigator & Institution: Kim, Arianna L.; Dermatology; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2003; Project Start 21-APR-2003; Project End 31-MAR-2008 Summary: (provided by applicant): Basal Cell and squamous cell carcinomas (nonmelanoma skin cancers or NMSC) are the most common type of human malignancies with approximately one million new cases diagnosed annually in the United States. The vast majority of these tumors are the result of exposure to sunlight, particularly ultraviolet B (UVB) radiation. It is becoming increasingly clear that cell cycle regulators, including cyclin Dl, are potential targets for UVB-induced damages. We demonstrated that UVB irradiation of a transformed keratinocyte cell line lacking functional p53 results in cell cycle arrest in GI. This arrest coincided with the

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degradation of cyclin Dl and cdk4 proteins and was, in part, proteasome-dependent. This suggests that regulation of cyclin Dl protein stability is an early cellular response to UVB radiation. Furthermore, increased levels of cyclin Dl are found in various types of tumors. Indeed, our complete photocarcinogenesis study in a mouse model showed the early accumulation of cyclin Dl protein that increased gradually during UVB-induced skin carcinogenesis. Thus, regulation of cyclin Dl stability seems to be a key event of the short- and long-term responses to UVB radiation. We propose to study the mechanisms regulating cyclin Dl stability following U\JB radiation in cell lines and in mouse models for skin photocarcinogenesis. We will test the hypothesis that the mechanism(s) responsible for the rapid UVB-induced degradation of cyclin Dl are impaired in skin chronically exposed to UVB, thus participating in the accumulation of cyclin Dl leading to skin tumors formation. We anticipate that the combination of in vitro and in vivo approaches will help to better understand the molecular basis of skin cancer development. In addition, our studies could provide a rationale to develop new therapeutic tools targeted towards the protein degradation machinery. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHEMO-PREVENTION CARCINOMAS

OF

UVB-INDUCED

BASAL

CELL

Principal Investigator & Institution: Athar, Mohammad; Dermatology; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 30-APR-2005 Summary: (provided by applicant): Solar UVB radiation is a well-known major risk factor for the induction and development of non-melanoma skin cancers (NMSCs), which include both basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs). The carcinogenic effects of environmental UVB exposure are thought to retard the direct induction of structural changes in DNA, such as cyclobutane pyrimidine dimers and 6-4 photoproducts, leading to mutations in the form of C to T and CC to TT transitions (UVB signature mutations). These mutations are present in the p53 gene of the majority of SCCs, BCCs, actinic keratoses and in non-tumor skin adjacent to these lesions. Skin BCCs are the most common form of human cancer, affecting at least 750,000 Americans each year. The molecular mechanism of BCCs induction involves activation of the sonic hedgehog (shh) pathway. Extensive experimental evidence confirms that cutaneous UVB exposure induces UVB signature mutations both in p53 and in ptch genes, which together likely play an important role in blocking apoptosis and augmenting proliferation and clonal expansion of initiated cells leading to BCCs induction of BCes. We propose that rescuing mutant p53 and blocking shh pathway activation together using a combinatorial approach in ptchheterozygous mice could provide additive and/or synergistic protection against BCCs. To test this hypothesis, we will employ a genetically engineered murine model of BCCs development and use combination of a rescuer of mutant p53 conformation and function, CP-31398 and a specific inhibitor of the shh pathway, cyclopamine. It is our belief that this animal model combined with the study of chemical agents capable of rescuing mutant p53 and inhibiting shh pathway activation provides a uniquely effective approach for testing innovative mechanismbased strategies for the chemoprevention of NMSCs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CANCER

COMPREHENSIVE

OUTCOME

OF

NONMELANOMA

SKIN

Principal Investigator & Institution: Chren, Mary-Margaret; Associate Professor; Dermatology; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 28-FEB-2006 Summary: The applicant's long-term career goal is to improve the quality of care for chronic skin conditions. In the last five years, supported by a mentored Clinical Investigator (K08) Award, she has developed a quality-of-life outcomes measure for skin diseases, called Skindex. Her immediate career goal is to compare outcomes of treatments for nonmelanoma skin cancer (NMSC). Her research career development plan centers on a longitudinal cohort study of patients with NMSC. With the proposed support she will acquire enhanced skills by focusing on new research questions in this study sample. ENVIRONMENT. This proposal will be conducted at University of California at San Francisco (UCSF) and its affiliate, the San Francisco Veterans Affairs Medical Center (VAMC). The research will be conducted in the VAMC Survey Research Unit, a laboratory for survey research, chart review, and data management. To address incremental research questions, the applicant will collaborate with UCSF faculty in the Institute for Health and Aging and the Departments of Medicine and Epidemiology and Biostatistics. RESEARCH PROJECT. This proposal focuses on a prospective longitudinal observational study of a cohort of patients newly-diagnosed with NMSC at a private practice and a VAMC dermatology clinic. The goal is to compare treatment outcomes among patients treated in different ways. Principal sources of data are patient survey and medical record review. The primary outcome is skin-related quality of life measured by Skindex; additional analyses will compare tumor recurrence, patient satisfaction, and resource utilization among the treatment groups. The applicant will also learn additional analytic techniques to measure patterns of change in quality of life over time, and will address a new research question about how patients' a priori expectations for care relate to process and outcomes of that care. The proposal is significant because of the prevalence of NMSC and the importance of determining its optimal therapy. In addition, this proposal will provide an intensive novel research focus for the applicant. This opportunity will expand her ability to make a significant contribution to the science of health care quality improvement by determining how patients' expectations for care relate to the process and outcomes of their care, thus broadening conventional conceptualizations of health care quality. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORE--CELL CULTURE/TISSUE PREPARATION Principal Investigator & Institution: Holleran, Walter M.; Northern California Institute Res & Educ 4150 Clement Street (151-Nc) San Francisco, Ca 941211545 Timing: Fiscal Year 2003; Project Start 20-SEP-2003; Project End 31-JUL-2008 Summary: The Cell Culture Core supplies high quality cells for the Program Project investigators. The facility is maintained such that it meets and exceeds the relevant federal health and safety standards. The majority of cells provided by the facility are foreskin-derived normal human keratinocytes. These cells are plated with the media, conditions, and density required by each Program Project investigator. Presently the facility is providing over 250 million cells per week to investigators, but it can produce equal to or more than 500 million per week on demand. In addition, the facility has a large library of frozen cells, including transformed and genetically-altered lines, that are

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available to the investigators. Depending on need, these lines also are maintained at low levels allowing for rapid and efficient boosting of cell numbers at the investigator's request. The facility also routinely produces murine keratinocytes from both normal and transgenic sources, as required for individual Program Project investigators. Dr. Walter M. Holleran, Director, and Ms. Sally Pennypacker, Head Technician, not only provide in vitro culture knowledge and expertise for other investigators, but also insure that health and safety inspections are passed, hoods and incubators are tested and serviced regularly, and cultures are tested monthly for mycoplasma. Both Dr. Holleran and Ms. Pennypacker also possess expertise in working with organotypic cultures, as well as culturing adult skin keratinocytes and fibroblasts, late-passage keratinocytes, basal cell carcinoma cells, fetal rat and mouse keratinocytes, and various explant methods. Core A is developing methods for growth of Hailey-Hailey cells, cell-cell adhesion assays, improved lipid and lamellar body generation, and growth of adult and neonatal murine keratinocytes from various knockout animal models. A fundamental part of the operation of Core A is the interaction between its personnel and members of the Program Project, allowing researchers to obtain high-quality cultures specifically tailored to their needs, while providing direct feedback for optimization of techniques and protocols. The facility is now equipped with amber lights for work with lightsensitive compounds. Finally, Core A provides both maximum numbers of high quality cells and advice on in vitro methods to investigators, who rely heavily on this facility. The continued production of healthy keratinocytes will remain the priority of this key facility. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORE--TISSUE PROCUREMENT Principal Investigator & Institution: Clayman, Gary L.; Associate Professor; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 06-AUG-2001; Project End 31-MAR-2003 Summary: The Tissue Procurement Core Facility for t his Program Project will provide services to each investigator. This will enhance each project, increase the efficient use of time and funds, and ensure coordination between projects. The Core will obtain human tumor tissue and maintain a bank of frozen malignant tumors, adjacent non-malignant skin, non-sun exposed skin and peripheral blood lymphocytes. It will also maintain laboratory specimen coding to maintain patient confidentiality and prevent experimental bias. Tumor cell line will also be maintained in the Core and distributed amongst investigators as required. All specimens will be histologically verified. Central processing of tumors for mRNA, DNA, and protein will be provided for all projects through the Core facility allowing: 1) a safe, central repository of essential materials for the research project s with accurate coded record keeping capabilities. 2) efficient utilization of scarce materials by multiple investigators. 3) standardization of collection, storage, and processing procedures, ensuring uniformity of materials obtained by different investigators. 4) An efficient tracking, delivery, and processing system that adjusts and meets the tissue requirements for the program project. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CUTANEOUS ONCOLOGY Principal Investigator & Institution: Duvic, Madeleine; Professor and Chief; Dermatology; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030

12

Basal Cell Carcinoma

Timing: Fiscal Year 2002; Project Start 14-AUG-2000; Project End 31-JUL-2005 Summary: This is a mid-career development award application for Madeleine Duvic, Professor of Medicine and Chief of Dermatology at the MD Anderson Cancer Center. It would support a new program in Cutaneous Oncology and enable her to mentor new Assistant Professors, fellows, residents, and medical students in the field. The applicant has an outstanding track record in conducting patient oriented clinical research and is a leader in developing new therapies for the treatment of Cutaneous T Cell Lymphomas (CTCL). There is an unwavering commitment to the conduct of patient oriented research and mentoring at all levels of career development. The award would free the applicant from half of her current clinical duties, allowing her to spend greater than 60 percent of her time on patient oriented translational retinoid research and mentoring activities. A Clinical Research curriculum, an oncology fellows seminar series, and institutional conferences will enhance further career development of the applicant and students. Two translational research projects are proposed using retinoids for cancer. 1] The loss of a novel class II tumor suppressor, Tazarotene Induced Gene 3 (TIG-3), will be investigated in the development and progression of non-melanoma skin cancers. The finding that TIG-3 is significantly decreased in aggressive versus non-aggressive skin cancer and in basal and squamous carcinomas, compared to paired normal skin will be examined in a larger set of samples and by sequencing cDNAs and by loss of heterozygosity studies. Oral Accutane adjuvant therapy for patients with aggressive tumors may be related to upregulation of TIG-3. 2] Development of molecular markers for Targretin, an experimental RXR selective retinoid, Targretin, will be assessed in the topical and oral treatment of CTCL. Targretin may restore expression of RAR and RXR receptors in epidermis, by altering cytokines and fostering apoptosis of the lymphocytic infiltrates. Patient's skin lesions before and after therapy will be studied using immunohistochemistry and in situ hybridization for retinoid receptors, cytokines, and fas/fas ligand. Genetic basis of large cell progression and gene expression following retinoid therapy will be explored using genomic display and will enhance the training in molecular biology. Understanding the biology of skin cancer and CTCL and the mechanism of novel therapeutic agents should result in the development of better and less toxic therapies for cancer. Young physicians and students who receive advanced training in the proper detection, prevention, and treatment of skin cancers will be a resource and may improve outcomes for patients of the future. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DNA REPAIR AND CHROMOSOME INSTABILITY IN SKIN CANCERS Principal Investigator & Institution: Wei, Qingyi; Professor; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 06-AUG-2001; Project End 31-MAR-2003 Summary: Basal cell and squamous cell carcinomas (BCC and SCC) commonly occur on exposed sites such as the head and neck and are usually due to chronic exposure to solar ultraviolet radiations (UVR). The role of host susceptibility to UVR carcinogenesis is not well defined at either the molecular or cytogenetic level. We propose to conduct a casecontrol study to evaluate the association between genetic susceptibility to UVR (defined as decreased DNA repair capacity or increased mutagen sensitivity) and the development and progression of skin carcinomas. The DNA repair capacity will be measured by host-cell reactivation assay with UV- irradiated plasmids. Mutagen sensitivity will be measured by UVR induced chromosomal breaks and the frequency of break sites on chromosomes. We will use peripheral blood lymphocytes from 300

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untreated cases (150 BCC and 150 SCC) and 300 controls to perform these assays. The specific aims of this proposal are: (1) to examine the association between DNA repair capacity and the development of skin carcinomas, (2) to examine the association between mutagen sensitivity and athe development of skin carcinomas, and (3). To examine the association between the frequency of break sites on chromosomes and the development and progression of skin carcinomas, and (4) to evaluate the association of DNA repair capacity with mutagen sensitivity, frequency of chromosomal break sites, gene mutations, and epidemiologic and clinical variables such as sunlight exposure history, clinical stage of disease, and treatment outcomes. We will investigate the relationship between these two genetic susceptibility markers and the development of skin carcinomas in relation to phenotypic characters, family history, sunlight and other carcinogenic exposures, the frequency of mutations in ras oncogenes and p53 tumor suppressor genes clinical stage and progression of tumors (to be collected by Core B; Drs. Margaret Spitz, Randal Weber, and Honnavara Ananthaswamy) and treatment outcomes (to be measured by Drs. Scott Lippman and Reuben Lotan) from the same subjects. This study will provide information regarding the utility of these markers of genetic susceptibility in identifying individuals at high risk of developing skin carcinomas. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DNA REPAIR, GENETIC VARIATION AND SKIN CANCER Principal Investigator & Institution: Hunter, David J.; Director; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant)We propose to prospectively assess the association of low-penetrance polymorphisms and haplotypes in candidate DNA repair genes to the risk for melanoma and non-melanocytic skin cancers including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) in the Nurses' Health Study. We hypothesize that candidate polymorphisms and haplotypes in three important DNA repair genes (XPD in nucleotide excision repair; XRCC1 in base excision repair; XRCC3 in homologous recombination repair) are associated with higher risk of skin cancer. We will further examine whether the candidate polymorphisms modify the association between the sunlight exposure and the risk of skin cancer. After blood collection in 198990 up to 1998, we have accrued 743 incident cases of skin cancers (177 melanoma, 283 SCC, and 283 BCC which were randomly selected from diagnosed BCC cases); each case will be matched by age and race to a control in the nested case-control study. We will have >90% power to detect relative risks of 1.5 or greater for the main effects of most of the genotypes of interest. We will also have substantial power to detect interactions between these genotypes and lifetime sunlight exposure. This study will be among the first studies of the association of polymorphisms in candidate DNA repair genes with skin cancer, which assess potential interactions between genotype and sunlight exposure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ENVIRONMENT & GLI GENES IN NORMAL DEVELOPMENT & DISEASE Principal Investigator & Institution: Iannaccone, Philip M.; Professor; Children's Memorial Hospital (Chicago) Chicago, Il 606143394 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-JUL-2005

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Basal Cell Carcinoma

Summary: Developmental pathways are networks of genes which act coordinately to establish the body plan. Disruptions of these genes, which can be associated with environmental exposures, can result in serious dysmorphogenesis or cancer in both children and adults. An important goal of environmental science ought to be reduction of these poor outcomes. This will require an understanding of the genes affected by specific exposures and the consequence of alterations in these genes or their products which in turn will require a complete biochemical understanding of the pathways critical in development. The ligand Sonic hedgehog, the receptors Patched and Smoothened, and the GLI family of transcription factors represent one such pathway critical to the normal development of many organs due to their regulation functions at the nexus of mesenchymal differentiation. Environmental exposure to jervine or UVA and UCB disrupts the pathway. Although some gene targets of the pathway are not known from work in Drosophila key downstream targets and upstream regulators remain to be elucidated in mammals and the roles of these molecules established in normal development in order to better understand their role in dysmorphogenesis and neoplasia. For example, basal cell carcinoma (BCC) is the most common cancer in man and mutations in Patched or over-expression of GLI are both strongly associated with BCC. Prostatic cancer is a serious problem in the US and our preliminary evidence suggests an association of GLI expression with prostatic cancer in humans. We have established a unique team of co- investigators of GLI expression with pro-static cancer in humans. We have established a unique team of co-investigators at Northwestern University who study the regulation and function of the homologues of the GLI genes in C. elegans, Drosophila, mouse, and human. We have previously worked together to collaborate on studies of these genes and these efforts will be greatly enhanced by the current program project allowing use of data from Drosophila and C. elegans in the design of experiments in mouse, or with human material. We are uniquely suited to establish the regulation of the GLI genes at a transcriptional, post- transcriptional, and functional (protein-protein interactions) level. The long term goals of our work will be to determine pathways of development involving GLI genes and their interactions with environmental exposure, in order to establish mechanisms of interact with downstream targets. These experiments will provide data of great significance to both normal development, birth defects, and cancer. The work will very likely provide important general models of transcription factor activity whose utility will extend to a wide variety of developmental, birth defects, and cancer. The work will very likely provide important general models of transcription factor activity whose utility will extend to a wide variety of developmental and cancer problems. Clearly understanding the pathways and the biochemical mechanism of action of developmental genes will be necessary in order to determine the role of environmental exposures on human health. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EPITHELIAL MATRIX IN CARCINOMA DEVELOPMENT Principal Investigator & Institution: Marinkovich, M Peter.; Assistant Professor; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 27-SEP-2002; Project End 30-JUN-2003 Summary: (provided by applicant): Overview: The important roles that epithelial matrix interactions play in tumor invasion and tissue morphogenesis are just beginning to be understood. Data generated through our efforts during the previous funding cycle suggest important roles for laminin 5, bone morphogenic protein (BMP 1) isozymes and alpha 6 beta 4 integrin in squamous cell carcinoma (SCC) progression and an important role for laminin 10 in basal cell carcinoma (BCC) development. The current studies are

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directed at further defining the role of the extracellular matrix in development of non melanoma skin cancers. Through synergistic collaboration with the other Projects, the ultimate application of these studies will be to discover new molecular approaches to inhibit carcinoma development. They propose to: 1. Determine the roles of laminin 5 and beta 4 integrin in SCC progression. This Aim will determine the mechanisms by which laminin 5 and beta 4 integrin impact upon SCC tumors. They hypothesize that laminin 5 may inhibit and b4 integrin may promote SCC progression. This aim will utilize a Ras driven turnorigenesis model where keratinocytes are engineered to form SCC like tumors in immunodeficient mice. The effects of site directed mutagenesis of key domains on laminin 5 and beta 4 integrin cDNA will be examined in vivo for effects on SCC progression by in vitro and in vivo assays of cell and tumor invasion. Tumor size, morphology, differentiation, apoptosis and adhesion to host stroma will be evaluated. 2. Demonstrate the function of BMP I isozymes in SCC progression. Their preliminary results showed that BMP 1 isozyme mediated processing of laminin 5 supported SCC tumor invasion in vitro and characterized a potent and specific BMP 1 inhibitor with potential tumor inhibitory effects. In this Aim, they seek to extend these results to in vivo models of SCC tumor development. Expression of each of the four BMP 1 isozymes and the processing of laminin 5 will be evaluated in a survey of SCC tumors. The effect of BMP 1 isozyme mediated laminin 5 processing on SCC tumor progression will be studied through overexpression studies. Finally, specific BMP 1 isozyme inhibitors will be evaluated in vivo for their effects on tumor invasion. 3. Discover how laminins impact upon BCC development. Laminins perform important roles in tissue morphogenesis as well as carcinoma development. Their preliminary results show an important role for laminin 10 in hair development and suggest that laminin 10 supports BCC development as well. Additional studies suggest that laminin 5 may have an inhibitory effect on BCC. They will evaluate a number of tumor parameters in the study of the effects of laminin 10 inhibition in a BCC animal model. Multiple approaches will be utilized including the use of inhibitory antibodies and the use of laminin 5 mice. They will assess the effects of laminin 5 overexpression and underexpression on BCC development in an animal model using laminin 5 cDNAs delivered to primary and laminin 5 null EB keratinocytes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FREQ RESOLVED NEAR TOMOGRAPHY OF BURNS & CUTANEOUS

INFRARED

REFLECTANCE

Principal Investigator & Institution: Svaasand, Lars O.; University of California Irvine Irvine, Ca 926977600 Timing: Fiscal Year 2002 Summary: Optical techniques represent a valuable tool for non-invasive investigation of in vivo tissue properties and imaging of tissue structures. Diffuse light reflected from a tissue contains not only information on the properties of the tissue surface, but also information on tissue structures residing at depths of several millimeters. Such information is important for several clinical situations, e.g., in determining the depth and size of Port-wine stain vessels, the thickness of nodular basal cell carcinoma or the depth of necrosis in a burn. The aim is to develop a non-contact, near-infrared technique for tomographic mapping of a tissue surface with information of tissue properties to depths of 5-10 mm. This kind of information is important for establishing a proper protocol for various clinical modalities. One example can be to determine the depth of nodular basal cell carcinomas, where this information of depth is important for determining a proper drug and light dose for photodynamic therapy, or for

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Basal Cell Carcinoma

cryotherapy. Another example can be in treatment of burns, where the depth of necrosis and the blood perfusion has to be determined. The project will be based on available expertise in photon migration work present at the Beckman Laser Institute and the Norwegian Institute of Technology. The first phase of the work will aim to develop specific and optimized algorithms and subsequently test/verify the theoretical results on equipment which, has already been developed, in part, at the Beckman Laser Institute. Provided that the results from this first phase are satisfactory, a second phase can be initiated where the algorithms and the technical equipment will be optimized for various applications. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENE REGULATORY MECHANISMS OF EPIDERMAL GROWTH Principal Investigator & Institution: Khavari, Paul A.; Associate Professor; Dermatology; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 27-FEB-1999; Project End 31-JAN-2004 Summary: Dominantly acting proto-oncogenes and organizers of tissue polarity, such as the NF-kappaB/Rel and Hedgehog family proteins, control cellular growth via terminal downstream targets that are as yet largely unidentified. NF-kappaB and Sonic Hedgehog (SHH) exert profound but opposite effects on epidermal growth and may play significant roles in human skin disease. A role for NF-kappaB proteins in controlling epidermal growth has recently been identified by the principal investigator. SHH pathway activation in human basal cell carcinoma has also recently been demonstrated by a key collaborator on this proposal and recently confirmed by the principal investigator in studies with engineered human epidermis in vivo. These findings have led us to propose the following hypothesis: NF-kappaB helps trigger the growth arrest associated with terminal differentiation of suprabasal epidermis while SHH can promote a proliferative expansion of basal epithelium. We suggest that understanding the mode of action of these 2 dominant regulators may lead to fundamental insights into epithelial insights into epithelial biology and new therapeutic targets for clinical disorders of abnormal epidermal proliferation. The overall goal of this proposal is to define mechanisms of NF-kappaB and SHH action in epidermal growth regulation. First, we plan to characterize the genes downstream of NF-kappaB and SHH activation in epidermis. To do this, we will examine the impact of NF- kappaB and SHH on effector genes of known importance in the skin. In addition, we will search for new target genes using new screening approaches. Second, we plan to define the role of NF-kappaB in epidermal growth control. We will characterize NF-kappaB effects on cell cycle machinery, with a special emphasis on cyclin-dependent kinase inhibitors. In addition, we plan to characterize NF-kappaB in human disease of abnormal epithelial proliferation, including squamous cell carcinoma (SCC) of the skin and its precursors. At the end of this proposed funding period, we hope to have defined the gene regulatory mechanisms involved in NF-kappaB and SHH control of epidermal growth as a basis for fundamental insights into epithelial biology and new therapeutic biology and new therapeutic targets in clinical disorders of abnormal epidermal proliferation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENETIC ANALYSIS OF THE SONIC HEDGEHOG TARGET GENE BEG4 Principal Investigator & Institution: Callahan, Christopher A.; Associate Professor; Pathology; Stanford University Stanford, Ca 94305

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Timing: Fiscal Year 2002; Project Start 10-AUG-2001; Project End 31-JUL-2006 Summary: My long-term interest and the objective of this proposal are to better understand the pathogenesis of epithelial neoplasms, such as basal cell carcinomas (BCCs). I am completing training in anatomic pathology while serving as an autopsy fellow at Stanford University Medical Center. I propose to conduct a 5-year, mentored, research experience within the laboratory of Dr. Tony Oro to enhance my research skills in cutaneous tumor biology. This scientific training, combined with my continued and limited autopsy service work, will establish an exceptional foundation for my future independent research program. Basal cell carcinomas are one of the most common cancers worldwide and induction of Sonic hedgehog (Shh) target genes are critical to their pathogenesis. To isolate and characterize key Shh target genes involved in BCC formation, the Oro laboratory devised a model for human BCCs which formed the basis of a microarray screen for BCC-enriched genes (BEG's). One recently isolated gene, BEG4, is a Shh target gene and its overexpression in cultured, human keratinocytes leads to dramatic increases in keratinocyte growth. BEG4 is represented by a single, 5.5 kb transcript and encodes a novel, proline-rich protein with similarity to the WiskottAldrich Syndrome protein (WASp). Together, these findings suggest that BEG4 influences Shh-dependent tumor growth by coordinating and distributing growth factor signals to the actin cytoskeleton. This proposal aims to understand BEG4's role as a Shh pathway target gene and a mediator of epithelial growth by: l) characterizing BEG4 expression in skin and other tissues where Shh target genes are induced, 2) determining the importance of BEG4 function in vivo through the analysis of BEG4lmockout mice, and 3) determining the consequences of BEG4 overexpression in human and mouse skin. The proposed research fellowship will yield new insights into the pathogenesis of BCCs and other Shh pathway-related malignancies and may lead to the identification of new targets for prevention and therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HAIR FOLLICLE BULGE CELLS IN TUMORIGENESIS AND ALOPECIA Principal Investigator & Institution: Cotsarelis, George; Assistant Professor; Dermatology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-AUG-2005 Summary: (Verbatim) The long-term goals of this project are to better understand epithelial stem cell biology. Epithelial stem cells are responsible for the continual regeneration and homeostasis of all self-renewing tissues such as the epidermis, hair follicle, and corneal epithelium. We originally identified epithelial stem cells in the limbal epithelium of the cornea, and in the bulge region of the outer root sheath of the hair follicle. Recently, we demonstrated that cytokeratin 15 (K15) is selectively expressed by bulge cells, and our preliminary results show that K15 is also expressed in the limbal epithelium of the cornea. Now, we have isolated the K15 promoter, and we plan to use this as a tool to study the hypothesis that bulge cells play a major role in hair follicle cycling, alopecia, wound healing, and carcinogenesis. Specifically, we plan to: 1. characterize K15 promoter activity during development, throughout the hair follicle cycle and in response to hyperproliferative stimuli. We will test the hypothesis that K15 is preferentially expressed in other sites enriched in epithelial stem cells by examining its expression in corneal epithelium as well. Our primary goal is to develop a transgenic system that can be modulated by exogenous agents (e.g., retinoids, phorbol esters, corticosteroids) so that we can study tissue compartments rich in epithelial stem cells. 2. determine whether sonic hedgehog (shh) and activated beta-catenin, known to cause

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Basal Cell Carcinoma

basal cell carcinomas and hair follicle tumors, respectively, when expressed throughout the epidermal basal layer, cause similar or distinct tumors when targeted to the bulge cells by the K15 promoter in a transgenic system. 3. assess the role of the bulge cells in hair follicle cycling by analyzing the hair cycle in transgenic mice that over-express shh and activated beta-catenin. 4. ablate hair follicle bulge cells in adult transgenic mice carrying a K15 promoter/thymidine kinase suicide gene. This addresses the hypothesis that the bulge contains stem cells responsible for hair follicle cycling, epidermal renewal and sebaceous gland regeneration. We also plan to use this system as a model for studying scarring alopecias. Patients with disorders such as alopecia, basal cell carcinoma, hair follicle tumors, or chronic wounds may ultimately benefit from this research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HAND-HELD CONFOCAL LINE-SCANNER FOR INTRASURGICAL USE Principal Investigator & Institution: Eastman, Jay M.; Lucid, Inc. 50 Methodist Hill Dr Rochester, Ny 14623 Timing: Fiscal Year 2003; Project Start 14-SEP-2001; Project End 30-JUN-2006 Summary: (provided by applicant): Design of a laboratory prototype, product development and clinical testing of a real-time hand-held confocal line-scanner is proposed for imaging-guided microsurgery applications. Line scanning offers resolution, contrast and field of view that are required for intrasurgical imaging. In the Phase I feasibility project, the laboratory prototype successfully demonstrated imaging of nuclear and cellular detail in human epidermis in vivo with 5-10 microns resolution. In Phase II, the goals are to quantitatively characterize optical performance within living human skin, package the prototype into a hand-held confocal scanner product, and test the scanner for imaging basal cell cancers on patients during Mohs surgery. Vis-a-vis the current method based on frozen pathology, real-time in situ confocal imaging may save both Mohs surgeon and patient several hours in the operating room. The hand-held linescanning confocal microscope will have everything that surgeons and patients want: simple and robust design, inexpensive ($10K-20K), user-friendly package, controls and interface, and standard detection and display systems. The first application is for skin cancer but other tissues will be subsequently imaged as well. The intended users are surgeons, and the potential benefits to the patient are: painless, fast, less expensive and therefore significantly improved healthcare. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HEDGEHOG DEVELOPMENT

SIGNAL

MODULATION

IN

MAMMALIAN

Principal Investigator & Institution: Chuang, Pao-Tien; Assistant Professor; Cardiovascular Research Institute; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 30-JUN-2006 Summary: (provided by applicant): The long-term goal of our studies is to elucidate the molecular mechanisms of cell-cell interactions during vertebrate development. This proposal focuses on the Hedgehog (Hh) signaling-pathway, which plays a key role in many developmental events. Mutations in members of the pathway are associated with the development of cancer, including basal cell carcinoma, the most prevalent cancer in Western countries, and a seemingly unrelated number of human syndromes and

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malformations, such as holoprosencephaly and polydactyly. Consequently, understanding how a Hh signal is received, transduced and modulated will be critical to understand how cells proliferate, differentiate or survive in response to the Hh signal, as well as how deregulated Hh signaling leads to diseases. These studies will also make it possible to perform prenatal genetic diagnosis and help design rational therapies for treating these Hh signaling-related diseases. Our general strategy is to focus on three membrane proteins, Hedgehog-interacting-protein (Hip), Patched (Ptch) and Smoothened (Smo), essential for transducing/modulating the Hh signal. The overall goals for this proposal are to define the role of Hip and Ptch in mammalian development through genetic analysis; to define the molecular interactions between Hip, Ptch and Smo in transducing/modulating Hh signal; and to identify missing components in the Hh pathway. 1. To define Hip's role in Hedgehog signaling during mammalian development. A genetic approach utilizing transgenic knockout mice will be taken to dissect the distinct and overlapping roles Hip and Ptch play in modulating Hh signaling during mammalian development. 2. To elucidate the molecular interactions between the three known components of the Hh signaling pathway, Hip, Ptch and Smo, in transducing/modulating the Hh signal. Biochemical and cell culture approaches will be taken to investigate the molecular interactions between Hip, Ptch and Smo in transducing/modulating the Hh signal. 3. To use Hh-responsive cell lines, in combination with expression cloning and candidate gene strategies, to identify missing components in the Hh signaling pathway. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HEDGEHOG SIGNALING IN DROSOPHILA Principal Investigator & Institution: Kalderon, Daniel D.; Associate Professor; Biological Sciences; Columbia Univ New York Morningside 1210 Amsterdam Ave, Mc 2205 New York, Ny 10027 Timing: Fiscal Year 2002; Project Start 01-APR-1989; Project End 31-MAR-2006 Summary: Our objectives are to study the mechanisms of Hedgehog signal transduction in Drosophila and how Hedgehog signaling affects cell proliferation in the Drosophila ovary. Hedgehog family proteins are secreted molecules that instruct cell fate during development and can regulate cell proliferation even in adult organisms. These activities of Hedgehog (Hh) molecules are seen in many organisms from Drosophila, where Hh was first identified, to vertebrates including fish, frogs, mice and humans. In humans various defects in the Hh signaling pathway cause developmental abnormalities principally involving limbs, brain and facial structures (Holoprosencephaly, Grolin's syndrome, Greig's cephalopolysyndactyl, Pallister-Hall syndrome). In addition, a few specific cancers are associated with aberrantly activated Hh signaling pathway. Indeed, basal cell carcinoma, which is very widespread, is thought to be initiated exclusively by aberrant Hh signaling. The study of Hh signaling in Drosophila has brought many insights into the transduction process by which cells respond to a Hh signal and has also provided insight into how cells behaviors are altered by Hh signaling. The relative facility and sophistication of Genetic and Developmental analyses that are possible in Drosophila ensure that the pioneering role of such studies will continue. Subsequent studies have shown that most of the components and mechanisms of Hh signal transduction elucidated in Drosophila can also be demonstrated in vertebrate model organisms. In particular the role of Protein Kinase A (PKA) in silencing Hh signal transduction in the absence of a Hh signal is apparent in Drosophila and vertebrates. Our study of this role of PKA recently implicated additional protein kinases as regulators of Hh signaling. In this proposal we will define the role of these protein

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Basal Cell Carcinoma

kinases and PKA in Hh signaling. We also found that Hh regulates proliferation in the Drosophila ovary by acting specifically on stem cells. We will define which other signaling pathways regulate these stem cells and how Hh alters their behavior. These studies are likely to be directly relevant to the behavior of human stem cells that give rise to hair follicles and epidermis and should help us to understand how basal cell carcinomas can originate from those stem cells or their derivatives. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HYALURONAN-MEDIATED KERATINOCYTES

CD44

SIGNALING

IN

Principal Investigator & Institution: Bourguignon, Lilly Y.; Professor; Northern California Institute Res & Educ 4150 Clement Street (151-Nc) San Francisco, Ca 941211545 Timing: Fiscal Year 2003; Project Start 20-SEP-2003; Project End 31-JUL-2008 Summary: Hyaluronan (HA) is well known as a constituent of connective tissue extracellular matrices. Recent studies have also shown its abundance in stratified squamous epithelia, including the epidermis of skin. HA is often anchored to CD44, a ubiquitous, abundant, and structurally/functionally important surface receptor that displays HA binding site(s). Our preliminary findings indicate that both HA and CD44 participate in Ca 2+ mobilization and keratinocyte differentiation. Further analyses show that Rho/Rac and Src kinase signaling are closely coupled with HA/CD44induced Ca 2+ mobilization, cytoskeletal function and keratinocyte differentiation. In addition, our data reveal that several keratinocyte differentiation markers (e.g. involucrin and filaggrin) are significantly reduced in the skin of CD44-knock out (k/o) mice as compared to CD44-wild type mice. These observations suggest the importance of CD44 in normal epidermal physiology and keratinocyte differentiation. In this proposed project we plan to test the hypothesis that CD44 plays an important role in regulating Ca 2+signaling and differentiation. Specifically, CD44 interaction with Rhoactivated Rho-Kinase (ROK), Rac1-activated PLCT1 and Src kinases promotes IP3 receptor-mediated Ca2+ mobilization and cortactin-mediated cytosketetal reorganization/assembly leading to keratinocyte differentiation. Specifically, we will use a variety of biochemical, molecular biological techniques and immunohistochemical staining to elucidate HA-CD44 interaction with various signaling molecules [e.g. RhoKinase (ROK), PLCT1 and Src kinases] in regulating Ca 2+ signaling, and cytoskeleton reorganization/assembly and keratinocyte differentiation. Special emphasis will be placed on HA-mediated CD44-RhoA signaling and ROK in IP3 receptor-mediated Ca2+ mobilization during keratinocyte differentiation. We will also investigate HA-mediated CD44-Rac1 signaling and PLCgamma1 activation in regulating IP3 production, Ca 2+ mobilization and keratinocyte differentiation. In addition, we will analyze HA/CD44 interaction with c-Src/fyn kinases in regulating cortactin-actin binding and keratinocyte differentiation. Finally, we will evaluate the functional ramifications of CD44 interactions with various signaling molecules (e.g. ROK, PLCgamma1 and Src kinases) with respect to Ca 2+ signaling and cytoskeletal function and keratinocyte differentiation using cultured keratinocytes and/or skin tissues isolated from CD44wild type and knock-out (k/o) mice exposed to HA. We believe that the new information obtained from this proposal may establish an important role for HA/CD44mediated cellular signaling (e.g. Rho/Src & Ca 2+signaling) and cytoskeletal activation during keratinocyte function and normal epidermal development. A variety of skin diseases including psoriasis, squamous cell carcinoma (SCC) or basal cell carcinoma (BCC) have been shown to involve abnormal/defective HA-CD44 interactions in

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epidermal keratinocytes. Thus, dissection of HA and CD44-mediated intracellular events (e.g. Rho/Src activation, Ca 2+ signaling and cytoskeleton-regulated keratinocyte differentiation) should aid significantly our understanding of the keratinocyte biology underlying the clinical behaviors of HA/CD44-related skin diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IN VIVO MULTIMODALITY IMAGING OF NEOPLASTIC DISEASE Principal Investigator & Institution: Contag, Christopher H.; Assistant Professor; Radiology; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 03-AUG-2000; Project End 31-JUL-2004 Summary: Toward the establishment of a multimodality molecular and cellular imaging center at Stanford University we have assembled a team of investigators comprised of leaders in the fields of imaging, molecular biology, oncology, chemistry and immunology; and have established research themes and programmatic cores that unify the common interests and expertise of these scientists. This team of investigators will be supported by an administrative core that will coordinate and direct the significant existing resources in MR, nuclear medicine, optical imaging, device development, gene delivery and small animal imaging. We are responding to NCI's RFA CA-99-O2 for the P20 Planning Grant in coordination with this activity, and with the mission of developing a multimodality in vivo cellular and molecular imaging program for studying neoplastic disease. The program will address key issues in cancer from the level of gene expression and initiation of disease to cell death in response to novel therapeutic strategies. The specific aims that build this program are to: 1) maximize interaction among multidisciplinary investigators for a coordinated effort in cancer research and imaging, 2) develop an organizational structure to coordinate and manage the multidisciplinary programmatic cores and collaborative research efforts, 3) identify a set of development projects that maximize the use of the core facilities and program strengths, 4) generate significant preliminary data with in the selected projects that contribute to our understanding of disease mechanisms and therapeutic intervention as well as advance novel imaging strategies. These aims will be achieved by integrating the strengths of nine scientific cores - imaging, molecular biology, genetics, chemistry, biochemistry, drug delivery, computing/database and biostatistics, engineering, and immunology. This will provide us with a unique opportunity for a multifaceted study of neoplasia that will identify novel therapeutic targets and reveal basic mechanisms of disease through state of the art imaging. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SURGERY

INTRA-OPERATIVE

CONFOCAL

IMAGING-GUIDED

MOHS

Principal Investigator & Institution: Rajadhyaksha, Milind M.; Ctr for Subsurface Sensing & Imaging Systems; Northeastern University 360 Huntington Ave Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 20-SEP-2003; Project End 31-JUL-2007 Summary: (provided by applicant): The goal of this proposal is to develop and clinically test a real-time optical imaging modality based on confocal reflectance microscopy, with enhancement of nuclear-to-dermal contrast using acetic acid and crossed polarization, to intra-operatively examine basal cell cancers to guide Mohs micrographic surgery. Basal cell cancers (BCCs) are among the fastest growing cancers (>1.2 million new USA cases/year); because they occur most frequently on older people and in high risk

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Basal Cell Carcinoma

anatomical sites (near or on the eyes, mouth, nose, ears), precise microsurgery is necessary with minimum damage to the surrounding normal tissue. Mohs surgery is time-consuming (one to several hours) and tedious because several (2-20) excisions must be made, and frozen histology sections carefully prepared and examined for each. Realtime confocal reflectance imaging may make Mohs surgery significantly more efficient by enabling direct intraoperative examination for cancer nests and cancer-tonormal tissue margins on the patient; this will reduce the number of excisions and avoid frozen histology. Both the patient and surgeon will save several hours per procedure in the operating room. Although proposed for Mohs surgery of BCCs, this real-time intraoperative imaging modality may, in fact, prove useful in a variety of other microsurgical settings. The research will be a collaboration between Northeastern University (Boston) and Memorial Sloan-Kettering Cancer Center (New York). This project will be implemented in two phases: (1) an ex vivo study using freshly excised skin specimens from Mohs surgeries, to (a) design a confocal microscope that mimics the Mohs surgeon's examination of frozen histology: rapid low-resolution examination of BCC nests in wide fields-of-view followed by high-resolution inspection of nuclear morphology in small fields-of-view, and develop (b) optimum contrast enhancement methods using topical acetic acid (induces condensation of chromatin that increases light backscatter from nuclei) and optical crossed polarization (suppresses light backscatter from the surrounding normal dermis), (c) optimum hemostasis methods using either topical aluminum chloride or electrocautery, (d) image understanding by detailed correlation of images to histology; and (2) an intraoperative study, involving (a) design of a specialized confocal articulated telescope, to enable (b) imaging of BCCs on patients during surgery, to evaluate the optimum contrast enhancement and hemostasis methods, correlate confocal images to histology and quantitatively determine diagnostic/screening accuracy. The overall goal is to develop an optical (confocal) intraoperative imaging instrument for Mohs and other modes of microsurgery. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IRRADIANCE AND PHOTOBLEACHING METRICS IN ALA PDT Principal Investigator & Institution: Oseroff, Allan R.; Chairman; Roswell Park Cancer Institute Corp Buffalo, Ny 14263 Timing: Fiscal Year 2002; Project Start 01-JUL-2000; Project End 31-DEC-2003 Summary: Topical ALA-PDT is a promising treatment for superficial carcinomas. However, conventional treatments probably cause photodynamic oxygen depletion, limiting efficacy. In addition, there is significant irradiance-dependent pain. A therapeutic dilemma is that while low irradiances maximize oxygen availability within the carcinomas, they also can significantly prolong treatment time. Because photobleaching of PpIX appears oxygen dependent, the photobleaching rate monitored by loss of photosensitizer fluorescence is a surrogate metric for photodynamic damage. Efficient PDT will have a high photobleaching rate. The oxy/deoxy hemoglobin ratio, obtained from skin absorption measurements, provides an independent measure of the extent of photodynamic oxygen depletion as well as information about PDT- induced perfusion changes during treatment. Cutaneous perfusion is strongly temperature dependent, and small increases or decreases in skin temperature may have significant effects on blood flow in carcinomas and in normal skin, and on PDT selectivity. In addition to photobleaching, illumination causes the production of PpIX photoproducts and possibly other endogenous photosensitizers with different absorption wavelengths. When spectrally characterized, these products may be usefully activated during PDT. The goals of this pilot study are to use fluorescence and reflectance measurements to

