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

The aim of this study was to evaluate the prognostic significance of the Goseki factor in patients undergoing potentially curative resection for gastric cancer. From 1989 to 1999 202 patients with gastric cancer came in for observation to the Ist Surgical Clinic of Catania University. For the purposes of this study we examined 86 patients with a 5-year follow-up, from whom it was possible to obtain samples which were mounted in paraffin blocks and stained (haematoxylin-eosin and PAS-Alcian blue). The 5-year survival rates of patients with Goseki I and II tumours with good tubular differentiation were 90% and 30% as compared with 42% and 32% in patients with tumours that showed poor tubular differentiation (Goseki III and IV). In contrast, the 5-year survival rates in patients with mucin-poor tumours (Goseki I and III) were 90% and 42%, as against 30% and 32% in patients with mucin-rich tumours (P < 0.05). Our conclusion is that of the two components of the Goseki system, i.e. tubular differentiation and intracellular mucus, mucus production was found to be the more important determinant of clinical outcome. Mucus production has a greater impact on survival than the degree of tubular differentiation and is independent of it.
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PMID:Gastric cancer: prognostic significance of the Goseki histological classification. 1219 24

Various histologic classification systems have been proposed as prognostic factors for gastric cancer. We assessed the prognostic value of Goseki classification as well as the TNM staging system, histological tumour grading, Lauren, WHO, Goseki and Siewert classifications in 100 patients with cardia carcinoma undergoing curative surgery. Two patients were lost at follow-up. The median time of follow-up in the remaining patients was 32.9 months after surgery (range: 0.1-142.1 months). No differences in survival rates were observed according to tumour grading, Lauren or WHO histologic or Siewert topographical classification. No differences were found according to Goseki classes, when considering either the mucin content of the carcinoma (types I and III vs II and IV) or the differentiation grade (types I and II vs III and IV). Multivariate analysis showed that the only lymph node positivity was a significant predictor of survival: 7.2% of patients with, but 41.5% of those without nodal involvement were alive after five years (P=0.0001). In conclusion, we found no prognostic role for Goseki or the traditional histological indexes, while the TNM staging system and particularly lymph node positivity were the main predictors of survival in patients with cardia adenocarcinoma.
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PMID:Prognostic value of Goseki histological classification in adenocarcinoma of the cardia. 1256 83

alpha1,4-N-acetylglucosaminyltransferase (alpha4GnT) is a glycosyltransferase that forms a unique glycan, GlcNAcalpha1-->4Galbeta-->R, specifically present in gastric gland mucous cell-type mucin. Recently, we molecularly cloned human alpha4GnT and showed that alpha4GnT is expressed in the mucous cells that secrete this particular mucin. In the present study, we first demonstrated that alpha4GnT was frequently expressed in gastric cancer cells but not in peripheral blood cells using immunohistochemistry. To detect gastric cancer cells circulating in the peripheral blood of gastric cancer patients, we quantitatively analyzed the expression level of alpha4GnT mRNA in the mononuclear cell fraction of peripheral blood using real-time reverse transcription polymerase chain reaction. The transcripts of alpha4GnT were detected in the mononuclear cell fraction isolated from 62.2% of 37 gastric cancer patients but not from any of 23 healthy individuals. Significant correlation was found in the expression levels of alpha4GnT mRNA in peripheral blood and alpha4GnT protein in gastric cancer cells. Surprisingly, alpha4GnT mRNA was detectable in 80% of five patients with an early stage of gastric cancer when the cancer cells were limited to the gastric mucosa, and the expression levels of alpha4GnT mRNA were increased in association with tumor progression. In three patients with gastric cancer, during postsurgical follow-up, the expression levels of alpha4GnT mRNA were decreased after surgical removal of gastric cancer. However, significant amounts of the alpha4GnT transcripts were again detected in two patients, who eventually developed to the recurrence of gastric cancer. Although alpha4GnT was detected in 33.3% of nine patients with Helicobacter pylori-infected chronic active gastritis as well as all of four patients with peptic ulcer, the mean expression level of alpha4GnT mRNA in these benign disorders was lower than that in gastric cancer. These results altogether indicate that the quantitative analysis of alpha4GnT mRNA expressed in the peripheral blood is useful for the detection and, possibly, monitoring of gastric cancer.
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PMID:Usefulness of the real-time reverse transcription-polymerase chain reaction assay targeted to alpha1,4-N-acetylglucosaminyltransferase for the detection of gastric cancer. 1259 34

