Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001418 (adenocarcinoma)
 68,496 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The vacuolating cytotoxin VacA of Helicobacter pylori plays an important but yet unknown role in pathogenesis. We studied the impact of the vacuolating cytotoxin on H. pylori invasion of and survival within AGS cells (human gastric cell line derived from an antral adenocarcinoma). Isogenic vacA and cagA mutants were constructed in a wild-type clinical isolate H. pylori, AF4. An H. pylori VacA-deficient mutant, AF4(vacA::kan), was cultured in significantly lower numbers from AGS cells after 24 h incubation with gentamicin added to the culture medium than were the type I wild-type strain AF4 (P<0.03) and an isogenic cagA mutant (P<0.01). Complementation of the AF4 vacA mutant with broth culture supernatant from wild-type AF4 improved the intracellular survival of the vacA mutant. We conclude that H. pylori's vacuolating cytotoxin improves the intracellular survival of H. pylori within AGS cells, suggesting the role of the vacuolating cytotoxin in H. pylori pathogenesis.
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PMID:Reduced intracellular survival of Helicobacter pylori vacA mutants in comparison with their wild-types indicates the role of VacA in pathogenesis. 1126 41

alpha1,4-N-acetylglucosaminyltransferase (alpha4GnT) is a glycosyltransferase that mediates transfer of GlcNAc to betaGal residues with alpha1,4-linkage, forming GlcNAcalpha1--> 4Galbeta-->R structures. In normal human tissues, glycoproteins having GlcNAcalpha1-->4Galbeta-->R structures at non-reducing terminals are exclusively limited to the mucins secreted from glandular mucous cells of gastric mucosa, Brunner's gland of duodenum, and accessory gland of pancreaticobiliary tract. Recently, we have isolated a cDNA encoding human alpha4GnT by expression cloning. Although alpha4GnT plays a key role in producing this unique glycan in vitro, the actual localization of alpha4GnT was not determined. In this study we examined the localization of alpha4GnT in various human tissues, including gastrointestinal mucosa, using a newly developed antibody against human alpha4GnT. The specificity of the antibody was confirmed by analyses of human gastric adenocarcinoma AGS cells transfected by alpha4GnT cDNA. Expression of alpha4GnT was largely associated with the Golgi region of mucous cells that produce the mucous glycoproteins having GlcNAcalpha1-->4Galbeta-->R, such as the glandular mucous cells of stomach and Brunner's gland. An immunoprecipitation experiment disclosed that two distinct mucin proteins, MUC5AC and MUC6 present in gastric mucin, carried the GlcNAcalpha1-->4Galbeta-->R structures. These results indicate that alpha4GnT is critical to form the mucous glycoproteins having GlcNAcalpha1-->4Galbeta-->R on MUC6 and MUC5AC in vivo.(J Histochem Cytochem 49:587-596, 2001)
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PMID:Immunohistochemical demonstration of alpha1,4-N-acetylglucosaminyltransferase that forms GlcNAcalpha1,4Galbeta residues in human gastrointestinal mucosa. 1130 96

We found that commercially available sialidases prepared from Clostridium perfringens ATCC10543 were contaminated with an endoglycosidase capable of releasing the disaccharide GlcNAcalpha1-->4Gal from glycans expressed in the gastric gland mucous cell-type mucin. We have isolated this enzyme in electrophoretically homogeneous form from the culture supernatant of this organism by ammonium sulfate precipitation followed by affinity chromatography using a Sephacryl S-200 HR column. The enzyme was specifically retained by and eluted from the column with methyl-alpha-Glc. By NMR spectroscopy, the structure of the disaccharide released from porcine gastric mucin by this enzyme was established to be GlcNAcalpha1-->4Gal. The specificity of this enzyme as an endo-beta-galactosidase was established by analyzing the liberation of GlcNAcalpha1-->4Gal from GlcNAcalpha1-->4Galbeta1-->4GlcNAcbeta1-->6(GlcNAcalpha1--> 4Galbeta1-->3)GalNAc-ol by mass spectrometry. Because this novel endo-beta-galactosidase specifically releases the GlcNAcalpha1-->4Gal moiety from porcine gastric mucin, we propose to call this enzyme a GlcNAcalpha1-->4Gal-releasing endo-beta-galactosidase (Endo-beta-Gal(GnGa)). Endo-beta-Gal(GnGa) was found to remove the GlcNAcalpha1-->4Gal epitope expressed in gastric adenocarcinoma AGS cells transfected with alpha1,4-N-acetylglucosaminyltransferase cDNA. Endo-beta-Gal(GnGa) should become useful for studying the structure and function of glycoconjugates containing the terminal GlcNAcalpha1-->4Gal epitope.
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PMID:A novel endo-beta-galactosidase from Clostridium perfringens that liberates the disaccharide GlcNAcalpha 1-->Gal from glycans specifically expressed in the gastric gland mucous cell-type mucin. 1138 76

