Part I. Historical Perspectivesn n Dietary Fatty Acids, COX-2 Blockade, and Carcinogenesisn Rashida A. Karmalin n Historical Aspects of COX-2: Cloning and Characterization of the cDNA, Protein and Genen Harvey R. Herschmann n Part II. Epidemiology of NSAIDs and Cancern n Epidemiology of Nonsteroidal Anti-Inflammatory Drugs and Colorectal Cancern Michael J. Thun and S. Jane Henleyn n Epidemiology of Breast Cancer and Nonsteroidal Anti-Inflammatory Drugs: Extension of the Dietary Fat Hypothesis of Breast Cancern Randall E. Harrisn n Part III. Animal Models of Carcinogenesisn n Role of Synthetic and Naturally Occurring Cyclooxygenase Inhibitors in Colon Cancer Preventionn Bandaru S. Reddy and Chinthalapally V. Raon n Chemoprevention of Breast Cancer by Nonsteroidal Anti-Inflammatory Drugs and Selective COX-2 Blockade in Animalsn Hussein M. Abou-Issa, Galal A. Alshafie, and Randall E. Harrisn n The Role of Cyclooxygenase-2 in the Prevention and Therapy of Lung Cancern Hildegard M. Schullern n Nonsteroidal Anti-Inflammatory Drugs, Prostaglandins, and Apc-Driven Intestinal Tumorigenesisn Jay Whelan and Michael F. McEnteen n Cyclooxygenase-1 and Cyclooxygenase-2 Knockout Mice Provide Insights into Beneficial and Adverse Effects of Nonsteroidal Anti-Inflammatory Drugsn Robert Langenbachn n Part IV. Molecular Biology of COX-2n n Cyclooxygenase-2, Prostaglandins, and Colorectal Carcinogenesisn Rajnish A. Gupta and Raymond N. DuBoisn n Regulation of Expression and Potential Carcinogenic Role of Cyclooxygenase-2n Byeong-Churl Jang and Timothy Hlan n Cyclooxygenase-2 and Cancern Alane T. Koki, Kathleen M. Leahy, Janet M. Harmon, and Jaime L. Masferrern n Interactions of Cyclooxygenase and Aromatase Pathways in Normal and Malignant Breast Cellsn Jeanette A. Richards and Robert W. Brueggemeiern n Association of COX-2 and PPARs in Carcinogenesis and Chemopreventionn Tong-Chuan Hen n Carcinogenesis Involving Cyclooxygenase and Lipoxygenasen Linda C. Hsi and Thomas E. Elingn n Part V. Clinical Applicationsn n The Development of Drugs that Target Cyclooxygenase-2n Timothy Maziasz, K. Nasir Khan, John Talley, James Gierse, and Karen Seibertn n Chemoprevention of Cancer by NSAIDs and Selective COX-2 Blockaden Gary J. Kelloff, Vernon E. Steele, and Caroline C. Sigmann n Potential for Inhibitors of Cyclooxygenase-2 to Enhance Tumor Radioresponsen Randy Burd, Hak Choy, and Adam Dickern n Potential Role of NSAIDs and COX-2 Blockade in Cancer Therapyn William F. Anderson, Asad Umar, Jaye L. Viner, and Ernest T. Hawkn n Cyclooxygenase-2 Blockade in Cancer Prevention and Therapy: Widening the Scope of Impactn Randall E. Harrisn n Index
The revelation that aspirin and aspirin-like compounds have notableantineo plastic properties has revolutionized cancer research. COX-2 Blockade in Cancer Prevention and Therapy chronicles the evidence and presents exciting new op portunities for the use of cyclooxygenase-2 (COX-2) blockade in the prevention and treatment of cancer. The text is divided broadly into five areas. First, an historical overview documents the scientific discovery ofCOX-2 and the pharma ceutical development of nonsteroidal anti-inflammatory drugs (NSAIDs) designed for selective COX-2 inhibition. The process by which essential poly unsaturated fatty acids (PUF As) stimulate prostaglandin biosynthesis and cancer development, and its interruption by COX-2 inhibition, is elucidated. This is followed by a section on the epidemiology of NSAIDs and cancers of the colon and breast, and other anatomic sites. These chapters reflect significant cancer protection owing to the regular use of common NSAIDs such as aspirin and ibuprofen. A section on animal models of carcinogenesis presents comprehensive evidence that general NSAIDs inhibit a variety of malignant neoplasms in vivo, and highlights recent findings which show that COX-2 blocking agents produce striking chemopreventive effects against colon cancer and breast cancer as well as other malignancies. Genetic models are presented confirming the critical role of COX-2 in carcinogenesis. Section IV then discusses the molecular biology of COX -2 vis-a-vis the role of COX -2 and, to a lesser extent, COX -1, in modulating a number of important processes in molecular carcinogenesis such as mutagen esis, cell division, angiogenesis, cell differentiation, and apoptosis.