COX-2 Inhibition in Esophagitis, Barretts Esophagus and Esophageal Cancer

Author(s): E. Piazuelo, P. Jimenez, A. Lanas.

Journal Name: Current Pharmaceutical Design

Volume 9 , Issue 27 , 2003

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Abstract:

There is extensive evidence that cyclooxygenase-2 (COX-2) plays a significant role in the process of carcinogenesis in different tumors. Although most of these evidences derive from studies in colorectal cancer, data obtained from recent studies strongly suggest that COX-2 might play an important role in the neoplastic transformation of esophageal epithelium. NSAIDs use is associated with a reduction of the risk of developing esophageal cancer, including adenocarcinoma. Up-regulation of COX-2 has been reported in different stages of the carcinogenic sequence leading to esophageal adenocarcinoma. Treatment with selective COX-2 inhibitors has been shown to reduce the damage induced by acid and pepsin in the esophageal mucosa of rabbits, the incidence of tumors in an animal model of esophageal adenocarcinoma and to decrease proliferation and induce apoptosis in both Barretts epithelial and adenocarcinoma cells. The first clinical study has shown that selective inhibition of COX-2 is followed by a significant decrease of cell proliferation in human Barretts metaplasia. Clinical trials have begun in order to assess the efficacy of selective COX-2 inhibitors to prevent the progression of Barretts esophagus to adenocarcinoma. Bile salts and acid are likely to early induce COX-2 in this sequence, although other factors, such as proinflammatory cytokines, inducible nitric oxide synthase and growth factors such as TGF-beta, are potential COX-2 inducers in the esophagus. Further studies are necessary in order to better understand factors involved in COX-2 up-regulation and mechanisms of COX-2 associated tumorigenesis in the esophagus.

Keywords: cyclooxygenase, esophagitis, esophageal adenocarcinoma, nonsteroidal antiinflammatory drugs, selective cox-2 inhibitors, prostaglandins, apoptosis, proliferation, angiogenesis

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Article Details

VOLUME: 9
ISSUE: 27
Year: 2003
Page: [2267 - 2280]
Pages: 14
DOI: 10.2174/1381612033454009
Price: $58

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