The discovery that aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) have notable antineoplastic properties has revolutionized cancer research. In COX-2 Blockade in Cancer Prevention and Therapy, a panel of leading experts chronicles the evidence for the chemopreventive and therapeutic effects of cyclooxygenase-2 (COX-2) inhibitors against virtually all forms of cancer and presents exciting new opportunities for the use of COX-2 blockade in their prevention and treatment. These highly experienced authors elucidate the process by which COX-2 inhibitors interrupt prostaglandin biosynthesis and cancer development, examine the positive epidemiological effects of such NSAIDs as aspirin and ibuprofen on various cancers, and demonstrate through animal models that NSAIDs inhibit a variety of malignant neoplasms in vivo. They also present genetic models confirming the critical role of COX-2 in carcinogenesis and discuss how its molecular biology modulates carcinogenesis via such processes as mutagenesis, cell division, angiogenesis, cell differentiation, and apoptosis. In addition, the authors review the clinical applications of selected NSAIDs that are immediately relevant to cancer prevention and control and outline the future prospects of COX-2 blocking agents.
Comprehensive and up-to-date, COX-2 Blockade in Cancer Prevention and Therapy demonstrates how COX-2 inhibitors and other NSAIDs reduce the risk of most cancers and provides cancer investigators today with a clear and authoritative guide to the development of novel agents with significant antineoplastic properties.

Klappentext

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.

Inhalt

Part I. Historical Perspectives Dietary Fatty Acids, COX-2 Blockade, and Carcinogenesis Rashida A. Karmali Historical Aspects of COX-2: Cloning and Characterization of the cDNA, Protein and Gene Harvey R. Herschman Part II. Epidemiology of NSAIDs and Cancer Epidemiology of Nonsteroidal Anti-Inflammatory Drugs and Colorectal Cancer Michael J. Thun and S. Jane Henley Epidemiology of Breast Cancer and Nonsteroidal Anti-Inflammatory Drugs: Extension of the Dietary Fat Hypothesis of Breast Cancer Randall E. Harris Part III. Animal Models of Carcinogenesis Role of Synthetic and Naturally Occurring Cyclooxygenase Inhibitors in Colon Cancer Prevention Bandaru S. Reddy and Chinthalapally V. Rao Chemoprevention of Breast Cancer by Nonsteroidal Anti-Inflammatory Drugs and Selective COX-2 Blockade in Animals Hussein M. Abou-Issa, Galal A. Alshafie, and Randall E. Harris The Role of Cyclooxygenase-2 in the Prevention and Therapy of Lung Cancer Hildegard M. Schuller Nonsteroidal Anti-Inflammatory Drugs, Prostaglandins, and Apc-Driven Intestinal Tumorigenesis Jay Whelan and Michael F. McEntee Cyclooxygenase-1 and Cyclooxygenase-2 Knockout Mice Provide Insights into Beneficial and Adverse Effects of Nonsteroidal Anti-Inflammatory Drugs Robert Langenbach Part IV. Molecular Biology of COX-2 Cyclooxygenase-2, Prostaglandins, and Colorectal Carcinogenesis Rajnish A. Gupta and Raymond N. DuBois Regulation of Expression and Potential Carcinogenic Role of Cyclooxygenase-2 Byeong-Churl Jang and Timothy Hla Cyclooxygenase-2 and Cancer Alane T. Koki, Kathleen M. Leahy, Janet M. Harmon, and Jaime L. Masferrer Interactions of Cyclooxygenase and Aromatase Pathways in Normal and Malignant Breast Cells Jeanette A. Richards and Robert W. Brueggemeier Association of COX-2 and PPARs in Carcinogenesis and Chemoprevention Tong-Chuan He Carcinogenesis Involving Cyclooxygenase and Lipoxygenase Linda C. Hsi and Thomas E. Eling Part V. Clinical Applications The Development of Drugs that Target Cyclooxygenase-2 Timothy Maziasz, K. Nasir Khan, John Talley, James Gierse, and Karen Seibert Chemoprevention of Cancer by NSAIDs and Selective COX-2 Blockade Gary J. Kelloff, Vernon E. Steele, and Caroline C. Sigman Potential for Inhibitors of Cyclooxygenase-2 to Enhance Tumor Radioresponse Randy Burd, Hak Choy, and Adam Dicker Potential Role of NSAIDs and COX-2 Blockade in Cancer Therapy William F. Anderson, Asad Umar, Jaye L. Viner, and Ernest T. Hawk Cyclooxygenase-2 Blockade in Cancer Prevention and Therapy: Widening the Scope of Impact Randall E. Harris Index