COX-2 inhibition in colorectal carcinoma: changes in gene expression and impact on prostaglandin metabolites

Abstract

Cyclooxygenase-2 (COX-2) has long been known to be a facilitator of colorectal neoplasia, specifically in the development and progression of adenomatous polyps to colorectal carcinoma. The purpose of the studies conducted and reported hereafter in this thesis was to evaluate biologic changes in patients and their colorectal disease after pharmacologic inhibition of COX-2 with a selective inhibitor, celecoxib. In this thesis, I report our experience both with urine levels of the protstaglandin E2 metabolite (PGE-M) among patients with colorectal disease and changes in gene expression in rectal carcinomas after treatment with celecoxib. This research has led to the discovery of a potential biomarker of colorectal neoplasia and identified several specific genes and biologic pathways that are differentially expressed when COX-2 is pharmacologically inhibited.