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examine the initial photobleaching rates as a function of irradiance and skin temperature. We seek to define an "optimum" initial light dose rate that provides adequate oxygenation, short illumination times, and low PDT- induced pain. In patients with superficial basal cell carcinomas treated with ALA-PDT, the Specific Aims/Objectives are to: 1. Examine the effect of irradiance on the initial PpIX photobleaching (PB) rate and PDT-induced pain. 2. Examine the effects of skin temperature on photobleaching rate, carcinoma selectivity and discomfort. 3. Determine the irradiance-dependent formation of photoproducts or other endogenous photosensitizers, the changes in hemoglobin oxygenation, and the alterations in tissue optical properties. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MATRIX PROTEIN IN HUMAN EPIDERMAL NEOPLASIA Principal Investigator & Institution: Kimmel, Robin A.; Biological Sciences; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-MAR-2008 Summary: (provided by applicant): The epidermis is the site of the first and second most common cancers in the U.S., basal cell carcinoma and squamous cell carcinoma (SCC). Human tumor samples and mouse models of SCC induction show a correlation between upregulation of basement membrane proteins and tumor progression. The medical relevance of murine studies of SCC, however, is limited by major differences between mouse and human skin and by greater ease of transformation of murine tissues. While the importance of cell-matrix interactions in tumor initiation and growth is wellappreciated, no studies have yet addressed the need for specific stromal elements and their cellular receptors in this process. Their our lab's recent evidence that integrin and its ligand laminin 5 are required for SCC development implies that hemidesmosomemediated adhesion may potentiate tumorigenesis. The overall goal of this proposal is to determine the role of specific epidermal matrix components in promoting human epidermal tumor formation. First, the roles of Type XVII collagen (BP180, BPAG2) and Type VII collagen, which interact with integrin alpha6beta4 and laminin 5, will be examined. Primary keratinocytes deficient in collagen XVII and collagen VII from patients with the inherited skin disease epidermolysis bullosa (EB) will be used to assess the tumor formation potential of deficient cells as compared to cells with restored protein expression. Corrected and uncorrected cells will be transduced with Ras and other retrovectors and assayed for their ability to support subcutaneous tumor growth. Additional studies will assess the effect of laminin 5 ablation on the continued growth of epidermal tumors. Laminin 5 blocking antibodies will be tested for their ability to inhibit growth of established Ras-induced tumors. Furthermore, a genetic approach will be used in which Cre recombinase inducibly removes retrovirally restored laminin 5 eDNA from EB cells within a growing Ras-induced epidermal tumor. These studies provide an initial evaluation of matrix components involved in the establishment and growth of tumors. Subsequent explorations that include delineation of specific functional domains within the matrix proteins found to enhance tumor growth may provide potential targets for therapeutic interference with SCC progression. At the end of the funding period, they hope to have defined the functional importance of epidermal matrix components in invasive human epidermal neoplasia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Basal Cell Carcinoma

Project Title: MOLECULAR BASIS OF EPITHELIAL SKIN CANCER Principal Investigator & Institution: Dlugosz, Andrzej A.; Associate Professor; Dermatology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 01-JUL-2000; Project End 30-JUN-2004 Summary: The skin has served as an extremely useful model for studying factors regulating normal epithelial growth and development and the perturbation of these processes that occurs during neoplasia. Although much previous work has centered on squamous cell carcinoma, there has been increased interest in basal cell carcinoma (BCC) following the discovery that deregulated Sonic hedgehog (Shh) signaling is linked to the development of these tumors. Shh pathway activation may be the result of loss-of- function mutations (involving the Shh receptor PTCH1), or gain- of-function mutations (involving SMO, which is normally repressed by PTCH1). While uncontrolled Shh pathway activation is associated with tumor development, we and others have shown that targeted disruption of Shh results in severe impairment of hair follicle morphogenesis. Although it is clear that Shh signaling has important functions in normal skin and BCC, the pivotal nuclear target(s) mediating keratinocyte responses to this pathway have yet to be identified. Much of what is known about this pathway is based on genetic analysis in Drosophila, where the transcription factor Cubitus interruptus (Ci) mediates responses to the Shh homolog Hedgehog. We will explore the notion that one or more of the vertebrate Ci homologs (Gli1, Gli2, Gli3) plays a central role in Shh signaling in keratinocytes. We propose a series of comprehensive studies focusing on the biological, biochemical, and molecular consequences of Gli protein overexpression in keratinocytes. Although there is substantial evidence implicating deregulated Shh signaling in BCC, there is little insight into how activation of this pathway leads to tumor formation. The results of the proposed studies will provide new information to fill in this gap in our knowledge. In addition to BCCs, several other neoplasms have been linked to the Shh pathway, including medulloblastomas and rhabdomyosarcomas. Moreover, precisely-controlled Shh signaling is essential for embryonic patterning in multiple tissues, with deregulation of this pathway leading to a variety of developmental abnormalities. Thus, the knowledge gained during the course of the proposed studies is likely to have relevance to a variety of clinical disorders, and may ultimately lead to improved treatments for BCC and other tumors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MOLECULAR CARCINOGENESIS

BASIS

OF

HEDGEHOG

SIGNALING

IN

Principal Investigator & Institution: Xie, Jingwu; Pharmacology and Toxicology; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2002; Project Start 29-JAN-2002; Project End 31-DEC-2006 Summary: (PROVIDED BY APPLICANT) Hedgehog signaling, originally described in Drosophila, is one of the most important pathways in vertebrate development. Disruption of this pathway leads to developmental disorders and cancers, particularly basal cell carcinoma. Basal cell carcinoma is the most common form of human cancer, affecting 750,000 Americans per year. UV radiation is the most important risk factor for basal cell carcinomas. Basal cell carcinoma is now understood to be associated with both somatic and germ line gene mutations in the sonic hedgehog signaling pathway. Two genes are commonly mutated, patched or smoothened (SMO). SMO signaling activity is regulated by the sonic hedgehog receptor-patched. However, most of the

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sonic hedgehog signaling pathway downstream of SMO is unknown or poorly understood. We have shown that the mutant SMO is oncogenic; it can transform cultured cells, and can lead to tumor formation when expressed in mouse skin. Our overall hypothesis is that SMO is the key signal transducer of the pathway, and Gli1 is the ultimate downstream effector for basal cell carcinoma formation. Activation of this pathway leads to increased cell proliferation and tumor formation. Therefore inhibiting the pathway could be effective in slowing tumor formation. In this proposal, we will use the mutant SMO molecule and the downstream molecule Gli1 as biological probes for the identification, isolation and functional dissection of molecular components that collaborate to regulate the hedgehog pathway in basal cell carcinomas. We proposed three specific aims: 1) To determine the significance of PDGFRalpha for basal cell carcinoma formation (Aim 1); 2) To determine how Glil phosphorylation is regulated by PKA and upstream signals (Aim 2); 3) To determine the mechanism of SMO signaling (Aim 3). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR CALSSIFICATION OF BASAL CELL CARCINOMAS Principal Investigator & Institution: Bale, Allen E.; Associate Professor; Genetics; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2003; Project Start 26-AUG-2003; Project End 31-JUL-2005 Summary: (provided by applicant): Basal cell carcinoma of the skin is by far the most common type of cancer in the United States, representing nearly one half of all newly diagnosed malignancies. Although these tumors infrequently cause cancer mortality, they are associated with significant morbidity due to local invasion and tissue destruction. Basal cell carcinomas are extremely variable in gross and microscopic appearance and biological behavior, and a common histopathologic classification system divides the tumors into five main categories which differ in aggressiveness, prognosis, and response to therapy. My laboratory isolated a gene for hereditary basal cell carcinomas (human patched; gene symbol PTCH) and showed that this gene is mutated in sporadic BCCs as well. Exactly analogous to the two-hit paradigm established for retinoblastoma, almost all sporadic basal cell tumors have two somatically-derived, inactivating PTCH mutations. PTCH is a member of the hedgehog signal transduction pathway. The few BCCs lacking mutations in PTCH have activating mutations in smoothened (SMO), another member of the hedgehog pathway whose protein is normally repressed by the patched protein. All subtypes of BCCs have mutations in PTCH or SMOH, indicating that mutations in one or the other of these genes are essential to the development of BCCs but do not dictate the histologic subtype. Furthermore, other genetic alterations known to occur in BCCs, such as p53 or RAS gene mutations, do not correlate with variation in biologic behavior. The purpose of this study is to identify the genetic causes and molecular correlates of different histologic subtypes of basal cell carcinomas. Specific aims are to 1) determine if genetic variation in members of the hedgehog pathway downstream from PTCH and SMO contribute to variation in biological behavior of these tumors, and 2) as an indirect method of examining other genetic and epigenetic phenomena in BCCs, use microarray analysis to try to classify these tumors and identify a set of genes whose expression predicts their biological behavior. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Basal Cell Carcinoma

Project Title: MOLECULAR CHARACTERIZATION OF BREAST BASAL-LIKE TUMORS Principal Investigator & Institution: Perou, Charles M.; Associate Professor; Genetics; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2003; Project Start 28-MAY-2003; Project End 30-APR-2008 Summary: (provided by applicant): Human breast tumors show great diversity in their morphologies, natural histories and in their responses to therapy. This wide tumor diversity" poses one of the central challenges to the accurate diagnosis, prevention and treatment of breast tumors. We have used genome-wide gene expression profiling and found that infiltrating ductal and lobular carcinomas of the breast segregated into five distinct and reproducible subtypes [1, 2]. Included within these five subtypes was a new class of tumors that was Estrogen Receptor (ER) and HER2 negative, and which showed characteristics of breast basal/myoepithelial cells. We next demonstrated that this "basal-like" subtype had on average, the fastest proliferation rates and the shortest overall patient survival times [2]. The development of a prevention strategy for this deadly type of breast tumor is needed because of the unique clinical and biological properties of these tumors. We propose to characterize human basal-like tumors using cellular and genetic assays in order to identify the molecular alterations that are present within this subtype as a first step towards the prevention of this ER-negative subtype of breast tumor. Next, we will determine if breast basal-like tumors progress through a Carcinoma In Situ (CIS) stage, and determine if the most common chemoprevention targets are ever present within these tumors or their precursor lesions. Finally, we will expression profile mouse mammary tumors and compare these results to our human data to identify murine models of basal like tumors, and to identify targets that are present in both hormonally non-responsive animal models and in basal-like tumors of humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MOLECULAR EPIDEMIOLOGY OF NON-MELANOMA SKIN CANCER Principal Investigator & Institution: Nelson, Heather H.; Cancer Cell Biology; Harvard University (Sch of Public Hlth) Public Health Campus Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 30-SEP-1999; Project End 31-JUL-2003 Summary: Non-melanoma skin cancer is the most prevalent malignancy in the US, resulting in significant morbidity and health-care expense. Epidemiologic investigations have identified exposure to ultraviolet radiation as the primary risk factor for this disease; other environmental exposures that contribute to risk include ionizing radiation, arsenic, polycyclic aromatic hydrocarbons, and chronic immunosuppression. Host factors associated with increased risk for non-melanoma skin cancer include increasing age, male gender, and sun sensitive skin type. Basal cell and squamous cell carcinomas have been shown to contain alterations in the p53 gene, and recent work has identified a gene on chromosome 9q22, ptch, that is hypothesized to be critical in basal cell carcinoma tumorigenesis. These findings, while informative, are derived from relatively small, selected groups of patients and reflects the paucity of population-based molecular epidemiology for this disease. We propose to expand a large, well-established case-control study of non-melanoma skin cancer in New Hampshire to include investigation of genetic susceptibility. The project will focus on genes that potentially modify ultraviolet radiation exposure, including polymorphisms in the glutathione S-

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transferases (GSTM1, GSTT1, and GSTP1) and the newly identified variants in DNA excision repair genes (ERCC2/XPD, and XPF). In addition, we will collect tumor specimens from cases for characterization of mutations at p53 and 9q22/ptch. We will determine mutation spectra examine associations of mutation with carcinogenic exposures and patient traits, and refine a novel model of skin tumorigenesis. These studies will increase our understanding of host susceptibility to non-melanoma skin cancer and advance current models of skin carcinogenesis through identification of patterns of gene inactivation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FUNCTION

MOLECULAR

MECHANISMS

OF

HEDGEHOG

RECEPTOR

Principal Investigator & Institution: Beachy, Philip A.; Molecular Biology and Genetics; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-JUL-2000; Project End 30-JUN-2005 Summary: (appended verbatim from investigator's abstract): Holoprosencephaly (HPE) a defect in developmental patterning of the face and forebrain is the most common malformation in early human pregnancy with an incidence of 1/250 during the first trimester. Basal cell carcinoma (BCC) is the most common form of cancer in Caucasians with 750,000 cases treated annually in the United States alone. Both conditions are associated with inappropriate activity of the Hedgehog (Hh) signaling pathway, a deficit during the embryonic period in the case of HPE and excess postnatal activity in the case of BCC. This proposal centers on the mechanisms by which the Hedgehog extracellular protein signal is sensed and transmitted to intracellular components and on the mechanisms by which a localized source of Hedgehog signal elicits a graded pattern of pathway activity in cells of a developing tissue. The Hedgehog receptor comprises two polytopic transmembrane proteins Patched (Ptc) and Smoothened (Smo) with twelve and seven transmembrane spans respectively. Genetic evidence suggests that Ptc suppresses the activity of Smo and that Hh binding to Ptc relieves this suppression allowing for activation of downstream targets. Although Smo is related to the Frizzled family of Wnt receptors and more distantly to members of the Gprotein coupled receptor family, other components of the Hh pathway have no counterparts in other signaling pathways. Molecular mechanisms of Hh receptor action thus remain unknown and experimental observations are not adequately explained by current models. We have recently developed several novel tools including various purified protein and antibody reagents a series of specific Hh receptor inhibitors sensitive cultured cell signaling assays and methods for selecting cells with high or low levels of Hh pathway activity. Using these tools together with a broadlybased experimental approach that incorporates pharmacological biochemical molecular and cell biological methods we propose: (1) to determine how components of the Hh receptor transduce the signal across the membrane; 2) to determine how Hh receptor activation affects intracellular components; and 3) to understand how a localized Hh signal elicits a graded pattern of pathway activity from cells within developing tissues such as the limb bud or neural tube. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR MECHANISMS OF HEDGEHOG SIGNALING Principal Investigator & Institution: Sztul, Elizabeth S.; Cell Biology; University of Alabama at Birmingham Uab Station Birmingham, Al 35294

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Basal Cell Carcinoma

Timing: Fiscal Year 2002; Project Start 01-APR-1999; Project End 31-JAN-2004 Summary: The long term objective of this research is to understand the molecular mechanisms that control cell-cell signaling in developing and adult tissues. Hedgehog (Hh) signaling proteins control cell fates and proliferation during animal development by regulating the specific gene expression. In vertebrates, Hh proteins pattern diverse tissues such as the developing limb, spinal column, and brain. The membrane protein Patched (Ptc) opposes Hh to inactivate specific gene expression. In Drosophila, ptc mutations cause misexpression of Hh target genes and result in abnormal development and cell proliferation. Mutations in a human homolog of ptc, PTCH1 lead to the very common skin tumor, basal cell carcinoma, and to the brain tumor, medulloblastoma. PTCH1 is also mutated in the basal cell nevus syndrome, an inherited disorder characterized by many developmental defects and tumors. The molecular mechanisms of Hh signal reception and transduction are largely unknown. Central to understanding the role of Hh signaling in development and disease is learning how Ptc functions and identifying proteins with which it interacts. Ptc is proposed to bind Hh proteins and to associate with and regulate, Smoothened, (Smo), a membrane protein required for Hh signaling. Ptc also sequesters Hh to limit its range of action. How and where Ptc mediates these important regulatory processes is not known. Ptc may function in vesicle movement as suggested by its sequence similarity to NPC1, a membrane protein implicated in the intracellular trafficking of cholesterol. The proposed studies will identify the critical functional domains of Ptc and characterize the cellular localization of Ptc and its interacting proteins following ligand binding. Using Drosophila, new components of Hh signaling will be identified by a genetic screen involving a specific ptc phenotype. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NON-MELANOMA SKIN CANCER IN NEW HAMPSHIRE Principal Investigator & Institution: Karagas, Margaret R.; Professor; Community and Family Medicine; Dartmouth College 11 Rope Ferry Rd. #6210 Hanover, Nh 03755 Timing: Fiscal Year 2002; Project Start 10-APR-1993; Project End 31-MAY-2005 Summary: (provided by applicant): Population-based epidemiologic data on nonmelanoma skin cancers (NMSCs) remain sparse. In the USA, the last national surveys were conducted in the 1970's. Therefore, in 1993, we established a population-based incidence registry for NMSC in New Hampshire involving a collaborative network of dermatologists and pathologists. Compared to survey data from 1979/80, our findings suggest a dramatic rise in the incidence rates of both basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), and a disproportionate increase in SCC, particularly among women. To understand recent trends in these malignancies, we propose to analyze patterns of BCC and SCC occurrence over a complete decade (1993/94 to 2002/03). These data will permit us to analyze temporal changes in level of invasion and tumor size, indicators of enhanced detection unavailable from prior studies. As part of our study, we established a population-based case-control study of BCC and SCC to identify current risk factors. In the USA and elsewhere, artificial tanning has gained widespread popularity especially among young adults and women. We propose to test the hypothesis that artificial tanning relates to the risk of early onset BCC (age under 50 years at diagnosis) (n about 450) as well as SCC. Based on recent findings, we also will test the hypothesis that prolonged use of photosensitizing drugs enhances risk of SCC (n about 450). In New Hampshire, a growing segment of the population relies on private, unregulated water systems such as bedrock wells (35 to 40 percent currently), and over 10 percent of these contain arsenic concentrations above the present EPA maximum

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contaminant level of 10 micrograms/L. We propose to examine whether environmental arsenic levels affect risk of multiple BCC (n about 725), a characteristic of chronic high dose exposure. To measure an individual's arsenic exposure, we will test toenail clippings for trace elements and determine drinking water levels from both current and previous households. History of artificial tanning, photosensitizing drug use and other factors will be derived from an in-person interview along with semi-objective and objective assessments. Each case group (multiple BCC, early onset BCC and SCC) will be compared to an age- and gender-matched control group selected from population lists (total n about 1,640). Using the original tumor blocks from NMSC cases, we will perform a histopathology review for diagnostic verification and extent of actinic damage. We will archive both tumor specimens and blood or buccal samples, providing a unique population-based biologic tissue bank for NMSC from which to streamline molecularepidemiologic investigations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NOVEL NANOSTRUCTURES FOR TOPICAL PHOTODYNAMIC THERAPY Principal Investigator & Institution: Wharton, Tim J.; Lynntech, Inc. College Station, Tx 77840 Timing: Fiscal Year 2003; Project Start 08-AUG-2003; Project End 31-JUL-2005 Summary: (provided by applicant): The objective of this proposal is to synthesize and evaluate novel, carbon-based nanostructure photosensitizers (PS) for the topical treatment of a variety of non-melanoma, pre-malignant and malignant cutaneous lesions, inflammatory dermatoses, and localized bacterial and fungal infections by topical photodynamic therapy (PDT). Our concept is based on a recently discovered family of molecules that have shown a remarkable ability to sensitize singlet oxygen under a variety of conditions. The visible light-absorbing photosensitizer has been shown in previous work to exhibit no dark toxicity. It has also been shown by our preliminary in vitro work to be internalized into a murine cancer cell line and a grampositive bacterium where significant phototoxicity was observed upon irradiation. It is easily "tailored" by the methods of organic synthesis, which has the potential of leading to a combinatorial library of PS for different applications. After topical application of the PS to the affected area followed by a period of incubation, the area is selectively irradiated with light of appropriate wavelength and intensity. This causes the formation of reactive oxygen species (ROS) by the catalytic action of the nanostructure PS on molecular oxygen. The ROS cause a loss of viability in the affected cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: OPTICAL MAPPING OF NONMELANOMA SKIN CANCERS Principal Investigator & Institution: Yaroslavsky, Anna N.; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2003; Project Start 20-SEP-2003; Project End 31-AUG-2006 Summary: (provided by applicant): More than a million cases of non-melanoma skin cancers (i.e. basal cell and squamous cell carcinomas) are diagnosed every year. These cancers are more common than all other human cancers. Almost all basal cell and squamous cell carcinomas are curable by surgery if detected early. Unfortunately, in most cases the contrast of the lesions is poor, which complicates tumor localization and precise excision. Treatment of cancer patients could benefit greatly if a real-time noninvasive, reliable and cost-effective technique for delineating tumor margins were

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available. Therefore there is a strong need for practical, reliable, rapid, and precise methods for tumor localization, to guide surgery and other treatments of skin cancer. Once developed, such methods may potentially be useful for epithelial cancers of other organs. The overall goal of this proposal is to develop a practical way to detect skin cancer margins and guide tumor excision surgery using non-invasive optical imaging techniques. Specifically, spectrally resolved and polarization sensitive imaging methods and equipment, which are applicable for both reflectance and fluorescence imaging will be developed and implemented. The specific aims are: (i) Design and build multispectral polarization-enhanced reflectance and fluorescence imaging system for in vivo localization of skin cancers that can rapidly image large tumor affected areas in clinical setting. (ii) Develop methods for reliable localization of skin tumors based on polarized light reflectance imaging, dye enhanced polarized light reflectance imaging, and exogenous dye fluorescence-depolarization imaging. (iii) Develop and verify algorithms for quantitative assessment of skin tumor localization. (iv) Integrate the developed algorithms and imaging techniques into an efficient bedside guidance tool for tumor localization and excision. (v) Evaluate the clinical prototype and the developed imaging methods in a surgical practice environment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ORGAN CULTURE OF BASAL CELL CARCINOMA Principal Investigator & Institution: Elder, James T.; Professor; Dermatology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 28-SEP-2001; Project End 31-MAR-2004 Summary: (provided by applicant): Hedgehog (Hh) signaling is implicated not only in the development of basal cell carcinoma (BCC), but also in epithelial-mesenchymal interactions critical to hair follicle development and cycling, However, the more distal downstream effectors of Hh signaling remain to be elucidated. Hair follicle development is profoundly affected by a variety of natural and engineered mutations affecting ErbB signaling, and our preliminary data demonstrate that increased and qualitatively altered expression of ErbB proteins is a characteristic feature of BCCs. These findings suggest the hypothesis that ErbB signaling is an important distal effector of Hh signaling in BCC and follicular development. BCC tumors are highly invasive. Matrix metalloproteinases (MMPs) are strongly implicated in tumor invasiveness, and ErbB signaling is in turn strongly implicated in the control of MMP activity in the skin. BCC and early anagen hair follicles display high levels of MMP-1, MMP-2, and MMP-9 expression and activity, whereas in normal skin, the same MMPs are present but inactive. Our preliminary data indicate that secretion and activation of MMP- I and MMP-9 are markedly reduced in response to pharmacologic blockade of ErbB signaling in short-term organ cultures of BCC. However, we do not know whether the MMPs we are observing derive from BCC tumor cells, from the surrounding stroma, or from reactive normal epithelium, and we do not know which ErbB species are responsible for the observed MMP activities. Due to its simplicity and flexibility, organ culture offers significant opportunities to probe distal signaling pathways downstream of Hh signaling in BCC. However, prior efforts to maintain BCC for extended periods in organ culture have been unsuccessful. We have previously developed conditions for successful long-term maintenance of normal skin in organ culture (up to 30 days). We also have IRB-approved access to an abundant supply of clinically well-characterized, fresh BCC tumors. Here we propose to use these resources: (i) to determine whether specific blockade of ErbB signaling specifically reduces tyrosine phosphorylation and the activation of MMPs in BCC tumor cells, and (ii) to define optimal conditions for the long-term organ culture of BCC.

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

Project Title: PHOTODYNAMIC THERAPY MECHANISM OF TUMOR IMMUNITY Principal Investigator & Institution: Gollnick, Sandra O.; Roswell Park Cancer Institute Corp Buffalo, Ny 14263 Timing: Fiscal Year 2003; Project Start 15-MAY-2003; Project End 30-APR-2008 Summary: Preclinical and clinical studies have shown that Photodynamic Therapy (PDT) augments the host immune response. We have made that novel discovery that the direct effects of Photofrin-PDT on tumor cells are sufficient to stimulate the host immune system. The overall goal of this project is understand how PDT enhances the immunogenicity of tumor cells, in vivo and in vitro. We hypothesize the PDT treatment of tumor cells, in vivo or in vitro enhances their ability to be recognized by the host immune system. We have shown that increased tumor immunogenicity can be correlated with an ability to mature and activate antigen-presenting cells and we hypothesize that Photofrin-PDT stimulates the expression of immune mediators that are able to increase the activity of antigen-presenting cells. In Specific Aim I of this proposal we will identify the factor(s) present in Photofrin-PDT generated tumor cell lysates that activate dendritic cells. We further hypothesize that the secretion of immune enhancing factors is dependent upon the initial immunogenicity of the tumor and the type of PDT regimen employed. This hypothesis will be tested in Specific Aim II. In Specific Aim III we will test whether clinical PDT, like preclinical PDT, augments the anti-tumor immune response. The studies outlined in this project will further our knowledge of how PDT affects the host immune response. An understanding of these mechanisms will potentially allow for the development of an optimal "immune enhancing" PDT protocol, which may provide a means of improving the patients ability to combat tumor and/or metastases outside the treatment field. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PILOT--METHYLATION PROFILES OF TUMOR SUPPRESSOR GENES IN SKIN CANCERS Principal Investigator & Institution: Gazdar, Adi F.; Professor; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2006 Summary: Specific aims: Aim 1. Collect skin tumors (approximately 40 squamous cell (SCC) and basal cell (BCC) carcinomas (approximately 40 each) and malignant melanomas (MM)(approximately 20). Skin tags will be collected from sun exposed (approximately 50) and non exposed (approximately 25) skin of adults. Aim 2. We will select a panel of 15 tumor suppressor genes involved in growth cycle regulation, apoptosis, cell adhesion, differentiation, tissue invasion and metastasis and which are known to be down regulated in many tumor types by aberrant gene methylation of promoter regions. We will determine the methylation profile of our tumor and skin samples. Aim 3. We will compare and contrast the methylation patterns of the major forms of skin cancer and between sun exposed and non exposed skin samples. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PTHRP & INDIAN HEDGEHOG IN SKELETAL DEVELOPMENT Principal Investigator & Institution: Serge, Gino V.; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114

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Timing: Fiscal Year 2002 Summary: Taken directly from the application) The endochondral developmental program is four dimensional, one in which spatial relationships among its cells change over time. This proposal focuses on understanding the roles the PTHrP and IHH systems and their secondary mediators play in this complex process, both individually and through effects each system has on the other. Both PTHrP and IHH have strong, but distinguishable influences on this process. Also, there is evidence that PTHrP may mediate some but not all of the actions of IHH, and that the two systems are participants in a feedback system within the developing bone. Our approach takes advantage of genetically-altered mice models: mice null for genes encoding PTHrP, its receptor, or IHH. It also features study of murine hindlimb explants in vitro, where chondrocytic development faithfully mimics in vivo events, and use of carrier beads embedded in explants to deliver local gradients of factors. Aim I determines the molecules involved in mediating IHH's actions and the interrelationships among these mediators. Aim II tests the hypothesis that PTHrP antagonizes IHH signaling in IHH-target cells. Aim III characterizes the roles PTHrP plays in cartilage biology in addition to its role in delaying differentiation, i.e. stimulation of chondrocyte proliferation and actions as a competence factor. These fundamental inquiries into endochondral bone biology have important implications for human disease: deficiencies in genes from the hedgehog signaling pathway have been implicated in such varied conditions as nevoid basal cell carcinoma syndrome and Greig cephalopolysyndactyly syndrome, Jansen's metaphyseal dysplasia is the consequence of a constitutively-active PTH/PTHrP receptor. Furthermore, IHH is the only hedgehog family member whose expression is found postnatally in the skeleton, and the IHH and PTHrP systems as well as their putative secondary mediators have also been shown to be active in fracture repair in adults. Increasing understanding of fundamental issues regarding cartilage biology will yield insight for more rational approaches for treating children with short stature and potentially for treating bone loss diseases, such as osteoporosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RAS DEPENDENT HUMAN CUTANEOUS NEOPLASIA Principal Investigator & Institution: Ridky, Todd W.; Dermatology; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2006 Summary: (provided by applicant): Although cutaneous basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most common cancers in the US, specific mechanisms driving human epidermal transformation are not well understood. Ras is the most commonly mutated proto-oncogene in human cancer and has been implicated in human SCC. A model for human SCC has recently been developed in our laboratory employing Ras and cyclin dependent kinase 4 (CDK4) to create a malignant epidermal cell population that accurately mimics naturally occurring human SCC. This transformation is driven by only two genetically defined elements, and represents an ideal system with which to accomplish the primary goal of advancing a more complete understanding of specific mechanisms mediating Ras driven human epidermal neoplasia. First, the relative contribution of each of the three major Ras downstream effector arms in driving epidermal neoplasia with CDK4 will be identified by activating each signaling pathway individually. Constitutively active Ras mutants known to activate either the Raf, PI3K, or RalGDS pathways will be expressed with CDK4 in human keratinocytes and grafted onto immunodeficient mice where effects on epidermal growth and differentiation will be examined. Individual pathways will also

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be activated in limited combinations as multiple effector arms may act in concert to reproduce the completely transformed invasive SCC. Second, the necessity of individual Ras effector arms will be defined further through both genetic and pharmacologic blockade of specific components in the Ras signaling pathways. This will identify key points for potential therapeutic intervention. Finally, new technologies utilizing small tissue penetrating polypeptides will be developed to interact specifically and inhibit critical components of the Ras signaling pathway in human epidermis. At the end of the funding period, we hope to have defined specific mechanisms through which Ras drives epidermal neoplasia to advance an understanding of human tissue tumorigenesis and to guide development of future targeted molecular therapies for cancers of the skin and other tissues. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RECONSTITUTION OF HEDGEHOG SIGNALING COMPLEX Principal Investigator & Institution: Robbins, David J.; Assistant Professor; Molecular Genetics, Biochemistry & Microbiology; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2002; Project Start 01-JUL-1999; Project End 30-APR-2004 Summary: Mutations in components of the Hedgehog (Hh) signal transduction pathway underlie a number of human developmental disorders, and contribute to a diverse array of tumors. Gorlin's syndrome is one example of the role this pathway plays in both development and cancer. Besides numerous developmental abnormalities, individuals afflicted with this disorder have an inherited predisposition to basal cell carcinoma as well as to a variety of primitive neuroectodermal tumors, such as medulloblastoma. Similar components are also found mutated in sporadic forms of these same malignancies, or highly amplified in glioblastoma. Our long-term goals are to elucidate how this signal transduction pathway is usurped in these different human pathologies. Hedgehog signal transduction occurs through a large multi-component microtubulebound protein complex, that when disrupted blocks signaling. This Hedgehog signaling complex (HSC) is an approximately 1000 kDa multi-protein complex with three known members, the protein kinase Fused (Fu), the transcription factor Cubitus Interuptus (Ci), and the kinesin-like protein Costal2 (Cos2). In addition to Fu, Ci, and Cos2, we hypothesize that the HSC contains a number of as yet unknown, but functionally important protein components. The goals of this project are to identify these components, and evaluate their role in HSC function and organization. The specific aims of our studies are: 1) Develop an in vitro reconstitution system for members of the HSC using a baculovirus expression system, this will allow us to isolate modified forms of the various HSC components in large amounts for various in vitro studies; 2) Identify additional members of a Hh dependent signaling complex. This will be done through a combination of both affinity and conventional chromatography, as well as using a candidate gene approach. Identifying these other components will provide insight into the role this large protein machine plays in Hh signal transduction. It will also provide the framework necessary to identify the human orthologs of the HSC, and elucidate their role in oncogenesis (in future work). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: REFINEMENT & UTILIZATION OF PTC +/- MODEL OF BCC Principal Investigator & Institution: Aszterbaum, Michelle; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747

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Basal Cell Carcinoma

Timing: Fiscal Year 2002 Summary: (Applicant's Description) We have established the first practical murine model of the most common human cancer-basal cell carcinomas-by exposing the skin of ptc +/- mice to repeated ultraviolet light irradiation. We propose a series of experiments first to refine this model by varying the wavelength, the degree, and the frequency of irradiation. We will test several additional variables including the effects of alternative environmental insults that appear to provoke human basal cell carcinomas-ionizing irradiation and arsenic as well as chemical carcinogens. We will validate the utility of this model by assessing chemopreventive agents that have been studied on humansretinoids, green tea aqueous extract, and low-fat diet and then will utilize the model to test for chemopreventive efficacy of tea preparations and inhibitors of COX-1 and of COX-2. We will also assess the influence of varied genetic backgrounds both on photoinduction of efficacy of chemopreventive agents. Lastly, we will survey human extracutaneous cancers aberrant hedgehog pathway signaling. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF CNS AND LIMB POLARITY BY SONIC HEDGEHOG Principal Investigator & Institution: Mcmahon, Andrew P.; Professor; Molecular and Cellular Biology; Harvard University Holyoke Center 727 Cambridge, Ma 02138 Timing: Fiscal Year 2002; Project Start 01-DEC-1994; Project End 30-NOV-2004 Summary: (adapted from investigator's abstract): The goal of this project is to understand the mechanisms by which information encoded in extracellular signals is converted complex patterns in the developing mammalian embryo. This proposal focuses on the role of Sonic hedgehog (Shh) signaling. The Shh signaling pathway is not only essential for the induction of clinically relevant neurons within the CNS, but inappropriate activation of Shh signaling has been linked to the development of several l of tumor, most notably basal cell carcinoma (BCC), the most common form of skin cancer, and medullablastoma, the most common brain tumor of children. Further, loss of Shh signaling underlies many cases of familial an spontaneous holoprosencephaly. Consequently, understanding how a Shh signal is received, transduced and modulated is likely to lead to new insights with direct relevance to human health. In view of its close relation. to the human embryo, and the availability of genetic approaches which can precisely modify gene activity, the mouse is used as an experimental system. An active Shh signal is generated by an unusual autocatalytic cleavage which leads to the covalent attachment of cholesterol to the l9 kcal signaling peptide. Cholesterol modification may play several roles in Shh-signaling, for example preventing free diffusion of ligand or participating in receptor recognition. Aim 1 proposes to explore the biological significance of cholesterol modification by generating a non-tethered allele of Shh (N-Shh). The activity of this allele in CNS and limb patterning will be addressed in the presence of normal or reduced levels of two Hedgehog binding proteins, Hip and Ptc, negative modulators of Shh signaling. Aim 2 proposes to characterize the Shh interaction domain of Hip using truncated forms of Hip produced by cultured cells, or by limited proteolysis of purified Hip. Hip's role in embryogenesis and its genetic interactions with Ptc-l, will be examined in mice carrying Hip and Ptc null mutations. A mouse strain (Shh') has been generated in which an essential exon of Shh is flanked by the target recognition sequences (loxP sites) of the P1 phage integrase, CRE. Intercrossing the conditional allele with transgenic lines express CRE allows the spatial and temporal removal of Shh function. Aim 3 proposes to adopt this strategy to address

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Shh action in the limb and specific regions of the developing CNS, where its role cannot be assessed with existing null mutations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF THE CI PROTEIN BY SIGNAL TRANSDUCTION Principal Investigator & Institution: Holmgren, Robert A.; Professor; Biochem/Molecular & Cell Biol; Northwestern University 633 Clark Street Evanston, Il 60208 Timing: Fiscal Year 2003; Project Start 01-MAY-1998; Project End 30-NOV-2006 Summary: (provided by applicant): The Hedgehog (Hh) signal transduction cascade has been conserved from Drosophila through mammals and plays a key role in many developmental processes. The goal of the proposed research is to use the advantages of Drosophila to understand this signaling system in detail. A key target of Hh signaling is the transcription factor Cubitus interruptus (Ci). In previous work, Ci's role in the expression of Hh target genes was examined, and its regulation by other components of the Hh signaling pathway studied. The results demonstrated that Ci function is regulated at three levels, proteolytic cleavage, nuclear import and activation. By specifically regulating these different functions, distinct domains of gene expression are established in response to Hh signaling. This research will be extended by pursuing the following aims: 1) Genetic and biochemical approaches will be used to elucidate the molecular basis of Ci regulation by Hh. Activation of Ci appears to require direct phosphorylation by protein kinase A (PKA). Is there a specific PKA site required for Ci activation, and how does phosphorylation lead to activation? Are other phosphorylation sites on Ci Hh regulated? 2) The cell biology of Hh signal transduction will be studied using EM on the embryonic epidermis and light microscopy of salivary glands. Does the Ci signaling complex exist in different forms? Do these complexes have different subcellular distributions, and is one a precursor to the other? 3) Work will be continued on Ci regulation of the dpp-HO enhancer. Is binding of Ci necessary to for the formation of the enhancer complex, and are there distinctions between the initiation of expression and its maintenance? Hh signal transduction has been implicated in a number of congenital abnormalities and a variety of cancers including basal cell carcinoma. By understanding the details of this conserved pathway, it should be possible to design better diagnostics and therapeutics for these important diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ROLE OF GLI IN TUMOR PROGRESSION Principal Investigator & Institution: Ruppert, Michael J.; Associate Professor; Medicine; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2007 Summary: (provided by applicant): Signaling by sonic hedgehog (SHH) during development and in normal adult tissues is an important regulatory mechanism for proliferation and morphogenesis. SHH binds to and antagonizes the activity of the tumor suppressor PTCH, a gatekeeper molecule important in basal cell carcinoma of the skin (BCC), medulloblastoma, and rhabdomyosarcoma. Loss-of-function and gainof-function studies support a role for the GLI family of zinc finger transcription factors in transmission of the hedgehog signal. In BCC, a most common form of carcinoma, GLI expression is consistently induced as a result of mutation of PTCH or of other molecules in the pathway. Expression of GLI or GL12 in mouse skin is sufficient to induce BCC. To better understand the role of GLI in tumor progression, we extensively characterized

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GLI-expressing RK3E epithelial cells to identify putative target genes. The techniques of suppression subtractive hybridization and microarray analysis were used in combination to identify GLI-induced transcripts. The identified transcripts were not altered in association with transformation by several other oncogenes, including RAS, cMYC, or GKLF/KLF4. Compared with control cells, mouse embryo cells harboring defective alleles of PTCH exhibited increased expression of several of these transcripts, suggesting that expression of endogenous GLI is sufficient for some of the observed transcriptional effects. mRNA in situ hybridization revealed increased expression of GLI-induced transcripts in GLI-positive hair follicles and in human BCC, compared with GLI-negative hair follicles. Unlike other oncogenes that transform RK3E, GLI specifically induced expression of molecules or oncogenes known to induce epithelialmesenchymal transition (EMT) in development. Multiple alterations in gene expression previously observed in human BCC were likewise induced by GLI in vitro. We propose to identify transcripts that correspond to direct transcriptional target genes, to determine a role for specific GLI-induced transcripts in a mouse model of BCC, and to characterize specific GLI-induced transcripts as potential effectors of transformation in vitro and in vivo. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF GLIL IN BASAL CELL CARCINOMA DEVELOPMENT Principal Investigator & Institution: Ruiz I Altaba, Ariel Ruiz I.; Associate Professor; Cell Biology; New York University School of Medicine 550 1St Ave New York, Ny 10016 Timing: Fiscal Year 2002; Project Start 01-JUL-1998; Project End 30-APR-2004 Summary: (adapted from the investigator's abstract) The goal of the project in this grant application is to understnad the molecular mechanisms underlying the development of basal cell cancer. Specifically, they focus their research in the potential role of Gli1 in inducing BCC development and in the understanding of the mechanisms regulated by this zinc finger transcription factor. They have previously shown that Gli1, but not Gli3, is consistently expressed in human sporadic BCCs and that it is sufficient to induce epidermal tumor formation in the skin of frog embryos. Because Gli1 is a target and mediator of Sonic hedgehog (Shh) signaling, Gli1 transcription represents the activation of the Shh signaling pathway. This is consistent with previous findings in which the gene Patched, encoding a transmembrane receptor for Shh having a negative effect on the pathway, is mutated in familial BCCs. Mutations in Patched are thought to be responsible for the Basal cell Nevus Syndrome. They propose to test for the role of Gli2 in BCC formation using the frog embryo assay and to test for the prevalence of its expression in sporadic human BCCs. In addition, they propose to develop a mouse model for BCC formation by the generation of an inducible Gli1 protein in transgenic mice. Finally, they propose to create an in vivo reporter assay for Gli1 function. The experiments are designed to provide a good model to study the molecular basis of BCC formation which may offer the opportunity to develop anti-cancer agents in the future. In addition, understanding how deregulation of the Shh signaling pathway and Gli1 function lead to BCC formation, will shed light into the normal role of this gene in follicle development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ROLE OF THE PPARB IN EPITHELIAL CELL PROLIFERATION Principal Investigator & Institution: Peters, Jeffrey M.; Assistant Professor; Veterinary Science; Pennsylvania State University-Univ Park 201 Old Main University Park, Pa 16802

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Timing: Fiscal Year 2002; Project Start 15-JUN-2001; Project End 31-MAY-2005 Summary: (provided by applicant): Since it was first identified as a member of the peroxisome proliferator-activated receptors (PPARs) in 1994, specific roles for the PPARI3 have remained elusive. Despite numerous roles elucidated for the PPARa and PPARy that contribute to diseases including hyperlipidemias, atherosclerosis, obesity, diabetes and cancer, the function of PPARb has remained a mystery. The recent phenotypical description of a PPARb-null mouse has provided the first direct, in vivo evidence that the PPARb is involved in epithelial cell proliferation. Topical application of the tumor promoter TPA causes enhanced epidermal cell proliferation in PPARb-null mice compared to controls suggesting that the hyperplastic response induced by TPA is attenuated by the PPARb. Further, the non-steroidal anti-inflammatory drug (NSAID), sulindac, inhibits TPA-induced inflammation and epidermal hyperplasia in wild-type mice and this effect is not found in similarly treated PPARb-null mice. This suggests that the beneficial effects of sulindac are modulated by the PPARb. The overall hypothesis of this proposal is that the PPARb3 is central to the epithelial cell proliferative response that results in skin tumor formation from genetic or chemical factors. A secondary hypothesis is that PPARb-null mice will be refractory to the influence of sulindac in preventing epidermal hyperplasia that contributes to skin tumor formation. The first specific aim is to develop three model systems to test these hypotheses. The first model will utilize crossing the PPARb-null mice with patched +1/- mice that are genetically more sensitive to ultraviolet or ionizing radiation-induced skin tumors. The second model will assess two-stage carcinogenicity in the PPARb-null mouse and the last model will characterize a keratinocyte culture system using cells from PPARb-null mice so that it can be utilized to further mechanistically define the role of the PPARb in the TPAinduced epidermal cell proliferative response. Since preliminary data indicate that PPARb attenuates TPA-induced COX-2 mRNA expression, the second specific aim will determine if PPARb-specific alterations in eicosanoid function contribute to the mechanisms of enhanced epidermal cell proliferation. The third specific aim will identify and initially characterize PPARbdependent gene expression in skin cells resulting from treatment with TPA. Results from this work will determine if PPARb influences epidermal cell proliferation that contribute to the incidence of skin cancer, determine if PPARb-dependent alterations in eicosanoid metabolism underlie enhanced cell proliferation induced by TPA in PPARb-null mice, and characterize PPARb target genes in epithelial cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SIGNALING CELL SPECIFICATION FOREBRAIN Principal Investigator & Institution: Karlstrom, Rolf O.; Assistant Professor; Biology; University of Massachusetts Amherst 408 Goodell Building Amherst, Ma 01003 Timing: Fiscal Year 2002; Project Start 01-JUL-2000; Project End 30-JUN-2004 Summary: (Applicant's abstract reproduced verbatim): The hedgehog (Hh) family of secreted proteins plays a fundamental role in cell differentiation within the brain, spinal cord, limbs, somites and circulatory system. Defects in Hh signaling during embryonic development are associated with human congenital malformations, including holoprosencephaly. Mis-regulation of Hh signaling later in life is associated with basal cell carcinoma, the most common form of cancer affecting fair-skinned adults. The study of Hh signaling during development is thus important for understanding human congenital malformations as well as the formation of certain tumors. The major goal of this project is to understand how Hh signaling contributes to cell differentiation during normal development in the zebrafish embryo. We have used a genetic approach to

