OVARIAN CANCER – BASIC SCIENCE PERSPECTIVE   Edited bySamir A. Farghaly           Ovarian Cancer – Basic Science Perspective Edited by Samir A. Farghaly Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2012 InTech All chapters are Open Access distributed under the Creative Commons Attribution 3.0 license, which allows users to download, copy and build upon published articles even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. After this work has been published by InTech, authors have the right to republish it, in whole or part, in any publication of which they are the author, and to make other personal use of the work. Any republication, referencing or personal use of the work must explicitly identify the original source. 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Publishing Process Manager Dragana Manestar Technical Editor Teodora Smiljanic Cover Designer InTech Design Team First published February, 2012 Printed in Croatia A free online edition of this book is available at www.intechopen.com Additional hard copies can be obtained from orders@intechweb.org Ovarian Cancer – Basic Science Perspective, Edited by Samir A. Farghaly p. cm. ISBN 978-953-307-812-0   Contents  Preface IX Chapter 1 Epidemiology and Etiology of Ovarian Cancer 3 Ana Fernández Montes, Jesús García Gómez, Miguel Nuñez Viejo, Miguel Alonso Bermejo, Susana Alonso Urrutia and Jesús García Mata Chapter 2 Inflammation and Ovarian Cancer 17 Antonio Macciò and Clelia Madeddu Chapter 3 Photonic Sensor System for Screening Serum Biomarker Proteins in Ovarian Cancer 51 Debra Wawro, Shelby Zimmerman, Robert Magnusson and Peter Koulen Chapter 4 The Role of MUC16 Mucin (CA125) in the Pathogenesis of Ovarian Cancer 67 Claudine Rancourt, Isabelle Matte, Denis Lane and Alain Piché Chapter 5 Apoptosis Pathways in Ovarian Cancer 85 Christine Sers, Reinhold Schafer and Irina Nazarenko Chapter 6 Oncogenic Pathway Signatures and Survival Outcome 105 Xuan Bich Trinh, Peter A. Van Dam, Luc Y. Dirix, Steven J. van Laere and Wiebren A. A. Tjalma Chapter 7 Dysregulated TGFSignaling in Ovarian Cancer 121 Kyle Bauckman, Christie Campla and Meera Nanjundan Chapter 8 New Tumor Biomarkers in Ovarian Cancer and Its Prognostic and Clinical Relevance139 Malgorzata Banys, Natalia Krawczyk and Tanja Fehm Chapter 9 Sensitive Detection of Epithelial Ovarian Cancer Biomarkers Using Tag-Laser Induced Breakdown Spectroscopy 153 Yuri Markushin and Noureddine Melikechi VI Contents Chapter 10 Homeobox Genes and Their Functional Significance in Ovarian Tumorigenesis 171 Bon Quy Trinh and Honami Naora Chapter 11 Transcriptomic Analysis of Human Ovarian Cancer Cells: Changes Mediated by Luteinizing Hormone Receptor Activation 197 Juan Cui, Ying Xu and David Puett Chapter 12 Potential Tumor Biomarkers for Ovarian Cancer 213 Ryan Serio and Blase Billack Chapter 13 Ectoenzymes in Epithelial Ovarian Carcinoma: Potential Diagnostic Markers and Therapeutic Targets 245 Nicola Lo Buono, Simona Morone, Rossella Parrotta, Alice Giacomino, Erika Ortolan and Ada Funaro Chapter 14 P53 Network in Ovarian Cancer 271 Fabiola Moretti and Francesca Mancini Chapter 15 Gene Amplification in Ovarian Carcinomas: Lessons from Selected Amplified Gene Families 287 Stéphanie Gaillard Chapter 16 Nitric Oxide/Protein Kinase G-Iα Promotes c-Src Activation, Proliferation and Chemoresistance in Ovarian Cancer 315 Ronald R. Fiscus, Elaine L. Leung, Janica C. Wong and Mary G. Johlfs Chapter 17 VEGF Targeting Agents in Ovarian Cancer 335 Seiji Mabuchi, Atsuko Wakabayashi and Tadashi Kimura Chapter 18 Autotaxin – A Target for the Treatment of Drug-Resistant Ovarian Cancer? 355 John King-Underwood, Steven M. Allin, Charles W. Redman and Alan Richardson Chapter 19 Potential Monoclonal Antibody Therapy for the Treatment of Ovarian Cancer 385 Gregory Lee, Mingang Zhu and Bixia Ge   Preface  Worldwide, 204,449 new cases of ovarian cancer are diagnosed each year, with an estimated 124,860 disease-related deaths. In the United States, ovarian cancer is the leading cause of gynecologic cancer–related morbidity and mortality due to the difficulty in detecting early-stage disease. Ovarian cancer is the fifth leading cause of death by cancer in the USA, only behind lung, breast, colorectal and pancreatic. The contributors come from several academic medical institutions in the USA, Europe and Asia. The purpose of this book is to provide a broad background of several aspects of