The aim of the study was to evaluate expression, prognostic value and correlation between COX-2 and VEGF expression in esophageal adenocarcinoma (EAC).
Indomethacin and parecoxib inhibit the growth of human esophageal adenocarcinoma xenografts in nude mice, which suggests a potential role for NSAIDs or selective COX-2 inhibitors for EAC chemotherapy.
The role of cyclooxygenase-2 (COX-2) and chronic inflammation in the progression of BE toward adenocarcinoma of the esophagus has not been extensively studied in experimental models of BE in animals and in human subjects.
In a population-based case-control study, we examined associations of the COX-2 8473 T>C and iNOS Ser(608) Leu (C>T) polymorphisms with risk of esophageal adenocarcinoma, Barrett's esophagus, and reflux esophagitis.
We also correlated COX-2 and FGF-2 expression with clinico-pathologic findings and outcome in a well-characterized series of surgically resected EADC tissues.
Previous studies from our laboratory and others have suggested that increased expression of cox-2 is important in the genesis of esophageal adenocarcinoma.
Our study was initiated to test whether expression of COX isoforms (COX-1 and COX-2) is linked to expression of potent inducers of angiogenesis [vascular endothelial growth factor (VEGF)-A] and lymphangiogenesis (VEGF-C) in esophageal adenocarcinoma.
Immunohistochemical analysis revealed significantly more nuclear accumulation of beta-catenin and overexpression of cyclooxygenase-2 in patients with esophageal adenocarcinoma, compared with patients with cardiac carcinoma.
These results confirm the important role of Cox-2 amplification in the pathogenesis of esophageal adenocarcinoma, but the unexpected down-regulation of Cox-1 raises questions about its role in carcinogenesis.
The COX-2 enzyme has been reported to be over-expressed in premalignant and malignant states, including in Barrett's esophagus and esophageal adenocarcinoma.
COX-2 inhibition induces apoptosis and blocks proliferation in COX-2-expressing esophageal adenocarcinoma cells in vitro, and blocks angiogenesis in both in vivo and in vitro models.
Aberrant arachidonic acid metabolism in esophageal adenocarcinogenesis, and the effects of sulindac, nordihydroguaiaretic acid, and alpha-difluoromethylornithine on tumorigenesis in a rat surgical model.
Indomethacin-induced apoptosis in esophageal adenocarcinoma cells involves upregulation of Bax and translocation of mitochondrial cytochrome C independent of COX-2 expression.
The aim of our study was to determine whether selective inhibition of COX-2 by NS-398 would alter the rates of cell growth and apoptosis in human Barrett's-associated esophageal adenocarcinoma cell lines.