Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024623 (gastric cancer)
 36,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bombesin (BBS) and its mammalian equivalent, gastrin-releasing peptide (GRP), exhibit diverse biological functions, including that of a neurotransmitter, a regulator of gastrointestinal hormone release, and a trophic factor for various normal and neoplastic tissues. Bombesin stimulates the growth of normal cells of the stomach, pancreas, and bronchial epithelium as well as cells in breast cancer, gastrinoma, and small cell lung cancer. The purpose of this study was to determine whether BBS regulates the growth of a human gastric cancer cell line (SIIA) in vitro, and if so, to examine the mechanisms of signal-transduction that are involved. We found that BBS stimulated the growth of SIIA cells in vitro. The GRP receptor antagonists, BIM 26189 and BIM 26226, had no effect on growth of SIIA cells. Although these antagonists blocked the BBS-induced increase of [Ca2+]i, they failed to block the growth-stimulatory effect of BBS. BBS stimulated intracellular tyrosine phosphorylation of multiple proteins, with a predominant protein of apparent molecular weight of 125 kDa. Inhibition of intracellular tyrosine kinases by tyrphostin blocked the growth-stimulatory effect of BBS on SIIA cells. These results indicate that BBS exerts its trophic effect on SIIA cells through a receptor(s) linked to tyrosine kinase pathway, but not to the phospholipase C (PLC) pathway.
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PMID:Bombesin stimulates the in vitro growth of a human gastric cancer cell line. 796 32

The supernatant of a cell line of squamous cell carcinoma of the head and neck (SCCHN), PCI-50, was previously shown to induce activation, promote proliferation and increase antitumor cytotoxicity of freshly purified human natural killer (NK) cells and CD4+ T lymphocytes [Arch Otolaryngol Head Neck Surg (1994) in press]. This supernatant was found also to promote the growth of a variety of hematopoietic cell lines, including Jurkat, THP-1, K562, NK-92 or Epstein-Barr-virus-transformed B cell lines. The Jurkat cell line was selected as a reporter cell in an 18-h proliferation assay established to measure the growth-promoting activity of PCI-50 supernatant. The presence of soluble tumor-derived factors able to induce proliferation of Jurkat cells was demonstrated in the supernatant produced by several other SCCHN cell lines but not in that produced by a gastric cancer cell line (HR) or renal cell carcinoma line (5117G8). The growth-promoting PCI-50 supernatant was shown to contain 28 +/- 0.5 pg/ml interleukin-6 (IL-6) in vitro but was negative for interferon gamma, IL-1, IL-2, IL-4, tumor necrosis factor alpha, granulocyte/macrophage-colony-stimulating factor and IL-12. The addition of any of these recombinant cytokines to Jurkat cell cultures did not significantly promote growth, while PCI-50 supernatant was consistently growth-stimulatory. This supernatant neither enhanced intracellular Ca2+ concentration in Jurkat cells nor induced up-regulation of activation antigens on the cell surface, although it supported growth of Jurkat cells in the absence of IL-2. The growth-promoting activity in the PCI-50 supernatant was acid-labile at pH 2 for 4 h, heat-resistant at 96 degrees C for 1 h and sensitive to treatments with trypsin and pepsin. Preincubation of the PCI-50 producer cells with tunicamycin or cyclohexamide reduced the level of growth-promoting activity in the supernatant. A partial purification of this activity was achieved using Amicon filtration, chromatography on concanavalin-A-Sepharose and then a hydroxyapatite column and high-pressure liquid chromatography gel filtration. The partially purified glycoprotein had a molecular mass of 50-70 kDa, as determined by gel filtration.
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PMID:Proliferation of hematopoietic cell lines induced by a soluble factor derived from human squamous cell carcinomas of the head and neck. 800 Oct 29

This study examined the expression of receptors of the bombesin (BBS) family in human gastric-cancer cell lines. Of 5 cell lines screened, only one, St42, demonstrated specific binding sites for 125I-Tyr4-BBS, which have been further characterized. This binding was saturable, and temperature- and time-dependent. Scatchard analysis of displacement data performed at 37 degrees C revealed 2 binding sites: a high-affinity, low-capacity site (KD = 0.13 nM, Bmax = 1500 sites/cell) and a lower-affinity, higher-capacity site (KD = 11 nM, Bmax = 35,000 sites/cell); the latter was lost when internalization of peptide was prevented, suggesting that it may be an artefact. Displacement assays with gastrin-releasing peptide (GRP) and neuromedin B (NMB) revealed that the receptor was of the GRP-preferring sub-type (GRP IC50 = 0.35 nM; NMB IC50 = 112 nM). Co-valent cross-linking of 125I-Tyr4-BBS to the receptor demonstrated the presence of a single band corresponding to a molecular weight of 37 to 44 kDa on SDS-PAGE, similar to that of the cloned GRP receptor protein core. G-protein linkage of this receptor was demonstrated by selective inhibition of 125I-Tyr4-BBS binding by guanosine nucleotides. The binding of BBS to the receptor resulted in a rise in intracellular calcium. Three of four structurally distinct BBS antagonists bound to the receptor with high affinity, but [DPhe12, Leu14]-bombesin did not cause any displacement of 125I-Tyr4-BBS even at 10 mM. The functional significance of GRP receptors on human gastric-cancer cells is as yet unknown, but further studies may determine whether such receptors have importance in the therapy of gastric cancer.
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PMID:Characterization of a bombesin/gastrin-releasing peptide receptor on a human gastric-cancer cell line. 819 83