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study the role of Hh signaling in the formation of a defined region of the nervous system, the post optic area of the ventral forebrain. We have recently shown that two zebrafish forebrain mutations encode Hh-responsive transcription factors of the gli family. Cell differentiation defects in the zebrafish forebrain mutants appear to be caused by mis-regulation of Hh signaling. Consistently, it was also recently demonstrated that another zebrafish forebrain mutation encodes sonic hedgehog. The fact that three of the zebrafish forebrain mutants encode members of the Hh pathway underscores the importance of this signaling cascade in development. This application focuses on a fourth zebrafish forebrain mutant called umleitung (uml). Like the known Hh pathway mutations, uml interferes with Hh signaling and cell differentiation in the ventral forebrain. We now have evidence that uml may encode another zebrafish gli gene. While gli genes appear to be central to the regulation of Hh signaling, little is known about how gli genes function in vertebrates. There is evidence that some gli genes activate the transcription of Hh target genes, while others act to repress Hh targets. We propose to analyze the role of gli mediated hedgehog signaling in zebrafish forebrain development by A) identifying the gene encoded by uml, determining the genetic lesion in uml, and isolating null alleles of uml, B) determining how gli genes contribute to cell differentiation in the ventral forebrain, C) determining how gli genes regulate, and in turn are regulated by, Hh signaling in vivo, and D) identifying and characterizing genes that are transcriptionally regulated by gli genes in the zebrafish embryo. The zebrafish embryo provides a powerful model for the study of Hh regulation in vertebrates as it allows a genetic approach to be combined with ectopic expression studies. The combination of these two approaches is well suited to the study of molecular signaling pathways that regulate cell fate decisions and promises to provide insights not readily attainable in other vertebrate systems. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SPORE IN SKIN CANCER Principal Investigator & Institution: Herlyn, Meenhard; Professor and Chairman; Wistar Institute Philadelphia, Pa 191044268 Timing: Fiscal Year 2002; Project Start 28-SEP-2001; Project End 31-AUG-2004 Summary: (provided by applicant): Cancers of the skin investigated in this SPORE include, melanoma, cutaneous T cell lymphoma, and squamous cell carcinoma (SCC) and basal cell carcinomas (BCC). The projects and pilot studies are based on a broad existing infrastructure of active basic and translational research in cancers of the skin. They span the fields of cancer epidemiology, biology, immunology, pathology, and therapy to assess cancer risk, diagnosis and detection, prognosis, treatment, and treatment outcome. Immune surveillance genes are investigated as candidate melanoma susceptibility genes (Project 1). Prognostic models are developed for primary melanoma to better design patients? treatment and follow-up (Project 2). Lymphocyte populations from melanoma patients are analyzed to develop new strategies for passive and active immune therapy (Project 3). Patients with cutaneous T cell lymphoma are evaluated that fail therapy with the cytokine IL-12 (Project 4). A melanoma vaccine is being developed that utilizes new principles in antigen presentation (Project 5). Developmental funds will be made available to increase the number of investigators in translational studies. Pilot studies are designed for melanoma, SCC and BCC for disease diagnosis, detection and therapy. All pilot studies utilize novel technologies and approaches to extend the existing infrastructure allowing the group to develop new projects in cancer prevention, diagnosis and therapy. Resource centers provide the investigators with support for all projects. By building on a strong existing infrastructure, which will be further

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strengthened through this SPORE, the proposed studies are expected to have a major impact on the control of cancers of the skin. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FORMATION

STROMAL

REGULATION

OF

BASAL

CELL

CARCINOMA

Principal Investigator & Institution: Oro, Anthony E.; Dermatology; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 31-MAY-2006 Summary: (Adapted from the investigator's abstract) Basal cell carcinomas (BCCs) are the most common cancer in the US with an annual incidence of 750,000. The highly stromal-dependent growth of BCCs makes them ideal models for the analysis of tumorstromal interactions. Recently the central role of the Sonic hedgehog (Shh) signaling pathway in the epithelium of these tumors has been elucidated. Their preliminary evidence supports the hypothesis that the surrounding tumor stroma regulates BCC growth by controlling the transcriptional induction of Shh target genes in the epithelium. Greater knowledge is needed to understand mechanistically how stromal cells accomplish this crucial function. The aim of this grant is identify the stromal cells and genes that regulate epithelial Shh target gene induction to maintain BCC growth and malignant potential. They proposes to: 1) Determine why keratinocytes fail to induce the Gli genes in the absence of a stromal environment; 2) Identify the stromal cells which allow epithelial Shh target gene expression in organotypic skin cultures; and 3) Identify candidate stromal signaling genes using high density cDNA arrays. At the end of the proposed funding period they will have a greater mechanistic understanding how epithelial Shh target genes are regulated by signals from the surrounding stroma. Their studies should give insight into how the growth of other epithelial tumors are regulated by their stroma and may lead to the development of new anti-tumor agents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SUBMILLIMETER IMAGING AND MEDICAL DIAGNOSTICS Principal Investigator & Institution: Siegel, Peter H.; None; California Institute of Technology Mail Code 201-15 Pasadena, Ca 91125 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2007 Summary: Abstract: (provided by applicant): The candidate is a principal research engineer at the California Institute of Technology Jet Propulsion Laboratory. His specialty area is millimeter and submillimeter wave technology development and instrumentation, especially THz space sensor systems. He is interested in applying this technology, for the first time, towards medical applications, in particular to bioimaging and disease diagnosis. Medical imaging is a well developed field with perhaps the widest range of spectral coverage of any science save astrophysics. True diffraction limited imaging can be obtained at frequencies from kHz (ultrasound) to a 100 quadrillion Hz (1017 or X-Rays). However, there is at least one wavelength range with substantial biochemical absorption and potential contrast mechanisms that is still completely unexplored - the THz domain P.H. Siegel, "Terahertz Technology," Special 50th Anniversary Issue of IEEE Transactions on Microwave Theory and Techniques, March 2002]. This task will apply state-of-the-art THz sensor technology, developed originally for NASA space science, Earth and planetary remote sensing, to biomedical problems. Targeted areas of investigation include development of measurement techniques for absorption, reflection and scattering of THz beams; algorithms for 2D and

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3D tomographic imaging; cataloging of biomaterial transmission properties and identification of contrast mechanisms in body fluids, lipids, tissue and bone at THz frequencies; effects of THz energy on cell function and finally disease diagnosis and perhaps even treatment. There is now very strong evidence that THz imaging techniques can be used to distinguish normal and carcinogenic skin cells non-invasively and in-vivo [R. M. Woodward, V. P. Wallace, R. Pye, B. Cole, E. H. Linfield, D. D. Arnone and M. Pepper, "Terahertz Pulse Imaging of Basal Cell Carcinoma", First International Conference on Biomedical Imaging and Sensing Applications of THz Technology (BISAT2001), Leeds, UK, Nov.29-Dec. 1, 2001], however the underlying contrast mechanisms are not yet understood. The field of THz imaging is in its early infancy and there is much to be learned before we can make a judgment on the effectiveness of this wavelength range in resolving problems of interest to the medical and biomedical communities. Since there has been so little commercial development in the THz field, this task can have a major impact in starting us down a road that will likely be both long and fruitful. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SUNNY DAYS HEALTHY WAYS GRADES 6-8 SUN SAFETY CURRICULUM Principal Investigator & Institution: Buller, David B.; Senior Scientist and Vice President; Cooper Institute Dallas, Tx 75230 Timing: Fiscal Year 2001; Project Start 02-SEP-1998; Project End 31-MAY-2004 Summary: U. of Arizona Cancer Center (ACC) and U. of Alabama, Birmingham (UAB) will develop a sun safety curriculum for children in grades 6-8 that contains classroom instruction and interactive multimedia computer programs and evaluate its ability to increase children's sun protection attitudes and behaviors (limit time in sun and use protective clothing, sunscreen, and shade), produce a sun safety norm, and decrease tanning norms in a community trial in public schools. Skin cancer is epidemic. Childhood solar protection could reduce UVR exposure and the risk of skin cancer since severe childhood sunburns and intermittent exposure may promote melanoma and basal cell carcinoma and lifetime sun exposure (most occurs in childhood) is associated with squamous cell carcinoma. The curriculum will integrate with the ACC's successful Sunny Days, Healthy Ways grade K-5 sun safety curriculum and build upon a pilot middle school program by UAB. In Phase I (Y1 and Y2), curriculum components will be created for each grade, containing interactive exercises by teachers and interactive multimedia programs utilizing peer models. Social Cognitive Theory and persuasion theories will guide curriculum design. It will focus on outcome and self-efficacy expectations, goal-setting, behavioral skills, self-monitoring, and reinforcements for sun safety. Student and teacher focus groups, an external advisory board, and assessment of school policies and environment will aid curriculum designers. Student surveys will be pilot-tested. The curriculum will be evaluated in Phase II (Y3 and Y4) in a pair-matched randomized pretest-posttest control group community trial, enrolling 15 pairs of schools from five public school districts in AZ, AL, and FL (150+ students tested per school). Process evaluation will monitor implementation and multimedia use. Outcome evaluation will assess changes in attitudes and behaviors, self-efficacy and outcome expectations, and tanning and sun safety norms with a first implementation in the 19992000 academic year and a second implementation in 2000-01. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: VALIDATION OF TRANSILLUMINATION AND THE NEVOSCOPE Principal Investigator & Institution: Mullani, Nizar A.; Translite, Llc 8410 Highway 90A Sugar Land, Tx 774783195 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 30-SEP-2004 Summary: (provided by applicant): Skin cancer is the most common of all cancers and melanoma is a deadly skin cancer that accounts for over 75% of all the skin cancer deaths in the United States. The incidence of melanoma is rising at approximately 3% per year. Early detection of melanoma results in 95% cure rate. But, early detection of melanoma is difficult because of the subtle changes that differentiate a malignant melanoma from a benign mole. Better methods to detect these subtle changes, and more frequent screening for skin cancer, will significantly improve the early detection of melanoma and possibly reduce the number of deaths caused by this disease. Early detection of melanoma requires better methods for examining subtle changes in the pigmentation of the suspicious moles. Side-transillumination, whereby light is directed into the skin from around the suspicious mole, is a new method that makes the skin translucent so that the subsurface structures can be examined with clarity. This technique is used in a prototype device called the Nevoscope and has the potential for improving the early detection of skin cancers such as melanoma and basal cell carcinoma. The goal of this research project is to validate the use of sidetransillumination for the detection of melanoma by comparing its detection accuracy to the established oil epiluminescence method. The second goal of the research project is to develop a commercial model of the Nevoscope for clinical use by the dermatologists that would be easy to use and affordable. The clinical validation study will digitally image 240 skin lesions suspicious for malignancy using the oil-based imaging and the side-transillumination imaging in the same lesion. Two dermatologists that are blinded to the patient history, and who will make a diagnosis based on a semi quantitative scoring method, will read these images. Diagnostic accuracy for melanoma will be computed for the two methods based on pathology-determined diagnosis of the excised lesion. The long-term goal of this research is to validate the side-transillumination method and develop the Nevoscope device into a commercial product for improved early diagnoses of skin cancers. 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 “basal cell carcinoma” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for basal cell carcinoma in the PubMed Central database: 3 4

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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A role of PDGFR[alpha] in basal cell carcinoma proliferation. by Xie J, Aszterbaum M, Zhang X, Bonifas JM, Zachary C, Epstein E, McCormick F.; 2001 Jul 31; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=55407

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DNA Repair and Aging in Basal Cell Carcinoma: A Molecular Epidemiology Study. by Wei Q, Matanoski GM, Farmer ER, Hedayati MA, Grossman L.; 1993 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=45925

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Identification of a small molecule inhibitor of the hedgehog signaling pathway: Effects on basal cell carcinoma-like lesions. by Williams JA, Guicherit OM, Zaharian BI, Xu Y, Chai L, Wichterle H, Kon C, Gatchalian C, Porter JA, Rubin LL, Wang FY.; 2003 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153604

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Induction of basal cell carcinomas and trichoepitheliomas in mice overexpressing GLI-1. by Nilsson M, Unden AB, Krause D, Malmqwist U, Raza K, Zaphiropoulos PG, Toftgard R.; 2000 Mar 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=16258

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Notch signalling is linked to epidermal cell differentiation level in basal cell carcinoma, psoriasis and wound healing. by Thelu J, Rossio P, Favier B.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111189

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 basal cell carcinoma, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “basal cell carcinoma” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for basal cell carcinoma (hyperlinks lead to article summaries): •

A case of basal cell carcinoma arising in epidermal nevus. Author(s): Ceylan C, Ozdemir F, Ozturk G, Akalin T. Source: International Journal of Dermatology. 2002 December; 41(12): 926-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12492992&dopt=Abstract

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 case of basal cell carcinoma of the nipple and areola with intraductal spread. Author(s): Yamamoto H, Ito Y, Hayashi T, Urano N, Kato T, Kimura Y, Tanigawa T, Endo W, Kurokawa E, Kikkawa N, Taniguchi H. Source: Breast Cancer. 2001; 8(3): 229-33. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11668245&dopt=Abstract

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A case of naevus lipomatosus cutaneus superficialis of the scalp associated with pedunculated basal cell carcinoma. Author(s): Maeda A, Aragane Y, Ueno K, Yamazaki F, Kawada A, Tezuka T. Source: The British Journal of Dermatology. 2003 May; 148(5): 1084-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12786865&dopt=Abstract

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A monoclonal antibody established from the immunization of basal cell carcinoma (BCC) tissues reacts to the intercellular space of BCC and hair follicles. Author(s): Kore-eda S, Matsuyoshi N, Ueda M, Horiguchi Y, Miyachi Y, Imamura S. Source: The Journal of Dermatology. 2002 November; 29(11): 718-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12484434&dopt=Abstract

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A new germline mutation of the PTCH gene in a Japanese patient with nevoid basal cell carcinoma syndrome associated with meningioma. Author(s): Tate G, Li M, Suzuki T, Mitsuya T. Source: Japanese Journal of Clinical Oncology. 2003 January; 33(1): 47-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12604725&dopt=Abstract

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Actin expression in purely nodular versus nodular-infiltrative basal cell carcinoma. Author(s): Law AM, Oliveri CV, Pacheco-Quinto X, Horenstein MG. Source: Journal of Cutaneous Pathology. 2003 April; 30(4): 232-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12680952&dopt=Abstract

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Adenoid cystic/basal cell carcinoma of the prostate: clinicopathologic findings in 19 cases. Author(s): Iczkowski KA, Ferguson KL, Grier DD, Hossain D, Banerjee SS, McNeal JE, Bostwick DG. Source: The American Journal of Surgical Pathology. 2003 December; 27(12): 1523-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14657711&dopt=Abstract

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Adequate depth of excision for basal cell carcinoma of the nose. Author(s): Terashi H, Kurata S, Hashimoto H, Asada Y, Shibuya H, Fujiwara S, Takayasu S. Source: Annals of Plastic Surgery. 2002 February; 48(2): 214-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11910234&dopt=Abstract

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Adjuvant cytokeratin staining in Mohs micrographic surgery for basal cell carcinoma. Author(s): Smeets NW, Stavast-Kooy AJ, Krekels GA, Daemen MJ, Neumann HA. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 2003 April; 29(4): 375-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12656816&dopt=Abstract

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Allele loss on chromosome 9q22.2-22.3 in sporadic basal cell carcinoma in Chinese. Author(s): He C, Zhang X, Wang Y, Sun K, Chen HD. Source: Chinese Medical Journal. 1999 June; 112(6): 497-500. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11601325&dopt=Abstract

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Altered distribution of 1-2B7B antigen in basal cell carcinoma, squamous cell carcinoma and Bowen's disease. Author(s): Zhang XM, Horiguchi Y, Ueda M, Yoshiki T, Imamura S. Source: Journal of Dermatological Science. 1992 January; 3(1): 46-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1591227&dopt=Abstract

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Amyloid deposition in basal cell carcinoma: a cause of apparent lack of sensitivity to radiotherapy. Author(s): Cox NH, Nicoll JJ, Popple AW. Source: Clinical and Experimental Dermatology. 2001 September; 26(6): 499-500. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11678874&dopt=Abstract

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An interdisciplinary approach to the management of basal cell carcinoma of the head and neck. Author(s): Baker SR, Swanson NA, Grekin RC. Source: J Dermatol Surg Oncol. 1987 October; 13(10): 1095-106. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3655080&dopt=Abstract

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An open case series of patients with basal cell carcinoma treated with topical 5% imiquimod cream. Author(s): Cowen E, Mercurio MG, Gaspari AA. Source: Journal of the American Academy of Dermatology. 2002 October; 47(4 Suppl): S240-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12271286&dopt=Abstract

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Analyses of the tumour suppressor ING1 expression and gene mutation in human basal cell carcinoma. Author(s): Chen B, Campos EI, Crawford R, Martinka M, Li G. Source: International Journal of Oncology. 2003 April; 22(4): 927-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12632089&dopt=Abstract

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Analysis of 14-3-3sigma expression in hyperproliferative skin diseases reveals selective loss associated with CpG-methylation in basal cell carcinoma. Author(s): Lodygin D, Yazdi AS, Sander CA, Herzinger T, Hermeking H. Source: Oncogene. 2003 August 21; 22(35): 5519-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12934112&dopt=Abstract

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Association of chromosome 19q13.2-3 haplotypes with basal cell carcinoma: tentative delineation of an involved region using data for single nucleotide polymorphisms in two cohorts. Author(s): Rockenbauer E, Bendixen MH, Bukowy Z, Yin J, Jacobsen NR, Hedayati M, Vogel U, Grossman L, Bolund L, Nexo BA. Source: Carcinogenesis. 2002 July; 23(7): 1149-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12117772&dopt=Abstract

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Audit of basal cell carcinoma: registration practice. Author(s): McLoone NM, Middleton RJ, Gavin AT, Walsh M, Dolan OM. Source: The British Journal of Dermatology. 2003 February; 148(2): 371. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12588403&dopt=Abstract

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Axillary basal cell carcinoma. Author(s): LeSueur BW, DiCaudo DJ, Connolly SM. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 2003 November; 29(11): 1105-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14641334&dopt=Abstract

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Axillary basal cell carcinoma: literature survey and case report. Author(s): Gardner ES, Goldberg LH. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 2001 November; 27(11): 966-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11737133&dopt=Abstract

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Basal cell carcinoma involving the lacrimal canaliculus. A documented mechanism of tumor spread. Author(s): Fosko SW, Gibney MD, Holds JB. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 1997 March; 23(3): 203-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9145964&dopt=Abstract

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Basal cell carcinoma metastatic to the salivary glands: differential diagnosis in fineneedle aspiration cytology. Author(s): Stanley MW, Horwitz CA, Bardales RH, Stern SJ, Korourian S. Source: Diagnostic Cytopathology. 1997 March; 16(3): 247-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9099547&dopt=Abstract

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Basal cell carcinoma occurring in multiple familial trichoepithelioma: detection of loss of heterozygosity in chromosome 9q. Author(s): Harada H, Hashimoto K, Toi Y, Yotsunoto S, Ko MS. Source: Archives of Dermatology. 1997 May; 133(5): 666-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9158430&dopt=Abstract

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Basal cell carcinoma of the dorsum of the hand. Author(s): Vandeweyer E, Herszkowicz A. Source: Acta Chir Belg. 2003 June; 103(3): 300-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12914367&dopt=Abstract

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Basal cell carcinoma of the scrotum. Author(s): Schleicher SM, Milstein HJ, Ilowite R. Source: Cutis; Cutaneous Medicine for the Practitioner. 1997 March; 59(3): 116. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9071548&dopt=Abstract

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Basal cell carcinoma of the toenail unit. Author(s): Herzinger T, Flaig M, Diederich R, Rocken M. Source: Journal of the American Academy of Dermatology. 2003 February; 48(2): 277-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12582403&dopt=Abstract

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Basal cell carcinoma of the umbilicus: a case report and literature review. Author(s): Etter L, Cook JL. Source: Cutis; Cutaneous Medicine for the Practitioner. 2003 February; 71(2): 123-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12635891&dopt=Abstract

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Basal cell carcinoma on the right hallux. Author(s): Matsushita K, Kawada A, Aragane Y, Tezuka T. Source: The Journal of Dermatology. 2003 March; 30(3): 250-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12692366&dopt=Abstract

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Basal cell carcinoma presenting as a large pore. Author(s): Benedetto AV, Benedetto EA, Griffin TD. Source: Journal of the American Academy of Dermatology. 2002 November; 47(5): 72732. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12399765&dopt=Abstract

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Basal cell carcinoma showing connections with epidermal cysts. Author(s): Tanaka M, Terui T, Sasai S, Tagami H. Source: Journal of the European Academy of Dermatology and Venereology : Jeadv. 2003 September; 17(5): 581-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12941101&dopt=Abstract

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Basal cell carcinoma with matrical differentiation. Author(s): Kim SH, Lee MG, Lee KG. Source: Yonsei Medical Journal. 2003 June 30; 44(3): 523-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12833592&dopt=Abstract

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Basal cell carcinoma with pulmonary and lymph node metastasis causing death. Author(s): Robinson JK, Dahiya M. Source: Archives of Dermatology. 2003 May; 139(5): 643-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12756102&dopt=Abstract

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Basal cell carcinoma with sarcomatoid features (sarcomatoid carcinoma): report of a case and review of the literature. Author(s): Gomez-Espejo C, Herrera-Sabal A, Rios-Martin JJ, Camacho-Martinez F. Source: The Journal of Dermatology. 2003 July; 30(7): 543-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12928545&dopt=Abstract

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Basal cell carcinoma with tricholemmal (at the lower portion) differentiation within seborrheic keratosis. Author(s): Misago N, Satoh T, Narisawa Y. Source: Journal of Cutaneous Pathology. 2003 March; 30(3): 196-201. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12641780&dopt=Abstract

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Basal cell carcinoma workload in two district general hospitals. Author(s): Shankar S, Darley CR, Harland CC, Banerjee P, Stewart A, Freeman S. Source: Clinical and Experimental Dermatology. 2003 September; 28(5): 559-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12950357&dopt=Abstract

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Basal cell carcinoma, squamous cell carcinoma and melanoma of the skin: analysis of the Singapore Cancer Registry data 1968-97. Author(s): Koh D, Wang H, Lee J, Chia KS, Lee HP, Goh CL. Source: The British Journal of Dermatology. 2003 June; 148(6): 1161-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12828744&dopt=Abstract

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Basal cell carcinoma. Author(s): Wong CS, Strange RC, Lear JT. Source: Bmj (Clinical Research Ed.). 2003 October 4; 327(7418): 794-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14525881&dopt=Abstract

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Basal cell carcinoma: a dermatopathological and molecular biological update. Author(s): Saldanha G, Fletcher A, Slater DN. Source: The British Journal of Dermatology. 2003 February; 148(2): 195-202. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12588368&dopt=Abstract

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Bilateral basal cell carcinoma symmetrically appearing on lower eyelids: a case report. Author(s): Askar I, Kilinc N, Aytekin S. Source: Acta Chir Plast. 2003; 45(2): 49-51. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12921259&dopt=Abstract

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Bowenoid basal cell carcinoma of the thumb: a case report and review of the literature. Author(s): Galeano M, Lentini M, Stagno D'Alcontres F, Colonna M. Source: Hand Surgery : an International Journal Devoted to Hand and Upper Limb Surgery and Related Research : Journal of the Asia-Pacific Federation of Societies for Surgery of the Hand. 2002 December; 7(2): 295-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12596295&dopt=Abstract

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Can smoking and/or occupational UV exposure have any role in the development of the morpheaform basal cell carcinoma? A critical role for peritumoral mast cells. Author(s): Erbagci Z, Erkilic S. Source: International Journal of Dermatology. 2002 May; 41(5): 275-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12100702&dopt=Abstract

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Carcinogen-specific mutation pattern in the p53 tumour suppressor gene in UV radiation-induced basal cell carcinoma. Author(s): Weihrauch M, Bader M, Lehnert G, Wittekind C, Tannapfel A, Wrbitzky R. Source: International Archives of Occupational and Environmental Health. 2002 April; 75(4): 272-6. Epub 2002 January 26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11981662&dopt=Abstract

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Case 3. Scarring from previous acne vulgaris. Basal cell carcinoma (BCC). Author(s): Brown SJ, Taylor AE. Source: Clinical and Experimental Dermatology. 2002 January; 27(1): 82-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11952685&dopt=Abstract

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Chest wall resection and reconstruction for metastatic basal cell carcinoma. Author(s): Cunnick GH, Sayer RE. Source: European Journal of Surgical Oncology : the Journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 1997 April; 23(2): 189-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9158200&dopt=Abstract

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Chronic varicella zoster infection mimicking a basal cell carcinoma in an AIDS patient. Author(s): Tsao H, Tahan SR, Johnson RA. Source: Journal of the American Academy of Dermatology. 1997 May; 36(5 Pt 2): 831-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9146560&dopt=Abstract

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Clinical diagnostic accuracy of basal cell carcinoma. Author(s): Presser SE, Taylor JR. Source: Journal of the American Academy of Dermatology. 1987 May; 16(5 Pt 1): 988-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3584583&dopt=Abstract

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Clinical manifestations in 105 persons with nevoid basal cell carcinoma syndrome. Author(s): Kimonis VE, Goldstein AM, Pastakia B, Yang ML, Kase R, DiGiovanna JJ, Bale AE, Bale SJ. Source: American Journal of Medical Genetics. 1997 March 31; 69(3): 299-308. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9096761&dopt=Abstract

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Clinicopathological and immunohistochemical study of basal cell carcinoma with reference to the features of basement membrane. Author(s): Kirihara Y, Haratake J, Horie A. Source: The Journal of Dermatology. 1992 March; 19(3): 161-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1640022&dopt=Abstract

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Comparative morphometric analysis of primary versus recurrent basal cell carcinoma and of histological subtypes. Significance of morphometry of the nuclei. Author(s): Bierhoff E, Appel K, Appel T, Buettner R, Wardelmann E. Source: Anticancer Res. 2003 May-June; 23(3B): 2697-700. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12894560&dopt=Abstract

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Comparison of the expression of p53, p21, Bax and the induction of apoptosis between patients with basal cell carcinoma and normal controls in response to ultraviolet irradiation. Author(s): Murphy M, Mabruk MJ, Lenane P, Liew A, McCann P, Buckley A, Flatharta CO, Hevey D, Billet P, Robertson W, Javed S, Leader M, Kay E, Murphy GM. Source: Journal of Clinical Pathology. 2002 November; 55(11): 829-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12401820&dopt=Abstract

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Comparison of the microvasculature of basal cell carcinoma and actinic keratosis using intravital microscopy and immunohistochemistry. Author(s): Newell B, Bedlow AJ, Cliff S, Drysdale SB, Stanton AW, Mortimer PS. Source: The British Journal of Dermatology. 2003 July; 149(1): 105-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12890202&dopt=Abstract

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Complete spontaneous regression of a basal cell carcinoma. Author(s): Gupta M, Puri P, Kamal A, Nelson ME. Source: Eye (London, England). 2003 March; 17(2): 262-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12640425&dopt=Abstract

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Correlation of histological subtypes of basal cell carcinoma with age, sex and distribution of skin lesions: a five-year study at Ramathibodi Hospital. Author(s): Puavilai S, Sirapan S. Source: J Med Assoc Thai. 2002 May; 85(5): 560-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12188385&dopt=Abstract

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Critique of 'a management approach to incompletely excised basal cell carcinoma of the skin'. Author(s): Smee R. Source: International Journal of Radiation Oncology, Biology, Physics. 1992; 22(1): 223-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1727123&dopt=Abstract

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Culture of basal cell carcinoma. Author(s): Brysk MM, Santschi CH, Bell T, Wagner RF Jr, Tyring SK, Rajaraman S. Source: The Journal of Investigative Dermatology. 1992 January; 98(1): 45-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1370231&dopt=Abstract

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CUSP/p63 expression in basal cell carcinoma. Author(s): Dellavalle RP, Walsh P, Marchbank A, Grayson TE, Su LJ, Parker ER, DeGregori J, Penheiter K, Aszterbaum M, Epstein EH Jr, Lee LA. Source: Experimental Dermatology. 2002 June; 11(3): 203-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12102658&dopt=Abstract

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Cutaneous basal cell carcinoma of the back metastasizing to the ipsilateral latissimus dorsi muscle. Author(s): Kiffer JD, Morris HG. Source: Clin Oncol (R Coll Radiol). 2003 May; 15(3): 136-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12801052&dopt=Abstract

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Cutaneous leishmaniasis and basal cell carcinoma in a patient from Al Baha, Saudi Arabia. Author(s): Morsy TA, Mangoud AM, al Seghayer SM. Source: J Egypt Soc Parasitol. 1992 April; 22(1): 167-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1578163&dopt=Abstract

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Cutaneous melanin density of Caucasians measured by spectrophotometry and risk of malignant melanoma, basal cell carcinoma, and squamous cell carcinoma of the skin. Author(s): Dwyer T, Blizzard L, Ashbolt R, Plumb J, Berwick M, Stankovich JM. Source: American Journal of Epidemiology. 2002 April 1; 155(7): 614-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11914188&dopt=Abstract

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Cutaneous undifferentiated small (Merkel) cell carcinoma, that developed synchronously with multiple actinic keratoses, squamous cell carcinomas and basal cell carcinoma. Author(s): Aydin A, Kocer NE, Bekerecioglu M, Sari I. Source: The Journal of Dermatology. 2003 March; 30(3): 241-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12692363&dopt=Abstract

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Decreased expression of galectin-3 in basal cell carcinoma of the skin. Author(s): Castronovo V, Liu FT, van den Brule FA. Source: International Journal of Oncology. 1999 July; 15(1): 67-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10375595&dopt=Abstract

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Deletion analysis of the adenomatous polyposis coli and PTCH gene loci in patients with sporadic and nevoid basal cell carcinoma syndrome-associated medulloblastoma. Author(s): Vortmeyer AO, Stavrou T, Selby D, Li G, Weil RJ, Park WS, Moon YW, Chandra R, Goldstein AM, Zhuang Z. Source: Cancer. 1999 June 15; 85(12): 2662-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10375116&dopt=Abstract

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Dense inflammation does not mask residual primary basal cell carcinoma during Mohs micrographic surgery. Author(s): Katz KH, Helm KF, Billingsley EM, Maloney ME. Source: Journal of the American Academy of Dermatology. 2001 August; 45(2): 231-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11464184&dopt=Abstract

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Dermoscopy of pigmented basal cell carcinoma. Author(s): Menzies SW. Source: Clinics in Dermatology. 2002 May-June; 20(3): 268-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12074864&dopt=Abstract

52

Basal Cell Carcinoma

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Detection of loss of heterozygosity on chromosome 9q22.3 in microdissected sporadic basal cell carcinoma. Author(s): Shen T, Park WS, Boni R, Saini N, Pham T, Lash AE, Vortmeyer AO, Zhuang Z. Source: Human Pathology. 1999 March; 30(3): 284-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10088546&dopt=Abstract

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Diagnosing basal cell carcinoma by dermatoscopy. Author(s): Carroll DM, Billingsley EM, Helm KF. Source: Journal of Cutaneous Medicine and Surgery. 1998 October; 3(2): 62-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9822777&dopt=Abstract

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Diagnostic and therapeutic dilemma: facial palsy attributable to basal cell carcinoma. Author(s): Barton JR. Source: The American Journal of Otology. 1992 January; 13(1): 90-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1598995&dopt=Abstract

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Diet and risk of basal cell carcinoma of the skin in a prospective cohort of women. Author(s): Hunter DJ, Colditz GA, Stampfer MJ, Rosner B, Willett WC, Speizer FE. Source: Annals of Epidemiology. 1992 May; 2(3): 231-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1342273&dopt=Abstract

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Differences in age and body site distribution of the histological subtypes of basal cell carcinoma. A possible indicator of differing causes. Author(s): McCormack CJ, Kelly JW, Dorevitch AP. Source: Archives of Dermatology. 1997 May; 133(5): 593-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9158412&dopt=Abstract

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Differences in age, site distribution, and sex between nodular and superficial basal cell carcinoma indicate different types of tumors. Author(s): Bastiaens MT, Hoefnagel JJ, Bruijn JA, Westendorp RG, Vermeer BJ, Bouwes Bavinck JN. Source: The Journal of Investigative Dermatology. 1998 June; 110(6): 880-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9620293&dopt=Abstract

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Differentiation among basal cell carcinoma, benign lesions, and normal skin using electric impedance. Author(s): Beetner DG, Kapoor S, Manjunath S, Zhou X, Stoecker WV. Source: Ieee Transactions on Bio-Medical Engineering. 2003 August; 50(8): 1020-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12892329&dopt=Abstract

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Digital syringomatous carcinoma mimicking basal cell carcinoma. Author(s): Goto M, Sonoda T, Shibuya H, Terashi H, Kai Y, Sato T, Takayasu S, Yokohama S. Source: The British Journal of Dermatology. 2001 February; 144(2): 438-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11251603&dopt=Abstract

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Discordance between facial wrinkling and the presence of basal cell carcinoma. Author(s): Brooke RC, Newbold SA, Telfer NR, Griffiths CE. Source: Archives of Dermatology. 2001 June; 137(6): 751-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11405765&dopt=Abstract

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Discriminating basal cell carcinoma from its surrounding tissue by Raman spectroscopy. Author(s): Nijssen A, Bakker Schut TC, Heule F, Caspers PJ, Hayes DP, Neumann MH, Puppels GJ. Source: The Journal of Investigative Dermatology. 2002 July; 119(1): 64-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12164926&dopt=Abstract

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Disseminated basal cell carcinoma. Author(s): Tuncel A, Adanali G, Senen D, Erdogan B. Source: Plastic and Reconstructive Surgery. 2003 February; 111(2): 949-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12560736&dopt=Abstract

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DNA ploidy and cyclin D1 expression in basal cell carcinoma of the head and neck. Author(s): Staibano S, Lo Muzio L, Pannone G, Mezza E, Argenziano G, Vetrani A, Lucariello A, Franco R, Errico ME, De Rosa G; Association of Directors of Anatomic and Surgical Pathology. Source: American Journal of Clinical Pathology. 2001 June; 115(6): 805-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11392875&dopt=Abstract

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DNA repair synthesis in fibroblast strains from patients with actinic keratosis, squamous cell carcinoma, basal cell carcinoma, or malignant melanoma after treatment with ultraviolet light, N-acetoxy-2-acetyl-aminofluorene, methyl methanesulfonate, and N-methyl-N-nitrosourea. Author(s): Thielmann HW, Edler L, Burkhardt MR, Jung EG. Source: Journal of Cancer Research and Clinical Oncology. 1987; 113(2): 171-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3558453&dopt=Abstract

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Does having basal cell carcinoma increase a person's risk of melanoma? Author(s): Strayer SM. Source: Health News. 2003 August; 9(8): 12. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12971322&dopt=Abstract

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Does wound healing contribute to the eradication of basal cell carcinoma following curettage and electrodessication? Author(s): Nouri K, Spencer JM, Taylor JR, Hayag M, DeVoursney J, Shah N. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 1999 March; 25(3): 183-7; Discussion 187-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10193964&dopt=Abstract

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Downregulation of expression of a novel cadherin molecule, T-cadherin, in basal cell carcinoma of the skin. Author(s): Takeuchi T, Liang SB, Ohtsuki Y. Source: Molecular Carcinogenesis. 2002 December; 35(4): 173-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12489108&dopt=Abstract

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Efficacy of topical 5% imiquimod cream for the treatment of nodular basal cell carcinoma: comparison of dosing regimens. Author(s): Shumack S, Robinson J, Kossard S, Golitz L, Greenway H, Schroeter A, Andres K, Amies M, Owens M. Source: Archives of Dermatology. 2002 September; 138(9): 1165-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12224977&dopt=Abstract

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Eosinophilic pustular folliculitis in association with nevoid basal cell carcinoma syndrome. Author(s): Kishimoto S, Yamamoto M, Nomiyama T, Kawa K, Takenaka H, Tukitani K. Source: Acta Dermato-Venereologica. 2001 June-July; 81(3): 202-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11558878&dopt=Abstract

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Epidemiology of basal cell carcinoma and squamous cell carcinoma of the pinna. Author(s): Ahmad I, Das Gupta AR. Source: The Journal of Laryngology and Otology. 2001 February; 115(2): 85-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11320842&dopt=Abstract

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Epidemiology of basal cell carcinoma of the eyelid in south-western Finland. Author(s): Saari KM, Paavilainen V, Tuominen J, Collan Y. Source: Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Fur Klinische Und Experimentelle Ophthalmologie. 2001 March; 239(3): 230-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11405074&dopt=Abstract

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Evidence that superficial basal cell carcinoma is monoclonal from analysis of the Ptch1 gene locus. Author(s): Saldanha G, Shaw JA, Fletcher A. Source: The British Journal of Dermatology. 2002 November; 147(5): 931-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12410703&dopt=Abstract

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Evidence-based review of the use of cryosurgery in treatment of basal cell carcinoma. Author(s): Kokoszka A, Scheinfeld N. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 2003 June; 29(6): 566-71. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12786697&dopt=Abstract

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Excision of head and neck basal cell carcinoma with a rapid, cross-sectional, frozensection technique. Author(s): Bentkover SH, Grande DM, Soto H, Kozlicak BA, Guillaume D, Girouard S. Source: Archives of Facial Plastic Surgery : Official Publication for the American Academy of Facial Plastic and Reconstructive Surgery, Inc. and the International Federation of Facial Plastic Surgery Societies. 2002 April-June; 4(2): 114-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12020207&dopt=Abstract

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Excision vs Mohs surgery for basal cell carcinoma. Author(s): Otley CC. Source: Archives of Facial Plastic Surgery : Official Publication for the American Academy of Facial Plastic and Reconstructive Surgery, Inc. and the International Federation of Facial Plastic Surgery Societies. 2003 March-April; 5(2): 203. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12633217&dopt=Abstract

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Expansion of microvascular bed and increased solute flux in human Basal cell carcinoma in vivo, measured by fluorescein video angiography. Author(s): Stanton AW, Drysdale SB, Patel R, Mellor RH, Duff MJ, Levick JR, Mortimer PS. Source: Cancer Research. 2003 July 15; 63(14): 3969-79. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873993&dopt=Abstract

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Expression of 92-kDa type IV collagenase mRNA by eosinophils associated with basal cell carcinoma. Author(s): Stahle-Backdahl M, Sudbeck BD, Eisen AZ, Welgus HG, Parks WC. Source: The Journal of Investigative Dermatology. 1992 October; 99(4): 497-503. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1402008&dopt=Abstract

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Expression of a sonic hedgehog signal transducer, hedgehog-interacting protein, by human basal cell carcinoma. Author(s): Tojo M, Kiyosawa H, Iwatsuki K, Kaneko F. Source: The British Journal of Dermatology. 2002 January; 146(1): 69-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11841368&dopt=Abstract

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Expression of Basigin in human fetal, infantile and adult skin and in basal cell carcinoma. Author(s): Chen X, Kanekura T, Kanzaki T. Source: Journal of Cutaneous Pathology. 2001 April; 28(4): 184-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11426825&dopt=Abstract

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Expression of beta-catenin in basal cell carcinoma. Author(s): El-Bahrawy M, El-Masry N, Alison M, Poulsom R, Fallowfield M. Source: The British Journal of Dermatology. 2003 May; 148(5): 964-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12786827&dopt=Abstract

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Expression of CD40 and Fas ligand in Bowen's disease, squamous cell carcinoma and basal cell carcinoma. Author(s): Jang TJ. Source: Yonsei Medical Journal. 2002 June; 43(3): 304-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12089736&dopt=Abstract

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Expression of human lymphocyte antigen (HLA)-DR on tumor cells in basal cell carcinoma. Author(s): Kohchiyama A, Oka D, Ueki H. Source: Journal of the American Academy of Dermatology. 1987 April; 16(4): 833-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2952686&dopt=Abstract

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Expression of the GLI2 oncogene and its isoforms in human basal cell carcinoma. Author(s): Tojo M, Kiyosawa H, Iwatsuki K, Nakamura K, Kaneko F. Source: The British Journal of Dermatology. 2003 May; 148(5): 892-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12786818&dopt=Abstract

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Expression of vascular endothelial growth factor in basal cell carcinoma and cutaneous squamous cell carcinoma of the head and neck. Author(s): Bowden J, Brennan PA, Umar T, Cronin A. Source: Journal of Cutaneous Pathology. 2002 November; 29(10): 585-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12453295&dopt=Abstract

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Extensive cerebral invasion of a basal cell carcinoma of the scalp. Author(s): Schroeder M, Kestlmeier R, Schlegel J, Trappe AE. Source: European Journal of Surgical Oncology : the Journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2001 August; 27(5): 510-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11504526&dopt=Abstract

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Extensive morphea-form basal cell carcinoma invasion of the iris and the orbital contents. Author(s): Barsky D, Vasileff WJ. Source: Henry Ford Hosp Med J. 1987; 35(1): 71-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3679886&dopt=Abstract

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Eyewear, cataracts, and periorbital basal cell carcinoma. Author(s): Sherertz EF, Leshin B, Schappell D. Source: Cutis; Cutaneous Medicine for the Practitioner. 1992 October; 50(4): 312-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1424800&dopt=Abstract

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Facial wrinkling and basal cell carcinoma. Author(s): Corona R. Source: Archives of Dermatology. 2002 February; 138(2): 267-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11843655&dopt=Abstract

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Factors influencing the linear depth of invasion of primary basal cell carcinoma. Author(s): Takenouchi T, Nomoto S, Ito M. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 2001 April; 27(4): 393-6. Erratum In: Dermatol Surg 2001 July; 27(7): 696. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11298714&dopt=Abstract

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Failure of interferon alfa and isotretinoin combination therapy in the nevoid basal cell carcinoma syndrome. Author(s): Sollitto RB, DiGiovanna JJ. Source: Archives of Dermatology. 1996 January; 132(1): 94-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8546496&dopt=Abstract

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Familial subconjunctival epithelial cysts associated with the nevoid basal cell carcinoma syndrome. Author(s): Levine DJ, Robertson DB, Varma VA. Source: Archives of Dermatology. 1987 January; 123(1): 23-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3800416&dopt=Abstract

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Fas ligand downregulation with antisense oligonucleotides in cells and in cultured tissues of normal skin epidermis and basal cell carcinoma. Author(s): Ji J, Wernli M, Buechner S, Erb P. Source: The Journal of Investigative Dermatology. 2003 June; 120(6): 1094-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12787140&dopt=Abstract

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Fatal outcome in a metatypical, giant, “horrifying” basal cell carcinoma. Author(s): Bianchini R, Wolter M. Source: J Dermatol Surg Oncol. 1987 May; 13(5): 556-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3571694&dopt=Abstract

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Females vastly outnumber males in basal cell carcinoma of the upper lip. A peculiar subset of high risk young females is described. Author(s): Rowe D, Gallagher RP, Warshawski L, Carruthers A. Source: J Dermatol Surg Oncol. 1994 November; 20(11): 754-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7962937&dopt=Abstract

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Fetal rhabdomyoma and nevoid basal cell carcinoma syndrome. Author(s): DiSanto S, Abt AB, Boal DK, Krummel TM. Source: Pediatr Pathol. 1992 May-June; 12(3): 441-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1409143&dopt=Abstract

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Fibroepithelioma of Pinkus. Eccrine duct spread of basal cell carcinoma. Author(s): Stern JB, Haupt HM, Smith RR. Source: The American Journal of Dermatopathology. 1994 December; 16(6): 585-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7864295&dopt=Abstract

