Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01350 (gastrin)
 9,683 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fas (CD95) is a cell surface glycoprotein that mediates apoptotic cell death when cross-linked with agonistic anti-Fas monoclonal antibodies (MAbs) or the endogenous Fas ligand. In this study, we investigated the in vitro biological properties of a panel of anti-human Fas MAbs. We found that five anti-Fas MAbs of IgG1 subclass (B.E28, B.G30, B.L25, DX2, and B.G34) induced marked apoptotic cell death in Fas-expressing leukemia cells, although this killing was delayed when compared to the cytolytic effect mediated by the prototypic anti-Fas MAb of IgM subclass (clone CH-11). On the other hand, four clones (ZB4, B.G27, B.D29, and B.K14) efficiently blocked apoptotic cell death induced by the CH-11 MAb or Fas ligand. The ability of these MAbs to inhibit cell death appeared to correlate with their relative affinity for the Fas molecule. Furthermore, different clones recognized the same epitope and elicited different effects (induction or inhibition of cell killing); conversely, different clones elicited the same effect but recognized different epitopes. These results suggest that the different biological effects of anti-Fas MAbs would not be mediated in an epitope-restricted manner. The relative binding affinity might correlate to some extent with the biological properties of the MAb.
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PMID:Epitopes and functional responses defined by a panel of anti-Fas (CD95) monoclonal antibodies. 1060 25

Hypergastrinemia in INS-GAS mice leads to accelerated carcinogenesis of the stomach, but the mechanisms have not been well defined. We investigated the possible role of gastrin-induced gastric cell apoptosis in the development of gastric cancer. We examined apoptosis and the expression of Bcl-2 family proteins in INS-GAS mice of different ages, as well as in gastrin-deficient (GAS-KO) mice after gastrin-17 (G-17) infusion. In addition, we studied the effects of the gastrin/cholecystokinin-2 (CCK-2) receptor antagonist YF476 and/or histamine H2 (H-2) receptor antagonist loxtidine on apoptosis and atrophy in INS-GAS mice with or without Helicobacter felis (H. felis) infection. INS-GAS mice had age-associated increases in Bax protein expression and decreases in Bcl-2 protein expression, along with increased glandular and epithelial cell apoptosis. At 8-week gastrin infusions in GAS-KO mice resulted in a similar pattern of altered Bax and Bcl-2 expression, followed by gastric cell apoptosis. H. felis infection of INS-GAS mice led to increased apoptosis and the development of atrophy, whereas treatment with either YF476 and/or loxtidine strongly inhibited both apoptosis and atrophy. In vitro studies with Fas-expressing RGM1 cells showed that gastrin stimulation alone directly induced apoptosis via gastrin/CCK-2 receptor and synergized with FasL stimulation. These results indicate that gastrin can induce apoptosis in gastric epithelial cells and contribute to the development of gastric carcinogenesis.
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PMID:Gastrin-induced apoptosis contributes to carcinogenesis in the stomach. 1689 54

Helicobacter pylori is known to be the cause of most gastric diseases, including both peptic ulcer disease and gastric cancer. In the absence of eradication, infection tends to be lifelong and the immune response ineffective in clearing the bacteria. A number of groups have investigated whether the immune clearance of infection can be achieved through a vaccination strategy, but to date, the results have been inconclusive. In fact, in most cases of natural infection, the host immune response leads to a chronic inflammation within the gastric mucosa that actually promotes the development of atrophy and neoplasia. In most cases, eradication of the organism leads to resolution of inflammation, which in many instances can result in reduction in atrophy and gastric cancer risk. This finding suggests that even at late stages, cancer progression is dependent, to a large extent, on infection/immune response. Work from a number of laboratories has led to the hypothesis that T-cells and the Th1 immune response, governed largely by host genetic factors, are strongly associated with the H. pylori-mediated induction of atrophy and cancer. Interleukin-1beta appears to be a particularly important cytokine that inhibits acid secretion and increases serum gastrin levels, factors strongly associated with cancer induction. The induction by H. pylori of cytokines and chemokines and growth-related genes is mediated by the MAPK and NF-kappaB signaling pathway. Recent studies have shown that NF-kappaB is activated through a NF-kappaB-inducing kinase/p21-activated kinase 1 pathway. H. pylori can also promote cellular apoptosis through a number of mechanisms, the most important of which is upregulation of the Fas/FasL pathway. Finally, understanding of H. pylori pathogenesis has been broadened and deepened by the application of genomics and proteomics to the organism.
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PMID:Helicobacter pylori infection: pathogenesis. 1703 Dec 25