UMLS:C0024623 - FACTA Search

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

Helicobacter pylori is the causative agent of chronic gastritis, peptic ulcers, and is also associated with gastric cancer. Eradication of H pylori infection has proven to be difficult to confirm. The authors developed a nonradioactive in situ hybridization method for detection of H pylori and compared it with conventional methods for diagnosis of the infection. Reverse transcription followed by polymerase chain reaction (PCR) with two 22-base primers was used to amplify a 520 base pair (bp) segment of 16S rRNA from H pylori. The PCR product was labeled with digoxigenin and used as a probe. Specificity of the probe was tested by dot blot hybridization against DNA from 30 different strains of related and unrelated bacteria. Specificity of in situ hybridization assay was proven by the lack of hybridization on sections with gram negative and positive bacteria other than H pylori, with an unrelated probe, without probe, and after RNase treatment. A random sample of 15 biopsy specimens was blindly studied by in situ hybridization method and the results were compared with those of culture and conventional histology. Comparison of in situ hybridization and conventional histology showed agreement in all 15 specimens (5 negative and 10 positive). Between culture and in situ hybridization there was agreement in 13 cases (8 positive, 5 negative). Two cases were negative by culture but positive by in situ hybridization and histology. Nonradioactive in situ hybridization provides a sensitive and specific method for detection of H pylori infection. It should be particularly useful for confirmation of infection in cases equivocal with other methods, and potentially useful in post-treatment evaluation.
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PMID:Detection of Helicobacter pylori in paraffin-embedded gastric biopsy specimens by in situ hybridization. 881 86

Fibroblast growth factor (FGF), a key regulatory factor of cell growth and differentiation, is involved in embryonic development, angiogenesis, and tumorigenesis. To date, four different FGF receptors (FGFRs) have been cloned and characterized. We examined the expression of four FGFRs in human gastric cancer tissues and cell lines using Northern analysis, ribonuclease protection assay, and immunohistochemistry. The mRNAs of FGFR-1 (10/14), FGFR-2 (9/14), and FGFR-4 (9/14) were up-regulated in cancer compared with normal tissues. FGFR-3 mRNAs were barely detectable in both normal and cancer tissues. These FGFR mRNAs were co-expressed in various combinations of two or three in the same tissue. Immunohistochemistry confirmed specific staining of multiple FGFRs, except FGFR-3, in the cancer specimens. To investigate the functional significance of FGFR co-expression we examined the invasive property of SNU-16 cells, which exhibited gene amplification of FGFR-2, -3, and -4 as well as over-expression of keratinocyte growth factor receptor (KGFR), a splice variant of FGFR-2, and FGFR-4 mRNA. KGF plus acidic FGF (aFGF), KGF, and aFGF treatment enhanced the invasive potential of SNU-16 cells over the control by 100%, 107%, and 47%, respectively, indicating that neither additive nor synergistic effect was induced by stimulation with aFGF plus KGF. These results suggest that co-expression of FGFRs in various combinations may cause subtle changes in the progression of gastric cancer.
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PMID:Up-regulation and co-expression of fibroblast growth factor receptors in human gastric cancer. 1100 64

Alpha-fetoprotein (AFP) producing gastric cancer (AFP-GC) is very malignant and highly metastatic compared with common gastric cancer. However, the causal relationship between AFP production and the high malignancy of AFP-GC is unclear. We investigated AFP gene regulation in AFP-GC by an active transcription factor, HNF1 (hepatocyte nuclear factor 1) and a repressive transcription factor, ATBF1 (AT motif binding factor 1). RNase protection assays revealed that the production of AFP in gastric cancer cells did not directly associate with HNF1 expression. An inverse relation between the expressions of ATBF1 and AFP was clearly observed in gastric cancer cells. CAT assays showed the direct inhibition of AFP gene expression by ATBF1. Methylation analysis of the AFP promoter region in gastric cancer cells suggested that methylation itself could not explain the silencing of the AFP gene. Immunohistochemistry of resected clinical samples revealed that AFP producing cells lacked ATBF1 immunoreactivity. Our data suggests that the absence of ATBF1 is responsible for AFP gene expression in gastric cancer, and the absence of ATBF1 is a distinct characteristic of AFP-GC and might be important for its highly malignant nature.
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PMID:Alpha-fetoprotein producing gastric cancer lacks transcription factor ATBF1. 1131 20

