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)

We successfully established a human gastric cancer cell line, HuGC-OOHIRA, from the ascites of a 60-year-old patient with advanced gastric cancer (poorly differentiated adenocarcinoma) complicated by peritonitis carcinomatosa and leukocytosis of unknown origin. Morphologically, the cells were polygonal and adhered weakly to the culture flask. They tended to pile up upon reaching confluence. Chromosome analysis revealed that the cell line has two modes of chromosome number, namely near diploidy and tetraploidy. Double minutes (DMs) were present in abundance in each cell. The doubling time was 25-30 hr. The cell line was successfully transplanted into nude mice, and their peripheral leukocyte counts increased in proportion to the growth of the tumors. At 2 weeks after the transplantation, the serum rG-CSF level was elevated to 2,893 pg/ml. The concentration of human G-CSF in the culture supernatants was an extraordinary high level of 145,380 pg/ml/day. Secretion of GM-CSF and IL-6 was also detected. The intracellular localization of the G-CSF was identified for the first time by immunofluorescence. Moreover, Northern blot analysis detected G-CSF mRNA in this cell line. Anti-recombinant human G-CSF serum suppressed the propagation of HuGC-OOHIRA cell line. Therefore, it is likely that the autocrine growth loop by G-CSF is present in this cell line. This cell line would be very useful for understanding both the cellular and molecular basis for the production of various cytokines such as G-CSF as well as cytokine-dependent tumor proliferation.
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PMID:Establishment and characteristics of a gastric cancer cell line (HuGC-OOHIRA) producing high levels of G-CSF, GM-CSF, and IL-6: the presence of autocrine growth control by G-CSF. 754 2

Gastric infection with Helicobacter pylori activates a mucosal inflammatory response by mononuclear cells and neutrophils that includes expression of cytokines interleukin-1 beta (IL-1 beta), IL-6, tumor necrosis factor alpha, and IL-8. In this study, we analyzed the IL-8 response of human gastric cancer cell lines (Kato III, AGS, and MKN28) to H. pylori infection in vitro. IL-8 mRNA expression was detected by reverse transcription-PCR amplification of RNA extracted from epithelial cells after incubation with different H. pylori wild-type and mutant strains, and IL-8 secretion was measured by an enzyme-linked immunosorbent assay. Exposure to viable H. pylori induced IL-8 mRNA and protein synthesis in all three gastric cell lines but not in nongastric epithelial cell lines. Heat-killed H. pylori and a crude cytotoxin preparation did not induce significant IL-8 secretion. IL-8 mRNA peaked between 2 and 4 h postinfection, and IL-8 protein production was maximal 24 h postinfection. Exposure of gastric carcinoma cells to other gastrointestinal bacteria, such as Pseudomonas aeruginosa, Campylobacter jejuni, and Escherichia coli, but not Campylobacter fetus, induced IL-8 synthesis. Wild-type strains that expressed the vacuolating cytotoxin (Tox+) and a cytotoxin-associated gene (cagA) product (CagA+) induced significantly more IL-8 than did CagA- Tox- strains. However, there was no decrease in IL-8 induction by isogenic mutants of CagA-, Tox-, or Cag- Tox- strains or by a mutant lacking the urease subunits. These results indicate that exposure to H. pylori and other gram-negative organisms that do not colonize the gastric mucosa induces IL-8 production by gastric carcinoma cells in vitro. Although the CagA+ Tox+ phenotype of H. pylori is associated with enhanced IL-8 production by gastric cell lines, other bacterial constituents are clearly essential.
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PMID:Interleukin-8 response of gastric epithelial cell lines to Helicobacter pylori stimulation in vitro. 772 72

In order to evaluate the biological response after intraperitoneal administration of OK-432 and CDDP, we studied the changes of cytokine levels in ascitic fluid. A total of 53 gastric cancer patients were included in this study. OK-432 20KE was administered in 7 patients and CDDP was administered in 4 patients intraperitoneally during operation. The IL-6, IL-8, TNF-alpha and sTNF RI levels in ascitic fluid were measured from 0 to 5 postoperative day. These results were compared with those obtained from the control groups (42 patients). The ascitic level of IL-6 increased immediately after operation, then gradually decreased. The elevations of IL-6 from 0 to 5 postoperative day were remarkably higher in the OK-432 treated group, and those on 0 and 1 postoperative days were remarkably lower in CDDP treated group than in the control group. Similarly, the ascitic level of IL-8 elevated soon after operation and then decreased gradually. In the OK-432 treated group, the ascitic level of IL-8 was significantly higher than in the control group from 0 to 2 postoperative day. Ascitic TNF-alpha was detectable only in the ascites soon after operation in the OK-432 treated group. The ascitic level of sTNF RI peaked on 2 postoperative day in the control and the OK-432 treated group and 1 postoperative day in the CDDP treated group. There were no significant differences between these groups.
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PMID:[Changes of cytokine levels in ascitic fluid after intraperitoneal administration of OK-432 or CDDP]. 794 71