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Fibroepithelioma of Pinkus: eccrine duct spread of basal cell carcinoma. Author(s): Sina B, Kauffman CL. Source: The American Journal of Dermatopathology. 1995 December; 17(6): 634-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8599483&dopt=Abstract

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Fine mapping of the locus for nevoid basal cell carcinoma syndrome on chromosome 9q. Author(s): Unden AB, Stahle-Backdahl M, Holmberg E, Larsson C, Toftgard R. Source: Acta Dermato-Venereologica. 1997 January; 77(1): 4-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9059667&dopt=Abstract

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Fine needle aspiration cytology of basal cell carcinoma of the skin: a clinical and cytopathological appraisal. Author(s): Fang X, Ma B. Source: The Journal of Dermatology. 1999 October; 26(10): 640-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10554429&dopt=Abstract

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Five-year results of Mohs' micrographic surgery for aggressive facial basal cell carcinoma in Sweden. Author(s): Wennberg AM, Larko O, Stenquist B. Source: Acta Dermato-Venereologica. 1999 September; 79(5): 370-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10494714&dopt=Abstract

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Fluorescence contrast and threshold limit: implications for photodynamic diagnosis of basal cell carcinoma. Author(s): Ericson MB, Sandberg C, Gudmundson F, Rosen A, Larko O, Wennberg AM. Source: Journal of Photochemistry and Photobiology. B, Biology. 2003 February; 69(2): 121-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12633984&dopt=Abstract

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Follicular differentiation in basal cell carcinoma and the trend to designate benign or questionable lesions as malignant. Author(s): Rapini RP. Source: Journal of the American Academy of Dermatology. 2002 November; 47(5): 792-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12399779&dopt=Abstract

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Fractional cryosurgery. A new technique for basal cell carcinoma of the eyelids and periorbital area. Author(s): Goncalves JC. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 1997 June; 23(6): 475-81. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9217800&dopt=Abstract

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Frequency of facial basal cell carcinoma does not correlate with site-specific UV exposure. Author(s): Heckmann M, Zogelmeier F, Konz B. Source: Archives of Dermatology. 2002 November; 138(11): 1494-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12437456&dopt=Abstract

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Frequent p53 accumulation in the chronically sun-exposed epidermis and clonal expansion of p53 mutant cells in the epidermis adjacent to basal cell carcinoma. Author(s): Urano Y, Asano T, Yoshimoto K, Iwahana H, Kubo Y, Kato S, Sasaki S, Takeuchi N, Uchida N, Nakanishi H, et al. Source: The Journal of Investigative Dermatology. 1995 June; 104(6): 928-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7769260&dopt=Abstract

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Full-face carbon dioxide laser resurfacing in the management of a patient with the nevoid basal cell carcinoma syndrome. Author(s): Doctoroff A, Oberlender SA, Purcell SM. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 2003 December; 29(12): 1236-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14725671&dopt=Abstract

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Further evidence for an association of HLA-DR7 with basal cell carcinoma on the tropical island of Saba. Author(s): Bavinck JN, Bastiaens MT, Marugg ME, Beckers RC, Westendorp RG, Vermeer BJ, Claas FH. Source: Archives of Dermatology. 2000 August; 136(8): 1019-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10926738&dopt=Abstract

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Gene expression of matrix metalloproteinase-1 (interstitial collagenase) and matrix metalloproteinase-3 (stromelysin-1) in basal cell carcinoma by in situ hybridization using chondroitin ABC lyase. Author(s): Tsukifuji R, Sakai Y, Hatamochi A, Shinkai H. Source: The Histochemical Journal. 1997 May; 29(5): 401-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9184854&dopt=Abstract

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Genetic analysis of a trichoepithelioma and associated basal cell carcinoma. Author(s): Boni R, Fogt F, Vortmeyer AO, Tronic BS, Zhuang Z. Source: Archives of Dermatology. 1998 September; 134(9): 1170-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9762048&dopt=Abstract

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Genetic determinants of basal cell carcinoma risk. Author(s): Epstein E Jr. Source: Medical and Pediatric Oncology. 2001 May; 36(5): 555-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11340611&dopt=Abstract

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Genetic factors determining cutaneous basal cell carcinoma phenotype. Author(s): Ramachandran S, Fryer AA, Strange RC. Source: Medical and Pediatric Oncology. 2001 May; 36(5): 559-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11340612&dopt=Abstract

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Germline mutations of the PTCH gene in Japanese patients with nevoid basal cell carcinoma syndrome. Author(s): Minami M, Urano Y, Ishigami T, Tsuda H, Kusaka J, Arase S. Source: Journal of Dermatological Science. 2001 September; 27(1): 21-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11457640&dopt=Abstract

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Giant basal cell carcinoma affecting the lower abdominal, genital and bilateral inguinal regions. Author(s): Kikuchi M, Yano K, Kubo T, Hosokawa K, Yamaguchi Y, Itami S. Source: British Journal of Plastic Surgery. 2002 July; 55(5): 445-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12372380&dopt=Abstract

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Giant basal cell carcinoma and cigarette smoking. Author(s): Smith JB, Randle HW. Source: Cutis; Cutaneous Medicine for the Practitioner. 2001 January; 67(1): 73-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11204609&dopt=Abstract

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Giant basal cell carcinoma associated with systemic amyloidosis. Author(s): Yamamoto S, Johno M, Kayashima K, Matsunaga W, Ono T. Source: The Journal of Dermatology. 1996 May; 23(5): 329-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8675823&dopt=Abstract

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Giant basal cell carcinoma. Author(s): Piteiro AB, Perez-Espana L, Hervella M, Casado M. Source: The Journal of Dermatology. 2003 July; 30(7): 573-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12928553&dopt=Abstract

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Giant basal cell carcinoma: a series of seven T3 tumors without metastasis. Author(s): Manstein CH, Gottlieb N, Manstein ME, Manstein G. Source: Plastic and Reconstructive Surgery. 2000 September; 106(3): 653-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10987474&dopt=Abstract

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Giant basal cell carcinoma: improvement in the quality of life after extensive resection. Author(s): Takemoto S, Fukamizu H, Yamanaka K, Nakayama T, Kora Y, Mineta H. Source: Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery / Nordisk Plastikkirurgisk Forening [and] Nordisk Klubb for Handkirurgi. 2003; 37(3): 181-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12841621&dopt=Abstract

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Giant exophytic basal cell carcinoma treated with radiotherapy. Author(s): Rossi R, Campolmi P, Giomi B, Massi D, Cappugi P. Source: Journal of the European Academy of Dermatology and Venereology : Jeadv. 2002 July; 16(4): 374-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12224695&dopt=Abstract

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Giant polypoid basal cell carcinoma. Author(s): McElroy J, Knight TE, Chang-Stroman L. Source: Cutis; Cutaneous Medicine for the Practitioner. 1996 October; 58(4): 289-92. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8894428&dopt=Abstract

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Granular cell basal cell carcinoma of the skin. Report of a case with immunocytochemical positivity for lysozyme. Author(s): Boscaino A, Tornillo L, Orabona P, Staibano S, Gentile R, De Rosa G. Source: Tumori. 1997 May-June; 83(3): 712-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9267494&dopt=Abstract

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Granular cell basal cell carcinoma. Author(s): Mrak RE, Baker GF. Source: Journal of Cutaneous Pathology. 1987 February; 14(1): 37-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3558915&dopt=Abstract

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Granular cell basal cell carcinoma. Author(s): Reichel M. Source: Cutis; Cutaneous Medicine for the Practitioner. 1997 February; 59(2): 88-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9040978&dopt=Abstract

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Growth characteristics and differentiation of basal cell carcinoma in vitro-immunohistochemical, gel electrophoretic, and ultrastructural analysis. Author(s): Asada M, Schaart FM, Detmar M, Mischke D, de Almeida HL Jr, Gollnick H, Orfanos CE. Source: The Journal of Investigative Dermatology. 1992 October; 99(4): 474-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1383350&dopt=Abstract

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Guess what! Diagnosis: Extended ulcerating metatypical basal cell carcinoma (BCC) with soft tissue and bone destruction. Author(s): Hirschsteiner O, Maiwald G, Balda BR. Source: European Journal of Dermatology : Ejd. 2000 June; 10(4): 315-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10939863&dopt=Abstract

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Guess what! Superficial basal cell carcinoma of the scrotum. Author(s): Vandeweyer E, De Dobbeleer G, Van Geertruyden J. Source: European Journal of Dermatology : Ejd. 1999 April-May; 9(3): 237-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10408920&dopt=Abstract

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Guidelines of care for basal cell carcinoma. The American Academy of Dermatology Committee on Guidelines of Care. Author(s): Drake LA, Ceilley RI, Cornelison RL, Dobes WA, Dorner W, Goltz RW, Lewis CW, Salasche SJ, Turner ML, Graham GF, et al. Source: Journal of the American Academy of Dermatology. 1992 January; 26(1): 117-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1732317&dopt=Abstract

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Head and neck basal cell carcinoma: treatment using a 2-mm clinical excision margin. Author(s): Lalloo MT, Sood S. Source: Clinical Otolaryngology and Allied Sciences. 2000 October; 25(5): 370-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11012649&dopt=Abstract

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Heat shock protein HSP 27 is expressed in all types of basal cell carcinoma in low and high risk UV exposure groups. Author(s): Bayerl C, Dorfner B, Rzany B, Fuhrmann E, Coelho CC, Jung EG. Source: European Journal of Dermatology : Ejd. 1999 June; 9(4): 281-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10356405&dopt=Abstract

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Hemidesmosomes, collagen VII, and intermediate filaments in basal cell carcinoma. Author(s): Jones JC, Steinman HK, Goldsmith BA. Source: The Journal of Investigative Dermatology. 1989 November; 93(5): 662-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2477465&dopt=Abstract

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Hereditary factors in basal cell carcinoma of the skin: a population-based cohort study in twins. Author(s): Milan T, Kaprio J, Verkasalo PK, Jansen CT, Teppo L, Koskenvuo M. Source: British Journal of Cancer. 1998 December; 78(11): 1516-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9836487&dopt=Abstract

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Hereditary factors in basal cell carcinoma of the skin: a population-based cohort study in twins. Author(s): Bataille V, Snieder H, MacGregor A, Spector T. Source: British Journal of Cancer. 2000 January; 82(1): 247-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10638998&dopt=Abstract

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High frequency of loss of heterozygosity on chromosome region 9p21-p22 but lack of p16INK4a/p19ARF mutations in greek patients with basal cell carcinoma of the skin. Author(s): Saridaki Z, Koumantaki E, Liloglou T, Sourvinos G, Papadopoulos O, Zoras O, Spandidos DA. Source: The Journal of Investigative Dermatology. 2000 October; 115(4): 719-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10998150&dopt=Abstract

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Histologic cure of basal cell carcinoma treated with cryosurgery. Author(s): Giuffrida TJ, Jimenez G, Nouri K. Source: Journal of the American Academy of Dermatology. 2003 September; 49(3): 483-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12963913&dopt=Abstract

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Histologic evolution of basal cell carcinoma recurrence. Author(s): Dixon AY, Lee SH, McGregor DH. Source: The American Journal of Dermatopathology. 1991 June; 13(3): 241-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1867354&dopt=Abstract

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Histologic features predictive of basal cell carcinoma recurrence: results of a multivariate analysis. Author(s): Dixon AY, Lee SH, McGregor DH. Source: Journal of Cutaneous Pathology. 1993 April; 20(2): 137-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8320358&dopt=Abstract

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Histologic pattern analysis of basal cell carcinoma. Study of a series of 1039 consecutive neoplasms. Author(s): Sexton M, Jones DB, Maloney ME. Source: Journal of the American Academy of Dermatology. 1990 December; 23(6 Pt 1): 1118-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2273112&dopt=Abstract

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Histologic patterns of basal cell carcinoma based upon patient immunostatus. Author(s): Oram Y, Orengo I, Griego RD, Rosen T, Thornby J. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 1995 July; 21(7): 611-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7606372&dopt=Abstract

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Histology of basal cell carcinoma. Author(s): Maloney ME. Source: Clinics in Dermatology. 1995 November-December; 13(6): 545-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8882765&dopt=Abstract

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Histopathologic considerations in the management of basal cell carcinoma. Author(s): Metcalf JS, Maize JC. Source: Semin Dermatol. 1989 December; 8(4): 259-65. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2701714&dopt=Abstract

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Host-related and environmental risk factors for cutaneous basal cell carcinoma: evidence from an Italian case-control study. Author(s): Naldi L, DiLandro A, D'Avanzo B, Parazzini F. Source: Journal of the American Academy of Dermatology. 2000 March; 42(3): 446-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10688715&dopt=Abstract

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H-ras-1 gene mutations in basal cell carcinoma: automated direct sequencing of clinical specimens. Author(s): Wilke WW, Robinson RA, Kennard CD. Source: Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc. 1993 January; 6(1): 15-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8426854&dopt=Abstract

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Human cadaveric allograft for repair of nasal defects after extirpation of Basal cell carcinoma by Mohs micrographic surgery. Author(s): Carucci JA, Kolenik SA 3rd, Leffell DJ. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 2002 April; 28(4): 340-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11966793&dopt=Abstract

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Human GLI2 and GLI1 are part of a positive feedback mechanism in Basal Cell Carcinoma. Author(s): Regl G, Neill GW, Eichberger T, Kasper M, Ikram MS, Koller J, Hintner H, Quinn AG, Frischauf AM, Aberger F. Source: Oncogene. 2002 August 15; 21(36): 5529-39. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12165851&dopt=Abstract

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Human papillomavirus type 2-associated basal cell carcinoma in two immunosuppressed patients. Author(s): Obalek S, Favre M, Jablonska S, Szymanczyk J, Orth G. Source: Archives of Dermatology. 1988 June; 124(6): 930-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2837152&dopt=Abstract

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Human patched (PTCH) mRNA is overexpressed consistently in tumor cells of both familial and sporadic basal cell carcinoma. Author(s): Unden AB, Zaphiropoulos PG, Bruce K, Toftgard R, Stahle-Backdahl M. Source: Cancer Research. 1997 June 15; 57(12): 2336-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9192803&dopt=Abstract

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Hypercalcaemia and elevated levels of parathyroid hormone-related protein in cutaneous squamous/basal cell carcinoma. Author(s): Marino MT, Asp AA, Budayer AA, Marsden JS, Strewler GJ. Source: Journal of Internal Medicine. 1993 February; 233(2): 205-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8433083&dopt=Abstract

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Identification of a small molecule inhibitor of the hedgehog signaling pathway: effects on basal cell carcinoma-like lesions. Author(s): Williams JA, Guicherit OM, Zaharian BI, Xu Y, Chai L, Wichterle H, Kon C, Gatchalian C, Porter JA, Rubin LL, Wang FY. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 April 15; 100(8): 4616-21. Epub 2003 Apr 04. Erratum In: Proc Natl Acad Sci U S A. 2003 July 8; 100(14): 8607. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12679522&dopt=Abstract

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Imiquimod 5% cream for the treatment of superficial and nodular basal cell carcinoma: randomized studies comparing low-frequency dosing with and without occlusion. Author(s): Sterry W, Ruzicka T, Herrera E, Takwale A, Bichel J, Andres K, Ding L, Thissen MR. Source: The British Journal of Dermatology. 2002 December; 147(6): 1227-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12452875&dopt=Abstract

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Imiquimod 5% cream for the treatment of superficial basal cell carcinoma: a doubleblind, randomized, vehicle-controlled study. Author(s): Geisse JK, Rich P, Pandya A, Gross K, Andres K, Ginkel A, Owens M. Source: Journal of the American Academy of Dermatology. 2002 September; 47(3): 390-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12196749&dopt=Abstract

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Imiquimod 5% cream: a new treatment option for basal cell carcinoma. Author(s): Salasche S. Source: International Journal of Dermatology. 2002 May; 41 Suppl 1: 16-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12087814&dopt=Abstract

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Immunochemical determination of an initial step in thymine dimer excision repair in xeroderma pigmentosum variant fibroblasts and biopsy material from the normal population and patients with basal cell carcinoma and melanoma. Author(s): Roth M, Muller H, Boyle JM. Source: Carcinogenesis. 1987 September; 8(9): 1301-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3304692&dopt=Abstract

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Immunohistochemical study of angiotensin receptors in human anagen hair follicles and basal cell carcinoma. Author(s): Takeda H, Katagata Y, Kondo S. Source: The British Journal of Dermatology. 2002 August; 147(2): 276-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12174099&dopt=Abstract

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Immunohistochemical study of nerve fibres in basal cell carcinoma. Author(s): Panuncio A, Vignale R, Lopez G. Source: European Journal of Dermatology : Ejd. 2003 May-June; 13(3): 250-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12804983&dopt=Abstract

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Immunotherapy of basal cell carcinoma: evolving approaches. Author(s): Gaspari AA, Sauder DN. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 2003 October; 29(10): 1027-34. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12974699&dopt=Abstract

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Implant prosthodontic rehabilitation of a patient with nevoid basal cell carcinoma syndrome: a clinical report. Author(s): Markt JC. Source: The Journal of Prosthetic Dentistry. 2003 May; 89(5): 436-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12806318&dopt=Abstract

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Incomplete excision of basal cell carcinoma. Author(s): Malhotra R, Kaines A, Davis G. Source: Anz Journal of Surgery. 2003 June; 73(6): 460. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12801349&dopt=Abstract

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Incomplete excision of basal cell carcinoma: a prospective multicentre audit. Author(s): Kumar P, Watson S, Brain AN, Davenport PJ, McWilliam LJ, Banerjee SS, Bisset DL. Source: British Journal of Plastic Surgery. 2002 December; 55(8): 616-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12550113&dopt=Abstract

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Increased dermal mast cell prevalence and susceptibility to development of basal cell carcinoma in humans. Author(s): Grimbaldeston MA, Skov L, Finlay-Jones JJ, Hart PH. Source: Methods (San Diego, Calif.). 2002 September; 28(1): 90-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12231192&dopt=Abstract

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Inguinal keratotic Basal cell carcinoma mimicking giant solitary trichoepithelioma. Author(s): Sahin MT, Demir MA, Kaya Y, Can M, Inanir I, Ozturkcan S. Source: The Journal of Dermatology. 2003 May; 30(5): 395-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12773805&dopt=Abstract

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Intake of alcohol and alcoholic beverages and the risk of basal cell carcinoma of the skin. Author(s): Fung TT, Hunter DJ, Spiegelman D, Colditz GA, Rimm EB, Willett WC. Source: Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 2002 October; 11(10 Pt 1): 1119-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12376519&dopt=Abstract

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Interobserver agreement on dermoscopic features of pigmented basal cell carcinoma. Author(s): Peris K, Altobelli E, Ferrari A, Fargnoli MC, Piccolo D, Esposito M, Chimenti S. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 2002 July; 28(7): 643-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12135528&dopt=Abstract

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Interventions for basal cell carcinoma of the skin. Author(s): Bath FJ, Bong J, Perkins W, Williams HC. Source: Cochrane Database Syst Rev. 2003; (2): Cd003412. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12804465&dopt=Abstract

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Intralesional interferon therapy for basal cell carcinoma. Author(s): Epstein E. Source: Journal of the American Academy of Dermatology. 1992 January; 26(1): 142-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1732331&dopt=Abstract

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Intralesional recombinant interferon beta-1a in the treatment of basal cell carcinoma: results of an open-label multicentre study. Author(s): Kowalzick L, Rogozinski T, Wimheuer R, Pilz J, Manske U, Scholz A, Fierlbeck G, Mohr P, Ochsendorf F, Wagner G, Gaus W, Brzoska J, Jablonska S. Source: European Journal of Dermatology : Ejd. 2002 November-December; 12(6): 55861. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12459527&dopt=Abstract

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Invade or proliferate? Two contrasting events in malignant behavior governed by p16(INK4a) and an intact Rb pathway illustrated by a model system of basal cell carcinoma. Author(s): Svensson S, Nilsson K, Ringberg A, Landberg G. Source: Cancer Research. 2003 April 15; 63(8): 1737-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12702553&dopt=Abstract

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Invasive basal cell carcinoma with secondary giant mucocele formation. Author(s): Jinkins JR. Source: Neuroradiology. 1987; 29(2): 211. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3587598&dopt=Abstract

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Juvenile basal cell carcinoma. Author(s): Price MA, Goldberg LH, Levy ML. Source: Pediatric Dermatology. 1994 June; 11(2): 176-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8041662&dopt=Abstract

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Juvenile basal cell carcinoma. Author(s): Cullen KW, Bleach NR, Green DM. Source: Br J Clin Pract. 1989 November; 43(11): 419-20. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2611101&dopt=Abstract

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Karyometric study of basal cell carcinoma. Author(s): Sala MA, Komesu MC, Lopes RA, Maia Campos G. Source: Brazilian Dental Journal. 1994; 5(1): 11-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7833637&dopt=Abstract

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Kayser-Fleischer rings in a patient with basal cell carcinoma: fortuitous diagnosis of presymptomatic Wilson's disease. Author(s): Brodland DG, Bartley GB. Source: Mayo Clinic Proceedings. 1992 February; 67(2): 142-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1545578&dopt=Abstract

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Keloidal basal cell carcinoma. A new clinicopathological variant of basal cell carcinoma. Author(s): Requena L, Martin L, Farina MC, Pique E, Escalonilla P. Source: The British Journal of Dermatology. 1996 May; 134(5): 953-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8736345&dopt=Abstract

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Keratotic basal cell carcinoma of the upper eyelid. Author(s): Foley P, Mason G. Source: The Australasian Journal of Dermatology. 1995 May; 36(2): 95-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7646397&dopt=Abstract

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Keratotic basal cell carcinoma of the upper gingiva with cervical lymph node metastasis: report of a case. Author(s): Nishimura N, Sakurai K, Noguchi K, Urade M. Source: Journal of Oral and Maxillofacial Surgery : Official Journal of the American Association of Oral and Maxillofacial Surgeons. 2001 June; 59(6): 677-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11381394&dopt=Abstract

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Lack of selectivity of protoporphyrin IX fluorescence for basal cell carcinoma after topical application of 5-aminolevulinic acid: implications for photodynamic treatment. Author(s): Martin A, Tope WD, Grevelink JM, Starr JC, Fewkes JL, Flotte TJ, Deutsch TF, Anderson RR. Source: Archives of Dermatological Research. 1995; 287(7): 665-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8534131&dopt=Abstract

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Lamin expression in normal human skin, actinic keratosis, squamous cell carcinoma and basal cell carcinoma. Author(s): Tilli CM, Ramaekers FC, Broers JL, Hutchison CJ, Neumann HA. Source: The British Journal of Dermatology. 2003 January; 148(1): 102-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12534602&dopt=Abstract

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Langerhans' cell histiocytosis arising at the site of basal cell carcinoma excision. Author(s): Simonart T, Urbain F, Verdebout JM, Feoli F, Lespagnard L, Dargent JL. Source: Journal of Cutaneous Pathology. 2000 October; 27(9): 476-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11028820&dopt=Abstract

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Large basal cell carcinoma in a black patient. Author(s): Frank W, Morris D. Source: Plastic and Reconstructive Surgery. 1995 August; 96(2): 493-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7624434&dopt=Abstract

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Laser microsurgery for superficial T1-T2 basal cell carcinoma of the eyelid margins. Author(s): Bandieramonte G, Lepera P, Moglia D, Bono A, De Vecchi C, Milani F. Source: Ophthalmology. 1997 July; 104(7): 1179-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9224473&dopt=Abstract

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Lifestyle differences in twin pairs discordant for basal cell carcinoma of the skin. Author(s): Milan T, Verkasalo PK, Kaprio J, Koskenvuo M. Source: The British Journal of Dermatology. 2003 July; 149(1): 115-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12890204&dopt=Abstract

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Light microscopy: clues to systemic disease in reexcision specimens of basal cell carcinoma. Author(s): LeBoit PE, Davis-Reed L. Source: The American Journal of Dermatopathology. 1999 August; 21(4): 361-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10446778&dopt=Abstract

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Linear basal cell carcinoma. Author(s): da Silva MO, Dadalt P, Santos OL, Ishida CE, Sodre CT, Maceira JP. Source: International Journal of Dermatology. 1995 July; 34(7): 488. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7591413&dopt=Abstract

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Linear basal cell carcinoma: report of seventeen cases and review of the presentation and treatment. Author(s): Lim KK, Randle HW, Roenigk RK, Brodland DG, Bernstein SC, Marcil I. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 1999 January; 25(1): 63-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9935098&dopt=Abstract

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Lipid profile in actinic keratosis and basal cell carcinoma. Author(s): Vural P, Canbaz M, Sekcuki D, Murat A. Source: International Journal of Dermatology. 1999 June; 38(6): 439-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10397583&dopt=Abstract

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Local recurrence of basal cell carcinoma and cisplatinum containing chemotherapy. Author(s): Moeholt K, Pfeiffer P, Aagaard H, Hansen O. Source: Acta Oncologica (Stockholm, Sweden). 1997; 36(1): 87. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9090976&dopt=Abstract

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Long-term follow-up of cryosurgery of basal cell carcinoma of the eyelid. Author(s): Lindgren G, Larko O. Source: Journal of the American Academy of Dermatology. 1997 May; 36(5 Pt 1): 742-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9146537&dopt=Abstract

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Long-term results after surgical basal cell carcinoma excision in the eyelid region. Author(s): Pieh S, Kuchar A, Novak P, Kunstfeld R, Nagel G, Steinkogler FJ. Source: The British Journal of Ophthalmology. 1999 January; 83(1): 85-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10209442&dopt=Abstract

72

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Long-term therapy with low-dose isotretinoin for prevention of basal cell carcinoma: a multicenter clinical trial. Isotretinoin-Basal Cell Carcinoma Study Group. Author(s): Tangrea JA, Edwards BK, Taylor PR, Hartman AM, Peck GL, Salasche SJ, Menon PA, Benson PM, Mellette JR, Guill MA, et al. Source: Journal of the National Cancer Institute. 1992 March 4; 84(5): 328-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1738183&dopt=Abstract

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Loss of protein kinase Calpha expression may enhance the tumorigenic potential of Gli1 in basal cell carcinoma. Author(s): Neill GW, Ghali LR, Green JL, Ikram MS, Philpott MP, Quinn AG. Source: Cancer Research. 2003 August 1; 63(15): 4692-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12907651&dopt=Abstract

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Low DNA repair is a risk factor in skin carcinogenesis: a study of basal cell carcinoma in psoriasis patients. Author(s): Dybdahl M, Frentz G, Vogel U, Wallin H, Nexo BA. Source: Mutation Research. 1999 January 26; 433(1): 15-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10047775&dopt=Abstract

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Low frequency of loss of heterozygosity at the nevoid basal cell carcinoma locus and other selected loci in appendageal tumors. Author(s): Takata M, Quinn AG, Hashimoto K, Rees JL. Source: The Journal of Investigative Dermatology. 1996 May; 106(5): 1141-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8618054&dopt=Abstract

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Management of periocular basal cell carcinoma with modified en face frozen section controlled excision. Author(s): Wong VA, Marshall JA, Whitehead KJ, Williamson RM, Sullivan TJ. Source: Ophthalmic Plastic and Reconstructive Surgery. 2002 November; 18(6): 430-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12439056&dopt=Abstract

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Mast cells in basal cell carcinoma express VEGF, IL-8 and RANTES. Author(s): Aoki M, Pawankar R, Niimi Y, Kawana S. Source: International Archives of Allergy and Immunology. 2003 March; 130(3): 216-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12660426&dopt=Abstract

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Mechanisms underlying imiquimod-induced regression of basal cell carcinoma in vivo. Author(s): Urosevic M, Maier T, Benninghoff B, Slade H, Burg G, Dummer R. Source: Archives of Dermatology. 2003 October; 139(10): 1325-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14568837&dopt=Abstract

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Medulloblastoma with extensive nodularity in nevoid basal cell carcinoma syndrome. Author(s): Aliani S, Brunner J, Graf N, Altmeyer K, Niedermayer I, Strowitzki M. Source: Medical and Pediatric Oncology. 2003 April; 40(4): 266-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12555262&dopt=Abstract

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Metastatic basal cell carcinoma presenting as unilateral axillary lymphadenopathy: report of a case and review of the literature. Author(s): Berlin JM, Warner MR, Bailin PL. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 2002 November; 28(11): 1082-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12460309&dopt=Abstract

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Metastatic basal cell carcinoma. Author(s): Spates ST, Mellette JR Jr, Fitzpatrick J. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 2003 June; 29(6): 650-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12786712&dopt=Abstract

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Molecular basis of basal cell carcinoma: analysis of differential gene expression by differential display PCR and expression array. Author(s): Welss T, Papoutsaki M, Michel G, Reifenberger J, Chimenti S, Ruzicka T, Abts HF. Source: International Journal of Cancer. Journal International Du Cancer. 2003 March 10; 104(1): 66-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12532421&dopt=Abstract

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Multiple pigmented basal cell carcinomas arising in the normal-appearing skin after radiotherapy for carcinoma of the cervix. Author(s): Handa Y, Miwa S, Yamada M, Ono H, Suzuki T, Tomita Y. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 2003 December; 29(12): 1233-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14725670&dopt=Abstract

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Multiple single nucleotide polymorphisms on human chromosome 19q13.2-3 associate with risk of Basal cell carcinoma. Author(s): Yin J, Rockenbauer E, Hedayati M, Jacobsen NR, Vogel U, Grossman L, Bolund L, Nexo BA. 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): 1449-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12433725&dopt=Abstract

74

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Mutations in the human homologue of Drosophila patched in Japanese nevoid basal cell carcinoma syndrome patients. Author(s): Fujii K, Kohno Y, Sugita K, Nakamura M, Moroi Y, Urabe K, Furue M, Yamada M, Miyashita T. Source: Human Mutation. 2003 April; 21(4): 451-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12655573&dopt=Abstract

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Nevoid basal cell carcinoma syndrome - clinical manifestations and mutation analysis of a Taiwanese family. Author(s): Chung CH, Wong TY, Shieh TY, Shieh DB, Chao SC. Source: J Formos Med Assoc. 2003 November; 102(11): 793-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14724726&dopt=Abstract

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Nevoid basal cell carcinoma syndrome associated with lymphomatoid papulosis. Author(s): Anderson BE, Helm KF. Source: Dermatology (Basel, Switzerland). 2003; 207(1): 86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12835561&dopt=Abstract

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Nevoid basal cell carcinoma syndrome in a person with dark skin. Author(s): Kulkarni P, Brashear R, Chuang TY. Source: Journal of the American Academy of Dermatology. 2003 August; 49(2): 332-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12894092&dopt=Abstract

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Nevoid basal cell carcinoma syndrome with medulloblastoma in an AfricanAmerican boy: a rare case illustrating gene-environment interaction. Author(s): Korczak JF, Brahim JS, DiGiovanna JJ, Kase RG, Wexler LH, Goldstein AM. Source: American Journal of Medical Genetics. 1997 March 31; 69(3): 309-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9096762&dopt=Abstract

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Nevoid basal cell carcinoma syndrome. A case report. Author(s): Piattelli A. Source: Acta Stomatol Belg. 1991 December; 88(4): 171-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1822063&dopt=Abstract

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Nevoid basal cell carcinoma syndrome: relation with desmoplastic medulloblastoma in infancy. A population-based study and review of the literature. Author(s): Amlashi SF, Riffaud L, Brassier G, Morandi X. Source: Cancer. 2003 August 1; 98(3): 618-24. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12879481&dopt=Abstract

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No evidence of mutation in the human PTC gene, responsible for nevoid basal cell carcinoma syndrome, in human primary squamous cell carcinomas of the esophagus and lung. Author(s): Suzuki K, Daigo Y, Fukuda S, Tokino T, Isomura M, Isono K, Wainwright B, Nakamura Y. Source: Japanese Journal of Cancer Research : Gann. 1997 March; 88(3): 225-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9140104&dopt=Abstract

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Nonhealing leg ulcers: a manifestation of basal cell carcinoma. Author(s): Goldman MP. Source: Journal of the American Academy of Dermatology. 1992 May; 26(5 Pt 1): 791-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1497723&dopt=Abstract

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Noninvasive imaging, treatment, and microscopic confirmation of clearance of basal cell carcinoma. Author(s): Goldgeier M, Fox CA, Zavislan JM, Harris D, Gonzalez S. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 2003 March; 29(3): 205-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12614409&dopt=Abstract

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Nucleolar organizer regions in aggressive and nonaggressive basal cell carcinoma of the skin. Author(s): De Rosa G, Staibano S, Barra E, Zeppa P, Salvatore G, Vetrani A, Palombini L. Source: Cancer. 1992 January 1; 69(1): 123-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1727656&dopt=Abstract

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Occult basal cell carcinoma arising in seborrheic keratosis. Author(s): ENdoh K, Ohara M, Kosegawa G, Akasaka T. Source: The Journal of Dermatology. 1998 June; 25(6): 374-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9675344&dopt=Abstract

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Occurrence of basal cell carcinoma among multiple trichoepitheliomas. Author(s): Johnson SC, Bennett RG. Source: Journal of the American Academy of Dermatology. 1993 February; 28(2 Pt 2): 322-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8436650&dopt=Abstract

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Occurrence of other malignancies in 1973 patients with basal cell carcinoma. Author(s): Lindelof B, Sigurgeirsson B, Wallberg P, Eklund G. Source: Journal of the American Academy of Dermatology. 1991 August; 25(2 Pt 1): 2458. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1918460&dopt=Abstract

76

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Odontogenic keratocysts in a 5-year-old: initial manifestations of nevoid basal cell carcinoma syndrome. Author(s): Dowling PA, Fleming P, Saunders ID, Gorlin RJ, Napier SS. Source: Pediatr Dent. 2000 January-February; 22(1): 53-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10730288&dopt=Abstract

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On rugged shape of skin tumor (basal cell carcinoma). Author(s): Tohya S, Mochizuki A, Imayama S, Iwasa Y. Source: Journal of Theoretical Biology. 1998 September 7; 194(1): 65-78. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9778425&dopt=Abstract

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One-stage arm-preserving shoulder resection with latissimus dorsi flap for basal cell carcinoma. Author(s): Craig DM, Sullivan PK, Herndon JH, Edstrom LE. Source: Annals of Plastic Surgery. 1988 February; 20(2): 158-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3355064&dopt=Abstract

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Ophthalmic manifestation of metastatic basal cell carcinoma. Author(s): Snead JW, Comer JR, Kalemeris GC, Tsakalakis PJ. Source: Ophthalmic Plastic and Reconstructive Surgery. 1989; 5(1): 56-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2487198&dopt=Abstract

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Otolaryngology quiz #6. Basal cell carcinoma. Author(s): Nishioka GJ, Renner GP, Zitsch RP 3rd. Source: Mo Med. 1995 July; 92(7): 327-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7651309&dopt=Abstract

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Overexpression of interleukin-6 in human basal cell carcinoma cell lines increases anti-apoptotic activity and tumorigenic potency. Author(s): Jee SH, Shen SC, Chiu HC, Tsai WL, Kuo ML. Source: Oncogene. 2001 January 11; 20(2): 198-208. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11313947&dopt=Abstract

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Overexpression of the human homologue of Drosophila patched (PTCH) in skin tumours: specificity for basal cell carcinoma. Author(s): Nagano T, Bito T, Kallassy M, Nakazawa H, Ichihashi M, Ueda M. Source: The British Journal of Dermatology. 1999 February; 140(2): 287-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10233224&dopt=Abstract

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Parasitism of basal cell carcinoma by lentigo maligna melanoma. Author(s): Wang H, Benda PM, Piepkorn MW. Source: Journal of the American Academy of Dermatology. 2003 May; 48(5 Suppl): S924. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734489&dopt=Abstract

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Permanent improvement of renal dysfunction and proteinuria with colchicine in a patient with tumoral amyloidosis and basal cell carcinoma. Author(s): Balal M, Seyrek N, Karayaylali I, Paydas S. Source: Renal Failure. 2003 July; 25(4): 677-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12911175&dopt=Abstract

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Photodynamic therapy using topical methyl aminolevulinate vs surgery for nodular basal cell carcinoma: results of a multicenter randomized prospective trial. Author(s): Rhodes LE, de Rie M, Enstrom Y, Groves R, Morken T, Goulden V, Wong GA, Grob JJ, Varma S, Wolf P. Source: Archives of Dermatology. 2004 January; 140(1): 17-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14732655&dopt=Abstract

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Pigmented basal cell carcinoma simulating melanoma in a burn scar. Author(s): White EA, Rabinovitz HS, Greene RS, Oliviero M, Kopf A. Source: Cutis; Cutaneous Medicine for the Practitioner. 2003 May; 71(5): 404-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12769409&dopt=Abstract

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Pomade crust on the scalp mimicking recurrent basal cell carcinoma. Author(s): Bechara FG, Rotterdam S, Hoffmann K, Altmeyer P, Stucker M, Jansen T. Source: Dermatology Nursing / Dermatology Nurses' Association. 2003 October; 15(5): 426-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14619319&dopt=Abstract

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Positive margins in basal cell carcinoma: relationship to clinical features and recurrence risk. A retrospective study of 248 patients. Author(s): Nagore E, Grau C, Molinero J, Fortea JM. Source: Journal of the European Academy of Dermatology and Venereology : Jeadv. 2003 March; 17(2): 167-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12705745&dopt=Abstract

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Positron emission tomography for basal cell carcinoma of the head and neck. Author(s): Fosko SW, Hu W, Cook TF, Lowe VJ. Source: Archives of Dermatology. 2003 September; 139(9): 1141-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12975155&dopt=Abstract

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Predictive variables for the biological behaviour of basal cell carcinoma of the face: relevance of morphometry of the nuclei. Author(s): Appel T, Bierhoff E, Appel K, von Lindern JJ, Berge S, Niederhagen B. Source: The British Journal of Oral & Maxillofacial Surgery. 2003 June; 41(3): 147-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12804537&dopt=Abstract

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Primary ovarian leiomyosarcoma as a new component in the nevoid basal cell carcinoma syndrome: a case report. Author(s): Seracchioli R, Colombo FM, Bagnoli A, Trengia V, Venturoli S. Source: American Journal of Obstetrics and Gynecology. 2003 April; 188(4): 1093-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12712116&dopt=Abstract

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Prognostic value of Ki-67, CD31 and epidermal growth factor receptor expression in basal cell carcinoma. Author(s): Yerebakan O, Ciftcioglu MA, Akkaya BK, Yilmaz E. Source: The Journal of Dermatology. 2003 January; 30(1): 33-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12598707&dopt=Abstract

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Quantitative and 3-dimensional analysis of Langerhans cells in basal cell carcinoma. A comparative study using light microscopy and confocal laser scanning microscopy. Author(s): Bergfelt L, Emilson A, Lindberg M, Scheynius A. Source: The British Journal of Dermatology. 1994 March; 130(3): 273-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7511926&dopt=Abstract

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Quantitative assessment of Langerhans cells in actinic keratosis, Bowen's disease, keratoacanthoma, squamous cell carcinoma and basal cell carcinoma. Author(s): McArdle JP, Knight BA, Halliday GM, Muller HK, Rowden G. Source: Pathology. 1986 April; 18(2): 212-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3763243&dopt=Abstract

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Rare presentations of basal cell carcinoma. Author(s): Nouri K, Romanelli P, Trent JT, Javid R, Jimenez G. Source: Journal of Cutaneous Medicine and Surgery. 2002 May-June; 6(3): 226-8. Epub 2002 April 15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11951127&dopt=Abstract

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Re: relationship between sunlight exposure and a key genetic alteration in basal cell carcinoma. Author(s): Lear JT, Strange RC, Fryer AA. Source: Journal of the National Cancer Institute. 1997 March 19; 89(6): 454-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9091648&dopt=Abstract

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Real-time, in vivo confocal reflectance microscopy of basal cell carcinoma. Author(s): Gonzalez S, Tannous Z. Source: Journal of the American Academy of Dermatology. 2002 December; 47(6): 86974. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12451371&dopt=Abstract

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Reconstruction of a perianal defect after basal cell carcinoma using bilateral V-Y advancement fasciocutaneous flaps. Author(s): Ruiz-de-Erenchun R, Rodriguez N, Hernandez JL, Garcia-Tutor E. Source: Plastic and Reconstructive Surgery. 2003 March; 111(3): 1360-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12621218&dopt=Abstract

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Recurrent basal cell carcinoma causing spinal cord compression. Author(s): Fogarty GB, Ainslie J. Source: Anz Journal of Surgery. 2001 February; 71(2): 129-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11413595&dopt=Abstract

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Recurrent basal cell carcinoma in margin-positive tumors. Author(s): Friedman HI, Williams T, Zamora S, al-Assaad ZA. Source: Annals of Plastic Surgery. 1997 March; 38(3): 232-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9088460&dopt=Abstract

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Recurrent morphoeic basal cell carcinoma at the lateral canthus with orbitocranial invasion. Author(s): Selva D, Hale L, Bouskill K, Huilgol SC. Source: The Australasian Journal of Dermatology. 2003 May; 44(2): 126-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12752187&dopt=Abstract

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Risk factors for basal cell carcinoma in a Mediterranean population: role of recreational sun exposure early in life. Author(s): Corona R, Dogliotti E, D'Errico M, Sera F, Iavarone I, Baliva G, Chinni LM, Gobello T, Mazzanti C, Puddu P, Pasquini P. Source: Archives of Dermatology. 2001 September; 137(9): 1162-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11559211&dopt=Abstract

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Risk of developing another basal cell carcinoma. A 5-year prospective study. Author(s): Robinson JK. Source: Cancer. 1987 July 1; 60(1): 118-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3581025&dopt=Abstract

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Role of PTCH and p53 genes in early-onset basal cell carcinoma. Author(s): Zhang H, Ping XL, Lee PK, Wu XL, Yao YJ, Zhang MJ, Silvers DN, Ratner D, Malhotra R, Peacocke M, Tsou HC. Source: American Journal of Pathology. 2001 February; 158(2): 381-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11159175&dopt=Abstract

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Sebaceous hyperplasia and basal cell carcinoma in a renal transplant patient receiving cyclosporine. Author(s): Pakula A, Garden J. Source: Journal of the American Academy of Dermatology. 1992 January; 26(1): 139-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1732329&dopt=Abstract

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Subungual basal cell carcinoma versus acral lentiginous melanoma. Author(s): Mehregan AH. Source: Journal of the American Academy of Dermatology. 1987 September; 17(3): 511-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3655030&dopt=Abstract

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Successful treatment of basal cell carcinoma on the face with imiquimod 5% cream. Author(s): Oster-Schmidt C, Altmeyer P, Stucker M. Source: Acta Dermato-Venereologica. 2002; 82(6): 477. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12575864&dopt=Abstract

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Successful treatment of basal cell carcinomas in a nevoid basal cell carcinoma syndrome with topical 5% imiquimod. Author(s): Stockfleth E, Ulrich C, Hauschild A, Lischner S, Meyer T, Christophers E. Source: European Journal of Dermatology : Ejd. 2002 November-December; 12(6): 56972. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12459530&dopt=Abstract

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Superficial radiotherapy for patients with basal cell carcinoma: recurrence rates, histologic subtypes, and expression of p53 and Bcl-2. Author(s): Zagrodnik B, Kempf W, Seifert B, Muller B, Burg G, Urosevic M, Dummer R. Source: Cancer. 2003 December 15; 98(12): 2708-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14669293&dopt=Abstract