The growth factor receptor oncogene, c-erb B-2, is frequently overexpressed in the adenocarcinomas of breast, ovary, lung and stomach. Although the mechanism of erb B-2 overexpression is thought as the result of transcriptional upregulation in many primary human carcinomas, expression rate of c-erb B-2 at mRNA level is usually lower than the level of translated protein. We also found that the expression of erb B-2 in SNU-1 stomach cancer cells was greater at post-transcription level (Bae et al., 1993). To explore the underlying mechanism of erb B-2 protein overexpression, we have chosen two cells lines, SNU-1 and SNU-16 where transcription rate of erb B-2 was closely resemble to each other while expressed protein levels were quite different. The synthesis rate of erb B-2 protein in SNU-1 cells was faster than SNU-16 cells while levels of erb B-2 mRNA were found to be similar in both cell lines. The half-life of the expressed erb B-2 protein was not significantly different in both cell lines. Analysis of the 5' untranslated region (UTR) of erb B-2 mRNA (-1approximately-323) showed no sequence abnormality in both cell lines. However, ribonuclease protection assay using cloned 5 UTR sequence revealed that the size of 5' UTR of erb B-2 mRNA which associate with transcription initiation site(s) in SNU-1 cells was longer than that in SNU-16. These results suggest that the increased erb B-2 protein synthesis rate possibly due to the redundant selection of transcription initiation might be a mechanism of erb B-2 overexpression in SNU-1 cells.
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PMID:Post-transcriptional control of c-erb B-2 overexpression in stomach cancer cells. 1132 80

AIM:To construct Hsp90 antisense RNA eukaryotic expression vector, transfect it into SGC7901 and SGC7901/VCR of MDR-type human gastric cancer cell lines, HCC7402 of human hepatic cancer and Ec109 of human esophageal cancer cell lines, and to study the cell cycle distribution of the gene transected cells and their response to chemotherapeutic drugs.METHODS:A 1.03kb cDNA sequence of Hsp90beta was obtained from the primary plasmid phHSP90 by EcoR I and BamH I nuclease digestion and was cloned to the EcoR I and BamH I site of the pcDNA by T4DNA ligase and an antisense orientation of Hsp90beta expression vector was constructed. The constructs were transfected with lipofectamine and positive clones were selected with G418. The expression of RNA was determined with dot blotting and RNase protection assay, and the expression of Hsp90 protein determined with western blot. Cell cycle distribution of the transfectants was analyzed with flow cytometry, and the drug sensitivity of the transfectants to Adriamycin (ADR), vincrinstine (VCR), mitomycin (MMC) and cyclophosphamide (CTX) with MTT and intracellular drug concentration of the transfectants was determined with flow cytometry.RESULTS:In EcoR I and BamH I restriction analysis, the size and the direction of the cloned sequence of Hsp90beta remained what had been designed and the gene constructs were named pcDNA-Hsp90.AH-SGC7901, AH-SGC7901/VCR, AH-HCC7402 and AH-Ec109 cell clones all expressed Hsp90 anti-sense RNA. The expression of Hsp90 was down-regulated in AH-SGC7901, AH-SGC7901/VCR, AH-HCC7402 and AH-Ec109 cell clones. Cell cycle distribution was changed differently. In AH-SGC7901/VCR and AH-Ec109 cells, G(1) phase cells were increased; S phase and G(2) phase cells were decreased as compared with their parental cell lines. In AH-SGC7901 cell, G(1)phase cells were decreased, G(2) phase cells increased and S phase cells were not changed, and in AH-HCC7402 cells G(1), S and G(2) phase cells remained unchanged as compared with their parental cell lines. The sensitivity of AH-SGC7901, AH-SGC7901/VCR, AH-HCC7402 and AH-Ec109 to chemotherapeutic drugs, the sensitivity of AH-SGC7901/VCR to ADR, VCR, MMC and CTX the sensitivity of AH-HCC7402 to ADR and VCR, and the sensitivity of Ec109 to ADR, VCR and CTX all increased as compared with their parental cell lines. The mean fluorescence intensity of ADR in AH-SGC7901, AH-SGC7901/VCR, AH-HCC7402 and AH-Ec109 was also significantly elevated (P < 0.05).CONCLUSION: Down-regulation of Hsp90 could change cell cycle distribution and increase the drug sensitivity of tumor cells.
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PMID:Down-regulation of Hsp90 could change cell cycle distribution and increase drug sensitivity of tumor cells. 1181 30