basic sciences related to ovarian cancer. The book provides state-of-the-art information on the molecular genetics and biology of ovarian cancer and new approaches to its diagnosis and management. Better understandings of the molecular events that underlie ovarian cancer development are very much needed. The epidemiology of ovarian cancer has been extensively studied; it is known that the incidence of ovarian cancer increases with age. Epithelial ovarian cancer is predominantly a disease of perimenopausal and postmenopausal women, with 80% of ovarian cancers occurring after the age of 40. Approximately 10% of all ovarian cancers can be associated with a familial genetic predisposition. The majority of hereditary ovarian cancers can be linked to two currently known syndromes, hereditary breast and ovarian cancer (HBOC) and hereditary nonpolyposis colorectal cancer (HNPCC). Epidemiology and etiology of hereditary and non-hereditary ovarian cancer is reviewed in Chapter 1. The role of inflammation in promoting ovarian tumorgenesis and cancer progression is presented in Chapter 2. Development of a portable sensor system for screening of serum biomarkers proteins in ovarian cancer is discussed in Chapter 3. The implications of MUC16 (CA125) mucin in the pathogenesis of ovarian cancer is reviewed in chapter 4. The cellular oncogenic pathways that have an effect on survival outcome by a bioinformatical approach in ovarian cancer are covered in Chapter 5. The mechanisms of H-REV 107-1/ HRLS3/ PLA2G16 and its related gene TIG/ RIG1/ PARRES suppression in ovarian cancer is reviewed in Chapter 6. Dysregulated Transforming Growth Factor B (TGFB) signaling in ovarian cancer development is discussed in Chapter 7. New biomarkers and hematogenous tumor cell dissemination in ovarian cancer is detailed in Chapter 8. The development of a transgenic mouse model and optimal techniques that yield sensitive detection of proteins is known to play a role in epithelial ovarian cancer is presented in X Preface Chapter 9. A Homeobox gene as molecular linkage between embryonic development and ovarian cancer is discussed in Chapter 10. Transcriptomic analysis of human ovarian cancer cells and changes mediated by luteinizing hormone receptor activation is discussed in Chapter 11. Known risk factors/conditions that make women susceptible to ovarian cancer and potential biomarkers for early diagnosis is presented in Chapter 12. Ectoenzymes in epithelial ovarian carcinoma as potential biomarkers and therapeutic targets are discussed in Chapter 13. Tumor suppressor gene p53 and its regulators MD M2 and MD M4 in ovarian cancer and their relationship with clinical and pathological presentations are reviewed in Chapter 14. Novel development updates in DNA copy number variations as pertains to ovarian cancer and identifying the most successful markers to be utilized in clinics are discussed in Chapter 15. Endogenous low-level nitric oxide and its action via cyclic GMP/protein kinase G type –I alpha signaling pathway and enhancement of Src tyrosine kinase activity and promotions of cell proliferation/DNA synthesis in ovarian cancer is presented in Chapter 16. Vascular Endothelial Growth Factor (VEGF) as a potent mediator of angiogenesis in epithelial ovarian cancer is reviewed in Chapter 17. Autotaxin as a target for the treatment of drug resistant ovarian cancer is discussed in Chapter 18. Finally, CA125, PK215 and GHR 106 antibodies as potential anti-cancer drugs for the treatment of ovarian cancer is presented in Chapter 19. This book volume is intended for all clinicians and basic medical scientists caring for women with ovarian cancer, including attending surgeons and physicians, fellows, and residents in the disciplines of gynecologic oncology, medical oncology, and primary care. Also PhD students and post-doctoral fellows in basic medical sciences. I hope that you find this book very useful, and benefit from the extensive experience of the knowledgeable team of contributors who have authored its contents.  Samir A. Farghaly, MD, PhD The Joan and Sanford Weill Medical College of Cornell University The New York Presbyterian Hospital Cornell University Medical Center, New York USA [...]