Modifications of mucosal phospholipids have been detected in samples from patients with Helicobacter pylori-positive gastritis. These alterations appear secondary to increased phospholipase A2 activity (PLA2). The cytosolic form of this enzyme (cPLA2), normally involved in cellular signaling and growth, has been implicated in cancer pathogenesis. The aim of this study was to investigate cPLA2 expression and PLA2 activity in the gastric mucosae of patients with and without H. pylori infection. In gastric biopsies from 10 H. pylori-positive patients, cPLA2 levels, levels of mRNA as determined by reverse transcriptase PCR, levels of protein as determined by immunohistochemistry, and total PLA2 activity were higher than in 10 H. pylori-negative gastritis patients. To clarify whether H. pylori had a direct effect on the cellular expression of cPLA2, we studied cPLA2 expression in vitro with different human epithelial cell lines, one from a patient with larynx carcinoma (i.e., HEp-2 cells) and two from patients with gastric adenocarcinoma (i.e., AGS and MKN 28 cells), incubated with different H. pylori strains. The levels of cPLA2, mRNA, and protein expression were unchanged in Hep-2 cells independently of cellular adhesion or invasion of the bacteria. Moreover, no change in cPLA2 protein expression was observed in AGS or MKN 28 cells treated with wild-type H. pylori. In conclusion, our study shows increased cPLA2 expression and PLA2 activity in the gastric mucosae of patients with H. pylori infection and no change in epithelial cell lines exposed to H. pylori.
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PMID:In vivo and in vitro studies of cytosolic phospholipase A2 expression in Helicobacter pylori infection. 1150 Apr 64

Adherence of Helicobacter pylori to the gastric epithelium is believed to be an important step in the induction of active inflammation of the mucosal layer. However, structural evidence showing a quantitative relationship between the adherence of H. pylori and severity of gastric mucosal inflammation is lacking. We therefore investigated the correlations between severity of gastritis and adherence of morphologically different forms of H. pylori. Fifty-seven biopsy specimens from the gastric bodies of patients with H. pylori-induced gastritis were examined. The severity of gastritis and the adherence and structure of H. pylori were determined with the use of light and scanning electron microscopy. We also investigated the ability of H. pylori organisms with different structural features to induce interleukin-8 secretion by human gastric adenocarcinoma (AGS) cells in vitro because production of interleukin-8 is related to H. pylori-associated gastritis. Furthermore, serum pepsinogen concentrations and cytotoxin-associated protein status in relation to adherence of H. pylori to the epithelial surface were examined. The results indicated that H. pylori organisms, which adhered firmly to the epithelial surface, were consistently long, tightly coiled bacilli. Histologically, those gastric mucosa samples with H. pylori firmly attached showed severe gastritis. H. pylori bacilli of greater length induced higher levels of interleukin-8 secretion. The serum pepsinogen I/II ratio showed a significant negative correlation with the grade of H. pylori adhesion (r = -0.401, P <.01). We also noted a significant correlation between cytotoxin-associated protein status and the adherence of H. pylori (r = 0.344, P <.05). A quantitative correlation was found between adherence of H. pylori and gastric inflammation. Both adherence and the induction of inflammation were found to be related to the structure of H. pylori.
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PMID:Adherence of Helicobacter pylori to gastric epithelial cells and mucosal inflammation. 1202 12

Although intracellular Helicobacter pylori have been described in biopsy specimens and in cultured epithelial cells, the fate of these bacteria is unknown. Using differential interference contrast (DIC) video and immunofluorescence microscopy, we document that a proportion of cell-associated H. pylori enter large cytoplasmic vacuoles, where they remain viable and motile and can survive lethal concentrations of extracellular gentamicin. Entry into vacuoles occurs in multiple epithelial cell lines including AGS gastric adenocarcinoma, Caco-2 colon adenocarcinoma and MDCK kidney cell line, and depends on the actin cytoskeleton. Time-lapse microscopy over several hours was used to follow the movement of live H. pylori within vacuoles of a single cell. Pulsed, extracellular gentamicin treatments show that the half-life of intravacuolar bacteria is on the order of 24 h. Viable H. pylori repopulate the extracellular environment in parallel with the disappearance of intravacuolar bacteria, suggesting release from the intravacuolar niche. Using electron microscopy and live fluorescent staining with endosomal dyes, we observe that H. pylori-containing vacuoles are similar in morphology to late endosomal multivesicular bodies. VacA is not required for these events, as isogenic vacA- mutants still enter and survive within the intravacuolar niche. The exploitation of an intravacuolar niche is a new aspect of the biological life cycle of H. pylori that could explain the difficulties in eradicating this infection.
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PMID:Helicobacter pylori enter and survive within multivesicular vacuoles of epithelial cells. 1236 4