Although debates still exist whether Helicobacter pylori infection is really class I carcinogen or not, H. pylori has been known to provoke precancerous lesions like gastric adenoma and chronic atrophic gastritis with intestinal metaplasia as well as gastric cancer. Chronic persistent, uncontrolled gastric inflammations are possible basis for ensuing gastric carcinogenesis and H. pylori infection increased COX-2 expressions, which might be the one of the mechanisms leading to gastric cancer. To know the implication of long-term treatment of antiinflammatory drugs, rebamipide or nimesulide, on H. pylori-associated gastric carcinogenesis, we infected C57BL/6 mice with H. pylori, especially after MNU administration to promote carcinogenesis and the effects of the long-term administration of rebamipide or nimesulide were evaluated. C57BL/6 mice were sacrificed 50 weeks after H. pylori infection. Colonization rates of H. pylori, degree of gastric inflammation and other pathological changes including atrophic gastritis and metaplasia, serum levels and mRNA transcripts of various mouse cytokines and chemokines, and NF-kappaB binding activities, and finally the presence of gastric adenocarcinoma were compared between H. pylori infected group (HP), and H. pylori infected group administered with long-term rebamipide containing pellet diets (HPR) or nimesulide mixed pellets (HPN). Gastric mucosal expressions of ICAM-1, HCAM, MMP, and transcriptional regulations of NF-kappaB binding were all significantly decreased in HPR group than in HP group. Multi-probe RNase protection assay showed the significantly decreased mRNA levels of apoptosis related genes and various cytokines genes like IFN-gamma, RANTES, TNF-alpha, TNFR p75, IL-1beta in HPR group. In the experiment designed to provoke gastric cancer through MNU treatment with H. pylori infection, the incidence of gastric carcinoma was not changed between HP and HPR group, but significantly decreased in HPN group, suggesting the chemoprevention of H. pylori-associated gastric carcinogenesis by COX-2 inhibition. Long-term administration of antiinflammatory drugs should be considered in the treatment of H. pylori since they showed the molecular and biologic advantages with possible chemopreventive effect against H. pylori-associated gastric carcinogenesis. If the final concrete proof showing the causal relationship between H. pylori infection and gastric carcinogenesis could be obtained, that will shed new light on chemoprevention of gastric cancer, that is, that gastric cancer could be prevented through either the eradication of H. pylori or lessening the inflammation provoked by H. pylori infection in high risk group.
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PMID:Chemoprevention of Helicobacter pylori-associated gastric carcinogenesis in a mouse model: is it possible? 1254 79

KiSS-1 is a promising candidate tumor-suppressor gene and may play a key role in the metastatic cascade. The expression profile and the role of KiSS-1 in cancer progression are largely unknown in most of the cancers, including gastric cancer. In this study, KiSS-1 expression was evaluated by RNase protection assay and localization was done by in situ hybridization in 40 gastric cancers and their adjacent normal gastric mucosa. For comparison with clinicopathologic characteristics and patient prognosis, all patients were divided into 2 groups having high and low KiSS-1 expression by using the median as the cutoff value of KiSS-1 expression as determined by the RNase protection assay. Gastric cancers with low KiSS-1 had frequent venous invasion, distant metastasis and tumor recurrence. Accordingly, patients with low KiSS-1-expressing tumors had a significantly worse overall and disease-free survival. In multivariate analysis, KiSS-1 became the strongest independent prognostic factor among the conventional prognosticators for gastric cancer patients. Collectively, these findings suggest that KiSS-1 may play a crucial role in gastric cancer invasion and could be a useful target for therapeutic intervention.
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PMID:Downregulation of KiSS-1 expression is responsible for tumor invasion and worse prognosis in gastric carcinoma. 1530 Jul 98