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Superpulsed CO2 laser treatment of basal cell carcinoma with intraoperatory histopathologic and cytologic examination. Author(s): Campolmi P, Brazzini B, Urso C, Ghersetich I, Mavilia L, Hercogova J, Lotti T. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 2002 October; 28(10): 909-11; Discussion 912. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12410674&dopt=Abstract

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Surgery for primary basal cell carcinoma including the eyelid margins with intraoperative frozen section control: comparative interventional study with a minimum clinical follow up of 5 years. Author(s): Conway RM, Themel S, Holbach LM. Source: The British Journal of Ophthalmology. 2004 February; 88(2): 236-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14736782&dopt=Abstract

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Symmetrical retroauricular papules. Basal cell carcinoma. Author(s): Chan LS. Source: Archives of Dermatology. 1992 November; 128(11): 1531-2, 1534-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1444510&dopt=Abstract

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Synchronous basal cell carcinoma and meningioma following cranial irradiation for a pilocytic astrocytoma. Author(s): Jenkinson MD, Javadpour M, du Plessis D, Shaw MD. Source: British Journal of Neurosurgery. 2003 April; 17(2): 182-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12820764&dopt=Abstract

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Syringocystadenoma papilliferum mimicking basal cell carcinoma on the lower eyelid: a case report. Author(s): Askar S, Kilinc N, Aytekin S. Source: Acta Chir Plast. 2002; 44(4): 117-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12661924&dopt=Abstract

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Terahertz pulse imaging of ex vivo basal cell carcinoma. Author(s): Woodward RM, Wallace VP, Pye RJ, Cole BE, Arnone DD, Linfield EH, Pepper M. Source: The Journal of Investigative Dermatology. 2003 January; 120(1): 72-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12535200&dopt=Abstract

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The cutaneous keratocyst: a rare hallmark of the nevoid basal cell carcinoma syndrome. Author(s): Hamel AF, den Dunnen WF, Suurmeijer AJ. Source: International Journal of Surgical Pathology. 2003 January; 11(1): 36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12598917&dopt=Abstract

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The garlic-derived organosulfur component ajoene decreases basal cell carcinoma tumor size by inducing apoptosis. Author(s): Tilli CM, Stavast-Kooy AJ, Vuerstaek JD, Thissen MR, Krekels GA, Ramaekers FC, Neumann HA. Source: Archives of Dermatological Research. 2003 July; 295(3): 117-23. Epub 2003 May 20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12756587&dopt=Abstract

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The incidence of incomplete excision in surgically treated basal cell carcinoma: a retrospective clinical audit. Author(s): Hussain M, Earley MJ. Source: Ir Med J. 2003 January; 96(1): 18-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12617437&dopt=Abstract

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The phosphotidyl inositol 3-kinase/Akt signal pathway is involved in interleukin-6mediated Mcl-1 upregulation and anti-apoptosis activity in basal cell carcinoma cells. Author(s): Jee SH, Chiu HC, Tsai TF, Tsai WL, Liao YH, Chu CY, Kuo ML. Source: The Journal of Investigative Dermatology. 2002 November; 119(5): 1121-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12445202&dopt=Abstract

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The role of interferon alpha 2b as an adjunctive treatment in the management of aggressive basal cell carcinoma of the eyelids. Author(s): Fenton S, Kennedy S, Moriarty P. Source: Acta Ophthalmologica Scandinavica. 2002 December; 80(6): 674-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12485296&dopt=Abstract

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The stretch test in basal cell carcinoma: a clinical indicator of tumour. Author(s): Mellor RH, Bulstrode N, Withey S, Moss AL, Mortimer PS. Source: British Journal of Plastic Surgery. 2002 October; 55(7): 594-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12529007&dopt=Abstract

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Topical 1% cidofovir for the treatment of basal cell carcinoma. Author(s): Calista D. Source: European Journal of Dermatology : Ejd. 2002 November-December; 12(6): 562-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12459528&dopt=Abstract

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Treatment of Bowen's disease and basal cell carcinoma of the nose with imiquimod 5% cream. Author(s): Wu JK, Siller G, Whitehead K. Source: The Australasian Journal of Dermatology. 2003 May; 44(2): 123-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12752186&dopt=Abstract

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Twelve single nucleotide polymorphisms on chromosome 19q13.2-13.3: linkage disequilibria and associations with basal cell carcinoma in Danish psoriatic patients. Author(s): Yin J, Vogel U, Gerdes LU, Dybdahl M, Bolund L, Nexo BA. Source: Biochemical Genetics. 2003 February; 41(1-2): 27-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12645871&dopt=Abstract

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Ultrastructural localization of gap junction protein connexin 43 in normal human skin, basal cell carcinoma, and squamous cell carcinoma. Author(s): Tada J, Hashimoto K. Source: Journal of Cutaneous Pathology. 1997 November; 24(10): 628-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9449490&dopt=Abstract

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Unilateral nevoid basal cell carcinoma syndrome. Author(s): Camisa C. Source: Journal of the American Academy of Dermatology. 1987 June; 16(6): 1270-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3597874&dopt=Abstract

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Urocanic acid isomers in patients with basal cell carcinoma and cutaneous malignant melanoma. Author(s): De Fine Olivarius F, Lock-Andersen J, Larsen FG, Wulf HC, Crosby J, Norval M. Source: The British Journal of Dermatology. 1998 June; 138(6): 986-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9747359&dopt=Abstract

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Use of a combination of chemotherapy and radiation therapy in the management of advanced basal cell carcinoma of the head and neck. Author(s): Robinson JK. Source: Journal of the American Academy of Dermatology. 1987 November; 17(5 Pt 1): 770-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3680656&dopt=Abstract

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Use of a monoclonal antibody (VM-2) plus the immunogold-silver technique to stain basal cell carcinoma cells. Author(s): Morhenn VB, Roth S, Roth R. Source: Journal of the American Academy of Dermatology. 1987 November; 17(5 Pt 1): 765-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2445798&dopt=Abstract

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Use of frozen section analysis in the treatment of basal cell carcinoma. Author(s): Cataldo PA, Stoddard PB, Reed WP. Source: American Journal of Surgery. 1990 June; 159(6): 561-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2349981&dopt=Abstract

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Use of Mohs micrographic surgery to establish quantitative proof of heightened tumor spread in basal cell carcinoma recurrent following radiotherapy. Author(s): Smith SP, Foley EH, Grande DJ. Source: J Dermatol Surg Oncol. 1990 November; 16(11): 1012-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2246406&dopt=Abstract

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Use of recombinant interferon alfa-2b in the treatment of basal cell carcinoma. Author(s): Chimenti S, Peris K, Di Cristofaro S, Fargnoli MC, Torlone G. Source: Dermatology (Basel, Switzerland). 1995; 190(3): 214-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7599384&dopt=Abstract

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UV-radiation-specific p53 mutation frequency in normal skin as a predictor of risk of basal cell carcinoma. Author(s): Ouhtit A, Nakazawa H, Armstrong BK, Kricker A, Tan E, Yamasaki H, English DR. Source: Journal of the National Cancer Institute. 1998 April 1; 90(7): 523-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9539248&dopt=Abstract

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UV-specific p53 and PTCH mutations in sporadic basal cell carcinoma of sun-exposed skin. Author(s): Ratner D, Peacocke M, Zhang H, Ping XL, Tsou HC. Source: Journal of the American Academy of Dermatology. 2001 February; 44(2): 293-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11174390&dopt=Abstract

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Value of p53 protein in biological behavior of basal cell carcinoma and in normal epithelia adjacent to carcinomas. Author(s): Demirkan NC, Colakoglu N, Duzcan E. Source: Pathology Oncology Research : Por. 2000; 6(4): 272-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11173659&dopt=Abstract

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Variable expressivity of the multiple nevoid basal cell carcinoma syndrome. Author(s): Pritchard LJ, Delfino JJ, Ivey DM, Sclaroff A, Giglio JA. Source: Journal of Oral and Maxillofacial Surgery : Official Journal of the American Association of Oral and Maxillofacial Surgeons. 1982 May; 40(5): 261-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6953173&dopt=Abstract

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Vascular expression of matrix metalloproteinase-13 (collagenase-3) in basal cell carcinoma. Author(s): Hattori Y, Nerusu KC, Bhagavathula N, Brennan M, Hattori N, Murphy HS, Su LD, Wang TS, Johnson TM, Varani J. Source: Experimental and Molecular Pathology. 2003 June; 74(3): 230-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12782009&dopt=Abstract

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Vitamin supplementation and reduced risk of basal cell carcinoma. Author(s): Wei Q, Matanoski GM, Farmer ER, Strickland P, Grossman L. Source: Journal of Clinical Epidemiology. 1994 August; 47(8): 829-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7730885&dopt=Abstract

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Vitamins and carotenoids intake and the risk of basal cell carcinoma of the skin in women (United States). Author(s): Fung TT, Hunter DJ, Spiegelman D, Colditz GA, Speizer FE, Willett WC. Source: Cancer Causes & Control : Ccc. 2002 April; 13(3): 221-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12020103&dopt=Abstract

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Volume-weighted mean nuclear volume of basal cell carcinoma and risk of recurrence. Author(s): Fitzgerald DA, Smith AG, Stonier C. Source: Clinical and Experimental Dermatology. 1997 January; 22(1): 64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9330067&dopt=Abstract

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Vulvar basal cell carcinoma. Author(s): Miller ES, Fairley JA, Neuburg M. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 1997 March; 23(3): 207-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9145965&dopt=Abstract

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Vulvar basal cell carcinoma: an infrequently metastasizing neoplasm. Author(s): Perrone T, Twiggs LB, Adcock LL, Dehner LP. Source: International Journal of Gynecological Pathology : Official Journal of the International Society of Gynecological Pathologists. 1987; 6(2): 152-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3692670&dopt=Abstract

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Vulvar basal cell carcinoma: two unusual presentations and review of the literature. Author(s): Mulayim N, Foster Silver D, Tolgay Ocal I, Babalola E. Source: Gynecologic Oncology. 2002 June; 85(3): 532-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12051887&dopt=Abstract

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What causes basal cell carcinoma to be the commonest cancer? Author(s): Gilbody JS, Aitken J, Green A. Source: Aust J Public Health. 1994 June; 18(2): 218-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7948343&dopt=Abstract

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What to do with basal cell carcinoma leftovers. Author(s): Dzubow LM. Source: Journal of the American Academy of Dermatology. 2002 April; 46(4): 639. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11907526&dopt=Abstract

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What's your assessment? Basal cell carcinoma. Author(s): Bielan B. Source: Dermatology Nursing / Dermatology Nurses' Association. 2001 October; 13(5): 364, 372. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11917624&dopt=Abstract

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When to suspect superficial basal cell carcinoma. Author(s): Naik NS, Brodell RT, Fatteh S. Source: Postgraduate Medicine. 1998 November; 104(5): 157-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9823392&dopt=Abstract

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Widespread basal cell carcinoma of the scalp treated by dermabrasion. Author(s): Melandri D, Carruthers A. Source: Journal of the American Academy of Dermatology. 1992 February; 26(2 Pt 1): 270-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1552072&dopt=Abstract

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CHAPTER 2. NUTRITION AND BASAL CELL CARCINOMA Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and basal cell carcinoma.

Finding Nutrition Studies on Basal Cell Carcinoma 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 “basal cell carcinoma” (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 “basal cell carcinoma” (or a synonym): •

Adhesion molecule expression in basal cell carcinoma. Author(s): Department of Dermatology, University Hospital Maastricht, P Debyelaan 25, 6202 AZ Maastricht, The Netherlands. Source: Verhaegh, M Beljaards, R Veraart, J Hoekzema, R Neumann, M Eur-J-Dermatol. 1998 June; 8(4): 252-5 1167-1122

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Basal cell carcinoma in young women: an evaluation of the association of tanning bed use and smoking. Author(s): Department of Medicine (Dermatology), Vanderbilt University, Nashville, TN, USA. Source: Boyd, Alan S Shyr, Yu King, Lloyd E Jr J-Am-Acad-Dermatol. 2002 May; 46(5): 706-9 0190-9622

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Collagenolytic and gelatinolytic matrix metalloproteinases and their inhibitors in basal cell carcinoma of skin: comparison with normal skin. Author(s): Department of Pathology, The University of Michigan Medical School, Ann Arbor 48109, USA. Source: Varani, J Hattori, Y Chi, Y Schmidt, T Perone, P Zeigler, M E Fader, D J Johnson, T M Br-J-Cancer. 2000 February; 82(3): 657-65 0007-0920

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Combined effects of gender, skin type and polymorphic genes on clinical phenotype: use of rate of increase in numbers of basal cell carcinomas as a model system. Author(s): Department of Biochemistry, Good Hope Hospital, Sutton Coldfield, West Midlands B75 7RR, UK. Source: Ramachandran, S Fryer, A A Lovatt, T J Smith, A G Lear, J T Jones, P W Strange, R C Cancer-Lett. 2003 January 28; 189(2): 175-81 0304-3835

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Curcumin induces a p53-dependent apoptosis in human basal cell carcinoma cells. Author(s): Department of Dermatology, College of Medicine, National Taiwan University, Taipei. Source: Jee, S H Shen, S C Tseng, C R Chiu, H C Kuo, M L J-Invest-Dermatol. 1998 October; 111(4): 656-61 0022-202X

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Differential expression of the bcl-2 oncogene in human basal cell carcinoma. Author(s): Central Medical Laboratories, Misericordia General Hospital, Winnipeg, Manitoba, Canada. Source: Crowson, A N Magro, C M Kadin, M E Stranc, M Hum-Pathol. 1996 April; 27(4): 355-9 0046-8177

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Increased concentrations of 3,4-didehydroretinol and retinoic acid-binding protein (CRABPII) in human squamous cell carcinoma and keratoacanthoma but not in basal cell carcinoma of the skin. Author(s): Department of Dermatology, University of Linkoping, Sweden. Source: Vahlquist, A Andersson, E Coble, B I Rollman, O Torma, H J-Invest-Dermatol. 1996 May; 106(5): 1070-4 0022-202X

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Increased expression of stromelysin-3 in basal cell carcinomas. Author(s): Department of Dermatology, University of Michigan, Ann Arbor 48109-0672. Source: Majmudar, G Nelson, B R Jensen, T C Voorhees, J J Johnson, T M Mol-Carcinog. 1994 January; 9(1): 17-23 0899-1987

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Indomethacin in basal cell carcinoma. Source: al Waili, N S J-Pak-Med-Assoc. 1989 May; 39(5): 134-6 0030-9982

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Intake of alcohol and alcoholic beverages and the risk of basal cell carcinoma of the skin. Author(s): Department of Nutrition, Simmons College, Boston, Massachusetts 02115, USA. Source: Fung, T T Hunter, D J Spiegelman, D Colditz, G A Rimm, E B Willett, W C Cancer-Epidemiol-Biomarkers-Prevolume 2002 October; 11(10 Pt 1): 1119-22 1055-9965

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On rugged shape of skin tumor (basal cell carcinoma). Author(s): Department of Biology, Faculty of Science, Kyushu University, Fukuoka 8128581, Japan. Source: Tohya, S Mochizuki, A Imayama, S Iwasa, Y J-Theor-Biol. 1998 September 7; 194(1): 65-78 0022-5193

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Plasma antioxidant defense in actinic keratosis and basal cell carcinoma. Author(s): Department of Biochemistry and Clinical Biochemistry, Istanbul Medical Faculty, Turkey. Source: Vural, P Canbaz, M Selcuki, D J-Eur-Acad-Dermatol-Venereol. 1999 September; 13(2): 96-101 0926-9959

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Prostaglandin E2 signalling pathway in human T lymphocytes from healthy and conjunctiva basal cell carcinoma-bearing subjects. Author(s): Istituto di Patologia Generale, Universita degli Studi di Messina, Policlinico Universitario, Messina, Italy. Source: Venza, I Giordano, L Piraino, G Medici, N Ceci, G Teti, D Immunol-Cell-Biol. 2001 October; 79(5): 482-9 0818-9641

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Relative importance of prior basal cell carcinomas, continuing sun exposure, and circulating T lymphocytes on the development of basal cell carcinoma. Author(s): Department of Dermatology, Northwestern University Medical School, Chicago, Illinois 60611. Source: Robinson, J K Rademaker, A W J-Invest-Dermatol. 1992 August; 99(2): 227-31 0022-202X

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The results of topical application of 13-cis-retinoic acid on basal cell carcinoma. A correlation of the clinical effect with histopathological examination and serum retinol level. Author(s): Department of General and Thoracic Surgery, Institute of Surgery, School of Medicine, Warsaw, Poland. Source: Sankowski, A Janik, P Jeziorska, M Swietochowska, B Ciesla, W Malek, A Przybyszewska, M Neoplasma. 1987; 34(4): 485-9 0028-2685

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Vitamins and carotenoids intake and the risk of basal cell carcinoma of the skin in women (United States). Author(s): Department of Nutrition, Simmons College, Boston, MA 02115, USA. [email protected] Source: Fung, T T Hunter, D J Spiegelman, D Colditz, G A Speizer, F E Willett, W C Cancer-Causes-Control. 2002 April; 13(3): 221-30 0957-5243

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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/

•

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

•

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

•

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

•

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

Nutrition

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The following is a specific Web list relating to basal cell carcinoma; 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: •

Food and Diet Cancer Prevention and Diet Source: Healthnotes, Inc.; www.healthnotes.com

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CHAPTER 3. ALTERNATIVE MEDICINE AND BASAL CELL CARCINOMA Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to basal cell carcinoma. 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 basal cell carcinoma 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 “basal cell carcinoma” (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 basal cell carcinoma: •

A randomized, 12-year primary-prevention trial of beta carotene supplementation for nonmelanoma skin cancer in the physician's health study. Author(s): Frieling UM, Schaumberg DA, Kupper TS, Muntwyler J, Hennekens CH. Source: Archives of Dermatology. 2000 February; 136(2): 179-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10677093&dopt=Abstract

•

Advances in cancer chemotherapy. Author(s): Salem PA. Source: J Med Liban. 1975; 28(1): 9-24. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=54428&dopt=Abstract

•

Apothecary to Mr Harriot. Author(s): Earles MP.

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Source: Pharm Hist (Lond). 2002 March; 32(1): 12-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12004906&dopt=Abstract •

Auto-mohs.com. Author(s): Brown CW Jr, Goldstein GD, Birkby CS. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 2001 November; 27(11): 975-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11737136&dopt=Abstract

•

Basal cell carcinoma in young women: an evaluation of the association of tanning bed use and smoking. Author(s): Boyd AS, Shyr Y, King LE Jr. Source: Journal of the American Academy of Dermatology. 2002 May; 46(5): 706-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12004311&dopt=Abstract

•

Basal cell carcinoma of the earlobe after auricular acupuncture. Author(s): Brouard M, Kaya G, Vecchietti G, Chavaz P, Harms M. Source: Dermatology (Basel, Switzerland). 2002; 204(2): 142-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11937742&dopt=Abstract

•

Basal cell carcinoma on nickel dermatitis after leech applying. Author(s): Shamsaddini S, Dabiri S. Source: East Mediterr Health J. 2000 January; 6(1): 197-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11370335&dopt=Abstract

•

Basal cell carcinoma: seven years' experience at the Institute of Dermatology in Bangkok. Author(s): Nakjang Y, Kullavanijaya P. Source: The Journal of Dermatology. 1994 September; 21(9): 660-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7962970&dopt=Abstract

•

Cancer incidence among Finnish psoriasis patients treated with 8-methoxypsoralen bath PUVA. Author(s): Hannuksela-Svahn A, Pukkala E, Koulu L, Jansen CT, Karvonen J. Source: Journal of the American Academy of Dermatology. 1999 May; 40(5 Pt 1): 694-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10321595&dopt=Abstract

•

Chemoprevention of basal cell carcinomas in the ptc1+/- mouse--green and black tea. Author(s): Hebert JL, Khugyani F, Athar M, Kopelovich L, Epstein EH Jr, Aszterbaum M.

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Source: Skin Pharmacology and Applied Skin Physiology. 2001 November-December; 14(6): 358-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11598435&dopt=Abstract •

Collagenase of human skin basal cell epithelioma. Author(s): Ohyama H, Hashimoto K. Source: Journal of Biochemistry. 1977 July; 82(1): 175-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=19452&dopt=Abstract

•

Collagenolytic enzymes in human neoplasms. Author(s): Dresden MH, Heilman SA, Schmidt JD. Source: Cancer Research. 1972 May; 32(5): 993-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4622841&dopt=Abstract

•

Consequences of using escharotic agents as primary treatment for nonmelanoma skin cancer. Author(s): McDaniel S, Goldman GD. Source: Archives of Dermatology. 2002 December; 138(12): 1593-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12472348&dopt=Abstract

•

Cutaneous diseases of the aged. Author(s): Christianson HB, Applewhite ML. Source: Geriatrics. 1967 November; 22(11): 153-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6054364&dopt=Abstract

•

Cutaneous electrosurgery in a patient with a deep brain stimulator. Author(s): Weaver J, Kim SJ, Lee MH, Torres A. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 1999 May; 25(5): 415-7. Erratum In: Dermatol Surg 1999 October; 25(10): 829. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10469084&dopt=Abstract

•

Diet and basal cell carcinoma of the skin in a prospective cohort of men. Author(s): van Dam RM, Huang Z, Giovannucci E, Rimm EB, Hunter DJ, Colditz GA, Stampfer MJ, Willett WC. Source: The American Journal of Clinical Nutrition. 2000 January; 71(1): 135-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10617958&dopt=Abstract

•

Distribution of 5-aminolevulinic acid-induced porphyrins in noduloulcerative basal cell carcinoma. Author(s): Peng Q, Warloe T, Moan J, Heyerdahl H, Steen HB, Nesland JM, Giercksky KE.

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Source: Photochemistry and Photobiology. 1995 November; 62(5): 906-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8570730&dopt=Abstract •

Effect of collagenolytic activity in basal cell epithelioma of the skin on reconstituted collagen and physical properties and kinetics of the crude enzyme. Author(s): Yamanishi Y, Dabbous MK, Hashimoto K. Source: Cancer Research. 1972 November; 32(11): 2551-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4343237&dopt=Abstract

•

Home treatment of basal cell carcinoma. Author(s): Weedon D, Chick J. Source: The Medical Journal of Australia. 1976 June 12; 1(24): 928. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=979751&dopt=Abstract

•

Metastatic basal cell carcinoma: report of a case responding to chemotherapy. Author(s): Woods RL, Stewart JF. Source: Postgraduate Medical Journal. 1980 April; 56(654): 272-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6159619&dopt=Abstract

•

Nodular basal cell carcinoma in vivo vs in vitro. Establishment of pure cell cultures, cytomorphologic characteristics, ultrastructure, immunophenotype, biosynthetic activities, and generation of antisera. Author(s): Grando SA, Schofield OM, Skubitz AP, Kist DA, Zelickson BD, Zachary CB. Source: Archives of Dermatology. 1996 October; 132(10): 1185-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8859029&dopt=Abstract

•

Photodynamic therapy of superficial basal cell carcinoma with 5-aminolevulinic acid with dimethylsulfoxide and ethylendiaminetetraacetic acid: a comparison of two light sources. Author(s): Soler AM, Angell-Petersen E, Warloe T, Tausjo J, Steen HB, Moan J, Giercksky KE. Source: Photochemistry and Photobiology. 2000 June; 71(6): 724-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10857368&dopt=Abstract

•

Podophyllin-salicylic acid solution in treatment of basal cell carcinomas. Author(s): Nelson LM. Source: Archives of Dermatology. 1966 April; 93(4): 457-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5862640&dopt=Abstract

•

Recurrent basal cell carcinoma of the skin. Author(s): VAN SLOOTEN EA, HAMPE JF, MONTANARI G.

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Source: Arch Chir Neerl. 1958; 10(4): 329-49. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13618157&dopt=Abstract •

Successful treatment of an intractable case of hereditary basal cell carcinoma syndrome with paclitaxel. Author(s): El Sobky RA, Kallab AM, Dainer PM, Jillella AP, Lesher JL Jr. Source: Archives of Dermatology. 2001 June; 137(6): 827-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11405789&dopt=Abstract

•

The garlic-derived organosulfur component ajoene decreases basal cell carcinoma tumor size by inducing apoptosis. Author(s): Tilli CM, Stavast-Kooy AJ, Vuerstaek JD, Thissen MR, Krekels GA, Ramaekers FC, Neumann HA. Source: Archives of Dermatological Research. 2003 July; 295(3): 117-23. Epub 2003 May 20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12756587&dopt=Abstract

•

The histological findings in normal skin and multiple superficial basal cell carcinoma treated with an ointment containing demecolcine. Author(s): JACKSON R. Source: Dermatologica. 1959 July; 119: 20-30. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14406310&dopt=Abstract

•

Treatment of basal cell carcinoma by electrodesiccation and curettage. Author(s): WILLIAMSON GS, JACKSON R. Source: Can Med Assoc J. 1962 May 12; 86: 855-62. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14007244&dopt=Abstract

•

Vitamin supplementation and reduced risk of basal cell carcinoma. Author(s): Wei Q, Matanoski GM, Farmer ER, Strickland P, Grossman L. Source: Journal of Clinical Epidemiology. 1994 August; 47(8): 829-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7730885&dopt=Abstract

•

Vitamins and carotenoids intake and the risk of basal cell carcinoma of the skin in women (United States). Author(s): Fung TT, Hunter DJ, Spiegelman D, Colditz GA, Speizer FE, Willett WC. Source: Cancer Causes & Control : Ccc. 2002 April; 13(3): 221-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12020103&dopt=Abstract

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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/

•

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

•

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

•

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

•

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

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

The following is a specific Web list relating to basal cell carcinoma; 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 Skin Cancer Source: Integrative Medicine Communications; www.drkoop.com

•

Herbs and Supplements Curcuma Alternative names: Turmeric; Curcuma longa L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org

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.

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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. CARCINOMA

CLINICAL

TRIALS

AND

BASAL

CELL

Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning basal cell carcinoma.

Recent Trials on Basal Cell Carcinoma The following is a list of recent trials dedicated to basal cell carcinoma.8 Further information on a trial is available at the Web site indicated. •

Aldara(tm) (Trademark) (Imiquimod) Cream to Treat Basal Cell Carcinoma Condition(s): Basal Cell Carcinoma Study Status: This study is currently recruiting patients. Sponsor(s): Warren G Magnuson Clinical Center (CC) Purpose - Excerpt: This study will evaluate the effectiveness of Aldara(tm) (Trademark) (Imiquimod) Cream in treating basal cell carcinoma (skin cancer). Patients 18 years of age and older with an untreated suspected basal cell carcinoma may be eligible for this study. First Visit: Participants will have a medical history taken. A blood sample will be drawn and a doctor will examine, measure, and photograph the skin lesion. Two punch skin biopsies (surgical removal of a small piece of tissue for microscopic examination), will be taken from the area of the skin cancer, each less than 1/8th inch in diameter. One sample will be examined to confirm the diagnosis of basal cell carcinoma; the other will be sent to a laboratory for special tests that will be compared with another skin sample taken after treatment. In addition, a small amount of tissue will be removed from the area of skin cancer with a very fine needle. Patients will be shown how to apply the study cream and will be given a dosing kit with a supply of cream to take home. The cream contains either Aldara cream or a placebo (look-alike cream with no active ingredient). Treatment Initiation Patients will be randomly assigned to one of four treatment dosing groups. They will apply the cream as instructed in their kit according to one of the following schedules: - Four doses, one dose every 12 hours, twice a day -

8

These are listed at www.ClinicalTrials.gov.

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Four doses, one dose every 24 hours, once a day - Eight doses, one dose every 12 hours, twice a day - Eight doses, one dose every 24 hours, once a day End-of-Treatment Visit Patients will come to the clinic about 24 hours after their last dose for an end-oftreatment visit. A doctor will examine and photograph the skin cancer area. A second punch biopsy and fine needle aspiration will be taken and sent for special tests at a research laboratory. The doctor will then surgically remove the entire skin cancer and send it to a laboratory to be examined for skin cancer cells. Upon starting treatment and at each clinic visit, participants will report any illnesses, side effects, or reactions to the study drug and will be asked about any medications they have taken. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00045851 •

Celecoxib in Preventing Basal Cell Carcinoma in Patients With Basal Cell Nevus Syndrome Condition(s): basal cell carcinoma of the skin Study Status: This study is currently recruiting patients. Sponsor(s): University of California, San Francisco; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development of cancer. The use of celecoxib may be an effective way to prevent the development of basal cell carcinoma. PURPOSE: Randomizedphase II trial to determine the effectiveness of celecoxib in preventing basal cell carcinoma in patients who have basal cell nevus syndrome. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00023621

•

Celecoxib in Preventing Skin Cancer Condition(s): basal cell carcinoma of the skin; squamous cell carcinoma of the skin Study Status: This study is currently recruiting patients. Sponsor(s): Herbert Irving Comprehensive Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Celecoxib may be effective in preventing skin cancer by decreasing redness caused by exposure to ultraviolet light and changing potential skin cancer biomarkers. It is not yet known whether celecoxib is more effective than a placebo in preventing skin cancer. PURPOSE: Randomizedphase II trial to study the effectiveness of celecoxib in preventing skin cancer in participants exposed to ultraviolet light. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00025051

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•

Photodynamic Therapy in Treating Patients With Skin Cancer Condition(s): basal cell carcinoma of the skin; squamous cell carcinoma of the skin Study Status: This study is currently recruiting patients. Sponsor(s): Roswell Park Cancer Institute Purpose - Excerpt: RATIONALE: Photodynamic therapy uses light and drugs that make cancer cells more sensitive to light to kill tumor cells. Photodynamic therapy using aminolevulinic acid cream may be effective in treating patients with skin cancer. PURPOSE: Randomizedphase II trial to study the effectiveness of photodynamic therapy in treating patients with skin cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002963

•

Topical Imiquimod Compared With Surgery in Treating Patients With Basal Cell Skin Cancer Condition(s): basal cell carcinoma of the skin Study Status: This study is currently recruiting patients. Sponsor(s): Cancer Research UK Purpose - Excerpt: RATIONALE: Biological therapies such as imiquimod use different ways to stimulate the immune system and stop cancer cells from growing. It is not yet known if topical imiquimod is more effective than surgery in treating basal cell skin cancer. PURPOSE: Randomizedphase III trial to compare the effectiveness of topical imiquimod with that of surgery in treating patients who have basal cell skin cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00066872

Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “basal cell carcinoma” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical

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trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •

For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/

•

For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html

•

For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/

•

For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm

•

For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm

•

For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm

•

For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp

•

For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm

•

For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/

•

For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm

•

For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm

•

For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm

•

For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm

•

For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm

•

For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials

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CHAPTER 5. PATENTS ON BASAL CELL CARCINOMA 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.9 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 “basal cell carcinoma” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on basal cell carcinoma, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Basal Cell Carcinoma By performing a patent search focusing on basal cell carcinoma, 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 will tell you how to obtain this information later in the chapter. 9Adapted

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

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The following is an example of the type of information that you can expect to obtain from a patent search on basal cell carcinoma: •

Adenocarcinoma cell basement membrane composition Inventor(s): Barsky; Sanford H. (Los Angeles, CA), Sternlicht; Mark (Los Angeles, CA) Assignee(s): The Regents of the University of California (oakland, Ca) Patent Number: 5,643,787 Date filed: January 31, 1995 Abstract: Methods and compositions are provided for the culture of human primary carcinomas and in situ carcinomas. Feeder layers derived from a human parotid basal cell carcinoma, having the HMS-1 phenotype, are able to support the growth of the primary carcinomas, and allow for spheroid formation. Invasion inhibiting factors active against human tumors, derived from HMS-1, are also provided.Human basement membrane and extracellular matrix is provided, produced by a tumorigenic cell line, where the basement membrane and extracellular matrix can be used for the growth of a variety of cells, in culture and in vivo. Other related cell lines are provided, which can serve to evaluate in vivo the response of tumorigenic cells to various agents, including basement membrane and extracellular matrix. The basement membrane and extracellular matrix finds use in allowing the growth of cells in culture and in vivo, particularly cells which are otherwise refractory to xenografting. Excerpt(s): The field of this invention relates to the in vitro culture of human myoepithelial and epithelial cells. Myoepithelial cells are thought to exert important paracrine effects on normal epithelial morphogenesis and mitogenesis in vivo through direct cell-cell interactions and through synthesis of a basement membrane extracellular matrix. Basement membranes are ubiquitous structures which are thought to be synthesized by several normal cell types including epithelial, endothelial, smooth muscle, Schwawn cells, and their derivatives. The transformed malignant counterparts of these latter cells, carcinomas and sarcomas, generally lose their ability to synthesize basement membranes and instead acquire basement membrane-degradative properties via the secretion of different families of proteases including metalloproteinases, serine proteinases and thiol proteinases. Primary human carcinomas and carcinomas in situ also arise in the setting of surrounding myoepithelial cells, therefore it is probable that similar paracrine effects are exerted on carcinoma mitogenesis, morphogenesis, and progression, including tumor invasion and metastasis by these surrounding myoepithelial cells. Studies designed to investigate tumor cell interactions with basement membranes have relied heavily upon utilizing matrix derived from the unusual non-metastasizing Engelbreth-Holm, Swarm ("EHS") tumor. The EHS tumor matrix is rich in laminin, type IV collagen, nidogen and heparin sulfate proteoglycan, as well as the small matrix glycoprotein BM-40. These molecules have been extracted individually and as an unfractionated extract which reconstitutes to form a threedimensional gel ("Matrigel") containing entrapped growth factors. This reconstituted basement membrane has been used extensively to study cellular differentiation, tumor cell invasion, angiogenesis and tumorigenicity. The coinjection of tumor cells and matrigel enables the in vivo growth of several otherwise non-tumorigenic cells and greatly stimulates the growth of a wide variety of primary and established tumor cells of both human and murine origin. However, matrigel has failed to support the growth of many primary human cancers, including prostatic and breast carcinoma. This is

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probably due to the failture of matrigel to recapitulate in vitro the paracrine relationship which exists in vivo. Web site: http://www.delphion.com/details?pn=US05643787__ •

Basal cell carcinoma tumor supressor gene Inventor(s): Bale; Allen E. (Northford, CT), Chenevix-Trench; Georgia (Toowong, AU), Chidambaram; Abirami (Frederick, MD), Christiansen; Jeffrey (Yeronga, AU), Dean; Michael Carlton (Frederick, MD), Gailani; Mae R. (Guilford, CT), Gerrard; Bernard (Frederick, MD), Gillies; Susan Alana (Newfarm, AU), Goldstein; Alisa Miriam (Rockville, MD), Hahn; Heidi Eve (Washington, DC), Holmberg-Lindstrom; Erika (Solna, SE), Leffell; David J. (New Haven, CT), Negus; Kylie (Queenslopes, AU), Pressman; Carol Leah (Houston, TX), Shanley; Susan Mary (Norman Park, AU), Smyth; Ian Mcleod (Fig Tree Pocket, AU), Toftgard; Rune Carl-Magnus (Skarholmen, SE), Unden; Anne Birgitte (Huddinge, SE), Vorechovsky; Igor (Huddinge, SE), Wainwright; Brandon (Bardon, AU), Wicking; Carol (Auchenflower, AU), Zaphiropoulos; Peter G (Tullinge, SE) Assignee(s): The United States of America AS Represented by the Department of Health and (washington, Dc) Patent Number: 6,552,181 Date filed: May 16, 1997 Abstract: This invention provides for a tumor suppressor gene inactivation of which is a causal factor in nevoid basal cell carcinoma syndrome and various sporadic basal cell carcinomas. The NBCCS gene is a homologue of the Drosophila patched (ptc) gene. Excerpt(s): This invention pertains to the field of oncology. In particular, this invention pertains to the discovery of a tumor suppressor gene implicated in the etiology of nevoid basal cell carcinoma syndrome (NBCCS) and various cancers including basal cell carcinomas. Many cancers are believed to result from a series of genetic alterations leading to progressive disordering of normal cellular growth mechanisms (Nowell (1976) Science 194:23, Foulds (1958) J. Chronic Dis. 8:2). In particular, the deletion or multiplication of copies of whole chromosomes or chromosomal segments, or specific regions of the genome are common (see, e.g., Smith et al. (1991) Breast Cancer Res. Treat. 18: Suppl. 1: 5-14; van de Vijer & Nusse (1991) Biochim. Biophys. Acta. 1072: 33-50; Sato et al. (1990) Cancer. Res. 50: 7184-7189). In particular, the amplification and deletion of DNA sequences containing proto-oncogenes and tumor-suppressor genes, respectively, are frequently characteristic of tumorigenesis. Dutrillaux et al. (1990) Cancer Genet. Cytogenet. 49: 203-217. One cancer-related syndrome that appears to have a strong genetic base is the nevoid basal cell carcinoma syndrome (NBCCS). The nevoid basal cell carcinoma syndrome, also known as Gorlin syndrome and the basal cell nevus syndrome, is an autosomal dominant disorder that predisposes to both cancer and developmental defects (Gorlin (1995) Dermatologic Clinics 13: 113-125). Its prevalence has been estimated at 1 per 56,000, and 1-2% of medulloblastomas and 0.5% of basal cell carcinomas (BCCs) are attributable to the syndrome (Springate (1986) J. Pediatr. Surg. 21: 908-910; Evans et al. (1991) British J. Cancer. 64: 959-961). In addition to basal cell carcinomas (BCCs) and medulloblastomas, NBCCS patients are also at an increased risk for ovarian fibromas, meningiomas, fibrosarcomas, rhabdomyosarcomas, cardiac fibromas and ovarian dermoids (Evans et al. (1991) supra., Evans et al. (1993) J. Med. Genet. 30: 460-464; Gorlin (1995) supra.).