In order to study the mechanism of cancer metastasis, AH100B rat hepatoma cells were transplanted to the stomach of male Donryu rats. Each hepatic metastatic nodule was collected with the respective primary gastric lesions. Each sample thus obtained was injected separately into the peritoneal cavity of male Donryu rats to make free cancer cells; then, intact cancer cells of the hepatic metastatic and primary gastric lesions were collected. After washing in Dulbecco's phosphate-buffered saline (Ca2+ and Mg(2+)-free, pH 7.2), the definite number of the metastatic and primary gastric cancer cells were incubated in the phosphate-buffered saline containing [1-14C] arachidonic acid at 25 degrees C for 30 min. Arachidonic acid metabolites formed during the incubation period were extracted and subjected to thin-layer chromatography, followed by autoradiography. Each radioactive spot was scraped off the plate and measured for its radioactivity. The pattern of the ability to produce PGs was different between the cancer cells which metastasized to the liver and those of the primary lesions, that is, percentage of PGF2 alpha was higher (p < 0.05) and that of PGE2 was quite higher (p < 0.01) in the hepatic metastatic cancer cells as compared with those of the primary gastric lesion. These results suggest that PGs produced by hepatic metastatic cancer cells might play an important role in hepatic metastatic formation.
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PMID:Some features of prostaglandin synthesis of the cancer cells metastasized into liver from gastric cancer lesions. 827 90

GDP-L-Fuc:N-acetyl-beta-D-glucosaminide:alpha1-6 fucosyltransferase (alpha1-6 FucT), which catalyzes the transfer of fucose from GDP-Fuc to N-linked type complex glycopeptides, was purified from a culture supernatant of human gastric cancer cell line MKN45. The purification procedures included chromatographies on Q-Sepharose Fast Flow, synthetic GDP-hexanolamine-Sepharose, and GnGn-bi-Asn-Sepharose columns. SDS-PAGE of the purified enzyme gave a major band corresponding to an apparent molecular mass of 60 kDa. The enzyme was recovered in a 12% final yield with an approximately 4,600-fold increase in specific activity. The pH optimum was 7.5, and the enzyme was fully active in the presence of 5 mM EDTA and did not require divalent cations, Mg2+ and Ca2+. Oligonucleotide primers designed from partial amino acid sequences were used to amplify and clone alpha1-6 FucT cDNA from a cDNA library of MKN45 cells. The cDNA encodes 575 amino acids in length, and contains the predicted N-terminal and internal amino acid sequences derived on lysyl endopeptidase digestion. The homology to porcine brain alpha1-6 FucT is 92.2% at the nucleotide level and 95.7% at the amino acid level. No putative N-glycosylation sites were found in the predicted amino acid sequence of the human MKN45 cell enzyme or that of porcine brain. Thus, the enzyme is distinct from other fucosyltransferases which catalyze alpha1-2, alpha1-3, and alpha1-4 fucose addition.
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PMID:Purification and cDNA cloning of GDP-L-Fuc:N-acetyl-beta-D-glucosaminide:alpha1-6 fucosyltransferase (alpha1-6 FucT) from human gastric cancer MKN45 cells. 913 35

Hepatocyte growth factor (HGF) has been found to stimulate proliferation and migration of human gastric carcinoma cells. Whether the HGF-induced responses are correlated with the expressed level of HGF receptors or the changes of ionic currents is not clear. The present study investigated the effects of HGF on the proliferation and ionic currents of two human gastric adenocarcinoma cell lines, which were found to express different amounts of HGF receptor. Results showed that HGF induced a dose-dependent growth stimulation and accelerated cell cycle progression in SC-M1 cells. In patch clamp study, HGF treatment induced an outward K+ current and increased the slope conductance at -80 mV from 110+/-15 pS/pF to 207+/-15 pS/pF. The HGF-induced K+ current was abolished when tetraethylammonium chloride was added in bathing solution or a low Ca2+ solution was included in the recording pipette. Furthermore, HGF (10 ng/ml) induced an oscillatory Ca2+-activated K+ current with a lag period of 5+/-3 min in SC-M1 cells. In contrast, HGF did not induce mitogenesis, cell cycle progression and changes in ionic currents in KATO-III cells, although this cell line expressed a higher level of HGF receptors than SC-M1 cells did. These findings provide evidence that the activity of Ca2+-activated K+ channel may be involved in the HGF-induced cell proliferation in human gastric cancer cells, but it did not correlate with the density of HGF receptors.
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PMID:Correlation of hepatocyte growth factor-induced proliferation and calcium-activated potassium current in human gastric cancer cells. 945 3

