Combined administration of γ-secretase and COX-2 inhibitor produced a marked inhibition of growth in AGS cells, which suggests that patients with poorly differentiated GC may benefit from the blockage of NICD, which potentially serves a role in GC differentiation.
Together, these findings provide new evidence for a positive feedback loop between STAT3 signaling and COX-2 in H. pylori pathogenesis and may lead to new approaches for early detection and effective therapy of gastric cancer
Five different classes of methylation behaviors were found: (1) genes methylated in GC only (GSTP1 and RASSF1A); (2) genes showing low methylation frequency (<12%) in CG, IM, and GA, but significantly higher methylation frequency in GC (COX-2, hMLH1, and p16); (3) a gene with low and similar methylation frequency (8.8-21.3%) in four-step lesions (MGMT); (4) genes with high and similar methylation frequency (53-85%) in four-step lesions (APC and E-cadherin); and (5) genes showing an increasing tendency with or without fluctuation of the methylation frequency along the progression (DAP-kinase, p14, THBS1, and TIMP3).
Both forced COX-2 overexpression and high-salt intake significantly increased the frequency of gastric cancer development in mice as compared with WT littermates treated with MNU alone.
From CSG to GA, IM, dysplasia and finally to gastric cancer, expression of COX-2 showed an ascending tendency, whereas COX-1 expression did not change significantly in the gastric mucosa.
Infection with H. pylori, especially that expressing CagA-positivity, is primum movens in developing GC and MALT-lymphoma and the upregulation of growth factors, particularly of gastrin, and COX-2 and dysregulation of the Bax/Bcl-2 system seem to contribute to gastric cancerogenesis.
We confirm loss of ANXA1 and overexpression of COX-2 in clinical gastric cancer, suggesting that the anti-proliferative function of ANXA1 against COX-2 production might be lost.
Thus, the purpose of our study was to assess the expression of COX-2 and iNOS messenger RNA (mRNA) in gastric cancer and to investigate the correlation between the expression of COX-2 and iNOS mRNA in these patients.
The over-expression of COX-2 (Cyclooxygenase 2) protein has been reported to play a key role in the incidence and development of Helicobacter pylori-associated gastric cancer.
Since gastrin is recognized as a effective gastric mitogen, it could be capable to induce COX-2, a potent tumor growth promoting and angiogenic factor, we decided 1) to compare the seroprevalence of HP and its cytotoxic protein, CagA, in gastric cancer patients with those in age- and gender-matched controls; 2) to determine the gene expression of gastrin and its receptors (CCK(B)-R) in gastric cancer, 3) to assess the plasma levels, gastric lumen and tumor tissue contents of gastrin and 4) to examine the mRNA and enzyme protein expression of COX-1 and COX-2 in cancer tissue and intact gastric mucosa before and after HP eradication.
COX-2 mRNA expression in gastric carcinoma tissue is correlated closely with depth of invasion, indicating that COX-2 is involved in the growth of gastric carcinoma.