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Web site: http://www.delphion.com/details?pn=US06552181__ •

Transgenic mouse model of basal cell carcinoma Inventor(s): Dlugosz; Andrzej A. (Ann Arbor, MI), Hui; Chi-Chung (Toronto, CA) Assignee(s): The Hospital for Sick Children (toronto, Ca), University of Michigan (ann Arbor, Mi) Patent Number: 6,689,937 Date filed: January 11, 2001 Abstract: The present invention provides transgenic non-human animal models of basal cell carcinoma which allows for the characterization of the disease as well as for providing a system for the development and testing of potential treatments. Excerpt(s): The present invention relates to transgenic non-human animal models of basal cell carcinoma. More specifically, the present invention is directed to mouse models of basal cell carcinoma allowing for the characterization of the mechanism of the disease as well as for developing and testing potential treatments. Throughout this application, various references are cited in parentheses to describe more fully the state of the art to which this invention pertains. Full bibliographic information for each citation is found at the end of the specification, immediately preceding the claims. The disclosures of these references are hereby incorporated by reference into the present disclosure. Approximately 1,000,000 epithelial skin cancers are diagnosed in the United States each year.sup.1, and the great majority of these are basal cell carcinomas (BCCs). The pathogenesis of these tumors involves constitutive activation of the Sonic hedgehog (Shh) signaling pathway.sup.2-4. In many BCCs this can be attributed to loss-of-function mutations involving PTCH1.sup.5,6, which encodes a SHH receptor and antagonist. However, the identity of the specific downstream effector in the Shh pathway leading to cancer development remains unknown. Web site: http://www.delphion.com/details?pn=US06689937__

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Treatment of basal cell carcinoma and actinic keratosis employing hyaluronic acid and NSAIDs Inventor(s): Asculai; Samuel Simon (Toronto, CA), Falk; Rudolf Edgar (Toronto, CA) Assignee(s): Hyal Pharmaceutical Corporation (mississauga, Ca) Patent Number: 5,639,738 Date filed: February 21, 1992 Abstract: A method of treating a mammal for a condition of the skin or exposed tissue selected from the group consisting of basal cell carcinoma and actinic keratosis is provided. The method consists essentially of topically administering to the site of the condition, more than once per day over a period of days sufficient to treat the condition, a non-toxic effective dosage amount of a composition consisting essentially of(a) a nonsteroidal anti-inflammatory drug (NSAID) in an amount sufficient to block prostaglandin synthesis,(b) hyaluronic acid or a pharmaceutically acceptable salt thereof in an amount effective to transport said NSAID into the skin or exposed tissue at the site of the condition. The concentration of the hyaluronic add or salt thereof is between 1-3% by weight of the composition. The molecular weight of the hyaluronic acid or salt

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thereof is between 150,000 and 750,000 Daltons. A pharmaceutical excipient suitable for topical application is included. The NSAID in the composition may be diclofenac sodium. Excerpt(s): This invention also relates to formulations suitable for use in such treatments, the use of such formulations in such treatments, methods of such treatment, and the delivery of drugs for such treatments. Basal cell carcinoma is presently treated by surgery. Each lesion, together with all surrounding and underlying tissue (dermis, epidermis, and subdermis), is cut out. In some instances, surgery, while necessary for the patient's welfare, may put the patient at risk in some other respect (for example, a lesion on a patient's temple whose removal (resection) may jeopardize the patient's health). Squamous cell tumours are also treated the same way as are other forms of cancer in the skin and exposed tissue. Furthermore, other conditions and diseases of the skin and exposed tissue are treated the same way or in ways that cause discomfort to the patient, for example melanoma, genital warts, cervical cancer, HPV (Human Papilloma Virus). Actinic keratoses lesion is dealt with similarly. Additionally, liquid nitrogen has been used to remove the lesion. Web site: http://www.delphion.com/details?pn=US05639738__ •

Treatment of basal cell carcinoma with product R, a peptide-nucleic acid preparation Inventor(s): Bregman; William (Miami Beach, FL) Assignee(s): Advanced Viral Research Corp. (hallandale, Fl) Patent Number: 5,902,786 Date filed: April 15, 1997 Abstract: The present invention discloses a method for treating patients having basal cell carcinoma comprising subcutaneous, intralesional or topical administration of Product R, a peptide-nucleic acid preparation. Excerpt(s): This invention relates to a method of treating basal cell carcinoma with Product R by administering subcutaneously and intralesionally Product R to a patient. Basal cell carcinomas are the most common cutaneous neoplasms found in humans. The majority of the 500,000 new cases of nonmelanoma skin cancers each year are basal cell carcinomas. Basal cell carcinomas exist in a variety of clinical and histological forms such as nodular-ulcerative, superficial, pigmented, morphealike, fibroepithelioma and nevoid syndrome. Present treatment methods include various surgical techniques such as electrodesiccation and curettage, excision, cryosurgery and irradiation. Cure rates for the surgical techniques are generally stated to be about 95%. Despite the high cure rates effected by surgical techniques, non-surgical methods of therapy are generally thought to be more desirable. Web site: http://www.delphion.com/details?pn=US05902786__

Patent Applications on Basal Cell Carcinoma As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take 10

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

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several years.) The following patent applications have been filed since December 2000 relating to basal cell carcinoma: •

Basal cell carcinoma tumor suppressor gene Inventor(s): Bale, Allen E.; (Northford, CT), Chenevix-Trench, Georgia; (Toowong, AU), Chidambaram, Abirami; (Frederick, MD), Christiansen, Jeffrey; (Yeronga, AU), Dean, Michael Carlton; (Frederick, MD), Gailani, Mae R.; (Guilford, CT), Gerrard, Bernard; (Frederick, MD), Gillies, Susan Alana; (Newfarm, AU), Goldstein, Alisa Miriam; (Rockville, MD), Hahn, Heidi Eve; (Goettingen, DE), Holmberg-Lindstrom, Erika; (Taby, SE), Leffell, David J.; (New Haven, CT), Negus, Kylie; (Queenslopes, AU), Pressman, Carol Leah; (Houston, TX), Shanley, Susan Mary; (Norman Park, AU), Smyth, Ian McLeod; (Fig Tree Pocket, AU), Toftgard, Rune Carl Magnus; (Skarholmen, SE), Unden, Anne Birgitte; (Djursholm, SE), Vorechovsky, Igor; (Huddinge, SE), Wainwright, Brandon; (Bardon, AU), Wicking, Carol; (Auchenflower, AU), Zaphiropoulos, Peter G.; (Tullinge, SE) Correspondence: Townsend And Townsend And Crew, Llp; Two Embarcadero Center; Eighth Floor; San Francisco; CA; 94111-3834; US Patent Application Number: 20030171566 Date filed: November 22, 2002 Abstract: This invention provides for a tumor suppressor gene inactivation of which is a causal factor in nevoid basal cell carcinoma syndrome and various sporadic basal cell carcinomas. The NBCCS gene is a homologue of the Drosophila patched (ptc) gene. Excerpt(s): This application is a continuation-in-part of U.S. application Ser. No. 60/017,906, filed on May 17, 1996 and U.S. application Ser. No: 60/019765, filed on Jun. 14, 1996, both of which are herein incorporated by reference for all purposes. This invention pertains to the field of oncology. In particular, this invention pertains to the discovery of a tumor suppressor gene implicated in the etiology of nevoid basal cell carcinoma syndrome (NBCCS) and various cancers including basal cell carcinomas. Many cancers are believed to result from a series of genetic alterations leading to progressive disordering of normal cellular growth mechanisms (Nowell (1976) Science 194:23, Foulds (1958) J. Chronic Dis. 8:2). In particular, the deletion or multiplication of copies of whole chromosomes or chromosomal segments, or specific regions of the genome are common (see, e.g., Smith et al. (1991) Breast Cancer Res. Treat. 18: Suppl. 1: 5-14; van de Vijer & Nusse (1991) Biochim. Biophlys. Acta. 1072: 33-50; Sato et al. (1990) Cancer. Res. 50: 7184-7189). In particular, the amplification and deletion of DNA sequences containing proto-oncogenes and tumor-suppressor genes, respectively, are frequently characteristic of tumorigenesis. Dutrillaux et al. (1990) Cancer Genet. Cytogenet. 49: 203-217. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Curcumin and curcuminoid inhibition of angiogenesis Inventor(s): Arbiser, Jack L.; (Atlanta, GA) Correspondence: Patrea L. Pabst; Holland & Knight Llp; Suite 2000, One Atlantic Center; 1201 West Peachtree Street, N.E.; Atlanta; GA; 30309-3400; US Patent Application Number: 20010025034 Date filed: January 18, 2001

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Abstract: Methods for treating diseases or disorders of the skin which are characterized by angiogenesis have been developed using curcumin and curcumin analogs. Based on the results obtained with curcumin, it has been determined that other angiogenesis inhibitors can also be used to treat these skin disorders. It has further been discovered that curcumin acts to inhibit angiogenesis in part by inhibition of basic fibroblast growth factor (bFGF), and thereby provides a means for treating other disorders characterized by elevated levels of bFGF, such as bladder cancer, using curcumin and other analogues which also inhibit bFGF. Representative skin disorders to be treated include the malignant diseases angiosarcoma, hemangioendothelioma, basal cell carcinoma, squamous cell carcinoma, malignant melanoma and Karposi's sarcoma, and the nonmalignant diseases or conditions including psoriasis, lymphangiogenesis, hemangioma of childhood, Sturge-Weber syndrome, verruca vulgaris, neurofibromatosis, tuberous sclerosis, pyogenic granulomas, recessive dystrophic epidermolysis bullosa, venous ulcers, acne, rosacea, eczema, molluscum contagious, seborrheic keratosis, and actinic keratosis. Excerpt(s): The invention is generally in the field of methods of inhibiting angiogenesis, and more specifically is drawn to methods and compositions for inhibiting angiogenesis. Current treatments of cancer and related diseases have limited effectiveness and numerous serious unintended effects. Based primarily on chemical, radiation and surgical therapy, these treatments have progressed only incrementally during more than thirty years of intensive research to discover the origins and devise improved therapies of neoplastic diseases. Current research strategies emphasize the search for effective therapeutic modes with less risk, including the use of natural products and biological agents. This change in emphasis has been stimulated by the fact that many of the consequences, to patients and their offspring, of conventional cancer treatment, including new cancers, mutations and congenital defects, result from their actions on genetic material and mechanisms. Hong et al., J. Natl. Cancer Inst. Monogr. 17:49-53 (1995). Efforts continue to discover the origins of cancer at the genetic level, and correspondingly new treatments, but such interventions also may have serious unanticipated effects. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods and materials for the diagnosis and treatment of sporadic basal cell carcinoma Inventor(s): Altaba, Ariel Ruiz i; (New York, NY) Correspondence: Klauber & Jackson; 411 Hackensack Avenue; Hackensack; NJ; 07601 Patent Application Number: 20030100032 Date filed: April 3, 2001 Abstract: Methods for detection of the onset or presence of sporadic basal cell carcinoma in an animal by measuring for elevated levels of extopic expression of Gli1 in the animal's epidermal tissue sample suspected of harboring sporadic basal cell carcinoma. Excerpt(s): The present invention relates generally to the diagnosis and treatment of pathologies involving tumor formation and neoplasia, and more particularly to the detection of a condition of skin cancer known as sporadic basal cell carcinoma (BCC), and to the identification of relevant therapeutic agents based on their effect on the level of expression and/or activity of the gene Gli1, as well as to the preparation of

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therapeutic compositions and methods of use. Inductive signaling plays a critical role in both normal and disease development as developmental pathways that become unregulated in the adult can lead to abnormal patterning, overproliferation and neoplasia. One signaling pathway that is involved in several patterning events during embryogenesis is that triggered by secreted sonic hedgehog (Shh.sup.1-4). Shh binding to the membrane patched (ptc)-smoothened (smo) receptor complex elicits a cascade of cytoplasmic signal transduction events, including the inhibition of protein kinase A (PKA.sup.5-12) that leads to the transcription of the zinc finger transcription factor gene Gli1.sup.11,13. Gli1 is a proto-oncogene first isolated as an amplified gene in a glioma.sup.14 that can transform fibroblasts in cooperation with EIA.sup.15. Gli1 is a member of a family comprising two other related genes: Gli2 and Gli3.sup.16,17. However, only Gli1 has been shown to be a target of Shh and mimic its effects.sup.13. In Drosophila, hedgehog signaling.sup.18 similarly leads to the action of cubitus interruptus (ci), a Gli homolog that activates transcription of hedgehog-target genes.sup.19-23. One of the processes in which Shh signaling is involved is the differentiation of ventral neural tube cell types acting as a notochord and floor platederived signal.sup.1,4,24-27. Previous work by the applicants herein on the role of sonic hedgehog signaling during neural plate patterning in frog (Xenopus laevis) embryos demonstrated that cells becoming floor plate respond to Shh by expressing Gli1, Pintallavis and HNF-3.beta., critical transcription factors that themselves can induce the differentiation of floor plate cells.sup.13,25,28,29. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Pharmaceutical formulation comprising an immune response modifier Inventor(s): Busch, Terri F.; (St. Paul, MN), Fretland, Mary; (Eagan, MN), Gust-Heiting, Amy L.; (Hudson, WI), Scholz, Matthew T.; (Woodbury, MN), Skwierczynski, Raymond D.; (Oakdale, MN) Correspondence: Attention: Dean A. Ersfeld; Office OF Intellectual Property Counsel; 3M Innovative Properties Company; P.O. Box 33427; ST. Paul; MN; 55133-3427; US Patent Application Number: 20030199538 Date filed: November 27, 2002 Abstract: Pharmaceutical formulations comprising an immune response modifier (IRM) chosen from imidazoquinoline amines, imidazotetrahydroquinoline amines, imidazopyridine amines, 6,7-fused cycloalkylimidazopyridine amines, 1,2-bridged imidazoquinoline amines, thiazolo-quinolineamines, oxazolo-quinolinamines, thiazolopyridinamines, oxazolo-pyridinamines, imidazonaphthyridine amines, tetrahydroimidazonaphthyridine amines, and thiazolonaphthyridine amines; a fatty acid; and a hydrophobic, aprotic component miscible with the fatty acid are useful for the treatment of dermal associated conditions. Novel topical formulations are provided. In one embodiment, the topical formulations are advantageous for treatment of actinic keratosis, postsurgical scars, basal cell carcinoma, atopic dermatitis, and warts. Excerpt(s): This application claims priority to Provisional Patent Application Serial No. 60/340,605, filed Nov. 29, 2001 and Provisional Patent Application Serial No. 60/378,452, filed May 6, 2002. The present invention is directed to pharmaceutical formulations comprising at least one immune response modifier chosen from imidazoquinoline amines, imidazopyridine amines, 6,7-fused cycloalkylimidazopyridine amines, 1,2-bridged imidazoquinoline amines, thiazoloquinoline amines, oxazoloquinoline amines, thiazolopyridine amines,

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oxazolopyridine amines, imidazonaphthyridine amines, imidazotetrahydronaphthyridine amines, and thiazolonaphthyridine amines. Embodiments of the present invention are directed to topical formulations for application to the skin of a mammal. Other embodiments of the present invention are directed to methods for treating dermal diseases. Many imidazoquinoline amine, imidazopyridine amine, 6,7-fused cycloalkylimidazopyridine amine, 1,2-bridged imidazoquinoline amine, thiazoloquinoline amine, oxazoloquinoline amine, thiazolopyridine amine, oxazolopyridine amine, imidazonaphthyridine amine, imidazotetrahydronaphthyridine amine, and thiazolonaphthyridine amine compounds have demonstrated potent immunostimulating, antiviral and antitumor (including anticancer) activity, and have also been shown to be useful as vaccine adjuvants. These compounds are hereinafter collectively referred to as "IRM" (immune response modifier) compounds. One of these IRM compounds, known as imiquimod, has been commercialized in a topical formulation, Aldara.TM., for the treatment of anogenital warts associated with human papillomavirus. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Transgenic animal model of basal cell carcinoma Inventor(s): Dlugosz, Andrzej A.; (Ann Arbor, MI), Hui, Chi-Chung; (Toronto, CA) Correspondence: Myers Bigel Sibley & Sajovec; PO Box 37428; Raleigh; NC; 27627; US Patent Application Number: 20010027566 Date filed: January 11, 2001 Abstract: The present invention provides transgenic non-human animal models of basal cell carcinoma which allows for the characterization of the disease as well as for providing a system for the development and testing of potential treatments. Excerpt(s): This application claims priority from U.S. patent application Ser. No. 60/175,637 filed Jan. 12, 2000. The present invention relates to transgenic non-human animal models of basal cell carcinoma. More specifically, the present invention is directed to mouse models of basal cell carcinoma allowing for the characterization of the mechanism of the disease as well as for developing and testing potential treatments. Throughout this application, various references are cited in parentheses to describe more fully the state of the art to which this invention pertains. Full bibliographic information for each citation is found at the end of the specification, immediately preceding the claims. The disclosures of these references are hereby incorporated by reference into the present disclosure. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Treatment of hyperproliferative, inflammatory and related mucocutaneous disorders using inhibitors of mevalonate synthesis and metabolism Inventor(s): Grayson, Stephen; (San Rafael, CA), Parks, Thomas P.; (San Mateo, CA) Correspondence: Townsend And Townsend And Crew; Two Embarcadero Center; Eighth Floor; San Francisco; CA; 94111-3834; US Patent Application Number: 20020010128 Date filed: April 11, 2001

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Abstract: The present invention provides methods for treating a variety of hyperproliferative and inflammatory mucocutaneous disorders, including, basal cell carcinoma, squamous cell carcinoma, psoriasis and atopic dermatitis, as well as skin irritation and disorders associated with skin aging and skin photodamage using inhibitors of cholesterol metabolism. The present invention further relates to the discovery that the combined use of several inhibitors of cholesterol metabolism produces synergistic effects. Furthermore, the present invention is directed to the use of inhibitors of cholesterol metabolism as excipients to enhance the effects of antiinflammatory drugs. Excerpt(s): This application claims the benefit of U.S. Provisional Patent Application Serial No. 60/197,357, filed Apr. 13, 2000, which is incorporated herein by reference in its entirety for all purposes. Hyperproliferative and inflammatory mucocutaneous disorders affect millions of individuals in the United States every year. Such disorders range from mild to life threatening, and include, for example, skin cancer, atopic dermatitis, psoriasis, and asthma due to the inflammation of the lung mucosa. In addition, extrinsic skin aging can be caused by chronic inflammation and insufficient repair due to repetitive exposures to environmental insults, e.g., ultraviolet radiation. Aging of skin and in particular extrinsic aging can lead to any of a number of skin conditions requiring treatment. While certain treatments have been developed for some of these conditions, the treatments are often ineffective, not tolerated by certain individuals, or associated with one or more side effects that limit their use. With some conditions, no effective treatments exist whatsoever. Clearly, new treatments for hyperproliferative and inflammatory skin disorders are needed. Eczema, also called eczematous dermatitis, is one example of a common inflammatory mucocutaneous disorder. Eczema is a red, itchy, noncontagious inflammation of the skin that may be acute or chronic, with red skin patches, pimples, crusts, or scabs occurring either alone or in combination. The skin may be dry, or it may discharge a watery fluid, resulting in an itching or burning sensation. The affected skin may become infected. The various causes of eczematous dermatitis are classified as either external (irritations, allergic reactions, exposure to certain microorganisms or chemicals, etc.), congenital (inherited predisposition) and environmental (stree, heat, etc.). Eczema may clear for years, only to reappear later at a different site. Eczema can come in any of several forms, including, most commonly, atopic dermatitis. Atopic dermatitis is very common in all parts of the world. This chronically relapsing inflammatory skin disorder affects about ten percent of infants and three percent of the U.S. population overall. The disease can occur at any age, but is most common in infants to young adults (see, Hanifin, J M et al, Arch. Dermatol, 135(12):1551 (1999), the teachings of which are incorporated herein by reference for all purposes). The face is often affected first, then the hands and feet. Sometimes dry red patches appear all over the body. In older children the skin folds are most often affected, especially the elbow creases and behind the knees. In adults the face and hands are more likely to be involved. The condition usually improves in childhood or sometime before the age of 25. Most people with atopic dermatitis have family members with similar problems. Serverity of the disease can be evaluated by an Eczema Area Severity Index (EASI) score (see, Hanifin, J M, et al., Exp. Dermatol., 10(1)11 - 18 (2001), the teachings of which are incorporated herein by reference for all purposes). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Keeping Current In order to stay informed about patents and patent applications dealing with basal cell carcinoma, 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 “basal cell carcinoma” (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 basal cell carcinoma. You can also use this procedure to view pending patent applications concerning basal cell carcinoma. 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 6. BOOKS ON BASAL CELL CARCINOMA Overview This chapter provides bibliographic book references relating to basal cell carcinoma. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on basal cell carcinoma include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.

Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print®). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “basal cell carcinoma” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “basal cell carcinoma” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “basal cell carcinoma” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

Selected abstracts on diagnosis and therapy of basal cell carcinoma of the skin (SuDoc HE 20.3173/3:OT-87/05) by U.S. Dept of Health and Human Services; ISBN: B000102584; http://www.amazon.com/exec/obidos/ASIN/B000102584/icongroupinterna

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Surgery of Basal Cell Carcinoma of the Face by Daniel Marchac; ISBN: 0387180346; http://www.amazon.com/exec/obidos/ASIN/0387180346/icongroupinterna

Chapters on Basal Cell Carcinoma In order to find chapters that specifically relate to basal cell carcinoma, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search

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to book chapters and basal cell carcinoma 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 “basal cell carcinoma” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on basal cell carcinoma: •

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 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.

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Premalignant and Malignant Epithelial Tumors of Mucosa and Skin 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.283-373. 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 premalignant and malignant epithelial tumors of mucosa and skin 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. Introductory sections review the biology of cancer, including the causes of cancer, cancer progression, oncogenes, tumor suppressor genes, biology of metastasis, and how cancer kills; and principles of cancer treatment, including surgical treatment, radiotherapy, chemotherapy, and management of the terminal cancer patient. The authors then discuss premalignant and nonpremalignant conditions, including erythroplakia and leukoplakia, nicotinic stomatitis, smokeless tobacco keratosis,

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submucous fibrosis, verrucous carcinoma, and proliferative verrucous leukoplakia; mucosal squamous cell carcinomas, including diagnostic considerations, and squamous cell carcinoma of the lips, oral tongue, pharyngeal tongue, floor of the mouth, buccal (cheek) mucosa, retromolar trigone, gingival, alveolar ridge, palate, and maxillary sinus, and undifferentiated nasopharyngeal carcinoma; premalignant conditions and malignancies of skin, including actinic keratosis, keratoacanthoma, basal cell carcinoma, squamous cell carcinoma of skin, and Merkel cell tumor; and malignant tumors of adnexal structures, including malignant syringoma (microcystic adnexal carcinoma), ductal eccrine carcinoma, mucinous eccrine carcinoma, pilomatrix carcinoma, and sebaceous carcinoma. For each condition, the authors discuss clinical presentation and pathogenesis, differential diagnosis, diagnostic work-up, histopathology, treatment, and prognosis. Full-color photographs illustrate the chapter. 111 figures. 5 tables. •

Chapter 208: Skin Cancers Source: in Berkow, R., ed. The Merck Manual of Medical Information: Home Edition (online version). Rahway, NJ: Merck and Company, Inc. 2000. 5 p. Contact: Available online from Merck and Company, Inc. (800) 819-9456. Website: www.merck.com/pubs/mmanual_home/contents.htm. Also available from your local book store. PRICE: $29.95 plus shipping. Summary: This chapter provides the general public and people who have skin cancer with information on the symptoms, diagnosis, and treatment of basal and squamous cell carcinoma, melanoma, Kaposi's sarcoma, and Paget's disease. Basal cell carcinoma is a cancer that usually develops on skin surfaces exposed to sunlight. The tumors originate in the lowest layer of the epidermis and begin as very small, shiny, firm, raised growths that enlarge very slowly. These tumors may ulcerate or form scabs in the center. The border of a basal cell carcinoma sometimes looks pearly white. The cancer may alternately bleed and form a scab and heal. Basal cell carcinomas usually do not invade and destroy surrounding tissues. A biopsy can confirm the diagnosis. The cancer can be removed by scraping and burning it with an electric needle or by cutting it out. Squamous cell carcinoma usually develops on sun exposed areas but may grow anywhere on the body. This form of cancer originates in the middle layer of the epidermis and begins as a red area with a scaly, crusted surface that does not heal. Most squamous cell carcinomas affect only the tissue around them, but some may spread to other parts of the body. A biopsy is performed to differentiate squamous cell cancer from similar looking diseases. Treatment is the same as for basal cell carcinoma. Melanoma, a cancer that originates in the pigment producing cells of the skin, can begin as a new, small, pigmented skin growth or can develop from existing pigmented moles. Melanoma spreads rapidly to other parts of the body. A biopsy is performed to confirm the diagnosis. Surgery can remove the entire melanoma, and the cure rate is close to 100 percent if the melanoma has not spread. Chemotherapy is used to treat melanomas that have spread, but the cure rate is low. Kaposi's sarcoma, which originates in the blood vessels, has two forms. One is a disease of the elderly, usually of European, Jewish, or Italian heritage, in whom the cancer grows very slowly and rarely spreads. The second form occurs in children and young men in equatorial Africa and in people with acquired immunodeficiency syndrome. The first form may not need any treatment, while the second has been treated with chemotherapy and interferon alfa. Paget's disease is a rare type of skin cancer that originates in glands in or under the skin. It is treated by surgically removing the growth.

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Lesions of Skin and Mucosa Source: in Miller, R.L., et al. General and Oral Pathology for the Dental Hygienist. St. Louis, MO: Mosby-Year Book, Inc. 1995. p. 267-280. 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 lesions of the skin and mucosa. Topics covered include paraoral skin lesions, including basal cell carcinoma, squamous cell carcinoma, seborrheic keratosis, and nevus; and intraoral skin disease, including lichen planus, pemphigus, pemphigoid, lupus erythematosus, erythema multiforme, contact stomatitis, medication stomatitis, and allergy. The chapter includes a list of learning objectives; illustrative case studies; and recommended readings. 17 figures.

•

Skin Disorders Source: in Mosby 's Patient Teaching Guides. St. Louis, MO: Mosby -Year Book, Inc. 1995. p. 113-33. Contact: Mosby -Year Book, Inc. 11830 Westline Industrial Drive, St. Louis, MO. 63146. ISBN: 0815158629. Summary: This section of Mosby 's Patient Teaching Guides examines the following skin disorders: acne; cystic acne; rosacea; the prevention of skin cancers such as basal cell carcinoma; malignant melanoma; contact dermatitis; atopic dermatitis; psoriasis and etretinate treatment; and scabies. Burn injuries and postoperative wound care at home are also addressed. Each section, where applicable, provides an explanation of the ailment, risk factors, diagnosis and treatment, and prevention tips.

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CHAPTER 7. PERIODICALS AND NEWS ON BASAL CELL CARCINOMA Overview In this chapter, we suggest a number of news sources and present various periodicals that cover basal cell carcinoma.

News Services and Press Releases One of the simplest ways of tracking press releases on basal cell carcinoma 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 “basal cell carcinoma” (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 basal cell carcinoma. 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 “basal cell carcinoma” (or synonyms). The following was recently listed in this archive for basal cell carcinoma: •

Phototherapy for basal cell carcinoma: effective with good cosmetic results Source: Reuters Medical News Date: February 12, 2004

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•

Findings shed light on how imiquimod clears basal cell cancer Source: Reuters Industry Breifing Date: November 07, 2003

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Curis to initiate phase I trial on potential basal cell carcinoma treatment Source: Reuters Industry Breifing Date: September 05, 2001

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Facial wrinkling linked to lower risk of basal cell carcinoma Source: Reuters Medical News Date: July 10, 2001

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Imiquimod cream appears effective in treating superficial basal cell carcinoma Source: Reuters Industry Breifing Date: June 25, 2001

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Imiquimod beneficial for patients with basal cell carcinoma, actinic keratoses Source: Reuters Industry Breifing Date: October 16, 2000

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Therapeutic Radiation Associated With Risk Of Basal Cell Carcinoma Source: Reuters Medical News Date: December 20, 1996

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Sunlight Exposure Not Only Cause Of Basal Cell Cancers: Researchers Discover Key Genetic Alteration Source: Reuters Medical News Date: April 01, 1996

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Incidence Of Basal Cell Carcinoma Increasing In The United States Source: Reuters Medical News Date: March 12, 1996 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

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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 “basal cell carcinoma” (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 “basal cell carcinoma” (or synonyms). If you know the name of a company that is relevant to basal cell carcinoma, 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/. 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 “basal cell carcinoma” (or synonyms).

Academic Periodicals covering Basal Cell Carcinoma Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to basal cell carcinoma. In addition to these sources, you can search for articles covering basal cell carcinoma 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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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 Institute11: •

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

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

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

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

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

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

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

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

11

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

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

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

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

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

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

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

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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

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

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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

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

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

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

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

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

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Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html

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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.12 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:13 •

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

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HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html

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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

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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/

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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

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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html

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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/

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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html

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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

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Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html

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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

12

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). 13 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

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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 Gateway14 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.15 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “basal cell carcinoma” (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 9452 60 942 6 41 10501

HSTAT16 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.17 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.18 Simply search by “basal cell carcinoma” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

14

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.

15

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). 16 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 17 18

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 Biologists19 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.20 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.21 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/.

The Genome Project and Basal Cell Carcinoma In the following section, we will discuss databases and references which relate to the Genome Project and basal cell carcinoma. Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for Biotechnology Information (NCBI).22 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI’s Entrez database of MEDLINE articles and sequence information. 19 Adapted 20

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. 21 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. 22 Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.

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To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “basal cell carcinoma” (or synonyms) into the search box, and click “Submit Search.” If too many results appear, you can narrow the search by adding the word “clinical.” Each report will have additional links to related research and databases. In particular, the option “Database Links” will search across technical databases that offer an abundance of information. The following is an example of the results you can obtain from the OMIM for basal cell carcinoma: •

Basal Cell Carcinoma, Infundibulocystic Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=604451 Genes and Disease (NCBI - Map)

The Genes and Disease database is produced by the National Center for Biotechnology Information of the National Library of Medicine at the National Institutes of Health. This Web site categorizes each disorder by system of the body. Go to http://www.ncbi.nlm.nih.gov/disease/, and browse the system pages to have a full view of important conditions linked to human genes. Since this site is regularly updated, you may wish to revisit it from time to time. The following systems and associated disorders are addressed: •

Cancer: Uncontrolled cell division. Examples: Breast and ovarian cancer, Burkitt lymphoma, chronic myeloid leukemia, colon cancer, lung cancer, malignant melanoma, multiple endocrine neoplasia, neurofibromatosis, p53 tumor suppressor, pancreatic cancer, prostate cancer, Ras oncogene, RB: retinoblastoma, von Hippel-Lindau syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Cancer.html

•

Immune System: Fights invaders. Examples: Asthma, autoimmune polyglandular syndrome, Crohn’s disease, DiGeorge syndrome, familial Mediterranean fever, immunodeficiency with Hyper-IgM, severe combined immunodeficiency. Web site: http://www.ncbi.nlm.nih.gov/disease/Immune.html

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Metabolism: Food and energy. Examples: Adreno-leukodystrophy, atherosclerosis, Best disease, Gaucher disease, glucose galactose malabsorption, gyrate atrophy, juvenile-onset diabetes, obesity, paroxysmal nocturnal hemoglobinuria, phenylketonuria, Refsum disease, Tangier disease, Tay-Sachs disease. Web site: http://www.ncbi.nlm.nih.gov/disease/Metabolism.html

•

Muscle and Bone: Movement and growth. Examples: Duchenne muscular dystrophy, Ellis-van Creveld syndrome, Marfan syndrome, myotonic dystrophy, spinal muscular atrophy. Web site: http://www.ncbi.nlm.nih.gov/disease/Muscle.html

•

Nervous System: Mind and body. Examples: Alzheimer disease, amyotrophic lateral sclerosis, Angelman syndrome, Charcot-Marie-Tooth disease, epilepsy, essential tremor, fragile X syndrome, Friedreich’s ataxia, Huntington disease, Niemann-Pick disease, Parkinson disease, Prader-Willi syndrome, Rett syndrome, spinocerebellar atrophy, Williams syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Brain.html

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•

Signals: Cellular messages. Examples: Ataxia telangiectasia, Cockayne syndrome, glaucoma, male-patterned baldness, SRY: sex determination, tuberous sclerosis, Waardenburg syndrome, Werner syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Signals.html

•

Transporters: Pumps and channels. Examples: Cystic fibrosis, deafness, diastrophic dysplasia, Hemophilia A, long-QT syndrome, Menkes syndrome, Pendred syndrome, polycystic kidney disease, sickle cell anemia, Wilson’s disease, Zellweger syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Transporters.html Entrez

Entrez is a search and retrieval system that integrates several linked databases at the National Center for Biotechnology Information (NCBI). These databases include nucleotide sequences, protein sequences, macromolecular structures, whole genomes, and MEDLINE through PubMed. Entrez provides access to the following databases: •

3D Domains: Domains from Entrez Structure, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

•

Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books

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Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome

•

NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/

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Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide

•

OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM

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PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset

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ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

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Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein

•

PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed

•

Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure

•

Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy

To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=genome, and then

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select the database that you would like to search. The databases available are listed in the drop box next to “Search.” Enter “basal cell carcinoma” (or synonyms) into the search box and click “Go.” Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database23 This online resource has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually limited or completely omitted in existing reference sources due to space limitations of the printed form. At http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html, you can search across syndromes using an alphabetical index. Search by keywords at http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html.

The Genome Database24 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB’s mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of scientific knowledge. Although GDB has historically focused on gene mapping, its focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis. To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “basal cell carcinoma” (or synonyms) into the search box, and review the results. If more than one word is used in the search box, then separate each one with the word “and” or “or” (using “or” might be useful when using synonyms).

23

Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 24 Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.

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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 basal cell carcinoma can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internetbased 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 basal cell carcinoma. 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 basal cell carcinoma. 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 “basal cell carcinoma”:

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Other guides Cancer http://www.nlm.nih.gov/medlineplus/cancer.html Bladder Cancer http://www.nlm.nih.gov/medlineplus/bladdercancer.html Head and Neck Cancer http://www.nlm.nih.gov/medlineplus/headandneckcancer.html Kidney Cancer http://www.nlm.nih.gov/medlineplus/kidneycancer.html Melanoma http://www.nlm.nih.gov/medlineplus/melanoma.html Multiple Myeloma http://www.nlm.nih.gov/medlineplus/multiplemyeloma.html Sun Exposure http://www.nlm.nih.gov/medlineplus/sunexposure.html Vulvar Cancer http://www.nlm.nih.gov/medlineplus/vulvarcancer.html

Within the health topic page dedicated to basal cell carcinoma, the following was listed: •

General/Overviews Skin Cancer http://www.nlm.nih.gov/medlineplus/tutorials/skincancerloader.html Skin Cancer Source: American Academy of Dermatology http://www.skincarephysicians.com/agingskinnet/Cancers.html Skin Cancer: Saving Your Skin from Sun Damage Source: American Academy of Family Physicians http://familydoctor.org/159.xml What Is Nonmelanoma Skin Cancer? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_4_1x_what_is_skin_cancer_51. asp?sitearea=

•

Diagnosis/Symptoms How Is Nonmelanoma Skin Cancer Diagnosed? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_4_3x_how_is_skin_cancer_diag nosed_51.asp?sitearea=cri How Is Nonmelanoma Skin Cancer Staged? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_4_3x_how_is_skin_cancer_stag ed_51.asp?sitearea=&level=

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How to Spot Skin Cancer Source: Skin Cancer Foundation http://www.skincancer.org/self_exam/spot_skin_cancer.html Melanoma: What to Look for Source: Skin Cancer Foundation http://www.skincancer.org/self_exam/look_for.html •

Treatment How Is Nonmelanoma Skin Cancer Treated? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_2_4x_how_is_nonmelanoma_s kin_cancer_treated_51.asp Merkel Cell Carcinoma (PDQ): Treatment Source: National Cancer Institute http://www.cancer.gov/cancerinfo/pdq/treatment/merkelcell/patient/ Skin Cancer (PDQ): Treatment Source: National Cancer Institute http://www.cancer.gov/cancerinfo/pdq/treatment/skin/patient/

•

Specific Conditions/Aspects About Basal Cell Carcinoma Source: Skin Cancer Foundation http://www.skincancer.org/basal/index.php Basic Facts about Actinic Keratoses Source: American Academy of Dermatology http://www.skincarephysicians.com/actinickeratosesnet/basicFacts.htm Golfers and Skin Cancer Source: American Cancer Society http://www.cancer.org/docroot/nws/content/nws_2_1x_golfers_and_skin_cancer .asp Indoor Tanning: All the Dangers of the Outdoor Sun, Including Skin Cancer Source: American Academy of Dermatology http://www.aad.org/PressReleases/indoor.html Merkel Cell Cancer Source: National Cancer Institute http://cis.nci.nih.gov/fact/6_11.htm Skin Cancer Quiz: Test Your Knowledge about Skin Cancer Source: American Academy of Dermatology http://www.aad.org/SkinCancerNews/WhatIsSkinCancer/skinquiz.html Squamous Cell Carcinoma Source: American Academy of Dermatology http://www.aad.org/pamphlets/sqamous.html What Should You Ask Your Physician about Nonmelanoma Skin Cancer? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_4_5x_what_should_you_ask_y

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our_physician_about_skin_cancer_51.asp?sitearea= •

Children ABCDs of Skin Cancer Source: American Academy of Dermatology http://www.aad.org/Kids/skincancer.html Sun Safety Source: Nemours Foundation http://kidshealth.org/parent/firstaid_safe/outdoor/sun_safety.html

•

From the National Institutes of Health What You Need to Know about Skin Cancer Source: National Cancer Institute http://www.cancer.gov/cancerinfo/wyntk/skin

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Latest News Cosmetic Results Good with Skin Cancer Therapy Source: 02/12/2004, Reuters Health http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_16042 .html

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Men Skin Cancer: Men Who Care about Their Skin Protect It Source: American Academy of Family Physicians http://familydoctor.org/615.xml

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Organizations American Academy of Dermatology http://www.aad.org/ American Cancer Society http://www.cancer.org/ American Society for Dermatologic Surgery http://www.asds-net.org/ National Cancer Institute http://www.cancer.gov/ Skin Cancer Foundation http://www.skincancer.org/

•

Pictures/Diagrams What Do Actinic Keratoses Look Like? Source: American Academy of Dermatology http://www.skincarephysicians.com/actinickeratosesnet/lookLike.htm

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Prevention/Screening Can Nonmelanoma Skin Cancer Be Prevented? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_4_2x_can_skin_cancer_be_prev ented_51.asp?sitearea=&level= Safer Sunning in Seven Steps http://www.fda.gov/opacom/lowlit/sunsafty.pdf Skin Cancer (PDQ): Prevention Source: National Cancer Institute http://www.cancer.gov/cancerinfo/pdq/prevention/skin/patient/ Skin Cancer (PDQ): Screening Source: National Cancer Institute http://www.cancer.gov/cancerinfo/pdq/screening/skin/patient/ What Are the Risk Factors for Nonmelanoma Skin Cancer? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_4_2x_what_are_the_risk_factor s_for_skin_cancer_51.asp?sitearea=

•

Research Long-Standing Studies Support UVB Radiation Is a Leading Cause of Skin Cancer Source: American Academy of Dermatology http://www.aad.org/PressReleases/UVBRadiation.html Sunning for Science: The Effects of Common Substances on Sun-Exposed Skin Source: Food and Drug Administration http://www.fda.gov/fdac/features/2002/602_sun.html What's New in Nonmelanoma Skin Cancer Research and Treatment? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_4_6x_whats_new_in_skin_canc er_research_and_treatment_51.asp?sitearea=cri

•

Statistics 2003 Skin Cancer Fact Sheet Source: American Academy of Dermatology http://www.aad.org/SkinCancerNews/WhatIsSkinCancer/SCancerFacts.html Facts and Statistics about Skin Cancer Source: National Center for Chronic Disease Prevention and Health Promotion http://www.cdc.gov/chooseyourcover/skin.htm What Are the Key Statistics for Nonmelanoma Skin Cancer Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_4_1x_what_are_the_key_statist ics_for_skin_cancer_51.asp?sitearea=cri

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Teenagers Skin Cancer: The Burden of Skin Cancer Source: Centers for Disease Control and Prevention http://www.cdc.gov/nccdphp/dash/skincancer/facts.htm Tanning Taboo Source: Nemours Foundation http://kidshealth.org/teen/safety/safebasics/tanning.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 Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on basal cell carcinoma. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •

NBCCS Support Network: For People Living and Coping with Nevoid Basal Cell Carcinoma Syndrome, Their Families, Health Care Professionals, and Others Who Care Source: Burtonsvile, MD: NBCCS Support Network. 2 p. Contact: Available from NBCCS Support Network. 3902 Greencastle Ridge Drive, Number 204, Burtonsville, MD 20866. (800) 264-8099 or (800) 815-4447. PRICE: Single copy free. Summary: This brochure describes the NBCCS Support Network, an organization formed to address the medical and psychosocial concerns of persons with nevoid basal cell carcinoma syndrome (NBCCS). The brochure first describes NBCCS and its treatments, then explains the NBCCS mission statement and how the Support Network operates. The brochure also includes a information form with which readers can get on the NBCCS mailing list, as well as a list of the NBCCS Support Network's medical advisory board members. A toll-free telephone number is also provided.

•

Basal Cell Carcinoma: The Most Common Cancer Source: New York, NY: Skin Cancer Foundation. 1995. 6 p. Contact: Available from Skin Cancer Foundation. 245 Fifth Avenue, Suite 1403, New York, NY 10016. (212) 725-5176. Fax (212) 725-5751. E-mail: [email protected]. PRICE: Single copy free; bulk orders available at cost.

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Summary: This pamphlet provides the general public with information about basal cell carcinoma, which is the most common of all cancers and is caused mainly by overexposure to sunlight. People who have a history of exposure to the sun can develop basal cell carcinoma; however, those who are at highest risk have fair skin, light hair, and blue, green, or gray eyes. People who work outdoors or spend leisure time in the sun are particularly susceptible. The pamphlet identifies the warning signs of basal cell carcinoma, including a persistent, nonhealing sore; an reddish patch that may crust; a smooth growth with an elevated, rolled border and an indentation in the center; a shiny bump that is pearly or translucent; and a scar-like area that often has poorly defined borders. In addition, the pamphlet briefly describes surgical and other methods for eradicating basal cell carcinoma and discusses the possibility of recurrence. 10 figures. •

Basal Cell Carcinoma Source: Schaumburg, IL: American Academy of Dermatology (AAD). 2001. 8 p. Contact: Available from American Academy of Dermatology, Marketing Department. P.O. Box 2289, Carol Stream, IL 60132-2289. (847) 240-1280. Fax (847) 240-1859. E-mail: [email protected]. Website: www.aad.org. PRICE: Single copy free; bulk prices available. Summary: This pamphlet uses a question and answer format to provide people who have basal cell carcinoma with information on the etiology, features, diagnosis, treatment, and prevention of this common skin cancer. Basal cell cancer does not metastasize or travel in the bloodstream to other organs. Most cases are believed to be caused by exposure to the harmful ultraviolet rays of the sun, and basal cell cancer most often appears on sun exposed areas. Basal cell tumors have several different forms, with the most common being a small dome shaped bump that has a pearly white color. Other presentations include a pimple like growth that heals but recurs or a smooth white or yellowish waxy scar. A very common sign of basal cell cancer is a sore that bleeds and heals up but recurs. Diagnosis is based on the results of a biopsy of the growth. Surgical options for removing the growth include electrodesiccation and curettage and simple surgical excision. Other treatments, such as cryosurgery, radiation therapy, and laser surgery, may be used in certain situations. Cosmetic outcomes following surgery are usually excellent. Untreated basal cell cancer will continue to grow locally and may cause serious problems if it is located near the eyes, ears, nose, or other important organs. People who have had one basal cell cancer are at a 40 percent risk of getting a second basal cell cancer within 5 years, and people who have had multiple basal cell cancers or other skin cancers are at an increased risk for melanoma. Proper sun protection may help prevent the development of further basal cell cancers. 4 figures. Healthfinder™

Healthfinder™ is sponsored by the U.S. Department of Health and Human Services and offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database:

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ABCD’s of Skin Cancer Summary: A general overview of three types of skin cancer-- basal cell carcinoma, squamous cell carcinoma, and melanoma are illustrated. Explains self-exam for skin cancer. Source: American Academy of Dermatology http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=5777 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 in some way to basal cell carcinoma. 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

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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

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

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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 basal cell carcinoma. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with basal cell carcinoma. 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 basal cell carcinoma. For more

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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. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “basal cell carcinoma” (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 “basal cell carcinoma”. 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 “basal cell carcinoma” (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 “basal cell carcinoma” (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.25

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

25

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)26: •

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)

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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

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California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html

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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

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California: Gateway Health Library (Sutter Gould Medical Foundation)

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California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/

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California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp

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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/

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California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/

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California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/

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California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html

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California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/

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Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/

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Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/

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Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/

26

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

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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

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Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/

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Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm

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Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html

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Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/

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Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm

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Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/

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Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/

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Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/

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Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm

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Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html

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Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm

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Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/

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Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/

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Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10

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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

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Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp

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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

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Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/

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Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html

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Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm

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Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp

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Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/

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Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html

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Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/

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Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm

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Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/

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Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html

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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

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Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330

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Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)

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National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html

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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/

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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/

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New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm

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New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm

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New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/

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New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html

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New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/

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New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html

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New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/

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Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm

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Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp

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Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/

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Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/

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Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml

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Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html

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Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html

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Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml

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Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp

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Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm

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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

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Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/

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Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/

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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

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MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp

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Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/

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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

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On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/

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Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp

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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). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on basal cell carcinoma: •

Basic Guidelines for Basal Cell Carcinoma Basal cell cancer Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000824.htm Basal cell carcinoma Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000824.htm Melanoma Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000850.htm Melanoma Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001442.htm

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Signs & Symptoms for Basal Cell Carcinoma Itching Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003217.htm

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Skin lesion Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003220.htm •

Diagnostics and Tests for Basal Cell Carcinoma Biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003416.htm

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Background Topics for Basal Cell Carcinoma Bleeding Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000045.htm Cauterization Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002359.htm Cryosurgery Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002322.htm Incidence Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002387.htm

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

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MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

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Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

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Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

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BASAL CELL CARCINOMA DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 3-dimensional: 3-D. A graphic display of depth, width, and height. Three-dimensional radiation therapy uses computers to create a 3-dimensional picture of the tumor. This allows doctors to give the highest possible dose of radiation to the tumor, while sparing the normal tissue as much as possible. [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] Aberrant: Wandering or deviating from the usual or normal course. [EU] Ablate: In surgery, is to remove. [NIH] Ablation: The removal of an organ by surgery. [NIH] Abscess: A localized, circumscribed collection of pus. [NIH] Acantholysis: Separation of the prickle cells of the stratum spinosum of the epidermis, resulting in atrophy of the prickle cell layer. It is seen in diseases such as pemphigus vulgaris (see pemphigus) and keratosis follicularis. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] 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] Acquired Immunodeficiency Syndrome: An acquired defect of cellular immunity associated with infection by the human immunodeficiency virus (HIV), a CD4-positive Tlymphocyte count under 200 cells/microliter or less than 14% of total lymphocytes, and increased susceptibility to opportunistic infections and malignant neoplasms. Clinical manifestations also include emaciation (wasting) and dementia. These elements reflect criteria for AIDS as defined by the CDC in 1993. [NIH] Actin: Essential component of the cell skeleton. [NIH] Actinic keratosis: A precancerous condition of thick, scaly patches of skin. Also called solar or senile keratosis. [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] 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. [NIH]

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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] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adjuvant Therapy: Treatment given after the primary treatment to increase the chances of a cure. Adjuvant therapy may include chemotherapy, radiation therapy, or hormone therapy. [NIH]

Adrenal Glands: Paired glands situated in the retroperitoneal tissues at the superior pole of each kidney. [NIH] Adverse Effect: An unwanted side effect of treatment. [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] Aggressiveness: The quality of being aggressive (= characterized by aggression; militant; enterprising; spreading with vigour; chemically active; variable and adaptable). [EU] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [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] Allograft: An organ or tissue transplant between two humans. [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-helix: One of the secondary element of protein. [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] Aluminum: A metallic element that has the atomic number 13, atomic symbol Al, and atomic weight 26.98. [NIH]

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Amber: A yellowish fossil resin, the gum of several species of coniferous trees, found in the alluvial deposits of northeastern Germany. It is used in molecular biology in the analysis of organic matter fossilized in amber. [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] Aminolevulinic Acid: A compound produced from succinyl-CoA and glycine as an intermediate in heme synthesis. [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] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Amyloidosis: A group of diseases in which protein is deposited in specific organs (localized amyloidosis) or throughout the body (systemic amyloidosis). Amyloidosis may be either primary (with no known cause) or secondary (caused by another disease, including some types of cancer). Generally, primary amyloidosis affects the nerves, skin, tongue, joints, heart, and liver; secondary amyloidosis often affects the spleen, kidneys, liver, and adrenal glands. [NIH] Anaerobic: 1. Lacking molecular oxygen. 2. Growing, living, or occurring in the absence of molecular oxygen; pertaining to an anaerobe. [EU] 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] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Anaphase: The third phase of cell division, in which the chromatids separate and migrate to opposite poles of the spindle. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Aneuploidy: The chromosomal constitution of cells which deviate from the normal by the addition or subtraction of chromosomes or chromosome pairs. In a normally diploid cell the

