Prevention of colorectal cancer using COX-2 inhibitors: basic science and clinical applications
| Autor: | Ben D Chen, Arthur J Chu, Ta-Hsu Chou |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Oncology
medicine.medical_specialty Genes APC Adenomatous polyposis coli Colorectal cancer Angiogenesis Apoptosis medicine.disease_cause Metastasis Familial adenomatous polyposis Internal medicine medicine Animals Humans Cyclooxygenase Inhibitors Neoplasm Metastasis Carcinogen Inflammation Sulfonamides biology Neovascularization Pathologic business.industry Anti-Inflammatory Agents Non-Steroidal DNA medicine.disease Disease Models Animal Adenomatous Polyposis Coli Celecoxib Cyclooxygenase 2 Mutation biology.protein Carcinogens Prostaglandins Pyrazoles business Carcinogenesis Colorectal Neoplasms medicine.drug |
| Zdroj: | Frontiers in bioscience : a journal and virtual library. 9 |
| ISSN: | 1093-9946 |
| Popis: | Cyclooxygenase-2 (COX-2), an inducible prostaglandin G/H synthase, is overexpressed in pre-neoplastic tissues and several human cancers including colorectal cancer. Evidence linking COX-2 activity to carcinogenesis was derived from epidemiologic studies and animal models with defect adenomatous polyposis coli (APC) gene. PGE2 induced by COX-2 exerts several biological properties that may be advantageous for tumorigenesis: 1) Promoting angiogenesis (increased VEGF, bFGF, and PDGF production), 2) Anti-apoptosis mechanism (via increased bcl-2 and Akt activity), 3) Stimulating tumor metastasis (by increasing matrix metalloproteinases) and 4) Decreased immune surveillance (decreased cytokine production and NK activity). In addition, COX-2 reaction can cause DNA oxidation and induce mutations. Chemoprevention of colorectal cancer has attracted great attention in recent years. Epidemiologic data showed that chronic intake of traditional nonsteroidal anti-inflammatory drugs (NSAIDs) could reduce the incidence of colorectal cancer. Recent clinical trial studies showed that celecoxib, a selective COX-2 inhibitor, is equally effective in reducing colorectal adenomas in animal models and patients with familial adenomatous polyposis (FAP), yet with superior GI safety. Two COX-2 inhibitors (celecoxib and refocoxib) have been approved by FDA as adjuncts to usual care in FPA patients, and are currently being studied in patients with sporadic adenomas and other types of cancers. These studies are expected to generate evidence in favor of targeting COX-2 and its gene products as chemopreventive strategies, which may provide an alternative in current approach to reducing the morbidity and mortality of this disease. |
| Databáze: | OpenAIRE |
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