non-steroidal anti-inflammatory drugs in the carcinogenesis of the gastrointestinal tract非甾体抗炎药在胃肠道的致癌作用.pdfVIP

Pharmaceuticals 2010, 3, 2495-2516; doi:10.3390/ph3082495 OPEN ACCESS pharmaceuticals ISSN 1424-8247 /journal/pharmaceuticals Review Non-Steroidal Anti-Inflammatory Drugs in the Carcinogenesis of the Gastrointestinal Tract Debora Compare, Olga Nardone and Gerardo Nardone * Gastroenterology Unit, Department of Clinical and Experimental Medicine, University of Naples “Federico II”, Via S. Pansini 5, 80131 Naples, Italy; E-Mails: comparedebora@libero.it (D.C.); olga.nardone@libero.it (O.N.) * Author to whom correspondence should be addressed; E-Mail: nardone@unina.it Tel.: +39-081-7462158; Fax: +39-081 Received: 20 July 2010; in revised form: 27 July 2010 / Accepted: 6 August 2010 / Published: 9 August 2010 Abstract: It is estimated that underlying infections and inflammatory responses are linked to 15–20% of all deaths from cancer worldwide. Inflammation is a physiologic process in response to tissue damage resulting from microbial pathogen infection, chemical irritation, and/or wounding. Tissues injured throughout the recruitment of inflammatory cells such as macrophages and neutrophils, generate a great amount of growth factors, cytokines, and reactive oxygen and nitrogen species that may cause DNA damage that in turn predisposes to the transformation from chronic inflammation to neoplasia. Cyclooxygenase (COX), playing a key role in cell homeostasis, angiogenesis and tumourigenesis, may represent the link between inflammation and cancer. Currently COX is becoming a pharmacologic