The results suggest that cyclooxygenase-2 is involved in the increased prostaglandin E2 synthesis in colonic cancers, and that activation of this isoenzyme is an early event in colon carcinogenesis.
We conclude that PHS-2 is transcribed abnormally in human colon cancers and that this may be one mechanism by which prostaglandins or related compounds that support carcinogenesis are generated.
Studies with the Min and APC-knockout mice provide the strongest evidence to date that the enzyme cyclooxygenase-2 plays a major role in colon carcinogenesis, and that nonsteroidal anti-inflammatory drugs that target cyclooxygenase-2 have great potential as colon cancer chemopreventive agents.
Overexpression of cyclooxygenase-2 (COX-2) has been implicated in carcinogenesis of human colorectal cancer which is one of the leading types of cancer in Western countries.
The results provide direct genetic evidence that COX-2 plays a key role in tumorigenesis, and indicate that COX-2-selective inhibitors can be a new class of therapeutic agents for colorectal polyposis and cancer.
Thus, the supply of arachidonic acid provided by PLA2-II/cPLA2 seems not to be the rate limiting step in PGE2 (a prostaglandin/mitogen) formation via COX-2 and PLA2-II plays a minor or no role in human colorectal carcinogenesis.
These results indicate that these two important modulators of colorectal tumorigenesis are differentially expressed and imply that the therapeutic benefit may be improved by combination therapy utilizing selective Cox-2 and matrilysin inhibitors.
Our results suggest that overexpression of COX-2 may play an important role in tumor progression of gastric cancer and also support the notion that gastric cancers with and without MSI represent distinctive pathways of carcinogenesis.
Taken together, our data suggest that COX-2 may play an important role in pancreatic tumorigenesis and therefore be a promising chemotherapeutic target for the treatment of pancreatic cancer.
Our results indicate that COX-2 is a sensitive marker for HGD and suggest that COX-2 may be involved in early stages of squamous carcinogenesis of the esophagus.
These findings suggest that inhibition of COX-2 development may lead not only to inhibition of the proliferation and metastasis of prostate carcinoma but also to the inhibition of prostate carcinogenesis.
We previously demonstrated that cyclooxygenase-2 (COX-2) was predominantly expressed in macrophages of sporadic human colonic adenomas; however, the role of COX-2-expressing cells during colon carcinogenesis has not yet been elucidated.
In contrast, in gastric cancer, COX-2 strongly predominates in the epithelium, suggesting that the transition to consistent epithelial COX-2 overexpression may be a critical molecular event in gastric carcinogenesis.