Steroid Enzymes and Cancer / Edition 1

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Overview

The expression and activity of key enzymes of sex steroid metabolism have major implications in both development and progression of various human hormone-related tumors, including breast, prostate, lung, and liver cancer.
This volume explores the role of local synthesis of steroid hormones, a process that has assumed an increasing importance in our understanding about several malignancies originating from steroid target tissues, wherein abnormal levels of individual steroids may promote tumor growth. In this framework, a divergent expression and/or activity of key gonadal steroid enzymes (including dehydrogenases, hydroxylases, sulfotransferases, sulfatases, and aromatase) may eventually lead to a differential accumulation of hormone derivatives with divergent biological activities in individual target tissues. This is of crucial importance in predicting the overall biological impact that sex steroids have on peripheral target tissues and, hence, on their potential role in cancer development and/or progression.

The volume focuses on five key enzymes in the metabolism of sex steroids: (1) 17βhydroxysteroid dehydrogenase; (2) 5αreductase; (3) hydroxylases and catechol-oxy methyltransferase; (4) sulfatase, sulfotransferases, and glucuronidase; and (5) aromatase.

The organization of the volume is designed to provide an updated picture of the existing knowledge about the association between steroid enzyme expression/function and the development and/or progression of major human cancers, including classical (breast, prostate) and nonclassical (lung, liver) hormone-related tumors. The resulting inferences for diagnosis, prognosis, and treatment are also presented, along with the experimental basis for developing preventive measures.

NOTE: Annals volumes are available for sale as individual books or as a journal. For information on institutional journal subscriptions, please visit www.blackwellpublishing.com/nyas.

ACADEMY MEMBERS: Please contact the New York Academy of Sciences directly to place your order (www.nyas.org). Members of the New York Academy of Science receive full-text access to the Annals online and discounts on print volumes. Please visit http://www.nyas.org/MemberCenter/Join.aspx for more information about becoming a member.

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Editorial Reviews

Doody's Review Service
Reviewer: Robert Treat Chatterton, PhD (Northwestern University Feinberg School of Medicine)
Description: This book is the result of a course originally designed and organized to provide an updated picture of the existing knowledge about the association between steroid enzyme expression and function, and the development and progression of major steroid hormone-dependent human cancers. Many of the authors have summarized studies from their laboratories elsewhere, but this is a convenient compendium for students.
Purpose: The articles are written by authorities in their respective research areas, and they provide good coverage of steroid enzymes in cancer. Most of the authors represent research groups that are acknowledged leaders in their fields.
Audience: It is written primarily for students of the medical sciences but it may serve as a convenient source of information for researchers as well. There is a good representation of topics in steroid enzyme studies in cancer, although the book includes a number of short poster papers and the keynote address, which had little relevance to the subject of the book.
Features: Although the book covers the major enzymes involved in the synthesis of steroids, it does not cover the biosynthesis of steroids from cholesterol or earlier precursors and has only two articles on the enzymes involved in inactivation and clearance of steroids. Its preponderant focus is on estrogen formation and metabolism, and largely in relation to breast cancer, although there are two articles on aldo-keto reductases (AKRs) in the prostate and aromatase is discussed in relation to liver and lung cancer. The book starts with a brief introduction to translational research in hormone-related cancer. This is followed by an article on genetic and epigenetic regulation of tumor formation, which has few if any examples of systems in which enzymes of steroid metabolism are involved. Following is a series of articles on AKRs in breast and prostate. These chapters provide a rather comprehensive review of the categorization and function of the 17beta-hydroxysteroid dehydrogenases in breast cancer and 5alpha-reductase in the prostate. Estrogen hydroxylation is discussed in relation to the ratios of less to more estrogenic products, and dietary and other factors that can alter this ratio. Next, three articles detail the opposing actions of sulfatase and sulfotransferase in formation of estradiol, and progress in developing a sulfatase inhibitor to suppress estradiol formation from sulfated steroid precursors. Eight articles cover aromatase from molecular characterization of aromatase to regulation of expression in breast cancer to opposing roles of estrogen in the prostate to genotoxic effects of estradiol metabolites. Two articles on aromatase inhibitors in breast cancer cover basic mechanisms and clinical efficacy. Also in relation to regulation of estrogenic activity, an article discusses how polymorphisms of P450 enzymes and glucuronidation affect the pharmacology of tamoxifen. Additional topics on aromatase in liver and lung cancers are presented. Following these presentations are summaries of 18 posters, only one of which is from an institution outside of Italy. One of the posters deals with aromatase expression, one with effect of different diseases on estradiol metabolism, one on inhibition of sulfatase, one on registry data documenting results of endocrine therapy in Palermo. The others deal with many aspects of oncology but not with steroids or enzymes of steroid metabolism.
Assessment: This book, from the Annals of the New York Academy of Sciences, represents the proceedings of a conference held in Italy in May 2008. All articles are written by different authors and, therefore, represent a range of expertise. Nevertheless, any reader interested in endocrinology and cancer will find a number of articles that will make the book worthwhile. The short papers at the end of the book for the most part are not representative of the topic and, therefore, may not find the audience they would like to serve.
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Product Details

