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Query: UMLS:C0024623 (gastric cancer)
 36,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mechanism of intracellular fluorescein accumulation was investigated by studying fluorescein accumulation kinetics in individual cells in culture. The experiments were done with K562 human erythroleukemia cell culture and a primary culture of human embryonic skin fibroblasts. Various experimental conditions were used by varying pH and ion composition of the external media, and/or temperature. All the experimental results obtained are in support of the proposed theoretical model describing fluorescein accumulation in cells along the pH gradient. In addition, we could show that fluorescein molecules are bound to some intracellular macromolecules. Fluorescein accumulation in the cells studied does not depend on their malignant nature. It is therefore reasonable to conclude that fluorescein accumulation observed in clinical investigations of human gastric cancer is governed by the ph gradient between the cells and the extracellular fluid; this gradient is much greater in the tumor than in normal tissues.
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PMID:Sodium fluorescein accumulation in cultured cells. 818 92

The bacterium Helicobacter pylori causes peptic ulcers and gastric cancer in human beings by mechanisms yet not fully understood. H. pylori produces urease which neutralizes the acidic medium permitting its survival in the stomach. We have previously shown that ureases from jackbean, soybean or Bacillus pasteurii induce blood platelet aggregation independently of their enzyme activity by a pathway requiring platelet secretion, activation of calcium channels and lipoxygenase-derived eicosanoids. We investigated whether H. pylori urease displays platelet-activating properties and defined biochemical pathways involved in this phenomenon. For that the effects of purified recombinant H. pylori urease (HPU) added to rabbit platelets were assessed turbidimetrically. ATP secretion and production of lipoxygenase metabolites by activated platelets were measured. Fluorescein-labelled HPU bound to platelets but not to erythrocytes. HPU induced aggregation of rabbit platelets (ED(50) 0.28 microM) accompanied by ATP secretion. No correlation was found between platelet activation and ureolytic activity of HPU. Platelet aggregation was blocked by esculetin (12-lipoxygenase inhibitor) and enhanced approximately 3-fold by indomethacin (cyclooxygenase inhibitor). A metabolite of 12-lipoxygenase was produced by platelets exposed to HPU. Platelet responses to HPU did not involve platelet-activating factor, but required activation of verapamil-inhibitable calcium channels. Our data show that purified H. pylori urease activates blood platelets at submicromolar concentrations. This property seems to be common to ureases regardless of their source (plant or bacteria) or quaternary structure (single, di- or tri-chain proteins). These properties of HPU could play an important role in pathogenesis of gastrointestinal and associated cardiovascular diseases caused by H. pylori.
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PMID:Helicobacter pylori urease activates blood platelets through a lipoxygenase-mediated pathway. 1975 69

Nucleolin is an abundant non-ribosomal protein found in nucleolus and a major component of silver-stained nucleolar organizer region (AgNOR), a histopathological marker of cancer which is highly elevated in cancer cells. We recently reported that nucleolin on the cell surface of mouse gastric cancer cells acts as a receptor for tumor necrosis factor-alpha-inducing protein (Tipalpha), a new carcinogenic factor of Helicobacter pylori. In this study, we first examined the localization of nucleolin on cell surface of five gastric cancer cell lines by cell fractionation and flow cytometry: We found that large amounts of nucleolin were present on surface of MKN-45, KATOIII, MKN-74, and AGS cells, with smaller amounts on surface of MKN-1 cells. The membrane fraction of normal epithelial cells of mouse glandular stomach did not contain much nucleolin, suggesting that translocation of nucleolin to the cell surface occurs during carcinogenesis, making for easier binding with Tipalpha. AS1411, a nucleolin targeted DNA aptamer, inhibited growth of gastric cancer cell lines in this order of potency: MKN-45>KATOIII>AGS>MKN-74=MKN-1, associated with induction of S-phase cell cycle arrest. Fluorescein isothiocyanate (FITC)-AS1411 was more rapidly incorporated into MKN-45 and AGS than into MKN-1 cells, based on varying amounts of cell surface nucleolin. We think that AS1411 first binds to nucleolin on the cell surface and that the binding complex is then incorporated into the cells. All results indicate that nucleolin on the cell surface is a new and promising therapeutic target for treatment of gastric cancer.
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PMID:Nucleolin on the cell surface as a new molecular target for gastric cancer treatment. 2046 Jul 57