... risk of mucinous epithelial ovarian cancer. Am J Epidemiol 2004 ;159:133-9 16 Ovarian Cancer – Basic Science Perspective Ziogas A, Gildea M, Cohen P, Bringman D, Taylor TH, Seminara D et al Cancer risk estimates for family members of a population-based family registry for breast and ovarian cancer Cancer Epidemiol Biomarkers Prev 2000 ;9(1):103-11 2 Inflammation and Ovarian Cancer 1Department Antonio... effects of oral contraceptives on ovarian cancer risk.Int J Cancer 2002 ;102(3):262-5 12 Ovarian Cancer – Basic Science Perspective Brunet JS, Narod SA, Tonin P, Foulkes WD BRCA1 mutations and survival in women with ovarian cancer N Engl J Med 1997 ;336(17):1256 Carroll JC, Cremin C, Allanson J, Blaine SM, Dorman H, Gibbons CA et al Hereditary breast and ovarian cancers.Can Fam Physician 2008 Dec;54(12):1691-2... Janicek M Ovarian carcinoma A review of the significance of familial risk factors and the role of prophylactic oophorectomy in cancer prevention .Cancer 1994 Jul 15;74(2):545-55 Olsen CM, Green AC, Whiteman DC, Sadeghi S, Kolahdooz F, Webb PM Obesity and the risk of epithelial ovarian cancer: a systematic review and meta-analysis Eur J Cancer 2007;43:690-709 14 Ovarian Cancer – Basic Science Perspective. .. ovarian cancer etiology is still poorly understood 2 Ovarian Cancer – Basic Science Perspective The learning objective of this chapter is to review some hormonal, environmental, inherited risk and protective factors associated with ovarian cancer 2 Risk and protective factors 2.1 Reproductive and hormonal factors Hormones such as estrogen and progesterone are believed to be involved in promoting ovarian. .. familiar ovarian cancer and hereditary ovarian cancer 4.1 Familiar aggregation Women with a single family member affected by epithelial ovarian cancer have a 4 to 5 percent risk, while those with two affected relatives have a 7 percent risk for developing the 7 Epidemiology and Etiology of Ovarian Cancer disease in absolute numbers (Carlson et al,1994) In relative numbers familiar ovarian cancer confers... of developing cancer by age 70 in BRCA mutation carriers with the general population 8 Ovarian Cancer – Basic Science Perspective In contrast to Lynch syndrome there are no defined criteria for this hereditary syndrome Some criteria have been described and these include several cases of breast cancer diagnosed before the age of 50, one or more relatives with both breast and ovarian cancer, the presence... microenvironment Both ovarian cancer cells and tumor-associated macrophages 20 Ovarian Cancer – Basic Science Perspective produce IL-6, and it is to date known that high serum levels of IL-6 are related with specific immune and metabolic alterations which finally lead to cancer cachexia, the main cause of death of EOC patients IL-6 has also been demonstrated to be involved in autocrine growth of ovarian cancer cells... from alcohol and caffeine intake and ovarian cancer risk are inconclusive The impact of diet and physical activity is unknown La Vecchia et al found in a case- control study between italian women that meat consumption over 7 portions versus less than 4 portions of meat per week (RR:1,6;95%CI:1,21-2,12) 6 Ovarian Cancer – Basic Science Perspective increased ovarian cancer risk and also the consumption... epithelial ovarian cancer J Natl Cancer Inst 2000;92:1172-7 Whiteman DC, Siskind V, Purdie DM, Green AC Timing of pregnancy and the risk of epithelial ovarian cancer. Cancer Epidemiol Biomarkers Prev 2003 ;12(1):42-6 Whittemore AS, Harris R, Itnyre J Characteristics relating to ovarian cancer risk: collaborative analysis of 12 US case-control studies IV The pathogenesis of epithelial ovarian cancer Collaborative... and ovarian cancer Breast cáncer before 30 years Bilateral breast cancer before 40 years Families with two affected breast or ovarian cancer an one of the next characteristics:     Male breast cancer Ovarian, primary peritoneal or Fallopian tube cancer Both two cases before 50 years One bilateral case and the other before 50 years Families with 3 or more affected members with breast or ovarian cancer . OVARIAN CANCER – BASIC SCIENCE PERSPECTIVE   Edited by Samir A. Farghaly           Ovarian Cancer – Basic Science Perspective Edited by Samir A. Farghaly Published by. different subtypes as are familiar ovarian cancer and hereditary ovarian cancer. 4.1 Familiar aggregation Women with a single family member affected by epithelial ovarian cancer have a 4 to 5 percent. Kyle Bauckman, Christie Campla and Meera Nanjundan Chapter 8 New Tumor Biomarkers in Ovarian Cancer and Its Prognostic and Clinical Relevance139 Malgorzata Banys, Natalia Krawczyk and Tanja Fehm