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

Gastrin and cholecystokinin-B receptor (CCK-B) were co-expressed in human gastric carcinoma tissues, suggesting that a functional autocrine loop, the gastrin and CCK-B receptor loop, may be presented in gastric cancer cells and play an important role in the pathogenesis and progression of gastric carcinomas. The present study was aimed at studying the effects of blocking the gastrin and CCK-B receptor loop on cell proliferation and apoptosis in gastric cancer cell line SGC-7901 cells (SGC-7901 cells). First, the expression of gastrin and CCK-B receptor mRNAs and gastrin protein in SGC-7901 cells were measured by RT-PCR and immunocytochemistry, respectively. Radioimmunoassay (RIA) was used to detect the concentrations of gastrin in culture medium. The gastrin-CCK-B receptor axis was blocked by using a specific neutralizing antibody against human gastrin and siRNA specifically targeting human CCK-B receptors, respectively. Flow cytometry was used to measure the cell cycle and apoptotic cells, and western blotting was used to measure the expression of CCK-B receptor, caspase-3, and matrix metalloproteinase-2 (MMP-2) in cells. The results showed that SGC-7901 cells not only coexpressed gastrin and CCK-B receptor mRNAs, but also endogenously secreted gastrin protein into the culture medium, thus forming gastrin-CCK-B receptor autocrine loop. Biologically, disrupting gastrin-CCK-B receptor autocrine loop by neutralizing the endogenous gastrin or by knocking down CCK-B receptor expression significantly inhibited the cell proliferation and decreased the percentage of cells residing in the S-phase of the cell cycle, and meanwhile promoted cell apoptosis and increased caspase-3 expression as well as decreased MMP-2 expression. An autocrine loop between endogenously secreted gastrin and CCK-B receptors may play a key role in the regulation of cell proliferation and apoptosis in SGC-7901 cells.
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PMID:Blocking gastrin and CCK-B autocrine loop affects cell proliferation and apoptosis in vitro. 2055 91

The objective of this study was to determine the effect of anti-gastrin antiserum in combination with varied dosages of cytotoxic drugs (5-Fluorouracil (5FU) + Cisplatin (CDDP)) in vivo growth of the human gastric cancer cell-line, SGC-7901, which expressed cholecystokininB/gastrin receptors and secreted gastrin. The anti-gastrin antiserum was obtained by immunizing rabbits using a novel immunogen vaccine, which was composed of the common amino-terminal portion of human carboxy-amidated gastrin-17 (G17) and glycine-extended gastrin-17 (gly-G17) and the common carboxy-terminal portion of progastrin (in a 50:50 mixture) all covalently linked to tetanus toxoid (TT) by specific peptide spacers. The antiserum neutralized both G17 and gly-G17 by enzyme-linked immunosorbent assay (ELISA), and a synthetic progastrin peptide, as well, using an E. coli expressed his-tagged progastrin. The tumor was implanted subcutaneously into the backside of BALB/c nude mice, and the combination antibody-drug treatment using low dose combination chemotherapy had significantly reduced median tumor volumes (62% reduction; p =0.0018) and tumor weights (53% reduction; p =0.0062) when compared to the conventional high dose chemotherapy treated control mice that had a corresponding similar reductive effect, using just the two standard cytotoxic drugs alone; namely by reducing the tumor volumes (65%; p =0.0016) and tumor weights (59% reduction; p=0.0033). Importantly, the immunological treatment had little of the toxicities and side-effects of the full chemotherapy doses alone, which was effected by using a significant decrease in the dosage of chemotherapeutic drugs, while maintaining the same level of efficacy at reduction of tumor growth.
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PMID:Anti-Gastrins Antiserum Combined with Lowered Dosage Cytotoxic Drugs to Inhibit the Growth of Human Gastric Cancer SGC7901 Cells in Nude Mice. 2587 8