Core 2 beta 1,6-N-acetylglucosaminyltransferase(C2GnT) and alpha 1,4-N-acetylglucosaminyltransferase are glycosyltransferases involved in the biosynthesis of mucin type glycoprotein(O-glycan). The transcripts of C2GnT, which forms core 2-branched O-glycan(Gal beta 1-->3 (GlcNAc beta 1-->6)GalNAc alpha-->Ser/Thr), were detected approximately in 2/3 cases of patients with colorectal or lung cancers. Then, carcinoma cells expressing C2GnT mRNA were shown to significantly progress compared with those lacking the C2GnT mRNA, indicating an important role of the core 2-branched O-glycan in tumor progression. On the other hand, gland mucous cell-type mucin secreted from the normal gastric mucosa characteristically contains GlcNAc alpha 1-->4Gal beta-->R structure, and the alpha 4GnT is critical for the biosynthesis of this unique glycan. This enzyme is also detected in gastric cancer cells but not in mononuclear cell fraction of the peripheral blood. Thus, the quantitative RT-PCR method targeted to alpha 4GnT mRNA will be useful for the detection of circulating gastric cancer cells in the peripheral blood.
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PMID:[Glycosyltransferase genes as tumor marker]. 1265 2

Gastric intestinal metaplasia (IM) and gastric cancer are associated with Helicobacter pylori, but the bacterium often is undetectable in these lesions. To unravel this apparent paradox, IM, H. pylori presence, and the expression of H. pylori virulence genes were quantified concurrently using histologic testing, in situ hybridization, and immunohistochemistry. H. pylori was detected inside metaplastic, dysplastic, and neoplastic epithelial cells, and cagA and babA2 expression was colocalized. Importantly, expression of cagA was significantly higher in patients with IM and adenocarcinoma than in control subjects. The preneoplastic "acidic" MUC2 mucin was detected only in the presence of H. pylori, and MUC2 expression was higher in patients with IM, dysplasia, and cancer. These novel findings are compatible with the hypothesis that all stages of gastric carcinogenesis are fostered by persistent intracellular expression of H. pylori virulence genes, especially cagA inside MUC2-producing precancerous gastric cells and pleomorphic cancer cells.
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PMID:Intracellular and interstitial expression of Helicobacter pylori virulence genes in gastric precancerous intestinal metaplasia and adenocarcinoma. 1269 95

The Tn determinant (GalNAc-O-Ser/Thr) is one of the most specific human tumor markers. In normal cells Tn is a cryptic structure in the peptide core of mucin type O-glycoproteins, and it is detected in an unmasked form in most human carcinomas evaluated by immunohistochemistry. Scarce data are available regarding the characteristics of soluble Tn bearing glycoproteins. We herein report the first comparative characterization of soluble Tn glycoproteins derived from different kinds of human tumors (breast, colon, gastric, ovarian and liver). Considerable heterogeneity was observed in the physicochemical properties of Tn soluble glycoproteins from all the tumor-associated effusions evaluated. In SDS-PAGE analysis Tn glycoproteins from liver and colon effusions migrated as a broad single major component (>500 kDa), while several components of >200 kDa were identified in samples from breast, ovarian, and gastric cancer. The results of perchloric acid (PCA) treatment and CsCl gradient ultracentrifugation indicated that the Tn glycoproteins in effusion fluids correspond predominantly to mucin-like glycoproteins. However, in samples from patients with colon and liver cancer, a fraction of Tn glycoproteins formed part of the immune complexes that precipitated in PCA, suggesting that the anti-Tn immune response in vivo could modify their physicochemical properties. The four apomucins evaluated (MUC1, MUC2, MUC5AC and MUC6) carried Tn epitopes in each of the effusions, indicating that soluble apomucin detection may reflect the abnormal expression of MUC genes inherent to these tumors. Taking together, these results indicate that apomucin expression profile is responsible, at least in part, for the high heterogeneity of soluble Tn glycoproteins, and suggest that the identification of Tn determinant on the different soluble apomucins could be useful for the development of new diagnostic tools as well as to evaluate the anti-tumor immune response in patients with cancer.
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PMID:Biochemical characterization of soluble Tn glycoproteins from malignant effusions of patients with carcinomas. 1288 44

Immunohistological studies demonstrated that MUC1 expression in gastric cancer is associated with a poor prognosis. As a mediator of cell-cell interactions, MUC1 may also be involved in metastasis. However, these aspects are of relevance since cytokine levels are locally increased as a consequence of peritumorous inflammatory response and coexisting chronic gastritis. Therefore we analyzed the potential influence of several cytokines on the expression of tumor-associated MUC1 and Lewis blood group antigens in gastric carcinoma cells. Gastric cancer cell lines AGS and KATOIII were incubated with the cytokines interleukin-1beta, interferon-gamma, tumor necrosis factor-alpha (TNF-alpha), and hepatocyte growth factor over a period of 72 h. Expressions of mucin antigens and cytokine secretion were measured by immunocytochemistry and/or enzyme-linked immunosorbent assay (ELISA). Analysis by fluorescence-activated cell sorter (FACS) demonstrated that MUC1 and sialyl Lewis A reactivities of AGS cells were increased significantly following TNF-alpha stimulation but not by other cytokines. Expression of mucin-associated antigens by cell line KATOIII was not affected by any of the employed cytokines. These data provide evidence that TNF-alpha can raise the expression of important mucin peptide as well as mucin-associated carbohydrate antigens and thereby potentially influence the progression of gastric carcinomas.
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PMID:Modulation of MUC1 and blood group antigen expression in gastric adenocarcinoma cells by cytokines. 1290 71