Human peripheral blood mononuclear cells (PBMCs) were treated with Helicobacter pylori (Hp) organisms alone or with Hp-stimulated AGS cells (a gastric adenocarcinoma cell line). Hp organisms were able per se to increase the percentage of CD8 +/- CD95 +/- cells, while number of CD25+ cells and HLA-DR molecule expression increased following pretreatment with Hp-stimulated AGS cells. A comparison was made with a test system in which PBMCs were stimulated with Escherichia coli (Ec) organisms and colo-cells (a colon carcinoma cell line). In this case, CD95+ cells and CD25+ cells increased when the combination Ec organisms/colo-cells was present in the culture. On the other hand, Hp bacteria in combination with colo-cells were not able to induce activation and/or apoptotic surface markers on PBMCs, while Ec-stimulated AGS cells increased the expression of CD95 on PBMC. Finally, the direct interaction of AGS cells with Hp was able to induce higher expression of CD95 on gastric epithelial cells than Hp-stimulated PBMCs. Taken together, these data support the interplay between bacteria and epithelial cells in the course of Hp-mediated gastropathy.
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PMID:Helicobacter pylori organisms induce expression of activation and apoptotic surface markers on human lymphocytes and AGS cells: a cytofluorimetric evaluation. 1251 Jul 91

Splice variant and authentic mRNAs for procathepsin E were measured at a ratio of 5:1 and 1:2 in Kato 3 and AGS cells, two human gastric adenocarcinoma cell lines. As a result of the precise splicing of the 3'-end of exon 6 to the 5'-end of exon 8, the variant lacked the 142 bp of exon 7 which encodes the second of the Asp residues that operate the catalytic mechanism of aspartic proteinases.
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PMID:An alternatively spliced variant of cathepsin E in human gastric adenocarcinoma cells. 1253 80

Gastrin is a gastrointestinal (GI) peptide that possesses potent trophic effects on most of the normal and neoplastic mucosa of the GI tract. Despite abundant evidence for these properties, the mechanisms governing gastrin-induced proliferation are still largely unknown. To elucidate the mechanisms by which gastrin might influence mitogenesis in gastric adenocarcinoma, we analyzed its effects on the human cell line AGS-B. Amidated gastrin (G-17), one of the major circulating forms of gastrin, induced a concentration-dependent increase in [3H]thymidine incorporation of cells in culture, with the maximum effective concentration occurring with 20 nM G-17. This effect was significantly attenuated by the gastrin-specific receptor antagonist L-365260. In addition, we found that G-17 induced a significant increase in the levels of cyclin D1 transcripts, protein, and promoter activity. The results of these studies indicate that gastrin appears to exert its mitogenic effects on gastric adenocarcinoma, at least in part, through changes in cyclin D1 expression.
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PMID:Gastrin-induced gastric adenocarcinoma growth is mediated through cyclin D1. 1260 5

Chronic gastritis induced by Helicobacter pylori is a strong risk factor for the development of distal gastric adenocarcinoma. A specific host response to H. pylori that may contribute to gastric carcinogenesis is epithelial cell apoptosis. The aim of this study was to investigate the capacity of H. pylori vacuolating toxin (VacA) to induce gastric epithelial cell apoptosis. When cocultured with AGS gastric epithelial cells, H. pylori strain 60190, which expresses a type s1/m1 VacA toxin, induced significantly higher levels of apoptosis than did an isogenic vacA null mutant strain. VacA purified from strain 60190 induced apoptosis in a dose-dependent manner, which required acid activation of the purified toxin and the presence of ammonium chloride. In contrast, apoptosis was not induced after incubation with a chimeric s2/m1 toxin (in which the s1 sequence at the NH(2) terminus of VacA from strain 60190 was replaced with the s2 sequence from the nontoxigenic strain Tx30a) or a VacA mutant protein (VacA Delta 6-27) that lacks a unique strongly hydrophobic region near the VacA NH(2) terminus. Moreover, when an equimolar mixture of purified VacA Delta 6-27 and purified wild-type VacA were added simultaneously to AGS cells, the mutant toxin exhibited a dominant negative effect, completely inhibiting the apoptosis-inducing activity of wild-type VacA. These results indicate that VacA induces gastric epithelial cell apoptosis and suggest that differences in levels of gastric mucosal epithelial apoptosis among H. pylori-infected persons may result from strain-dependent variations in VacA structure.
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PMID:Induction of gastric epithelial cell apoptosis by Helicobacter pylori vacuolating cytotoxin. 1261 8


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