To investigate the role of group II phospholipase A2(PLA2) in cancer, we examined the expression and secretion of group II PLA2 in response to the stimulation of interleukin 6(IL-6) in human gastric cancer cells in vitro. Group II PLA2 determined by a specific radioimmunoassay was constitutively produced in culture supernatant of KATO III (signet ring cell carcinoma) and MKN28 (well differentiated adenocarcinoma). This production in KATO III significantly increased with a treatment of IL-6, whereas that in MKN28 remained at a same level. Moreover, the quantitation by reverse transcription-polymerase chain reaction(RT-PCR) demonstrated the IL-6 inducible overexpression of group II PLA2 mRNA in KATO III. This transcription was mediated by NF-IL6, the same as in hepatocytes. These results suggest two possible mechanisms of group II PLA2 production by cancer cells in vivo, that is, cytokine-induced production and constitutive production.
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PMID:Group II phospholipase A2 in invasive gastric cancer cell line is induced by interleukin 6. 811 91

In order to evaluate the biological response after intraperitoneal administration of OK-432, we studied the changes of cytokine levels in ascitic fluid. In 6 advanced gastric cancer patients with peritoneal dissemination or extensive lymph node metastases, OK-432 20 KE was administered intraperitoneally during operation and the IL-6, IL-8 and IFN-gamma levels in ascitic fluid were measured from 0 to 5 postoperative days. These results were compared with those obtained from non-OK-432 administered control groups (17 cases). The ascitic level of IL-8 increased immediately after operation and gradually decreased. In the OK-432 treated group, the elevation of IL-8 on 0 and 1 postoperative days was remarkable, and there were statistically significant differences with the control group. Similarly, the ascitic level of IL-6 elevated soon after operation and then decreased gradually. In the OK-432 treated group, the ascitic level of IL-6 was significantly higher than in the control group after 3 postoperative days. There were no differences in changes of ascitic IFN-gamma levels between the groups. From these results, IL-6 and IL-8 appeared to be induced in ascitic fluid by intraperitoneal administration of OK-432.
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PMID:[Changes in cytokine levels in ascitic fluid after intraperitoneal administration of OK-432]. 837 2

Nine gastric cancer patients with simultaneous liver metastases were given intermittent transarterial administration of chemotherapeutics (adriamycin, mitomycin C or 5-fluorouracil) and biological response modifiers (BRM; OK-432 and interleukin (IL) -2) after gastrectomy. In terms of direct antitumor effect on liver metastases, a partial response was observed in 4 of 9 cases (44%). In addition, the concentration of 3 kinds of cytokines such as IL-6, tumor necrosis factor (TNF) -alpha and interferon (IFN) -gamma in the peripheral blood sera was measured immediately before and after transarterial administration of agents. While the concentration of IL-6 increased by BRM, chemotherapeutics could not alter the level of IL-6. As for TNF-alpha and IFN-gamma, no particular changing pattern was observed after transarterial administration. Furthermore, natural killer (NK) activity of peripheral blood mononuclear cells was measured. Administration of either BRM or BRM in combination with chemotherapeutics caused a decrease in NK activity, whereas chemotherapeutics did not. Flow cytometric analysis using 3 kinds of monoclonal antibodies (Anti-CD16, CD56 and CD57) revealed that the proportion of subset of both highly activated NK cells (CD16+.CD56+.CD57-) and moderately activated NK cells (CD16+.CD56+.CD57+) reduced after administration of BRM.
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PMID:[Immunological effects of locoregional immunochemotherapy for liver metastases of gastric cancer]. 837 5

To determine whether the liver plays an immunological role in certain extrahepatic disorders, we investigated the expression of interleukin (IL)-1 beta, IL-6, interferon (IFN)-gamma, and tumor necrosis factor (TNF)-alpha in 11 patients who had recovered from cholecystolithiasis, 12 patients with gastric cancer, 20 patients with chronic hepatitis, and 6 healthy controls. Cytokine mRNAs in the liver were detected by semiquantitative reverse transcribed-polymerase chain reaction. Serum cytokines and soluble IL-2 receptor (sIL-2R) were investigated by enzyme-linked immunosorbent assays. Increases in TNF-alpha, IL-6, IL-1 beta, and IFN-gamma mRNAs were found in the livers of patients with extrahepatic diseases. TNF-alpha and IL-6 peptides were increased in the sera of patients with gastric cancer. TNF-alpha in the sera and TNF-alpha mRNA in the liver were correlated in gastric cancer patients. Surprisingly, sIL-2R in the serum of gastric cancer patients was significantly higher than the level in healthy controls. Our findings suggest that the liver produces cytokines in reaction to extrahepatic lesions. Further, the increase in sIL-2R in gastric cancer patients indicates that malignancy may affect the immune network in vivo.
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PMID:Increased expression of cytokines in liver and serum in patients with extrahepatic diseases. 884 75

