@article{6b7c27ceb87e4176adba791b450f2a6e,
title = "The role of prostaglandins and other eicosanoids in the gastrointestinal tract",
abstract = "Nonsteroidal anti-inflammatory drugs (NSAIDs) are generally prescribed to ameliorate symptoms associated with acute pain and chronic inflammatory diseases such as arthritis. Recent epidemiologic studies and clinical trials indicate that use of NSAIDs and cyclooxygenase (COX)-2 selective inhibitors are associated with a reduced risk of certain malignancies, especially gastrointestinal cancer. The cyclooxygenase enzymes are the best known targets of NSAIDs; this diverse class of compounds blocks conversion of arachidonic acid to prostanoids. Prostaglandins and other eicosanoids derived from COX-1 and COX-2 are involved in a variety of physiologic and pathologic processes in the gastrointestinal tract. Recent efforts to identify the molecular mechanisms by which COX-2-derived prostanoids exert their proneoplastic effects have provided a rationale for the possible use of NSAIDs alone or in a combination with conventional or experimental anticancer agents for the treatment or prevention of gastrointestinal cancers.",
author = "Dingzhi Wang and Mann, {Jason R.} and Dubois, {Raymond N.}",
note = "Funding Information: Most of the available evidence suggests that nonselective NSAIDs and COX-2 selective inhibitors decrease the risk of colorectal, esophageal, and gastric cancers through reduction of PGE 2 synthesis. These inhibitors also cause regression of premalignant adenomas. The role of COX-2-derived PGE 2 is complex and involves the regulation of pathways involved in acute and chronic inflammation. Nonselective NSAIDs and COX-2 selective inhibitors may exacerbate in preexisting gastrointestinal inflammation by inhibiting ulcer healing. Therefore, it will be important to develop new therapeutic strategies involving combination treatments with minimal toxicity for inflammation-associated carcinogenesis. The ability of nonselective NSAIDs and COX-2 selective inhibitors to synergize with other anticancer and antiangiogenesis drugs provides a rationale for combination therapies in the future. In addition, experimental studies provide evidence that PGE 2 mediates the effects of elevated COX-2 in colorectal, esophageal, and gastric cancers through inhibition of apoptosis, promotion of invasion and metastasis, stimulation of angiogenesis, and induction of immunosuppression. Therefore, PGE 2 receptors and/or PGE synthases may be rational targets for chemoprevention and treatment of colorectal, esophageal, and gastric cancers. The authors thank the T. J. Martell Foundation and the National Colorectal Cancer Research Alliance (NCCRA) for generous support. ",
year = "2005",
month = may,
doi = "10.1053/j.gastro.2004.09.080",
language = "English (US)",
volume = "128",
pages = "1445--1461",
journal = "Gastroenterology",
issn = "0016-5085",
publisher = "W.B. Saunders Ltd",
number = "5",
}