Table of Contents

Preface: H. Leon Bradlow and Giuseppe Carruba

1. Translational Research in Hormone Related Cancer: Luisa M. Massimo and Giampaolo Tonini

2. Keynote Lecture: Organization, Integration and Assembly of Genetic and Epigenetic Regulatory Machinery in Nuclear Microenvironments: Implications for Biological Control in Cancer: Gary S. Stein, Sayyed K. Zaidi, Janet L. Stein, Jane B. Lian, Andre van Wijnen, Martin Montecino, Daniel W. Young, Amjad Javed, Jitesh Pratap, Je-Yong Choi, Syed A. Ali, Sandhya Pande, and Mohammad Q. Hassan

Part I: Hydroxysteroid Dehydrogenases:

3. Perspectives in understanding the role of human 17beta-hydroxysteroid dehydrogenases in health and disease: Marc Meier, Gabriele Möller, and Jerzy Adamski

4. 17beta-hydroxysteroid dehydrogenases in human breast cancer: Shuji Nagasaki, Yasuhiro Miki, Jun-ichi Akahira, Takashi Suzuki, and Hironobu Sasano

5. Steroid Hormone Transforming Aldo-Keto Reductases and Cancer: Trevor M. Penning, and Michael C. Byrns

6. 5α-Reductase Isozymes and Androgen Actions in The Prostate: Yuan-Shan Zhu and Julianne L. Imperato-McGinley

Part II: Hydroxylases:

7. Estrogen Hydroxylation-The Good and the Bad: Daniel W. Sepkovic and H. Leon Bradlow

8. Estrogen Metabolism and Breast Cancer: A Risk Model: Fritz F. Parl, Sheila Dawling, Nady Roodi, and Philip S. Crooke

Part III: Sulfatase, Sulfotransferase, and Glucuronidase:

9. New Developments in intracrinology of human breast cancer - estrogen sulfatase and sulfotransferase: Hironobu Sasano, Shuji Nagasaki, Yasuhiro Miki, and Takashi Suzuki

10. The development of steroid sulfatase inhibitors for hormone-dependent cancer therapy: Joanna M. Day, Atul Purohit, Helena J. Tutill, Paul A.

Foster, L.W. Lawrence Woo, Barry V.L. Potter, and Michael J. Reed

11. Estrogen Sulfotransferases in Breast and Endometrial Cancers: Jorge Pasqualini

12. Potential role of UGT pharmacogenetics in cancer treatment and prevention: focus on tamoxifen: Philip Lazarus, Andrea S. Blevins-Primeau, Yan Zheng, and Dongxiao Sun

Part IV: Aromatase I:

13. Molecular characterization of aromatase: Yanyan Hong, Hongzhi Li, Yate-Ching Yuan, and Shiuan Chen

14. Regulation of Aromatase Expression in Breast Cancer Tissue: Serdar E Bulun, Zhihong Lin, Hong Zhao, Meiling Lu, Sanober Amin, Scott Reierstad, and Dong Chen

15. Estrogen mediation of breast tumor formation involves estrogen receptor dependent, as well as independent, genotoxic effects: Richard Santen, Ercole Cavalieri, Eleanor Rogan, Jose Russo, Joseph Guttenplan, James Ingle, and Wei Yue

16. Phase 3 trials of aromatase inhibitors for breast cancer prevention: Following in the path of the selective estrogen receptor modulators: Barbara K. Dunn and Anne Ryan

Part V: Aromatase II:

17. Aromatase inhibitors and breast cancer: Luciana Furtado Macedo, Gauri Sabnis, and Angela Brodie

18. The Dual, Opposing Roles of Estrogen in the Prostate: Stuart Ellem and Gail Risbridger

19. Aromatase in human liver: Giuseppe Carruba

20. Targeting aromatase and estrogen signaling in human non-small cell lung Cancer: Diana C. Márquez-Garbán, Hsiao-Wang Chen, Lee Goodglick, Michael C. Fishbein, and Richard J. Pietras

21. Keynote Lecture: Inflammation and liver cancer: new molecular links: C. Berasain, J. Castillo, M.J. Perugorria, M.U. Latasa, J. Prieto, and M. A. Avila

Part VI: Poster Papers:

22. Application of a new breast cancer classification to a population-based series: demographic, clinical, and prognostic features of incident cases, Palermo Province, 2002-2004: Maurizio Zarcone, Rosalba Amodio, Ildegarda Campisi, Rosanna Cusimano, Cecilia Dolcemascolo, Vitale Miceli, Adele Traina, and Maurizio Macaluso