Chronic inflammation of the gastric epithelium is believed to induce mucosal changes that can eventually develop into gastric cancer. In gastrin-deficient (G-/-) mice exhibiting chronic inflammation in the hypochlorhydric stomach, we documented a prominent fundic mucous cell lineage sharing morphological similarity with preneoplastic changes reported in Helicobacter-infected mice. To study the identity and origin of this cell lineage, we screened for different gastric mucosal cell markers. The clusters of large, foamy cells stained for trefoil factor 2 (TFF2/SP), MUC6 and the lectin Griffonia Simplicifolia II (GSII), but not for the intestine-specific transcription factor Cdx2, suggested that they arise from gastric mucous neck cells. Ki67-labeled GSII-positive neck cells in Helicobacter felis-infected, but not G-/- stomachs, suggested that mucous neck cell proliferation accounted for expansion of this compartment in the H. felis model of gastritis, but not the G-/- model. Using RNase protection assays and quantitative PCR, we found that interferon gamma (IFNgamma) was the most abundant proinflammatory cytokine in the G-/- stomach. We also found that this Th1 cytokine can increase the abundance of mucous neck cells, since its infusion into mice recapitulated the appearance of these cells as observed in both G-/- and H. felis-infected mice. Using the human gastric cell line NCI-N87, we showed that IFNgamma induces the secretion of mucus and expression of MUC6, TFF2 and pepsinogen II, but not of pepsinogen I and intrinsic factor. In conclusion, our results demonstrate that inflammation, specifically the proinflammatory cytokine IFNgamma, induced expansion of the fundic mucous neck cell compartment, which likely represents both increased mucus production and cell number.
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PMID:Interferon gamma induction of gastric mucous neck cell hypertrophy. 1576 19

The joint international symposium of the 22nd Hiroshima Cancer Seminar and the 4th Japanese Association for RNA Interference focused on a pivotal role of microRNAs in carcinogenesis, progression and therapy of human cancer. Mammalian immune regulator MCPIP1 (Zc3h12a) RNase acts as a novel suppressor of microRNA activity and biogenesis, suggesting the involvement of MCPIP1 in the alteration of microRNA biogenesis in tumorigenesis. Gene set enrichment analysis and functional assignment of microRNAs via enrichment analysis enable the prediction of microRNA activities from mRNA expression data by combining rank-based enrichment analysis and weighted evaluation of microRNA-mRNA interactions. MiR-124 and miR-203 function as tumor-suppressor microRNAs silenced by DNA methylation in hepatocellular carcinoma. Stella-induced DNA hypomethylation would confer the pathogenic function of DNA hypomethylation in cancer. Senescence-associated microRNA, miR-22, suppresses tumor growth and metastasis in vivo in a murine breast cancer model, and exosomal senescence-associated microRNA may affect the tumor microenvironment. The therapeutic potential of microRNAs for preventing and treating lung cancer using the Kras(LSL-G12D/+);p53(LSL-R172H/+)mouse model suggests that miR-34 may be useful in sensitizing tumors to other conventional therapeutics. MiR-1 and miR-133a cluster may function as tumor suppressors regulating novel pathways in human cancers. The down-regulation of miR-148a is implicated in invasion of gastric cancer, while high miR-21 expression in colorectal cancer is associated with poor survival. Neutral sphingomyelinase 2 regulates exosomal microRNA secretion and promotes angiogenesis within the tumor microenvironment as well as metastasis; in particular, the exosomal miR-210 secretion by neutral sphingomyelinase 2 confers the formation of the tumor vessel network.
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PMID:MicroRNAs in Cancer: the 22nd Hiroshima Cancer Seminar/the 4th Japanese Association for RNA Interference Joint International Symposium, 30 August 2012, Grand Prince Hotel Hiroshima. 2348 40

Histone deacetylase inhibitors (HDACis) are a promising class of anticancer epigenetic drugs, however, molecular factors influencing the responses of individual tumors to HDACi therapies remain obscure. Here, we sought to identify genes associated with HDACi resistance in gastric cancer. Treating a panel of 17 gastric cancer cell lines with multiple HDACi compounds (trichostatin A, SAHA and MS275), we identified two distinct classes of lines exhibiting either HDACi sensitivity or resistance. Genomic comparisons between the sensitive and resistant classes using two independent microarray platforms identified RNH1, encoding a ribonuclease inhibitor, as a gene highly expressed in HDACi-resistant lines. Using genetic knockdown and overexpression assays, we show that RNH1 is both necessary and sufficient to induce HDACi resistance, and that RNH1 is likely to mediate this resistance through the dampening of HDACi-induced reactive oxygen species (ROS) in cancer cells. The discovery of RNH1 as a regulator of HDACi resistance in gastric cancer highlights a functional role for ROS induction in the cellular effects of this important drug class.
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PMID:RNH1 regulation of reactive oxygen species contributes to histone deacetylase inhibitor resistance in gastric cancer cells. 2358 80

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