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loss of a chromosome pair is termed nullisomy (symbol: 2N-2), the loss of a single chromosome is monosomy (symbol: 2N-1), the addition of a chromosome pair is tetrasomy (symbol: 2N+2), the addition of a single chromosome is trisomy (symbol: 2N+1). [NIH] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] Angiogenesis inhibitor: A substance that may prevent the formation of blood vessels. In anticancer therapy, an angiogenesis inhibitor prevents the growth of blood vessels from surrounding tissue to a solid tumor. [NIH] Angiography: Radiography of blood vessels after injection of a contrast medium. [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] Angiosarcoma: A type of cancer that begins in the lining of blood vessels. [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] Anogenital: Pertaining to the anus and external genitals. [EU] Anophthalmia: Absence of an eye or eyes in the newborn due to failure of development of the optic cup or to disappearance of the eyes after partial development. [NIH] Anterior chamber: The space in front of the iris and behind the cornea. [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] 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] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] 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-presenting cell: APC. A cell that shows antigen on its surface to other cells of the immune system. This is an important part of an immune response. [NIH] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU]

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Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antiproliferative: Counteracting a process of proliferation. [EU] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [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] 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] Areola: The area of dark-colored skin on the breast that surrounds the nipple. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Aromatic: Having a spicy odour. [EU] 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] Aseptic: Free from infection or septic material; sterile. [EU] Aspiration: The act of inhaling. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Astrocytoma: A tumor that begins in the brain or spinal cord in small, star-shaped cells called astrocytes. [NIH] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with

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cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] Atopic: Pertaining to an atopen or to atopy; allergic. [EU] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Attenuated: Strain with weakened or reduced virulence. [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] Auricular: Pertaining to an auricle or to the ear, and, formerly, to an atrium of the heart. [EU] Autopsy: Postmortem examination of the body. [NIH] Axillary: Pertaining to the armpit area, including the lymph nodes that are located there. [NIH]

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] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Bacteriophage lambda: A temperate inducible phage and type species of the genus lambdalike Phages, in the family Siphoviridae. Its natural host is E. coli K12. Its virion contains linear double-stranded DNA, except for 12 complementary bases at the 5'-termini of the polynucleotide chains. The DNA circularizes on infection. [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] 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 Cell Nevus Syndrome: Hereditary disorder consisting of multiple basal cell carcinomas, odontogenic keratocysts, and multiple skeletal defects, e.g., frontal and temporoparietal bossing, bifurcated and splayed ribs, kyphoscoliosis, fusion of vertebrae, and cervicothoracic spina bifida. Genetic transmission is autosomal dominant. [NIH] Basal cells: Small, round cells found in the lower part (or base) of the epidermis, the outer layer of the skin. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH]

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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] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Benign tumor: A noncancerous growth that does not invade nearby tissue or spread to other parts of the body. [NIH] Beta carotene: A vitamin A precursor. Beta carotene belongs to the family of fat-soluble vitamins called carotenoids. [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 Ducts: Tubes that carry bile from the liver to the gallbladder for storage and to the small intestine for use in digestion. [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] 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] Biotic: Pertaining to living organisms in their ecological rather than their physiological relations. [NIH]

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Bladder: The organ that stores urine. [NIH] Blister: Visible accumulations of fluid within or beneath the epidermis. [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 Fluids: Liquid components of living organisms. [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] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Burns: Injuries to tissues caused by contact with heat, steam, chemicals (burns, chemical), electricity (burns, electric), or the like. [NIH] Burns, Electric: Burns produced by contact with electric current or from a sudden discharge of electricity. [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] Callus: A callosity or hard, thick skin; the bone-like reparative substance that is formed round the edges and fragments of broken bone. [NIH] Cancer vaccine: A vaccine designed to prevent or treat cancer. [NIH] 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] Carcinogen: Any substance that causes cancer. [NIH]

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Carcinogenesis: The process by which normal cells are transformed into cancer cells. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]

Cardiac: Having to do with the heart. [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 series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Cataracts: In medicine, an opacity of the crystalline lens of the eye obstructing partially or totally its transmission of light. [NIH] Causal: Pertaining to a cause; directed against a cause. [EU] CDC2: It is crucial for entry into mitosis of eukaryotic cells. [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] 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] Cell Adhesion: Adherence of cells to surfaces or to other cells. [NIH] 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 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 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 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

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adaptability. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral hemispheres: The two halves of the cerebrum, the part of the brain that controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. The right hemisphere controls muscle movement on the left side of the body, and the left hemisphere controls muscle movement on the right side of the body. [NIH] 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] 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] 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] Chemotherapy: Treatment with anticancer drugs. [NIH] Cholangiography: Radiographic examination of the bile ducts. [NIH] 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] 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] Chromosome Abnormalities: Defects in the structure or number of chromosomes resulting in structural aberrations or manifesting as disease. [NIH] Chronic: A disease or condition that persists or progresses over a long period of 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] Cidofovir: A drug used to treat infection caused by viruses. [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

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system, is often considered part of the circulatory system. [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] Cleft Palate: Congenital fissure of the soft and/or hard palate, due to faulty fusion. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [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] Clone: The term "clone" has acquired a new meaning. It is applied specifically to the bits of inserted foreign DNA in the hybrid molecules of the population. Each inserted segment originally resided in the DNA of a complex genome amid millions of other DNA segment. [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] 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] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Colchicine: A major alkaloid from Colchicum autumnale L. and found also in other Colchicum species. Its primary therapeutic use is in the treatment of gout, but it has been used also in the therapy of familial Mediterranean fever (periodic disease). [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] Coloboma: Congenital anomaly in which some of the structures of the eye are absent due to incomplete fusion of the fetal intraocular fissure during gestation. [NIH] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH] Combinatorial: A cut-and-paste process that churns out thousands of potentially valuable compounds at once. [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

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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, 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] 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] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [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: 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] Contact dermatitis: Inflammation of the skin with varying degrees of erythema, edema and vesinculation resulting from cutaneous contact with a foreign substance or other exposure. [NIH]

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] 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]

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Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]

Conventional therapy: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional treatment. [NIH] Conventional treatment: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional therapy. [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] 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 Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Corticosteroids: Hormones that have antitumor activity in lymphomas and lymphoid leukemias; in addition, corticosteroids (steroids) may be used for hormone replacement and for the management of some of the complications of cancer and its treatment. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Cranial Irradiation: The exposure of the head to roentgen rays or other forms of radioactivity for therapeutic or preventive purposes. [NIH] Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Croton Oil: Viscous, nauseating oil obtained from the shrub Croton tiglium (Euphorbaceae). It is a vesicant and skin irritant used as pharmacologic standard for skin inflammation and allergy and causes skin cancer. It was formerly used as an emetic and cathartic with frequent mortality. [NIH] Cryosurgery: The use of freezing as a special surgical technique to destroy or excise tissue. [NIH]

Cryotherapy: Any method that uses cold temperature to treat disease. [NIH] Cultured cells: Animal or human cells that are grown in the laboratory. [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] Curettage: Removal of tissue with a curette, a spoon-shaped instrument with a sharp edge. [NIH]

Curette: A spoon-shaped instrument with a sharp edge. [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

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compounds that contain a ring of atoms in the nucleus. [EU] Cyclin: Molecule that regulates the cell cycle. [NIH] Cyclopia: Elements of the two eyes fused into one median eye in the center of the forehead of a fetal monster. [NIH] Cyclosporine: A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body. It is also used in clinical trials to make cancer cells more sensitive to anticancer drugs. [NIH] 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] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [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] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delivery of Health Care: The concept concerned with all aspects of providing and distributing health services to a patient population. [NIH] Demecolcine: An alkaloid isolated from Colchicum autumnale L. and used as an antineoplastic. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Dendritic cell: A special type of antigen-presenting cell (APC) that activates T lymphocytes. [NIH]

Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dentists: Individuals licensed to practice dentistry. [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] Dermal: Pertaining to or coming from the skin. [NIH]

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Dermatitis: Any inflammation of the skin. [NIH] Dermatology: A medical specialty concerned with the skin, its structure, functions, diseases, and treatment. [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] Diclofenac: A non-steroidal anti-inflammatory agent (NSAID) with antipyretic and analgesic actions. It is primarily available as the sodium salt, diclofenac sodium. [NIH] Diclofenac Sodium: The sodium form of diclofenac. It is used for its analgesic and antiinflammatory 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] 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] Dilatation: The act of dilating. [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] 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] 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] 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] Dorsum: A plate of bone which forms the posterior boundary of the sella turcica. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Duct: A tube through which body fluids pass. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dystrophic: Pertaining to toxic habitats low in nutrients. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular

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dystrophies. [EU] Ectopic: Pertaining to or characterized by ectopia. [EU] Eczema: A pruritic papulovesicular dermatitis occurring as a reaction to many endogenous and exogenous agents (Dorland, 27th ed). [NIH] 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] Elasticity: Resistance and recovery from distortion of shape. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] Electric Impedance: The resistance to the flow of either alternating or direct electrical current. [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] Electrodesiccation: The drying of tissue by a high-frequency electric current applied with a needle-shaped electrode. [NIH] 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] Emaciation: Clinical manifestation of excessive leanness usually caused by disease or a lack of nutrition. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryogenesis: The process of embryo or embryoid formation, whether by sexual (zygotic) or asexual means. In asexual embryogenesis embryoids arise directly from the explant or on intermediary callus tissue. In some cases they arise from individual cells (somatic cell embryoge). [NIH] Enamel: A very hard whitish substance which covers the dentine of the anatomical crown of a tooth. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endotoxic: Of, relating to, or acting as an endotoxin (= a heat-stable toxin, associated with the outer membranes of certain gram-negative bacteria. Endotoxins are not secreted and are released only when the cells are disrupted). [EU] 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] Enhancer: Transcriptional element in the virus genome. [NIH]

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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] 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]

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] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermal Cyst: Intradermal or subcutaneous saclike structure, the wall of which is stratified epithelium containing keratohyalin granules. [NIH] 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] 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] Epidermolysis Bullosa: Group of genetically determined disorders characterized by the blistering of skin and mucosae. There are four major forms: acquired, simple, junctional, and dystrophic. Each of the latter three has several varieties. [NIH] Epidural: The space between the wall of the spinal canal and the covering of the spinal cord. An epidural injection is given into this space. [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] 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]

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Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [NIH] Erythema Multiforme: A skin and mucous membrane disease characterized by an eruption of macules, papules, nodules, vesicles, and/or bullae with characteristic "bull's-eye" lesions usually occurring on the dorsal aspect of the hands and forearms. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Erythroplakia: A reddened patch with a velvety surface found in the mouth. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Essential Tremor: A rhythmic, involuntary, purposeless, oscillating movement resulting from the alternate contraction and relaxation of opposing groups of muscles. [NIH] Etretinate: An oral retinoid used in the treatment of keratotic genodermatosis, lichen planus, and psoriasis. Beneficial effects have also been claimed in the prophylaxis of epithelial neoplasia. The compound may be teratogenic. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Excipient: Any more or less inert substance added to a prescription in order to confer a suitable consistency or form to the drug; a vehicle. [EU] Excisional: The surgical procedure of removing a tumor by cutting it out. The biopsy is then examined under a microscope. [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] Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [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] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH]

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Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] Eye socket: One of the two cavities in the skull which contains an eyeball. Each eye is located in a bony socket or orbit. [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] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] 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] 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] 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] Flexor: Muscles which flex a joint. [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] 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] Follicles: Shafts through which hair grows. [NIH] Folliculitis: Inflammation of follicles, primarily hair follicles. [NIH] Foramen: A natural hole of perforation, especially one in a bone. [NIH] Furunculosis: An infection where furuncles are present over a period of weeks to months. Species of Staphylococcus are usually the causative agents. [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

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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] Gastric: Having to do with the stomach. [NIH] Gastrointestinal: Refers to the stomach and intestines. [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 Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [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] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genital: Pertaining to the genitalia. [EU] 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] 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] Glioblastoma: A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures. [NIH] Glioma: A cancer of the brain that comes from glial, or supportive, cells. [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] Glucuronic Acid: Derivatives of uronic acid found throughout the plant and animal kingdoms. They detoxify drugs and toxins by conjugating with them to form glucuronides in the liver which are more water-soluble metabolites that can be easily eliminated from the body. [NIH]

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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]

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] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycosaminoglycans: Heteropolysaccharides which contain an N-acetylated hexosamine in a characteristic repeating disaccharide unit. The repeating structure of each disaccharide involves alternate 1,4- and 1,3-linkages consisting of either N-acetylglucosamine or Nacetylgalactosamine. [NIH] Gout: Hereditary metabolic disorder characterized by recurrent acute arthritis, hyperuricemia and deposition of sodium urate in and around the joints, sometimes with formation of uric acid calculi. [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] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Gram-positive: Retaining the stain or resisting decolorization by alcohol in Gram's method of staining, a primary characteristic of bacteria whose cell wall is composed of a thick layer of peptidologlycan with attached teichoic acids. [EU] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Granulomas: Small lumps in tissues caused by inflammation. [NIH] Groin: The external junctural region between the lower part of the abdomen and the thigh. [NIH]

Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [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] Hair follicles: Shafts or openings on the surface of the skin through which hair grows. [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] Health Care Costs: The actual costs of providing services related to the delivery of health

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care, including the costs of procedures, therapies, and medications. It is differentiated from health expenditures, which refers to the amount of money paid for the services, and from fees, which refers to the amount charged, regardless of cost. [NIH] Health Expenditures: The amounts spent by individuals, groups, nations, or private or public organizations for total health care and/or its various components. These amounts may or may not be equivalent to the actual costs (health care costs) and may or may not be shared among the patient, insurers, and/or employers. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [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 A: Normal adult human hemoglobin. The globin moiety consists of two alpha and two beta chains. [NIH] Hemoglobinuria: The presence of free hemoglobin in the urine. [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]

Heparin: Heparinic acid. A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. [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] 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]

Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Histiocytosis: General term for the abnormal appearance of histiocytes in the blood. Based on the pathological features of the cells involved rather than on clinical findings, the

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histiocytic diseases are subdivided into three groups: Langerhans cell histiocytosis, nonLangerhans cell histiocytosis, and malignant histiocytic disorders. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Holoprosencephaly: Anterior midline brain, cranial, and facial malformations resulting from the failure of the embryonic prosencephalon to undergo segmentation and cleavage. Alobar prosencephaly is the most severe form and features anophthalmia; cyclopia; severe mental retardation; cleft lip; cleft palate; seizures; and microcephaly. Semilobar holoprosencepaly is characterized by hypotelorism, microphthalmia, coloboma, nasal malformations, and variable degrees of mental retardation. Lobar holoprosencephaly is associated with mild (or absent) facial malformations and intellectual abilities that range from mild mental retardation to normal. Holoprosencephlay is associated with chromosome abnormalities. [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] Hormonal: Pertaining to or of the nature of a hormone. [EU] 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 therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called endocrine therapy. [NIH] Horny layer: The superficial layer of the epidermis containing keratinized cells. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Host-cell: A cell whose metabolism is used for the growth and reproduction of a virus. [NIH] Human Development: Continuous sequential changes which occur in the physiological and psychological functions during the individual's life. [NIH] Human papillomavirus: HPV. A virus that causes abnormal tissue growth (warts) and is often associated with some types of cancer. [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] Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure or "monoclonal" antibodies or T-cell products, identical to those produced by the immunologically competent parent, and continually grow and divide as the neoplastic parent. [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] 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

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hydrophobic colloid. [EU] 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] 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] 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] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [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] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [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] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [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]

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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] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Incubators: Insulated enclosures in which temperature, humidity, and other environmental conditions can be regulated at levels optimal for growth, hatching, reproduction, or metabolic reactions. [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] 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] Infantile: Pertaining to an infant or to infancy. [EU] 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]

Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] 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] Inguinal: Pertaining to the inguen, or groin. [EU] 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] 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] Integrase: An enzyme that inserts DNA into the host genome. It is encoded by the pol gene of retroviruses and also by temperate bacteriophages, the best known being bacteriophage lambda. EC 2.7.7.-. [NIH]

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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 Alfa-2b: A recombinant alfa interferon consisting of 165 amino acid residues with arginine in position 23 and histidine in position 34. It is used extensively as an antiviral and antineoplastic agent. [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] Interleukin-6: Factor that stimulates the growth and differentiation of human B-cells and is also a growth factor for hybridomas and plasmacytomas. It is produced by many different cells including T-cells, monocytes, and fibroblasts. [NIH] Intermediate Filaments: Cytoplasmic filaments intermediate in diameter (about 10 nanometers) between the microfilaments and the microtubules. They may be composed of any of a number of different proteins and form a ring around the cell nucleus. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] 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] Interspecific: Occurring among members of different species. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Interstitial Collagenase: A member of the metalloproteinase family of enzymes that is principally responsible for cleaving fibrillar collagen. It can degrade interstitial collagens, types I, II and III. EC 3.4.24.7. [NIH] Intervertebral: Situated between two contiguous vertebrae. [EU] Intestinal: Having to do with the intestines. [NIH] Intestines: The section of the alimentary canal from the stomach to the anus. It includes the large intestine and small intestine. [NIH] Intracellular: Inside a cell. [NIH] Intracellular Membranes: Membranes of subcellular structures. [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]

Involuntary: Reaction occurring without intention or volition. [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

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positive charge are known as cations; those with a negative charge are anions. [NIH] Ipsilateral: Having to do with the same side of the body. [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] Irradiance: At a point of a surface, the quotient of the radiant flux incident on an element of the surface containing the point, by the area of that element. [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] 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] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [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] Keratin: A class of fibrous proteins or scleroproteins important both as structural proteins and as keys to the study of protein conformation. The family represents the principal constituent of epidermis, hair, nails, horny tissues, and the organic matrix of tooth enamel. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms an alpha-helix, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. [NIH] Keratinocytes: Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. [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] 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] Kinesin: A microtubule-associated mechanical adenosine triphosphatase, that uses the energy of ATP hydrolysis to move organelles along microtubules toward the plus end of the microtubule. The protein is found in squid axoplasm, optic lobes, and in bovine brain.

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Bovine kinesin is a heterotetramer composed of two heavy (120 kDa) and two light (62 kDa) chains. EC 3.6.1.-. [NIH] Kinetic: Pertaining to or producing motion. [EU] Lacrimal: Pertaining to the tears. [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] 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 Surgery: The use of a laser either to vaporize surface lesions or to make bloodless cuts in tissue. It does not include the coagulation of tissue by laser. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] 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] Leg Ulcer: Ulceration of the skin and underlying structures of the lower extremity. About 90% of the cases are due to venous insufficiency (varicose ulcer), 5% to arterial disease, and the remaining 5% to other causes. [NIH] Leiomyosarcoma: A tumor of the muscles in the uterus, abdomen, or pelvis. [NIH] Leishmaniasis: A disease caused by any of a number of species of protozoa in the genus Leishmania. There are four major clinical types of this infection: cutaneous (Old and New World), diffuse cutaneous, mucocutaneous, and visceral leishmaniasis. [NIH] Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Lentigo: Small circumscribed melanoses resembling, but differing histologically from, freckles. The concept includes senile lentigo ('liver spots') and nevoid lentigo (nevus spilus, lentigo simplex) and may also occur in association with multiple congenital defects or congenital syndromes (e.g., Peutz-Jeghers syndrome). [NIH] Lesion: An area of abnormal tissue change. [NIH] Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukoplakia: A white patch that may develop on mucous membranes such as the cheek, gums, or tongue and may become cancerous. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

Lichen Planus: An inflammatory, pruritic disease of the skin and mucous membranes, which can be either generalized or localized. It is characterized by distinctive purplish, flattopped papules having a predilection for the trunk and flexor surfaces. The lesions may be discrete or coalesce to form plaques. Histologically, there is a "saw-tooth" pattern of epidermal hyperplasia and vacuolar alteration of the basal layer of the epidermis along with an intense upper dermal inflammatory infiltrate composed predominantly of T-cells. Etiology is unknown. [NIH]

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Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Light microscope: A microscope (device to magnify small objects) in which objects are lit directly by white light. [NIH] Limb Bud: A swelling on the trunk of the vertebrate embryo that becomes a limb. Limb bud cultures are used in developmental, organogenesis, morphogenesis, and cell differentiation studies. The limb bud of the chick embryo is most commonly used but mouse and rat limb buds are also used. [NIH] 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] Linkage Disequilibrium: Nonrandom association of linked genes. This is the tendency of the alleles of two separate but already linked loci to be found together more frequently than would be expected by chance alone. [NIH] Lip: Either of the two fleshy, full-blooded margins of the mouth. [NIH] Lipid: Fat. [NIH] Lipid A: Lipid A is the biologically active component of lipopolysaccharides. It shows strong endotoxic activity and exhibits immunogenic properties. [NIH] Lipopolysaccharides: Substance consisting of polysaccaride and lipid. [NIH] 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] Local therapy: Treatment that affects cells in the tumor and the area close to it. [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] Long-Term Care: Care over an extended period, usually for a chronic condition or disability, requiring periodic, intermittent, or continuous care. [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] 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] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [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]

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Lymphadenopathy: Disease or swelling of the lymph nodes. [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] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphocyte Count: A count of the number of lymphocytes in the blood. [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] Lymphomatoid Papulosis: Clinically benign, histologically malignant, recurrent cutaneous eruption characterized by an infiltration of large atypical cells surrounded by inflammatory cells. The atypical cells resemble Reed-Sternberg cells of Hodgkin's disease or the malignant cells of cutaneous T-cell lymphoma. In some cases, lymphomatoid papulosis progresses to lymphomatous conditions including mycosis fungoides, Hodgkin's disease, cutaneous T-cell lymphoma, or Ki-1 lymphoma. [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] 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 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] 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] Maxillary Sinus: One of the paired paranasal sinuses, located in the body of the maxilla,

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communicating with the middle meatus of the nasal cavity. [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 Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Medulloblastoma: A malignant brain tumor that begins in the lower part of the brain and can spread to the spine or to other parts of the body. Medulloblastomas are sometimes called primitive neuroectodermal tumors (PNET). [NIH] 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] Melanoma vaccine: A cancer vaccine prepared from human melanoma cancer cells. It can be used alone or with other therapy in treating melanoma. [NIH] Membrane: A very thin layer of tissue that covers a surface. [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] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH]

Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from

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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] Methyl Methanesulfonate: An alkylating agent in cancer therapy that may also act as a mutagen by interfering with and causing damage to DNA. [NIH] MI: 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] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microfilaments: The smallest of the cytoskeletal filaments. They are composed chiefly of actin. [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] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Microsurgery: Surgical procedures on the cellular level; a light microscope and miniaturized instruments are used. [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] Miscible: Susceptible of being mixed. [EU] 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] Mitotic: Cell resulting from mitosis. [NIH] Mobilization: The process of making a fixed part or stored substance mobile, as by separating a part from surrounding structures to make it accessible for an operative procedure or by causing release into the circulation for body use of a substance stored in the body. [EU] 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

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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] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] Monosomy: The condition in which one chromosome of a pair is missing. In a normally diploid cell it is represented symbolically as 2N-1. [NIH] Morphogenesis: The development of the form of an organ, part of the body, or organism. [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] Mucinous: Containing or resembling mucin, the main compound in mucus. [NIH] Mucocutaneous: Pertaining to or affecting the mucous membrane and the skin. [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucositis: A complication of some cancer therapies in which the lining of the digestive system becomes inflamed. Often seen as sores in the mouth. [NIH] 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] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Muscular Atrophy: Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Mustard Gas: Severe irritant and vesicant of skin, eyes, and lungs. It may cause blindness and lethal lung edema and was formerly used as a war gas. The substance has been proposed as a cytostatic and for treatment of psoriasis. It has been listed as a known carcinogen in the Fourth Annual Report on Carcinogens (NTP-85-002, 1985) (Merck, 11th ed). [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]

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Mutagenic: Inducing genetic mutation. [EU] Mycoplasma: A genus of gram-negative, facultatively anaerobic bacteria bounded by a plasma membrane only. Its organisms are parasites and pathogens, found on the mucous membranes of humans, animals, and birds. [NIH] Mycosis: Any disease caused by a fungus. [EU] Mycosis Fungoides: A chronic malignant T-cell lymphoma of the skin. In the late stages the lymph nodes and viscera are affected. [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myoglobin: A conjugated protein which is the oxygen-transporting pigment of muscle. It is made up of one globin polypeptide chain and one heme group. [NIH] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [NIH] Naevus: A circumscribed area of pigmentation or vascularization, usually in the form of a congenital benign neoplasm occurring in the skin or in various ocular tissues. [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] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Needle biopsy: The removal of tissue or fluid with a needle for examination under a microscope. Also called fine-needle aspiration. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nephropathy: Disease of the kidneys. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [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 Tumors: Malignant neoplasms arising in the neuroectoderm, the portion of the ectoderm of the early embryo that gives rise to the central and peripheral nervous systems, including some glial cells. [NIH] Neurologic: Having to do with nerves or the nervous system. [NIH]

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Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neurophysiology: The scientific discipline concerned with the physiology of the nervous system. [NIH] 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] 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] Nickel: A trace element with the atomic symbol Ni, atomic number 28, and atomic weight 58.69. It is a cofactor of the enzyme urease. [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] Nonmelanoma skin cancer: Skin cancer that arises in basal cells or squamous cells but not in melanocytes (pigment-producing cells of the skin). [NIH] Notochord: The rod-shaped body, composed of cells derived from the mesoblast and defining the primitive axis of the embryo. In lower vertebrates, it persists throughout life as the main axial support of the body, but in higher vertebrates it is replaced by the vertebral column. [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 Medicine: A specialty field of radiology concerned with diagnostic, therapeutic, and investigative use of radioactive compounds in a pharmaceutical form. [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] 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 results. [NIH]

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Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] 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] Odour: A volatile emanation that is perceived by the sense of smell. [EU] 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] Oncology: The study of cancer. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Opportunistic Infections: An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. [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] Orbital: Pertaining to the orbit (= the bony cavity that contains the eyeball). [EU] Organ Culture: The growth in aseptic culture of plant organs such as roots or shoots, beginning with organ primordia or segments and maintaining the characteristics of the organ. [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] Ornithine: An amino acid produced in the urea cycle by the splitting off of urea from arginine. [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] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [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)

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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]

Oxygenation: The process of supplying, treating, or mixing with oxygen. No:1245 oxygenation the process of supplying, treating, or mixing with oxygen. [EU] P53 gene: A tumor suppressor gene that normally inhibits the growth of tumors. This gene is altered in many types of cancer. [NIH] Paclitaxel: Antineoplastic agent isolated from the bark of the Pacific yew tree, Taxus brevifolia. Paclitaxel stabilizes microtubules in their polymerized form and thus mimics the action of the proto-oncogene proteins c-mos. [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] Palsy: Disease of the peripheral nervous system occurring usually after many years of increased lead absorption. [NIH] 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] Papilloma: A benign epithelial neoplasm which may arise from the skin, mucous membranes or glandular ducts. [NIH] Papillomavirus: A genus of Papovaviridae causing proliferation of the epithelium, which may lead to malignancy. A wide range of animals are infected including humans, chimpanzees, cattle, rabbits, dogs, and horses. [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]

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] Parotid: The space that contains the parotid gland, the facial nerve, the external carotid artery, and the retromandibular vein. [NIH] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Particle: A tiny mass of material. [EU] Partnership Practice: A voluntary contract between two or more doctors who may or may not share responsibility for the care of patients, with proportional sharing of profits and losses. [NIH]

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Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathogen: Any disease-producing microorganism. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

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] Patient Education: The teaching or training of patients concerning their own health needs. [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] PDQ: Physician Data Query. PDQ is an online database developed and maintained by the National Cancer Institute. Designed to make the most current, credible, and accurate cancer information available to health professionals and the public, PDQ contains peer-reviewed summaries on cancer treatment, screening, prevention, genetics, and supportive care; a registry of cancer clinical trials from around the world; and directories of physicians, professionals who provide genetics services, and organizations that provide cancer care. Most of this information is available on the CancerNet Web site, and more specific information about PDQ can be found at http://cancernet.nci.nih.gov/pdq.html. [NIH] Pelvic: Pertaining to the pelvis. [EU] Pemphigus: Group of chronic blistering diseases characterized histologically by acantholysis and blister formation within the epidermis. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] 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] Perianal: Located around the anus. [EU] Perineural: Around a nerve or group of nerves. [NIH] Periorbital: Situated around the orbit, or eye socket. [EU] 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] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU]

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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 phenotype, characteristic of yeasts. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phorbol: Class of chemicals that promotes the development of tumors. [NIH] Phorbol Esters: Tumor-promoting compounds obtained from croton oil (Croton tiglium). Some of these are used in cell biological experiments as activators of protein kinase C. [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] 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] Photodynamic therapy: Treatment with drugs that become active when exposed to light. These drugs kill cancer cells. [NIH] Photosensitivity: An abnormal cutaneous response involving the interaction between photosensitizing substances and sunlight or filtered or artificial light at wavelengths of 280400 mm. There are two main types : photoallergy and photoxicity. [EU] Photosensitizer: A drug used in photodynamic therapy. When absorbed by cancer cells and exposed to light, the drug becomes active and kills the 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] Pigmentation: Coloration or discoloration of a part by a pigment. [NIH] Pilocytic: Made up of cells that look like fibers when viewed under a microscope. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [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]

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Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasmids: Any extrachromosomal hereditary determinant. Plasmids are self-replicating circular molecules of DNA that are found in a variety of bacterial, archaeal, fungal, algal, and plant species. [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] Pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Ploidy: The number of sets of chromosomes in a cell or an organism. For example, haploid means one set and diploid means two sets. [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] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] 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] Porphyrins: A group of compounds containing the porphin structure, four pyrrole rings connected by methine bridges in a cyclic configuration to which a variety of side chains are attached. The nature of the side chain is indicated by a prefix, as uroporphyrin, hematoporphyrin, etc. The porphyrins, in combination with iron, form the heme component in biologically significant compounds such as hemoglobin and myoglobin. [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] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postoperative: After surgery. [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Potentiate: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [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] Practicability: A non-standard characteristic of an analytical procedure. It is dependent on the scope of the method and is determined by requirements such as sample throughout and costs. [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

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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] 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] Prenatal: Existing or occurring before birth, with reference to the fetus. [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] Prickle: Several layers of the epidermis where the individual cells are connected by cell bridges. [NIH] Primary tumor: The original tumor. [NIH] Primitive neuroectodermal tumors: PNET. A type of bone cancer that forms in the middle (shaft) of large bones. Also called Ewing's sarcoma/primitive neuroectodermal tumor. [NIH] Private Practice: Practice of a health profession by an individual, offering services on a person-to-person basis, as opposed to group or partnership practice. [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] 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] 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] Prophylaxis: An attempt to prevent disease. [NIH] Prosencephalon: The part of the brain developed from the most rostral of the three primary vesicles of the embryonic neural tube and consisting of the diencephalon and telencephalon. [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

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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] 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] 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] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protective Clothing: Clothing designed to protect the individual against possible exposure to known hazards. [NIH] 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] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] Proteoglycan: A molecule that contains both protein and glycosaminoglycans, which are a type of polysaccharide. Proteoglycans are found in cartilage and other connective tissues. [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] 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]

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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] Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity. [NIH] Proto-Oncogene Proteins c-mos: Cellular proteins encoded by the c-mos genes. They function in the cell cycle to maintain maturation promoting factor in the active state and have protein-serine/threonine kinase activity. Oncogenic transformation can take place when c-mos proteins are expressed at the wrong time. [NIH] Proto-Oncogenes: Normal cellular genes homologous to viral oncogenes. The products of proto-oncogenes are important regulators of biological processes and appear to be involved in the events that serve to maintain the ordered procession through the cell cycle. Protooncogenes have names of the form c-onc. [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] Pruritic: Pertaining to or characterized by pruritus. [EU] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] PTC: Percutaneous transhepatic cholangiography (per-kyoo-TAN-ee-us trans-heh-PAT-ik ko-LAN-jee-AH-gra-fee). A procedure to x-ray the bile ducts. In this procedure, a dye is injected through a thin needle inserted through the skin into the liver or the gallbladder, and an x-ray picture is taken. [NIH] 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] 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]

Pupil: The aperture in the iris through which light passes. [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]

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Pustular: Pertaining to or of the nature of a pustule; consisting of pustules (= a visible collection of pus within or beneath the epidermis). [EU] Pyogenic: Producing pus; pyopoietic (= liquid inflammation product made up of cells and a thin fluid called liquor puris). [EU] Pyrimidine Dimers: Dimers found in DNA chains damaged by ultraviolet irradiation. They consist of two adjacent pyrimidine nucleotides, usually thymine nucleotides, in which the pyrimidine residues are covalently joined by a cyclobutane ring. These dimers stop DNA replication. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [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 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] Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease. [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] Reactivation: The restoration of activity to something that has been inactivated. [EU] Reactive Oxygen Species: Reactive intermediate oxygen species including both radicals and non-radicals. These substances are constantly formed in the human body and have been shown to kill bacteria and inactivate proteins, and have been implicated in a number of

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diseases. Scientific data exist that link the reactive oxygen species produced by inflammatory phagocytes to cancer development. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptors, Cytokine: Cell surface proteins that bind cytokines and trigger intracellular changes influencing the behavior of cells. [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] Reconstitution: 1. A type of regeneration in which a new organ forms by the rearrangement of tissues rather than from new formation at an injured surface. 2. The restoration to original form of a substance previously altered for preservation and storage, as the restoration to a liquid state of blood serum or plasma that has been dried and stored. [EU] 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] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Refractory: Not readily yielding to treatment. [EU] 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] 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] Reproductive cells: Egg and sperm cells. Each mature reproductive cell carries a single set of 23 chromosomes. [NIH] Resection: Removal of tissue or part or all of an organ by surgery. [NIH] Resolving: The ability of the eye or of a lens to make small objects that are close together, separately visible; thus revealing the structure of an object. [NIH] 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

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(= cell respiration). [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retinoid: Vitamin A or a vitamin A-like compound. [NIH] Retinol: Vitamin A. It is essential for proper vision and healthy skin and mucous membranes. Retinol is being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Retrospective: Looking back at events that have already taken place. [NIH] Retrospective study: A study that looks backward in time, usually using medical records and interviews with patients who already have or had a disease. [NIH] Rhabdomyosarcoma: A malignant tumor of muscle tissue. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Rod: A reception for vision, located in the retina. [NIH] Salicylic: A tuberculosis drug. [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 glands: Glands in the mouth that produce saliva. [NIH] Sarcoma: A connective tissue neoplasm formed by proliferation of mesodermal cells; it is usually highly malignant. [NIH] Scabies: A contagious cutaneous inflammation caused by the bite of the mite Sarcoptes scabiei. It is characterized by pruritic papular eruptions and burrows and affects primarily the axillae, elbows, wrists, and genitalia, although it can spread to cover the entire body. [NIH]

Sclera: The tough white outer coat of the eyeball, covering approximately the posterior fivesixths of its surface, and continuous anteriorly with the cornea and posteriorly with the external sheath of the optic nerve. [EU] Scleroproteins: Simple proteins characterized by their insolubility and fibrous structure. Within the body, they perform a supportive or protective function. [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [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

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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] Segmentation: The process by which muscles in the intestines move food and wastes through the body. [NIH] 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 as epilepsy or "seizure disorder." [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] 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] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [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] Sensory loss: A disease of the nerves whereby the myelin or insulating sheath of myelin on the nerves does not stay intact and the messages from the brain to the muscles through the nerves are not carried properly. [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] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Sex Determination: The biological characteristics which distinguish human beings as female or male. [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] 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

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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] 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] Skin Aging: The process of aging due to changes in the structure and elasticity of the skin over time. It may be a part of physiological aging or it may be due to the effects of ultraviolet radiation, usually through exposure to sunlight. [NIH] Skin Pigmentation: Coloration of the skin. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [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] 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] Somatic cells: All the body cells except the reproductive (germ) cells. [NIH] Somites: Paired, segmented masses of mesodermal tissue that form along the length of the neural tube during the early stage of embryonic development. They give rise to the vertebral column and other tissues including voluntary muscle, bone, connective tissue, and the dermal layers of the skin. [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

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types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrophotometry: The art or process of comparing photometrically the relative intensities of the light in different parts of the spectrum. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by 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] Spina bifida: A defect in development of the vertebral column in which there is a central deficiency of the vertebral lamina. [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] Spinal Cord Compression: Acute and chronic conditions characterized by external mechanical compression of the spinal cord due to extramedullary neoplasm; epidural abscess; spinal fractures; bony deformities of the vertebral bodies; and other conditions. Clinical manifestations vary with the anatomic site of the lesion and may include localized pain, weakness, sensory loss, incontinence, and impotence. [NIH] Spinal Fractures: Broken bones in the vertebral column. [NIH] Spinous: Like a spine or thorn in shape; having spines. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [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] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Sterile: Unable to produce children. [NIH] Steroids: Drugs used to relieve swelling and inflammation. [NIH] Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH]

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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] Stomatitis: Inflammation of the oral mucosa, due to local or systemic factors which may involve the buccal and labial mucosa, palate, tongue, floor of the mouth, and the gingivae. [EU]

Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [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] Stromal Cells: Connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the hematopoietic system and elsewhere. [NIH] Subacute: Somewhat acute; between acute and chronic. [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] Subconjunctival: Situated or occurring beneath the conjunctiva. [EU] Subcutaneous: Beneath the skin. [NIH] Submaxillary: Four to six lymph glands, located between the lower jaw and the submandibular salivary gland. [NIH] Submucous: Occurring beneath the mucosa or a mucous membrane. [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]

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] Supportive care: Treatment given to prevent, control, or relieve complications and side effects and to improve the comfort and quality of life of people who have cancer. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [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 consists of a single tube, a coiled body, and a superficial duct. [NIH] Symphysis: A secondary cartilaginous joint. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between

Dictionary 203

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] Systemic: Affecting the entire body. [NIH] Systemic disease: Disease that affects the whole body. [NIH] Teichoic Acids: Bacterial polysaccharides that are rich in phosphodiester linkages. They are the major components of the cell walls and membranes of many bacteria. [NIH] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [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] Testicles: The two egg-shaped glands found inside the scrotum. They produce sperm and male hormones. Also called testes. [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] Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamic Diseases: Disorders of the centrally located thalamus, which integrates a wide range of cortical and subcortical information. Manifestations include sensory loss, movement disorders; ataxia, pain syndromes, visual disorders, a variety of neuropsychological conditions, and coma. Relatively common etiologies include cerebrovascular disorders; craniocerebral trauma; brain neoplasms; brain hypoxia; intracranial hemorrhages; and infectious processes. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [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] Thymidine: A chemical compound found in DNA. Also used as treatment for mucositis. [NIH]

Thymidine Kinase: An enzyme that catalyzes the conversion of ATP and thymidine to ADP and thymidine 5'-phosphate. Deoxyuridine can also act as an acceptor and dGTP as a donor.