Helicobacter pylori is the major causative agent of chronic gastritis. It is associated with duodenal and gastric ulcer and with the majority of primary gastric B-cell lymphomas; furthermore, there is a strong epidemiological association with gastric cancer. One intriguing aspect of this infection is the ability of H pylori to persist despite the vast array of host immune responses. This article reviews what is known about the immune responses against H pylori, emphasizing what is generally accepted and applicable while highlighting areas of controversy. The first section delineates the genesis of the inflammatory responses, which initiate with the production of tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-1, IL-6, and IL-8 and continue with the recruitment of neutrophilic polymorphonuclear cells, lymphocytes, plasma cells, macrophages and eosinophils, and later with the development and recruitment of specifically committed cells (lymphocytes sensitized to H pylori antigens and B cells producing immunoglobulin (Ig)A, IgG, and possibly IgE antibodies against a variety of H pylori surface and flagellar proteins as well as bacterial toxins). The second part of the article focuses on the development of lymphoid follicles in the gastric mucosa, a phenomenon that for the first time links an immune response (the recruitment of mucosa-associated lymphoid tissue [MALT] to the gastric mucosa in response to H pylori infection) with the development of a neoplastic growth (the development of gastric MALT lymphomas). The local and systemic antibody responses are discussed in the light of their potential application in the development of diagnostic tests and vaccines. Particular emphasis is placed on the controversies surrounding the significance of antibodies directed against a 120 to 140 kDa protein apparently associated with more "aggressive" (sometimes also called "ulcerogenic" or "pathogenic") strains of H pylori.
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PMID:The immunobiology of Helicobacter pylori gastritis. 900 Apr 97

Interleukin (IL)-8, a potent chemoattractant and activator of neutrophils, has been implicated to have a major role in the pathogenesis of gastric mucosal injury by Helicobacter pylori infection. We examined the relationship between cytotoxicity and IL-8 secretion induced by H. pylori. Furthermore, whether the vacuolating cytotoxin of H. pylori mediates IL-8 secretion from gastric epithelial cell lines was examined. Among the inflammatory cytokines, messages for IL-6, IL-8 and transforming growth factor-beta 1 were produced by gastric cancer (MKN45) cells in response to exposure to the cytotoxic strain of H. pylori. MKN45 incubated with the viable cytotoxic strain of H. pylori secreted IL-8. In contrast, the supernatant of neither the cytotoxic nor the non-cytotoxic strain induced IL-8 secretion. There was no correlation between IL-8 secretion and the intensity of cytotoxicity. In conclusion, these findings suggest that IL-8 secretion from MKN45 induced by H. pylori is mediated by factors other than cytotoxicity.
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PMID:Analysis of interleukin-8 secretion induced by Helicobacter pylori from the gastric epithelial cell line MKN45: a mechanism independent of the intensity of cytotoxicity. 919 82

The acute phase protein, alpha1-acid glycoprotein (AGP), is a normal constituent of human blood (0.2-1 mg ml(-1)) and its glycosylation and concentration in the blood change during inflammation. In this review of our recent work, we discuss the immunomodulatory properties of AGP in connection with the structure of its carbohydrate chains. AGP samples prepared from normal donor serum (nAGP), serum obtained during abortion (fAGP), serum of cancer patients (cAGP), and ascitic fluid of patients with stomach cancer (sAGP) were subjected to analysis. All the samples except for fAGP had five N-linked chains of the 'complex' type, however, the numbers of bi-, tri-, and tetra-antennary chains, as well as glycan structures terminating these chains, were different. fAGP had three N-linked chains of the lactosamine and polylactosamine type and three O-chains which were not present in AGP isolated from the other sources. The glycoforms of nAGP and sAGP that were isolated using a ConA affinity column were similar in respect to their branching, but differed in their terminal oligosaccharides. sAGP was enriched in units ending in Le(x) and asialoagalacto (GlcNAc-terminating) forms. Immunomodulatory activity of different AGP preparations was tested in vitro by measuring their effect on the proliferative response of human lymphocytes stimulated by PHA, and by determining their influence on the production of IL-1, IL-2, IL-6, and TNF in the stimulated cells. nAGP was less active compared to cancer or fetal AGP in the proliferation test, but more active in affecting cytokine production. Some AGP glycoforms had opposite immunomodulatory effects. A new approach was developed in order to clarify the role of carbohydrate chains in the biological activity of AGP. A pool of N-linked oligosaccharide chains were attached to a soluble polyacrylamide matrix. This 'pseudoglycoprotein' was similar to AGP in its molecular weight; in its relative amounts of tetra-, tri-, and bi-antennary chains; and in the content of mono-, di-, tri-, and tetra-sialylated-oligosaccharides. This pseudo-AGP displayed a similar activity to its parent AGP in the biological tests. Analytical flow cytometry of leukocyte subpopulation from human peripheral blood showed that monocytes and granulocytes but not lymphocytes were the main targets for the binding of AGP and pseudo-AGP. This binding was inhibited by synthetic glycoconjugates containing mannose or sialic acid. The binding curve data suggested that there are two monocyte and granulocyte populations. These may have different carbohydrate specificities. All the evidence provided by these studies indicate that it is the carbohydrate chains on AGP that are important in modulating the immune system and not the AGP molecule itself.
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PMID:Carbohydrate composition and immunomodulatory activity of different glycoforms of alpha1-acid glycoprotein. 929 96


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