Bombesin (BBS) exhibits diverse biological functions including those of neurotransmitter, regulator of gastrointestinal hormone release, and mitogen. Gastrin-releasing peptide (GRP, the mammalian equivalent of BBS) is found in mucosal cells of the gastric fundus and antrum. We determined whether a human gastric cancer cell line (SIIA) expresses a functional GRP-receptor (GRP-R). BBS increased intracellular calcium ([Ca2+]i), and a specific GRP-R antagonist, ([D-Phe6, Des-Met14]-BBS (6-14)-ethylamide), blocked BBS-induced increase in [Ca2+]i. SIIA cells possess GRP-R mRNA by reverse transcriptase-PCR. Furthermore, these cells possess an 80-kDa cell surface protein that specifically binds BBS with two high-binding affinities (Kd1 = 0.6 nM, Kd2 = 6.7 nM). These findings indicate that SIIA cells possess a GRP-R that is capable of physiological signal transduction, though the cellular response remains unknown.
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PMID:A human gastric cancer cell line possesses a functional receptor for gastrin-releasing peptide. 947 46

The concentration of Mg, Ca and total hardness of well and tap water were examined in 98 towns and cities in Hyogo prefecture. The annual mortality rates of stomach cancer and CVD in these areas during 1975-1979 were analyzed by the concentration of Mg and Ca in well water. The mortality rate of stomach cancer was correlated significantly positively to Mg2+/Ca2+ ratio of well water, and a similar tendency was shown in tap water. A covariance analysis indicated Mg2+ to be correlated significantly to the mortality rate of stomach cancer. Thus, it is suggested that the relatively high concentration of Mg2+ compared to Ca2+ in drinking water might be one of the causes of stomach cancer in Japanese. But the concentration of Ca2+ was correlated significantly negatively to the mortality rate of CVD.
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PMID:Relationship between mortality rate of stomach cancer and cerebrovascular disease and concentrations of magnesium and calcium in well water in Hyogo prefecture. 948 82

The identification of genes predisposing to familial cancer is an essential step towards understanding the molecular events underlying tumorigenesis and is critical for the clinical management of affected families. Despite a declining incidence, gastric cancer remains a major cause of cancer death worldwide, and about 10% of cases show familial clustering. The relative contributions of inherited susceptibility and environmental effects to familial gastric cancer are poorly understood because little is known of the genetic events that predispose to gastric cancer. Here we describe the identification of the gene responsible for early-onset, histologically poorly differentiated, high grade, diffuse gastric cancer in a large kindred from New Zealand (Aotearoa). Genetic linkage analysis demonstrated significant linkage to markers flanking the gene for the calcium-dependent cell-adhesion protein E-cadherin. Sequencing of the E-cadherin gene revealed a G --> T nucleotide substitution in the donor splice consensus sequence of exon 7, leading to a truncated gene product. Diminished E-cadherin expression is associated with aggressive, poorly differentiated carcinomas. Underexpression of E-cadherin is a prognostic marker of poor clinical outcome in many tumour types, and restored expression of E-cadherin in tumour models can suppress the invasiveness of epithelial tumour cells. The role of E-cadherin in gastric cancer susceptibility was confirmed by identifying inactivating mutations in other gastric cancer families. In one family, a frameshift mutation was identified in exon 15, and in a second family a premature stop codon interrupted exon 13. These results describe, to our knowledge for the first time, a molecular basis for familial gastric cancer, and confirm the important role of E-cadherin mutations in cancer.
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PMID:E-cadherin germline mutations in familial gastric cancer. 953 25

The possible association between the risk of gastric cancer and the levels of calcium, magnesium, and nitrate in drinking water from municipal supplies was investigated in a matched case-control study in Taiwan. Records of gastric cancer deaths among eligible residents in Taiwan from 1987 through 1991 were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Controls were deaths from other causes and were pair-matched to the cases by sex, year-of-birth, and year-of-death. Each matched control was selected randomly from the set of possible controls for each case. Data on calcium, magnesium, and nitrate levels in drinking water throughout Taiwan were obtained from the Taiwan Water Supply Corporation. The municipality of residence of the cases and controls was assumed to be the source of the subject's calcium, magnesium, and nitrate exposure via drinking water. The subjects were divided into tertiles according to the levels of calcium, magnesium, and nitrate in their drinking water. The results of the present study show that there is a significant positive association between drinking water nitrate exposure and gastric cancer mortality. The present study also suggests that there was a significant protective effect of calcium intake from drinking water on the risk of gastric cancer. Magnesium also exerts a protective effect against gastric cancer, but only for the group with the highest levels.
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PMID:Calcium, magnesium, and nitrate in drinking water and gastric cancer mortality. 954 38


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