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(From Enzyme Nomenclature, 1992) EC 2.7.1.21. [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] 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 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] 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] 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] 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] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [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 both local and systemic cellular immunity to nonimmune recipients. [NIH] Transferases: Transferases are enzymes transferring a group, for example, the methyl group or a glycosyl group, from one compound (generally regarded as donor) to another compound (generally regarded as acceptor). The classification is based on the scheme "donor:acceptor group transferase". (Enzyme Nomenclature, 1992) EC 2. [NIH] Transillumination: Passage of light through body tissues or cavities for examination of

Dictionary 205

internal structures. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [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] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, practicability, etc., of these interventions in individual cases or series. [NIH]

Trees: Woody, usually tall, perennial higher plants (Angiosperms, Gymnosperms, and some Pterophyta) having usually a main stem and numerous branches. [NIH] Trisomy: The possession of a third chromosome of any one type in an otherwise diploid cell. [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] Tuberous Sclerosis: A rare congenital disease in which the essential pathology is the appearance of multiple tumors in the cerebrum and in other organs, such as the heart or kidneys. [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 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] 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] 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] Ultraviolet Rays: That portion of the electromagnetic spectrum immediately below the visible range and extending into the x-ray frequencies. The longer wavelengths (near-UV or biotic or vital rays) are necessary for the endogenous synthesis of vitamin D and are also called antirachitic rays; the shorter, ionizing wavelengths (far-UV or abiotic or extravital

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rays) are viricidal, bactericidal, mutagenic, and carcinogenic and are used as disinfectants. [NIH]

Umbilical Cord: The flexible structure, giving passage to the umbilical arteries and vein, which connects the embryo or fetus to the placenta. [NIH] Umbilicus: The pit in the center of the abdominal wall marking the point where the umbilical cord entered in the fetus. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [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] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [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] 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] 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] Vaccine adjuvant: A substance added to a vaccine to improve the immune response so that less vaccine is needed. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Varicella: Chicken pox. [EU] Varicose: The common ulcer in the lower third of the leg or near the ankle. [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] 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] 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] Verruca: A circumscribed, cutaneous excrescence having a papilliferous surface; a small, circumscribed, epidermal tumor. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vertebral: Of or pertaining to a vertebra. [EU]

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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] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] 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] Vitamin A: A substance used in cancer prevention; it belongs to the family of drugs called retinoids. [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] Vulgaris: An affection of the skin, especially of the face, the back and the chest, due to chronic inflammation of the sebaceous glands and the hair follicles. [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]

Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] Xeroderma Pigmentosum: A rare, pigmentary, and atrophic autosomal recessive disease affecting all races. It is manifested as an extreme photosensitivity to ultraviolet light as the result of a deficiency in the enzyme that permits excisional repair of ultraviolet-damaged DNA. [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] Zoster: A virus infection of the Gasserian ganglion and its nerve branches, characterized by

208

Basal Cell Carcinoma

discrete areas of vesiculation of the epithelium of the forehead, the nose, the eyelids, and the cornea together with subepithelial infiltration. [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]

209

INDEX 3 3-dimensional, 78, 153 A Abdomen, 153, 160, 173, 180, 181, 189, 201, 202, 207 Abdominal, 61, 153, 189, 206 Aberrant, 6, 19, 31, 34, 153 Ablate, 18, 153 Ablation, 23, 153 Abscess, 153, 201 Acantholysis, 153, 190 Acceptor, 153, 189, 203, 204 Acne, 48, 111, 120, 153, 179 Acne Vulgaris, 48, 153, 179 Acquired Immunodeficiency Syndrome, 119, 153 Actin, 17, 20, 43, 153, 184 Actinic keratosis, 50, 53, 70, 71, 78, 89, 108, 111, 112, 119, 153 Adaptability, 153, 161, 162 Adenocarcinoma, 106, 118, 153 Adenoma, 118, 153, 169 Adenomatous Polyposis Coli, 51, 153 Adenosine, 154, 179, 191 Adjuvant, 8, 12, 44, 154 Adjuvant Therapy, 12, 154 Adrenal Glands, 154, 155 Adverse Effect, 154, 179, 199 Affinity, 33, 154, 157, 200 Aggressiveness, 25, 154 Algorithms, 16, 30, 39, 154, 159 Alkaloid, 154, 163, 166 Alleles, 36, 38, 154, 181 Allograft, 65, 154 Allylamine, 154, 155 Alopecia, 17, 154 Alpha Particles, 154, 196 Alpha-helix, 154, 179 Alternative medicine, 122, 154 Aluminum, 22, 154 Amber, 11, 155 Amine, 113, 155 Amino Acid Sequence, 155, 156, 170, 172 Amino Acids, 155, 172, 190, 192, 194, 199, 206 Aminolevulinic Acid, 70, 95, 96, 103, 155 Ammonia, 155, 202, 206 Amplification, 107, 110, 155

Amyloidosis, 61, 77, 155 Anaerobic, 155, 186 Anaesthesia, 155, 177 Anal, 10, 155, 185 Analgesic, 155, 167, 202 Analogous, 25, 155, 204 Anaphase, 6, 155 Anatomical, 22, 155, 158, 168, 176, 181, 198 Anemia, 133, 155 Aneuploidy, 6, 155 Angiogenesis, 8, 106, 110, 111, 156, 182 Angiogenesis inhibitor, 111, 156 Angiography, 55, 156 Angiolymphoid Hyperplasia with Eosinophilia, 118, 156 Angiosarcoma, 111, 156 Animal model, 7, 9, 11, 15, 26, 108, 113, 156 Anogenital, 113, 156 Anophthalmia, 156, 175 Anterior chamber, 156, 179 Antibodies, 15, 23, 156, 173, 175, 176, 182, 192, 196 Antibody, 27, 43, 83, 154, 156, 163, 173, 175, 176, 177, 179, 183, 185, 196, 200, 207 Anticoagulant, 156, 194 Antigen, 31, 38, 44, 56, 154, 156, 164, 166, 175, 176, 177, 183 Antigen-presenting cell, 31, 156, 166 Anti-inflammatory, 37, 108, 156, 161, 167, 202 Anti-Inflammatory Agents, 156, 161 Antineoplastic, 156, 166, 178, 189 Antioxidant, 89, 157 Antiproliferative, 8, 157 Antipyretic, 157, 167 Antiviral, 113, 157, 178 Anus, 155, 156, 157, 160, 178, 190 Apoptosis, 6, 9, 12, 15, 31, 49, 81, 82, 88, 97, 157 Aqueous, 34, 157, 159, 166, 180, 181 Arachidonic Acid, 157, 193 Areola, 43, 157 Arginine, 157, 178, 188 Aromatic, 26, 157, 191 Arterial, 154, 157, 180, 194 Arteries, 157, 160, 165, 184, 206 Arterioles, 157, 160

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Basal Cell Carcinoma

Aseptic, 157, 188 Aspiration, 58, 102, 157 Assay, 12, 36, 157 Astrocytes, 157 Astrocytoma, 81, 157, 172 Ataxia, 132, 133, 157, 203 Atopic, 112, 114, 120, 158 Atrium, 158, 206 Atrophy, 132, 153, 158 Attenuated, 37, 158 Atypical, 158, 182 Auditory, 118, 158, 183, 205 Auricular, 94, 158 Autopsy, 17, 158 Axillary, 45, 73, 158 B Bacteria, 118, 156, 158, 168, 173, 184, 186, 196, 201, 203, 204, 206 Bactericidal, 158, 206 Bacteriophage, 158, 177, 204 Bacteriophage lambda, 158, 177 Bacterium, 29, 158 Basal Cell Nevus Syndrome, 6, 28, 102, 107, 158 Basal cells, 158, 187 Basal Ganglia, 158, 172 Basal Ganglia Diseases, 158 Base, 13, 107, 158, 159, 166, 172, 179, 203 Basement Membrane, 23, 49, 106, 159, 170, 180 Benign, 41, 52, 59, 118, 153, 156, 159, 169, 172, 179, 182, 186, 187, 189, 196 Benign tumor, 118, 159 Beta carotene, 93, 159 Bilateral, 48, 61, 79, 159 Bile, 159, 162, 169, 171, 181, 195 Bile Ducts, 159, 162, 195 Biochemical, 14, 19, 20, 24, 27, 35, 39, 82, 154, 159, 180 Biological response modifier, 159, 178 Biological therapy, 159, 173 Biological Transport, 159, 167 Biomarkers, 68, 73, 89, 102, 159 Biopsy, 66, 102, 119, 141, 152, 159, 170 Biosynthesis, 157, 159, 199 Biotechnology, 41, 42, 122, 129, 131, 132, 133, 159 Biotic, 159, 205 Bladder, 111, 136, 160, 177, 194, 206 Blister, 160, 190 Blood Glucose, 160, 174 Blood pressure, 160, 185, 200

Blood vessel, 119, 156, 160, 162, 168, 179, 182, 183, 190, 200, 202, 203, 206 Body Fluids, 40, 159, 160, 167, 200, 205 Bone Marrow, 160, 166, 176, 182, 185, 200, 202 Boron, 160, 165 Bowel, 155, 160, 167 Bowel Movement, 160, 167 Brachytherapy, 160, 178, 179, 196, 207 Branch, 149, 160, 182, 183, 188, 190, 195, 200, 203 Buccal, 29, 119, 160, 181, 202 Burns, 16, 160 Burns, Electric, 160 C Calcium, 160, 164, 182, 189, 199, 203 Callus, 160, 168, 179 Cancer vaccine, 160, 183 Carbon Dioxide, 60, 160, 197 Carcinogen, 6, 48, 160, 185 Carcinogenesis, 5, 6, 7, 9, 12, 17, 27, 45, 54, 66, 72, 161, 162 Carcinogenic, 6, 7, 9, 13, 27, 40, 161, 177, 188, 193, 205, 206 Cardiac, 107, 154, 161, 168, 169, 186 Carotene, 159, 161 Carotenoids, 85, 89, 97, 159, 161 Case report, 45, 46, 48, 74, 78, 81, 161 Case series, 44, 161 Cataracts, 57, 161 Causal, 107, 110, 161 CDC2, 6, 161 Celecoxib, 102, 161 Cell Adhesion, 11, 31, 161 Cell Cycle, 7, 8, 16, 161, 166, 195 Cell Death, 8, 21, 157, 161, 186 Cell Differentiation, 37, 42, 161, 181, 199 Cell Division, 132, 155, 158, 161, 173, 184, 191, 199 Cell membrane, 159, 161, 166, 191 Cell proliferation, 7, 19, 25, 28, 37, 161, 199 Cell Survival, 161, 173 Central Nervous System, 162, 172, 173 Cerebellar, 158, 162, 197 Cerebral, 56, 158, 162, 169, 170, 172 Cerebral hemispheres, 158, 162, 172 Cerebrum, 162, 205 Cerumen, 118, 162 Cervical, 70, 109, 162 Cervix, 73, 162 Chemoprevention, 7, 8, 9, 26, 94, 102, 162 Chemopreventive, 7, 8, 34, 162

Index 211

Chemotherapy, 71, 83, 93, 96, 118, 119, 154, 162 Cholangiography, 162, 195 Cholesteatoma, 118, 162 Cholesterol, 28, 34, 114, 159, 162 Chromatin, 22, 157, 162, 169 Chromosomal, 5, 6, 12, 107, 110, 155, 162 Chromosome, 26, 44, 45, 46, 52, 58, 63, 73, 82, 155, 162, 173, 175, 181, 185, 199, 205 Chromosome Abnormalities, 162, 175 Chronic renal, 162, 192 Cidofovir, 82, 162 Circulatory system, 37, 162 CIS, 8, 26, 89, 137, 163 Cleft Palate, 163, 175 Clinical Medicine, 163, 193 Clinical trial, 4, 8, 72, 101, 103, 129, 163, 164, 165, 166, 190, 194, 196 Clone, 5, 163 Cloning, 19, 159, 163 Coagulation, 160, 163, 174, 180, 203 Cofactor, 163, 187, 194, 203 Colchicine, 77, 163 Collagen, 23, 63, 96, 106, 159, 163, 170, 171, 178, 182, 193 Coloboma, 163, 175 Combination Therapy, 57, 163 Combinatorial, 9, 29, 163 Complement, 163, 164, 172, 182 Complementary and alternative medicine, 93, 98, 164 Complementary medicine, 93, 164 Computational Biology, 129, 131, 164 Congestion, 164, 170 Conjunctiva, 89, 164, 202 Connective Tissue, 20, 160, 163, 164, 171, 172, 181, 183, 194, 198, 200, 202 Connective Tissue Cells, 164 Contact dermatitis, 120, 164 Contraindications, ii, 164 Control group, 29, 40, 164 Controlled study, 66, 165 Conventional therapy, 165 Conventional treatment, 22, 165 Coordination, 11, 21, 165 Cornea, 17, 156, 165, 198, 202, 208 Corneum, 165, 169 Coronary, 165, 184 Coronary Thrombosis, 165, 184 Cortex, 158, 165, 170, 197 Corticosteroids, 17, 165 Cranial, 81, 165, 171, 175, 189, 190

Cranial Irradiation, 81, 165 Crossing-over, 165, 197 Croton Oil, 165, 191 Cryosurgery, 55, 59, 64, 71, 109, 141, 152, 165 Cryotherapy, 16, 165 Cultured cells, 25, 34, 165 Curative, 165, 203 Curcumin, 88, 110, 111, 165 Curettage, 54, 97, 109, 141, 165 Curette, 165 Cyclic, 165, 192, 194 Cyclin, 6, 8, 16, 32, 53, 166 Cyclopia, 166, 175 Cyclosporine, 80, 166 Cytokine, 38, 166 Cytoplasm, 157, 161, 166, 169, 173, 185 Cytoskeleton, 17, 20, 166, 184 Cytotoxic, 166, 196, 200 D Data Collection, 166, 171 Databases, Bibliographic, 129, 166 Deletion, 51, 107, 110, 157, 166, 181 Delivery of Health Care, 166, 174 Demecolcine, 97, 166 Dementia, 153, 166 Dendrites, 166, 187 Dendritic, 31, 166, 183 Dendritic cell, 31, 166 Density, 10, 39, 51, 166, 188 Dentists, 3, 166 Depolarization, 30, 166, 200 Dermal, 21, 67, 112, 113, 166, 180, 200 Dermatitis, 94, 112, 114, 118, 120, 167, 168 Diabetes Mellitus, 167, 174 Diagnostic procedure, 105, 123, 167 Diclofenac, 109, 167 Diclofenac Sodium, 109, 167 Diffusion, 34, 159, 167, 177 Digestive system, 104, 167, 185 Digestive tract, 167, 201 Dilatation, 167, 193 Diploid, 6, 155, 167, 185, 191, 192, 205 Direct, iii, 9, 11, 21, 22, 31, 34, 35, 36, 37, 65, 106, 163, 167, 168, 181, 197 Dissection, 21, 25, 167 Dissociation, 154, 167, 178 Distal, 30, 167, 168, 195 Dorsal, 167, 170, 192 Dorsum, 46, 167, 172 Drug Interactions, 167 Duct, 58, 167, 198, 202

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Basal Cell Carcinoma

Dysplasia, 32, 133, 167 Dystrophic, 111, 167, 169 Dystrophy, 132, 167 E Ectopic, 38, 168 Eczema, 111, 114, 168 Edema, 164, 168, 185 Effector, 16, 25, 30, 32, 108, 163, 168 Efficacy, 7, 22, 34, 40, 54, 168, 205 Elasticity, 168, 200 Elastin, 163, 168, 170 Electric Impedance, 52, 168 Electrode, 168 Electrodesiccation, 97, 109, 141, 168 Electrons, 157, 159, 168, 178, 189, 196 Emaciation, 153, 168 Embryo, 34, 36, 37, 161, 168, 177, 181, 186, 187, 206 Embryogenesis, 34, 112, 168 Enamel, 168, 179 Endemic, 168, 201 Endothelial cell, 156, 168, 171, 203 Endotoxic, 168, 181 End-stage renal, 162, 168, 192 Enhancer, 35, 168 Enterohepatic, 169, 202 Enterohepatic Circulation, 169, 202 Environmental Exposure, 14, 26, 169, 188 Environmental Health, 48, 128, 130, 169 Enzyme, 7, 96, 168, 169, 177, 179, 187, 194, 199, 203, 204, 207, 208 Eosinophils, 55, 156, 169, 173, 180 Epidemic, 40, 169, 201 Epidermal, 7, 16, 18, 20, 23, 32, 36, 37, 42, 47, 78, 111, 169, 179, 180, 183, 206 Epidermal Cyst, 47, 169 Epidermal Growth Factor, 78, 169 Epidermoid carcinoma, 169, 201 Epidermolysis Bullosa, 23, 111, 169 Epidural, 169, 201 Epinephrine, 169, 205 Epithelial, 3, 14, 16, 17, 24, 30, 36, 37, 39, 57, 106, 108, 118, 153, 159, 169, 170, 179, 180, 189 Epithelial Cells, 36, 37, 106, 169, 180 Epithelioma, 95, 96, 169 Epithelium, 16, 17, 30, 39, 159, 169, 179, 189, 208 Erythema, 120, 164, 170 Erythema Multiforme, 120, 170 Erythrocytes, 155, 160, 170 Erythroplakia, 118, 170

Esophagus, 75, 167, 170, 201, 202 Essential Tremor, 132, 170 Etretinate, 120, 170 Eukaryotic Cells, 161, 170, 176, 188 Evoke, 170, 201 Excipient, 109, 170 Excisional, 170, 207 Exogenous, 17, 30, 168, 170 Exon, 34, 170 Extensor, 170, 195 External-beam radiation, 170, 179, 196, 207 Extracellular, 15, 20, 27, 34, 106, 157, 164, 170, 171, 182, 200, 203 Extracellular Matrix, 15, 106, 164, 170, 171, 182 Extracellular Matrix Proteins, 170, 182 Extracellular Space, 170 Extremity, 171, 180 Eye socket, 171, 190 F Facial, 19, 52, 53, 55, 57, 59, 122, 171, 175, 183, 189 Facial Nerve, 171, 189 Family Planning, 129, 171 Fat, 34, 157, 159, 160, 161, 171, 181, 198, 200 Fatty acids, 171, 193 Fetus, 171, 193, 206 Fibroblast Growth Factor, 111, 171 Fibroblasts, 6, 11, 66, 112, 164, 171, 178 Fibrosis, 118, 119, 133, 154, 171, 198 Fine-needle aspiration, 45, 171, 186 Flexor, 170, 171, 180 Fluorescence, 22, 30, 59, 70, 171 Focus Groups, 40, 171 Follicles, 36, 171 Folliculitis, 54, 171 Foramen, 171, 174, 183 Furunculosis, 118, 171 G Gallbladder, 153, 159, 167, 171, 195 Gamma Rays, 171, 185, 196 Ganglia, 158, 171, 186, 190 Ganglion, 172, 207 Gas, 155, 160, 167, 172, 175, 185, 187 Gastric, 169, 172 Gastrointestinal, 169, 172, 202, 205 Gene Expression, 12, 21, 26, 28, 35, 36, 37, 39, 73, 133, 172 Genetic Code, 172, 187 Genetic Engineering, 159, 163, 172

Index 213

Genetics, 21, 25, 26, 27, 33, 49, 74, 82, 172, 190 Genital, 61, 109, 172 Genotype, 7, 13, 172, 191 Germ Cells, 172, 188, 200 Germline mutation, 43, 60, 172, 174 Gland, 118, 172, 181, 189, 191, 194, 198, 199, 201, 202, 204 Glioblastoma, 33, 172 Glioma, 112, 172 Glucose, 132, 160, 167, 172, 174, 177 Glucuronic Acid, 172, 174 Glutamic Acid, 173, 193 Glycine, 155, 173, 199 Glycoprotein, 106, 173, 180, 203 Glycosaminoglycans, 170, 173, 194 Gout, 163, 173 Governing Board, 173, 193 Grade, 40, 173 Graft, 173, 175 Gram-negative, 168, 173, 186 Gram-positive, 29, 173 Granulocytes, 173, 200, 207 Granulomas, 111, 173 Groin, 173, 177 Growth factors, 106, 173 H Hair follicles, 20, 30, 36, 43, 67, 171, 173, 207 Haploid, 173, 191, 192 Haplotypes, 13, 45, 173 Haptens, 154, 173 Health Care Costs, 7, 173, 174 Health Expenditures, 174 Heme, 155, 174, 186, 192 Hemoglobin, 22, 155, 170, 174, 192 Hemoglobin A, 174, 192 Hemoglobinuria, 132, 174 Hemorrhage, 174, 202 Hemostasis, 22, 174 Heparin, 106, 174 Hereditary, 25, 63, 97, 158, 172, 173, 174, 192, 198 Hereditary mutation, 172, 174 Heredity, 153, 172, 174 Herniated, 118, 174 Heterogeneity, 154, 174 Histidine, 174, 178 Histiocytosis, 70, 174 Histology, 22, 64, 175 Holoprosencephaly, 19, 27, 34, 37, 175 Homeostasis, 17, 175

Homologous, 13, 154, 165, 175, 195, 199, 203 Hormonal, 158, 175 Hormone, 154, 165, 169, 175, 183, 199, 204 Hormone therapy, 154, 175 Horny layer, 169, 175 Host, 12, 15, 26, 31, 65, 158, 175, 176, 177, 207 Host-cell, 12, 175 Human Development, 33, 128, 175 Human papillomavirus, 65, 113, 175 Hybrid, 163, 175 Hybridization, 36, 175 Hybridomas, 175, 178 Hydrogen, 153, 155, 159, 170, 175, 185, 187, 188, 190, 195 Hydrolysis, 175, 179, 191, 192, 194 Hydrophobic, 112, 175 Hydroxylysine, 163, 176 Hydroxyproline, 163, 176 Hyperplasia, 37, 80, 176, 180 Hypertrophy, 176 I Id, 90, 98, 132, 142, 148, 150, 176 Immune response, 31, 112, 154, 156, 173, 176, 182, 202, 206, 207 Immune Sera, 176 Immune system, 31, 103, 156, 159, 176, 182, 206, 207 Immunity, 153, 176, 204 Immunization, 43, 176 Immunodeficiency, 132, 153, 176 Immunogenic, 176, 181 Immunoglobulin, 156, 176, 185 Immunohistochemistry, 12, 50, 176 Immunologic, 176, 196 Immunology, 21, 38, 72, 154, 176 Impairment, 8, 24, 157, 176, 183 Implant radiation, 176, 178, 179, 196, 207 Impotence, 176, 201 In situ, 12, 18, 36, 60, 106, 176 In Situ Hybridization, 12, 36, 60, 176 In vitro, 8, 9, 11, 15, 29, 31, 32, 33, 36, 62, 96, 106, 177 In vivo, 5, 8, 9, 15, 16, 17, 18, 21, 30, 31, 32, 36, 37, 38, 55, 72, 79, 96, 106, 174, 177, 202 Incision, 177, 178 Incontinence, 177, 201 Incubation, 29, 177 Incubators, 11, 177 Indicative, 117, 177, 190, 206

214

Basal Cell Carcinoma

Induction, 5, 6, 7, 8, 9, 17, 23, 34, 39, 42, 49, 177, 196 Infancy, 40, 74, 177 Infantile, 56, 177 Infarction, 165, 177, 184 Infection, 49, 153, 157, 158, 159, 162, 171, 176, 177, 180, 181, 182, 188, 202, 207 Infiltration, 177, 182, 208 Inflammation, 37, 51, 114, 153, 156, 164, 165, 167, 171, 173, 177, 188, 196, 198, 201, 202, 207 Inguinal, 61, 68, 177 Initiation, 21, 23, 35, 101, 177, 204 Inositol, 82, 177 Insight, 19, 24, 32, 33, 39, 177 Integrase, 34, 177 Interferon, 8, 57, 68, 82, 84, 119, 178 Interferon Alfa-2b, 84, 178 Interferon-alpha, 8, 178 Interleukin-6, 76, 82, 178 Intermediate Filaments, 63, 178 Intermittent, 40, 178, 181 Internal radiation, 178, 179, 196, 207 Interspecific, 5, 178 Interstitial, 60, 160, 170, 178, 179, 207 Interstitial Collagenase, 60, 178 Intervertebral, 174, 178 Intestinal, 161, 178, 182 Intestines, 153, 169, 172, 178, 199 Intracellular, 21, 27, 28, 177, 178, 183, 194, 197, 199 Intracellular Membranes, 178, 183 Intrinsic, 154, 159, 178 Invasive, 15, 23, 29, 30, 33, 69, 176, 178 Involuntary, 158, 170, 178, 186 Ionization, 178 Ionizing, 26, 34, 37, 154, 169, 178, 196, 205 Ions, 159, 167, 175, 178 Ipsilateral, 50, 179, 197 Iris, 57, 156, 165, 179, 195 Irradiance, 22, 179 Irradiation, 8, 29, 34, 49, 109, 179, 196, 207 Ischemia, 158, 179 Isotretinoin, 57, 72, 179 Isozymes, 14, 179 J Joint, 118, 171, 179, 202 K Kb, 17, 128, 179 Keratin, 5, 179, 198 Keratinocytes, 7, 10, 15, 17, 20, 23, 24, 32, 39, 179

Keratoacanthoma, 78, 88, 119, 179 Keratosis, 47, 75, 111, 118, 120, 153, 179 Kidney Disease, 104, 128, 133, 179 Kinesin, 33, 179 Kinetic, 178, 180 L Lacrimal, 45, 171, 180 Laminin, 14, 23, 106, 159, 170, 180 Large Intestine, 167, 178, 180, 197 Laser Surgery, 141, 180 Latent, 180, 193 Lectin, 180, 183 Leg Ulcer, 75, 180 Leiomyosarcoma, 78, 180 Leishmaniasis, 51, 180 Lens, 161, 180, 197 Lentigo, 77, 180 Lesion, 8, 38, 41, 101, 109, 152, 179, 180, 181, 201, 205 Leukemia, 132, 180 Leukocytes, 160, 169, 173, 178, 180, 185 Leukoplakia, 118, 180 Library Services, 148, 180 Lichen Planus, 120, 170, 180 Ligament, 181, 194 Light microscope, 181, 184 Limb Bud, 27, 181 Linkage, 5, 82, 181 Linkage Disequilibrium, 5, 181 Lip, 58, 175, 181 Lipid, 11, 71, 181 Lipid A, 11, 181 Lipopolysaccharides, 181 Liquor, 181, 196 Liver, 153, 155, 157, 159, 167, 169, 171, 172, 174, 180, 181, 195, 206 Local therapy, 8, 181 Localization, 28, 29, 83, 176, 181 Localized, 27, 29, 118, 153, 155, 177, 180, 181, 191, 201, 205 Long-Term Care, 10, 181 Loss of Heterozygosity, 12, 46, 52, 63, 72, 181 Lucida, 180, 181 Lupus, 120, 181 Lymph, 47, 70, 73, 158, 162, 168, 181, 182, 186, 202 Lymph node, 47, 70, 158, 162, 181, 182, 186 Lymphadenopathy, 73, 182 Lymphatic, 177, 181, 182, 183, 200, 201, 204

Index 215

Lymphatic system, 181, 182, 200, 201, 204 Lymphocyte, 38, 56, 153, 156, 182, 183 Lymphocyte Count, 153, 182 Lymphocytic, 12, 182 Lymphoid, 156, 165, 182 Lymphoma, 38, 132, 182, 186 Lymphomatoid Papulosis, 74, 182 M Major Histocompatibility Complex, 173, 182 Malabsorption, 132, 182 Malformation, 27, 182 Malignancy, 7, 26, 41, 182, 189 Malignant tumor, 11, 118, 119, 182, 198 Malnutrition, 158, 182, 185 Mammary, 26, 182 Matrix metalloproteinase, 30, 60, 84, 88, 182 Maxillary, 119, 182, 189 Maxillary Sinus, 119, 182 Meatus, 183, 205 Medial, 118, 183 Mediate, 32, 183 Mediator, 17, 36, 183 Medical Records, 183, 198 MEDLINE, 129, 131, 133, 183 Medulloblastoma, 28, 33, 35, 51, 73, 74, 183 Melanin, 51, 179, 183, 191, 205 Melanocytes, 183, 187 Melanoma vaccine, 38, 183 Membrane Proteins, 19, 183 Meninges, 162, 183 Meningioma, 43, 81, 183 Mental Disorders, 104, 183 Mental Health, iv, 4, 104, 128, 130, 183, 195 Mental Retardation, 134, 175, 183 Mesenchymal, 14, 30, 36, 169, 183 Metastasis, 31, 47, 61, 70, 106, 118, 182, 183, 184 Metastasize, 141, 184, 198 Metastatic, 45, 49, 73, 76, 96, 184, 198 Methyl Methanesulfonate, 53, 184 MI, 108, 113, 152, 184 Microbe, 184, 204 Microfilaments, 178, 184 Microorganism, 163, 184, 190, 207 Microscopy, 21, 35, 50, 71, 78, 79, 159, 184 Microsurgery, 18, 22, 70, 184 Microtubules, 178, 179, 184, 189 Migration, 16, 184

Millimeter, 39, 184 Miscible, 112, 184 Mitochondrial Swelling, 184, 186 Mitosis, 6, 157, 161, 184 Mitotic, 6, 184 Mobilization, 20, 184 Modification, 7, 34, 172, 184, 196 Molecule, 25, 35, 42, 54, 66, 88, 156, 159, 164, 166, 167, 168, 175, 180, 184, 187, 189, 194, 196, 197, 199, 206 Monitor, 40, 185, 187 Monoclonal, 43, 54, 83, 175, 179, 185, 196, 207 Monocytes, 178, 180, 185 Monosomy, 156, 185 Morphogenesis, 14, 24, 35, 106, 181, 185 Morphological, 168, 183, 185 Morphology, 15, 22, 185 Mucinous, 119, 172, 185 Mucocutaneous, 113, 114, 180, 185 Mucosa, 114, 118, 120, 181, 185, 202 Mucositis, 185, 203 Mucus, 185 Multivariate Analysis, 64, 185 Muscle Fibers, 185 Muscular Atrophy, 132, 185 Muscular Dystrophies, 168, 185 Mustard Gas, 185 Mutagen, 12, 184, 185 Mutagenesis, 15, 185 Mutagenic, 186, 206 Mycoplasma, 11, 186 Mycosis, 182, 186 Mycosis Fungoides, 182, 186 Myocardium, 184, 186 Myoglobin, 186, 192 Myotonic Dystrophy, 132, 186 N Naevus, 43, 186 NCI, 1, 21, 102, 104, 127, 137, 163, 186, 190 Necrosis, 15, 157, 172, 177, 184, 186 Need, 3, 4, 11, 23, 30, 117, 119, 138, 143, 162, 182, 186 Needle biopsy, 171, 186 Neonatal, 11, 186 Neoplasia, 14, 21, 23, 24, 32, 111, 132, 170, 186 Neoplasm, 85, 169, 186, 189, 198, 201, 205 Neoplastic, 21, 111, 162, 175, 179, 181, 182, 186 Nephropathy, 179, 186

216

Basal Cell Carcinoma

Nerve, 67, 157, 166, 171, 172, 174, 183, 186, 190, 192, 198, 201, 204, 205, 207 Nervous System, 38, 132, 162, 183, 186, 187, 190 Networks, 14, 186 Neural, 27, 112, 186, 193, 200 Neuroectodermal Tumors, 186 Neurologic, 172, 186 Neurons, 34, 166, 171, 187, 203 Neurophysiology, 166, 187 Neutrons, 154, 179, 187, 196 Nevus, 36, 42, 120, 180, 187 Nickel, 94, 187 Nitrogen, 109, 154, 155, 170, 187, 205 Nonmelanoma skin cancer, 8, 10, 93, 95, 109, 187 Notochord, 112, 187 Nuclear, 18, 21, 24, 35, 85, 158, 168, 170, 171, 172, 186, 187, 196 Nuclear Medicine, 21, 187 Nuclei, 22, 49, 78, 154, 168, 172, 184, 187, 195 Nucleic acid, 109, 172, 175, 176, 187, 195 Nucleic Acid Hybridization, 175, 187 Nucleus, 157, 158, 162, 166, 169, 170, 171, 178, 185, 187, 195, 203 O Observational study, 10, 187 Ocular, 186, 188 Odds Ratio, 188, 197 Odour, 157, 188 Oncogene, 32, 45, 56, 65, 76, 88, 112, 132, 188 Oncogenic, 25, 188, 195 Oncology, 12, 21, 43, 44, 49, 50, 51, 53, 56, 60, 68, 73, 84, 85, 107, 110, 188 Opacity, 161, 166, 188 Opportunistic Infections, 153, 188 Oral Health, 4, 188 Orbit, 171, 188, 190 Orbital, 57, 188 Organ Culture, 30, 188 Organelles, 166, 179, 183, 185, 188 Ornithine, 7, 188 Osteoporosis, 32, 188 Otitis, 118, 188 Otolaryngologist, 118, 188 Otolaryngology, 63, 76, 118, 188 Otology, 52, 54, 118, 188 Ovary, 19, 188, 202 Oxidation, 153, 157, 188 Oxygenation, 23, 189

P P53 gene, 9, 26, 80, 189 Paclitaxel, 97, 189 Palate, 119, 163, 189, 202 Palliative, 189, 203 Palsy, 52, 189 Pancreas, 153, 159, 167, 189, 205 Pancreatic, 132, 189 Pancreatic cancer, 132, 189 Papilloma, 109, 169, 189 Papillomavirus, 189 Paranasal Sinuses, 182, 189 Parathyroid, 66, 189, 203 Parathyroid Glands, 189 Parathyroid hormone, 66, 189 Parotid, 106, 189 Paroxysmal, 132, 189 Particle, 189, 204 Partnership Practice, 189, 193 Patch, 7, 141, 170, 180, 190 Pathogen, 177, 190 Pathogenesis, 7, 17, 108, 119, 190 Pathologic, 157, 159, 165, 190, 195 Pathologic Processes, 157, 190 Pathologies, 33, 111, 118, 190 Patient Education, 140, 146, 148, 152, 190 Patient Satisfaction, 10, 190 PDQ, 137, 139, 190 Pelvic, 190, 194 Pemphigus, 120, 153, 190 Peptide, 34, 109, 171, 179, 190, 192, 194 Perfusion, 16, 22, 190 Perianal, 79, 190 Perineural, 8, 190 Periorbital, 57, 59, 190 Peripheral blood, 6, 11, 12, 178, 190 Peripheral Nervous System, 186, 189, 190, 202 PH, 16, 67, 190 Pharmacologic, 30, 33, 165, 190, 204 Phenotype, 28, 60, 88, 106, 191 Phenylalanine, 191, 205 Phorbol, 17, 191 Phorbol Esters, 17, 191 Phospholipases, 191, 200 Phospholipids, 171, 177, 191 Phosphorus, 160, 189, 191 Phosphorylation, 25, 30, 35, 191 Photodynamic therapy, 15, 29, 77, 96, 103, 191 Photosensitivity, 191, 207 Photosensitizer, 22, 29, 191

Index 217

Physiologic, 159, 191, 193, 197 Physiology, 20, 95, 118, 187, 191 Pigment, 119, 183, 186, 187, 191 Pigmentation, 41, 186, 191 Pilocytic, 81, 191 Pilot study, 22, 191 Pituitary Gland, 171, 191 Plants, 154, 160, 172, 180, 185, 191, 204, 205 Plasma, 89, 156, 161, 174, 186, 191, 192, 197, 199 Plasma cells, 156, 192 Plasmids, 12, 192 Platelet Activation, 192, 200 Pleated, 179, 192 Ploidy, 53, 192 Polycystic, 133, 192 Polymorphic, 88, 192 Polyp, 118, 192 Polypeptide, 155, 163, 169, 175, 186, 192, 208 Polyposis, 153, 192 Polysaccharide, 156, 192, 194 Porphyrins, 95, 192 Posterior, 155, 157, 167, 179, 189, 192, 198 Postmenopausal, 188, 192 Postnatal, 27, 192, 201 Postoperative, 120, 192 Postsynaptic, 192, 199 Potentiate, 23, 192 Potentiation, 192, 200 Practicability, 192, 205 Practice Guidelines, 130, 192 Precancerous, 153, 162, 193 Preclinical, 8, 31, 193 Precursor, 26, 35, 157, 159, 168, 191, 193, 205 Predisposition, 5, 33, 114, 193 Premalignant, 118, 193 Prenatal, 19, 168, 193 Prevalence, 10, 36, 67, 107, 188, 193 Prickle, 153, 179, 193 Primary tumor, 8, 193 Primitive neuroectodermal tumors, 33, 183, 193 Private Practice, 10, 193 Probe, 7, 30, 193 Progression, 12, 14, 23, 35, 106, 118, 156, 193 Progressive, 107, 110, 161, 162, 166, 173, 185, 186, 192, 193, 205 Proline, 17, 163, 176, 193

Promoter, 5, 17, 31, 37, 193 Prophylaxis, 170, 193 Prosencephalon, 175, 193 Prospective study, 79, 193 Prostaglandin, 89, 108, 193 Prostaglandins A, 194 Prostate, 43, 132, 159, 194, 205 Protease, 163, 194 Protective Clothing, 40, 194 Protein C, 33, 83, 155, 158, 179, 194, 206 Protein Kinases, 19, 194 Protein S, 9, 27, 133, 159, 172, 194 Proteinuria, 77, 194 Proteoglycan, 106, 194 Proteolytic, 35, 164, 194 Protocol, 15, 31, 194 Protons, 154, 175, 178, 195, 196 Proto-Oncogene Proteins, 189, 195 Proto-Oncogene Proteins c-mos, 189, 195 Proto-Oncogenes, 16, 107, 110, 195 Protozoa, 180, 184, 195 Proximal, 167, 195 Pruritic, 168, 180, 195, 198 Psoriasis, 20, 42, 72, 94, 111, 114, 120, 170, 185, 195 PTC, 6, 28, 33, 34, 75, 107, 110, 112, 195 Public Health, 7, 26, 85, 130, 195 Public Policy, 129, 195 Publishing, 41, 118, 195 Pulmonary, 47, 160, 195, 206 Pulse, 40, 81, 185, 195 Pupil, 165, 195 Purines, 195, 199 Pustular, 54, 153, 196 Pyogenic, 111, 196 Pyrimidine Dimers, 9, 196 Q Quality of Life, 8, 10, 61, 196, 202 R Race, 13, 184, 196 Radiation therapy, 8, 83, 141, 153, 154, 170, 178, 179, 196, 207 Radioactive, 175, 176, 178, 179, 187, 188, 196, 205, 207 Radioactivity, 165, 196 Radioimmunotherapy, 196 Radiolabeled, 179, 196, 207 Radiology, 21, 187, 196 Radiotherapy, 44, 61, 73, 80, 83, 118, 160, 179, 196, 207 Randomized, 8, 40, 66, 77, 93, 168, 196 Reactivation, 12, 196

218

Basal Cell Carcinoma

Reactive Oxygen Species, 7, 29, 196 Receptor, 20, 24, 26, 27, 32, 34, 36, 78, 108, 112, 156, 197, 199 Receptors, Cytokine, 12, 197 Recombinant, 68, 84, 178, 197, 206 Recombination, 13, 197 Reconstitution, 33, 197 Rectum, 157, 160, 167, 172, 177, 180, 194, 197 Recurrence, 4, 8, 10, 64, 71, 77, 80, 85, 141, 162, 197 Red Nucleus, 158, 197 Refer, 1, 160, 163, 181, 187, 196, 197 Refractory, 37, 106, 197 Regeneration, 17, 171, 197 Regimen, 31, 168, 197 Relative risk, 13, 197 Remission, 197 Reproductive cells, 172, 174, 197 Resection, 49, 61, 76, 109, 197 Resolving, 40, 197 Respiration, 160, 185, 197 Restoration, 196, 197, 198, 207 Retinoblastoma, 25, 132, 198 Retinoid, 8, 12, 170, 198 Retinol, 89, 198 Retrospective, 77, 82, 198 Retrospective study, 77, 198 Rhabdomyosarcoma, 35, 198 Risk factor, 7, 9, 24, 26, 28, 65, 72, 79, 120, 193, 197, 198 Rod, 158, 187, 198 S Salicylic, 96, 198 Saliva, 198 Salivary, 35, 45, 167, 171, 189, 198, 202 Salivary glands, 35, 45, 167, 171, 198 Sarcoma, 111, 119, 193, 198 Scabies, 120, 198 Sclera, 164, 198 Scleroproteins, 179, 198 Sclerosis, 132, 198 Screening, 16, 22, 41, 139, 163, 190, 198 Scrotum, 46, 62, 198, 203 Sebaceous, 18, 80, 119, 198, 207 Sebaceous gland, 18, 198, 207 Sebum, 153, 198 Secondary tumor, 184, 198 Secretion, 30, 31, 106, 153, 169, 185, 199 Segmentation, 175, 199 Segregation, 197, 199 Seizures, 172, 175, 189, 199

Sella, 167, 191, 199 Semen, 194, 199 Senile, 153, 180, 188, 199 Sensor, 39, 199 Sensory loss, 199, 201, 203 Sequencing, 12, 65, 199 Serine, 106, 195, 199 Serum, 89, 163, 176, 197, 199 Sex Determination, 133, 199 Shock, 63, 199, 205 Side effect, 102, 114, 154, 159, 199, 202, 204 Signal Transduction, 19, 25, 33, 35, 112, 177, 199 Skeletal, 158, 185, 200 Skeleton, 32, 153, 179, 194, 200 Skin Aging, 114, 200 Skin Pigmentation, 3, 200 Skull, 162, 171, 188, 200, 203 Smooth muscle, 106, 154, 164, 200, 202 Social Environment, 196, 200 Sodium, 167, 173, 200, 202 Soft tissue, 62, 118, 160, 200 Solid tumor, 8, 156, 200 Soma, 200 Somatic, 5, 24, 168, 184, 190, 200 Somatic cells, 184, 200 Somites, 37, 200 Specialist, 143, 200 Specificity, 76, 154, 200 Spectrophotometry, 51, 201 Spectrum, 165, 201, 205 Sperm, 162, 172, 174, 197, 201, 203 Spina bifida, 158, 201 Spinal cord, 37, 79, 157, 162, 169, 172, 183, 186, 190, 201 Spinal Cord Compression, 79, 201 Spinal Fractures, 201 Spinous, 169, 179, 201 Spleen, 155, 182, 201 Sporadic, 25, 33, 36, 44, 51, 52, 65, 84, 107, 110, 111, 198, 201 Squamous cells, 187, 201 Squamous Epithelium, 162, 201 Stem Cells, 17, 20, 201 Sterile, 157, 189, 201 Steroids, 165, 201 Stimulus, 7, 168, 201, 203 Stomach, 153, 167, 170, 172, 175, 178, 201, 202 Stomatitis, 118, 120, 202 Stress, 4, 7, 193, 202 Stroke, 104, 128, 202

Index 219

Stroma, 15, 30, 39, 179, 202 Stromal, 23, 39, 202 Stromal Cells, 39, 202 Subacute, 177, 202 Subclinical, 177, 199, 202 Subconjunctival, 57, 202 Subcutaneous, 23, 109, 168, 169, 202 Submaxillary, 169, 202 Submucous, 119, 202 Subspecies, 200, 202 Substance P, 197, 199, 202 Sulindac, 37, 202 Supplementation, 84, 93, 97, 202 Supportive care, 190, 202 Suppression, 27, 36, 202 Sweat, 162, 202 Sweat Glands, 162, 202 Symphysis, 194, 202 Synaptic, 200, 202 Synergistic, 8, 9, 15, 114, 203 Systemic, 61, 71, 155, 160, 169, 177, 179, 196, 202, 203, 204, 207 Systemic disease, 71, 203 T Teichoic Acids, 173, 203 Telangiectasia, 133, 203 Temporal, 28, 34, 183, 203 Teratogenic, 170, 179, 203 Testicles, 198, 203 Tetany, 189, 203 Thalamic, 158, 203 Thalamic Diseases, 158, 203 Therapeutics, 35, 203 Threonine, 195, 199, 203 Threshold, 59, 203 Thrombin, 194, 203 Thrombomodulin, 194, 203 Thrombosis, 194, 202, 203 Thymidine, 18, 203 Thymidine Kinase, 18, 203 Thymus, 176, 182, 204 Thyroid, 189, 204, 205 Thyroid Gland, 189, 204 Tinnitus, 188, 204 Tomography, 77, 204 Topical, 12, 22, 29, 37, 44, 54, 70, 77, 80, 82, 89, 103, 109, 112, 113, 179, 204 Toxic, iv, 12, 108, 167, 169, 176, 204 Toxicity, 29, 167, 204 Toxicology, 6, 24, 130, 204 Toxins, 156, 172, 177, 196, 204 Trace element, 29, 160, 187, 204

Transcription Factors, 14, 35, 38, 112, 204 Transduction, 19, 28, 33, 35, 199, 204 Transfection, 159, 204 Transfer Factor, 176, 204 Transferases, 27, 204 Transillumination, 41, 204 Translational, 12, 38, 205 Transmitter, 157, 183, 205 Transplantation, 162, 176, 182, 205 Trauma, 118, 158, 186, 203, 204, 205 Treatment Outcome, 10, 13, 38, 205 Trees, 155, 205 Trisomy, 156, 205 Tryptophan, 163, 205 Tuberculosis, 181, 198, 205 Tuberous Sclerosis, 111, 133, 205 Tumor marker, 159, 205 Tumor suppressor gene, 5, 13, 31, 107, 110, 118, 181, 189, 205 Tumorigenic, 72, 76, 106, 205 Tumour, 44, 48, 82, 172, 205 Tympanic membrane, 118, 205 Tyrosine, 30, 205 U Ulcer, 180, 205, 206 Ultraviolet Rays, 141, 205 Umbilical Cord, 206 Umbilicus, 46, 206 Unconscious, 176, 206 Urea, 188, 202, 206 Urethra, 194, 206 Urine, 160, 169, 174, 177, 194, 206 Uterus, 162, 180, 206 V Vaccine, 113, 154, 160, 194, 206 Vaccine adjuvant, 113, 206 Vagina, 162, 206 Varicella, 49, 206 Varicose, 180, 206 Vascular, 56, 84, 154, 156, 177, 204, 206 Vascular endothelial growth factor, 56, 206 Vector, 204, 206 Vein, 187, 189, 206 Venous, 111, 180, 194, 206 Ventral, 38, 112, 206 Ventricle, 195, 206 Venules, 160, 206 Verruca, 111, 206 Vertebrae, 158, 178, 201, 206 Vertebral, 187, 200, 201, 206 Vertigo, 188, 207

220

Basal Cell Carcinoma

Veterinary Medicine, 129, 207 Viral, 109, 188, 195, 204, 205, 207 Virulence, 158, 204, 207 Virus, 109, 153, 158, 168, 172, 175, 178, 204, 207 Viscera, 186, 200, 207 Visceral, 180, 207 Vitamin A, 177, 198, 207 Vitro, 11, 15, 31, 33, 36, 107, 174, 207 Vulgaris, 111, 153, 207 W Wart, 179, 207

White blood cell, 156, 180, 182, 185, 192, 207 Wound Healing, 17, 42, 54, 171, 182, 207 X Xenograft, 156, 207 Xeroderma Pigmentosum, 66, 207 X-ray, 171, 179, 185, 187, 195, 196, 205, 207 X-ray therapy, 179, 207 Y Yeasts, 191, 207 Z Zoster, 49, 207 Zymogen, 194, 208

Index 221

222

Basal Cell Carcinoma

Index 223

224

Basal Cell Carcinoma