We have explored the possibility that mitogen-activated protein kinase cascades play a role in mediating the effects of gastrin on transcription in a gastric cancer (AGS-B) cell line.
This study demonstrates that 1) gastrin stimulates the gene and protein expression of COX-2 and HGF in human cultured gastric cancer cells and 2) gastrin shows antiapoptotic activity through the upregulation of Bcl-2 and survivin.
Progastrin and amidated gastrin levels over their cutoff points (122 and 32 pM, respectively) were found in a significantly larger number of GC (59.4 and 44.5%) than in controls (9.0 and 16.8%, respectively).
Expression of gastrin and c-met protein was associated (P<0.01), but no significant difference was found on the changes of gastrin, c-met and c-erbB2 expression in gastric cancer with tumor stage, grade of differentiation or tumor type.
These results suggest the therapeutic usefulness of inhibitors of gastrin expression and release such as powerful somatostatin analogs (Sandostatin) or blockers of COX-2 (coxibs) in the control of GC development and progression as chemopreventive agents.
Expression of tissue PPARgamma, tissue levels of IL-1beta and IL-8, and plasma concentration of gastrin were significantly higher in H. pylori-positive GC compared to controls, but H. pylori eradication significantly reduced these parameters.
We also examined the effects of IL-8 expression in gastric cancer in INS-GAS mice that overexpress gastrin and IL-8Tg mice infected with Helicobacter felis.
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.
Receptor binding assays as well as transcriptional and growth studies provide evidence that gastrin-stimulated growth of human gastric cancer is mediated by CCK-B/gastrin-like receptors.
Elevation of gastrin may be the carcinogenic factor for <i>Helicobacter pylori</i> as well as the recently described increased risk of gastric cancer due to proton pump inhibitor treatment.
The aim of our study was to assess by means of a 'Gastropanel' blood test, including sPGI, sPGII, gastrin-17 (G-17) and antibodies anti-H. pylori (IgG-Hp). both functional and morphological features of gastric mucosa in Hp + ve subjects with a family history of gastric cancer.
So far, it has been demonstrated that serum pepsinogens (PGs), and gastrin 17 (G17) are useful for screening individuals at elevated risk to develop atrophic gastritis but they are suboptimal biomarkers to screen individuals for GC.
Expression of tissue PPARgamma, tissue levels of IL-1beta and IL-8, and plasma concentration of gastrin were significantly higher in H. pylori-positive GC compared to controls, but H. pylori eradication significantly reduced these parameters.