We examined which, and how many, mucin markers are necessary to define the phenotypes of gastric cancers, and re-evaluated the incidence of their mucin phenotypes and whether minute gastric carcinomas arise as unclassified type. Well-differentiated-type minute gastric carcinomas (n = 33) measuring <or=5 mm were examined using human gastric mucin (HGM) and MUC5AC, MUC6 and M-GGMC-1 (or paradoxical concanavalin A type III mucin (Con A)), MUC2 and CD10 stains, and a new method to separate the previous intestinal type into intestinal type and small intestinal type. The phenotypes of carcinomas were classified into gastric, gastrointestinal, intestinal, small intestinal, and unclassified types. MUC5AC or HGM, MUC6, MUC2, and CD10 stains were all necessary to define gastric cancer phenotypes. The incidence of gastric, gastrointestinal, intestinal, small intestinal, and unclassified type was 6%, 49%, 0%, 45%, and 0%, respectively, when the percentage of positive mucin phenotype was set at >0%, and was 33%, 33%, 3%, 30%, and 0%, respectively, when the percentage of positive mucin phenotype was set at >or=10%. Thus, a panel of MUC5AC (or HGM), MUC6, MUC2 and CD10 stains is indispensable for accurately determining the mucin phenotypes of gastric carcinomas, and the above-mentioned classification is important for studying changes in the histological types of well-differentiated-type adenocarcinomas during change to the poorly differentiated type, as well as corresponding genetic abnormalities.
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PMID:Re-evaluation of mucin phenotypes of gastric minute well-differentiated-type adenocarcinomas using a series of HGM, MUC5AC, MUC6, M-GGMC, MUC2 and CD10 stains. 1508 35

Both the availability of multiple treatment modalities and novel therapeutic targets make the correct prognostic stratification and the identification of truly predictive factors an issue of major debate in gastric cancer. Along with "classic" prognostic factors such as those related to the diffusion of the tumour at diagnosis (i.e., depth of gastric wall infiltration, locoregional lymph nodes or distant metastases) or those concerning the pathologic characteristics of the tumour, other, innovative, factors should be considered if a better definition of the characteristics of the tumour is to be given. These biological factors are often derived from the genetic process, which is thought to represent a crucial step to gastric cancer (DNA copy number changes, microsatellite instability, thymidilate synthase, E-cadherin, beta-catenin, mucin antigen, p53, c-erb B-2, COX-2, matrix metalloproteinases, VEGFR and EGFR). Some of those putative prognostic indicators can also be considered predictive of response to therapy as they are a molecular target either to chemotherapeutics (i.e., thymidilate synthase that is targeted by 5FU) or to a new class of antineoplastic molecules (i.e., c-erb B-2 targeted by trastuzumab, COX-2 by NSAIDs, matrix metalloproteinases, EGFR and VEGFR by specific inhibitors).
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PMID:Molecular biology of sporadic gastric cancer: prognostic indicators and novel therapeutic approaches. 1524 77

Helicobacter pylori causes gastritis, peptic ulcer disease and gastric cancer. The microbe is found in the gastric mucus layer where a pH gradient ranging from acidic in the lumen to neutral at the cell surface is maintained. The aim of the present study was to investigate the effects of pH on H. pylori binding to gastric mucins from healthy individuals. At pH 3, all strains bound to the most charged MUC5AC glycoform and to a putative mucin of higher charge and larger size than subunits of MUC5AC and MUC6, irrespective of host blood-group. In contrast, at pH 7.4 only Le(b)-binding BabA-positive strains bound to Le(b)-positive MUC5AC and to smaller mucin-like molecules, including MUC1. H. pylori binding to the latter component(s) seems to occur via the H-type-1 structure. All strains bound to a proteoglycan containing chondroitin sulphate/dermatan sulphate side chains at acidic pH, whereas binding to secreted MUC5AC and putative membrane-bound strains occurred both at neutral and acidic pH. The binding properties at acidic pH are thus common to all H. pylori strains, whereas mucin binding at neutral pH occurs via the bacterial BabA adhesin and the Le(b) antigen/related structures on the glycoprotein. Our work shows that microbe binding to membrane-bound mucins must be considered in H. pylori colonization, and the potential of these glycoproteins to participate in signalling events implies that microbe binding to such structures may initiate signal transduction over the epithelial layer. Competition between microbe binding to membrane-bound and secreted mucins is therefore an important aspect of host-microbe interaction.
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PMID:Effects of pH on Helicobacter pylori binding to human gastric mucins: identification of binding to non-MUC5AC mucins. 1526 Aug 2


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