23. Endocrine therapy in metastatic breast cancer: data from Breast Cancer Registry of Palermo (1999-2005): Rosalba Amodio, Maurizio Zarcone, Biagio Agostara, Maria Stella Adamo, Orazia Maria Granata, Giuseppe Carruba, and Adele Traina

24. Dietary enterolactone affects androgen and estrogen levels in healthy postmenopausal women: Orazia M. Granata, Adele Traina, Stefania Ramirez, Ildegarda Campisi, Maurizio Zarcone, Rosalba Amodio, Lucia M. Polito and Giuseppe Carruba

25. 16α-Hydroxyestrone inhibits Estrogen sulfotransferase activity in human liver cancer cells: Ildegarda Campisi, Orazia M. Granata, Letizia Cocciadiferro, Maurizio Calabrò, Lucia M. Polito, and Giuseppe Carruba

26. Clues to Understanding the Oxidation of Estradiol in Humans: Effects of Acute Infectious Hepatitis, Autoimmune Hepatitis and Chronic Liver Disease: Robert Lahita, Robert A. Schaefer, H. Leon Bradlow, and Mary-Jeanne Kreek

27. Aromatase and amphiregulin are correspondingly expressed in human liver cancer cells: Vitale Miceli, Melchiorre Cervello, Antonina Azzolina, Giuseppe Montalto, Maurizio Calabrò, and Giuseppe Carruba

28. Profiling Cancer Stem Cells in Androgen Responsive and Refractory Human Prostate Tumor Cell Lines: Letizia Cocciadiferro, Vitale Miceli, Kyung-Sun Kang, Lucia M. Polito, James E. Trosko, and Giuseppe Carruba

29. Sex steroids upregulate the IGF-IR in prostate cancer cells through a nongenotropic pathway: Giuseppe Pandini, Marco Genua, Francesco Frasca, Riccardo Vigneri, and Antonino Belfiore

30. Low levels of both xanthine dehydrogenase and cellular retinol binding protein are responsible for the retinoic acid deficiency in malignant human mammary epithelial cells: Gennaro Taibi, Giuseppe Carruba, Letizia Cocciadiferro, Grazia M. Granata, and Concetta M.A. Nicotra

31. Inhibition of human breast cancer cell growth and enzymatic activity by a fermented nutraceutical: an in vitro and in vivo study: F. Marotta, H.Yadav, S. Pathak, E. Minelli, P. Signorelli, A. Lorenzetti, and P. Marandola

32. Curcumin as a possible lead compound against hormone-indipendent multidrug resistant breast cancer: Manuela Labbozzetta, Monica Notarbartolo, Paola Poma, Annamaria Maurici, Luigi Inguglia, Paolo Marchetti, Michele Rizzi, Riccardo Baruchello, Daniele Simoni, and Natale D’Alessandro

33. Genetic determined down regulation of both type 1 and type 2 cytokine pathways might be protective against pancreatic cancer: Letizia Scola, Antonio Giacalone, Lorenzo Marasà, Monica Mirabile, Loredana Vaccarino, Giusi Irma Forte, Lydia Giannitrapani, Calogero Caruso, Giuseppe Montalto, and Domenico Lio

34. CCR5 proinflammatory allele in Prostate cancer risk: a pilot study in patients and centenarians from Sicily: Carmela Rita Balistreri, Giuseppe Carruba, Maurizio Calabro’, Ildegarda Campisi, Daniele Di Carlo, Domenico Lio, Giuseppina Colonna-Romano, Giuseppina Candore, and Calogero Caruso

35. Cyclooxygenase-2 expression in chronic liver diseases and hepatocellular carcinoma: an immunohistochemical study: Lydia Giannitrapani, Sabrina Ingrao, Maurizio Soresi, Ada Maria Florena, Emanuele La Spada, Luigi Sandonato, Natale D’alessandro, Melchiorre Cervello, and Giuseppe Montalto

36. Prostaglandin E2 receptors and COX enzymes in human hepatocellular carcinoma: role in the regulation of cell growth: Antonella Cusimano, Daniela Foderà, Nadia Lampiasi, Antonina Azzolina, Monica Notarbartolo, Lydia Giannitrapani, Natale D’alessandro, Giuseppe Montalto, and Melchiorre Cervello

37. Involvement of nitric oxide in nigrostriatal dopaminergic system

degeneration: a neurochemical study: Vincenzo Di Matteo, Massimo Pierucci, Arcangelo Benigno, Giuseppe Crescimanno, Ennio Esposito, and Giuseppe Di Giovanni

38. Unilateral nigral lesion induces dramatic bilateral modification on rat brain monoamine neurochemistry: Massimo Pierucci, Vincenzo Di Matteo, Arcangelo Benigno, Giuseppe Crescimanno, Ennio Esposito, and Giuseppe Di Giovanni

39. Parkinson disease and cancer: Insights for pathogenesis from epidemiology: Marco D’Amelio, Paolo Ragonese, Gabriella Sconzo, Paolo Aridon, and Giovanni Savettieri

Index of Contributors

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