Role of cyclooxygenase-2 in the development and treatment of oesophageal adenocarcinoma.
BACKGROUND
Various studies suggest that aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) are promising anticancer agents. Epidemiological studies have found that long-term use of NSAIDs is associated with a reduced incidence of colorectal, gastric and oesophageal cancers, while experimental and clinical studies have demonstrated that treatment with NSAIDs causes a statistically significant reduction in both the number and the size of polyps in familial adenomatous polyposis (FAP) patients.


METHODS
In this review, the mechanisms by which NSAIDs exert their chemopreventive and antineoplastic effects are described.


RESULTS
Although the precise anticancer actions of NSAIDs are not fully explained, they probably involve inhibition of cyclooxygenase (COX), which is the rate-limiting enzyme in the conversion of arachidonic acid to prostaglandins. Two isoforms of this enzyme (COX-1 and COX-2) have been identified. COX-1 is constitutively expressed and considered to be a housekeeping gene, while COX-2 is not usually detectable in normal tissues, but can be readily induced in processes like inflammation, reproduction and carcinogenesis. The mechanisms by which COX-2 is thought to be involved in the carcinogenesis include resisting apoptosis, increasing cell proliferation, stimulating angiogenesis and modulating the invasive properties of cancer cells.


CONCLUSIONS
This report reviews the mechanisms by which COX-2 can contribute to carcinogenesis, its role in prognosis, and the possible place of selective COX-2 inhibitors in the prevention and treatment of gastrointestinal malignancies, focusing particularly on oesophageal cancer.
Buskens
C J
CJ
Dept. of Surgery, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. C.J.Buskens@AMC.UVA.NL
Ristimäki
A
A
Offerhaus
G J A
GJ
Richel
D J
DJ
van Lanschot
J J B
JJ
D000230:Adenocarcinoma / Q000188:drug therapy / Q000503:physiopathology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001471:Barrett Esophagus / Q000503:physiopathology; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D003131:Combined Modality Therapy; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000503:physiopathology*; D006801:Humans; D007527:Isoenzymes / Q000187:drug effects / Q000502:physiology*; D008565:Membrane Proteins; D011379:Prognosis; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects / Q000502:physiology*; D016896:Treatment Outcome
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases