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 isolated human intercrine reduced in hepatomas (hIRH) as a mRNA whose expression was reduced in differential displays from human hepatocellular carcinoma. hIRH is equivalent to the alpha-chemokine SDF-1alpha/PBSF. We have previously demonstrated on Northern blot analysis that although hIRH mRNA expression is common in human normal tissues, it is absent from pre-malignant colonic adenomas and from 27 human malignant cell lines. However, there are no reports on the mRNA status of hIRH in other human cancers. The present study was designed to investigate semi-quantitatively the expression of hIRH/SDF-1alpha mRNA in hepatocellular carcinoma and digestive tract cancers by reverse transcription-polymerase chain reaction (RT-PCR). The expression of hIRH/SDF-1alpha in the majority of cancer tissues analyzed was markedly reduced compared with that in adjacent non-cancer tissue. RT-PCR was more sensitive than Northern blots in the detection of hIRH mRNA. The average (mean +/- SE) tumor/normal (T/N) ratio determined by RT-PCR was 0.40 +/- 0.07 in 10 pairs of hepatoma, 0.38 +/- 0.09 in 14 pairs of colon cancers, 0.43 +/- 0.07 in 10 pairs of esophageal cancers and 0.70 +/- 0.09 in 26 pairs of gastric cancers. As a control, the mean G3PDH T/N ratio was 1.16 +/- 0.06. The distribution of T/N ratios was significantly different between gastric cancer and the other cancers, but there was no correlation between hIRH/SDF-1alpha expression and clinicopathological characteristics in gastric cancer. Our findings demonstrate that hIRH/SDF-1alpha expression is reduced in the majority of gastrointestinal tumors.
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PMID:Reduced expression of the CXC chemokine hIRH/SDF-1alpha mRNA in hepatoma and digestive tract cancer. 939 42

The activation of coagulation, angiogenesis and inflammatory cytokines are considered to be related with tumour growth and metastasis. We investigated the plasma levels of platelet microparticles (PMP), vascular endothelial growth factor (VEGF), IL-6, and the chemokine RANTES in patients with gastric cancer (n=109) and in healthy controls (n=29). The plasma levels of PMP, IL-6 and RANTES were significantly higher in the patients than in the healthy controls, and plasma levels of PMP, VEGF, IL-6 and RANTES were significantly higher in patients with stage IV disease than those in patients with stage I or stage II/III. In terms of predicting distant metastasis, the sensitivities of PMP, VEGF, IL-6 and RANTES were 93.3%, 56.7%, 70.0% and 81.8%, respectively, and the corresponding specificities were 91.1%, 64.6%, 79.7% and 50.0%. Among these parameters, PMP had the highest diagnostic accuracy. Significant correlations were found between PMP, VEGF, IL-6 and RANTES. This study demonstrates that the plasma levels of PMP, VEGF, IL-6 and RANTES were markedly increased in patients with stage IV disease, and that these increased plasma levels of IL-6, RANTES, and especially PMP, might be useful for identifying metastatic gastric patients.
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PMID:Elevated levels of circulating platelet microparticles, VEGF, IL-6 and RANTES in patients with gastric cancer: possible role of a metastasis predictor. 1250 50

Since Marshall's discovery before 20 years, Helicobacter pylori (H. pylori) infection is reportedly to be associated with a variety of clinical outcomes including peptic ulcer disease and gastric cancer. The first step of the H. pylori colonization might be its adhesion to the surface epithelial cells, which evokes gastric inflammatory events initiated by neutrophil recruitment from the microcirculation. Mongolian gerbil is one of the suitable animal models for H. pylori infection, which exerts gastric ulcer and cancer with its bacterial infection. In H. pylori-colonized gerbils, extensive levels of microvascular leukocyte adhesion and migration into the parenchymal side and significant levels of inflammatory cell infiltration are encountered. Bacterial urease not only neutralizes gastric luminal acid, but also plays as an adhesion factor to the surface epithelium. Recently, such an adhesion to the epithelium is reported to be important for bacterial type IV secretory system, which intermediates Cag A injection into the epithelial cells. Then, multiple chemokine and cytokine networks are activated and mucosal inflammatory lesion formation would be completed. In the long-term colonization of H. pylori, gastric mucosal cell turnover would be modified due to persistent inflammation and then such deregulation of cell turnover might link to the precancerous lesion formation.
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PMID:Gastric mucosal response to Helicobacter pylori. 1252 36

The roles of chemokine receptors in cancer metastatic processes continue to draw research attention. Here we evaluated the expression profiles of the chemokine receptors CCR7 and CXCR4 in gastric cancer, and their potential use as prognostic markers. The expressions of CCR7 and CXCR4 mRNA were analyzed by RT-PCR in 10 human gastric cancer cell lines and in 43 gastric cancer tissues, and in an additional 307 gastric cancer tissues by immunohistochemistry. Clinicopathological features and the prognoses of patients were also evaluated versus the expression of these two cytokine receptors. CCR7 and CXCR4 mRNA were found to be expressed in all gastric cancer cell lines, whereas their mRNA expression rates in gastric cancer tissues were 83.7% (36/43) and 100% (43/43), respectively. Immunohistochemical staining of the 307 gastric cancer tissues showed that the expression rates of CCR7 and CXCR4 were 22.5% (69/307) and 36.5% (112/307), respectively. Multivariate analysis of the immunohistochemistry results showed that the expression rate of CCR7 was significantly higher in differentiated than in undifferentiated gastric cancertypes (35.1 vs. 15.3%, p<0.001), and that CXCR4 was expressed at a higher rate in intestinal cancer than in diffuse-type cancer (58.8 vs. 22.3%, p<0.001). However, in contrast to previous studies, the expressions of CCR7 or CXCR4 were not associated with lymph node metastasis. Moreover, the prognosis of patients with CCR7-positive tumors was better than that of patients with CCR7-negative tumors, but no such correlation was observed for CXCR4 expression. In conclusion, the expressions of the chemokine receptors CCR7 and CXCR4 were found to be high in differentiated and intestinal-type gastric cancers, respectively.
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PMID:Expression of chemokine receptors in human gastric cancer. 1586 78

Helicobacter pylori persistently infects the human stomach and can cause gastritis, gastric ulceration, and gastric cancer. The type IV secretion system (TFSS) of virulent H. pylori strains translocates the CagA protein, inducing the dephosphorylation of host cell proteins and leading to changes in the morphology or shape of AGS gastric epithelial cells. Furthermore, the TFSS is involved in the induction of proinflammatory cytokines. While the H. pylori genes required for TFSS function have been investigated systematically, little is known about possible host cell factors involved. We infected 19 different mammalian cell lines individually with H. pylori and analyzed CagA translocation, dephosphorylation of host cell proteins, chemokine secretion (interleukin-8 and macrophage inflammatory protein 2), and changes in cellular phenotypes. Our results demonstrate that not only bacterial but also host cell factors determine the cellular response to infection. The identification of such unknown host cell factors will add to our understanding of host-pathogen interactions and might help in the development of new therapeutic strategies.
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PMID:Analysis of cell type-specific responses mediated by the type IV secretion system of Helicobacter pylori. 1604 Sep 77

G protein-coupled receptors (GPCRs) play important roles in a variety of biological and pathological processes. They are considered among the most desirable targets for drug development. Recent studies have demonstrated that many GPCRs, such as endothelin receptors, chemokine receptors and lysophosphatidic acid receptors have been implicated in the tumorigenesis and metastasis of multiple human cancers. In this study, we conducted an in silico analysis of GPCR gene expression in primary human tumors by analyzing some publicly available gene expression profiling data. Statistical analysis was performed on eight microarray data sets of non-small cell lung cancer, breast cancer, prostate cancer, melanoma, gastric cancer and diffused large B cell lymphoma to identify GPCRs that are up-regulated in primary or metastatic cancer cells. Our analysis has demonstrated overexpression of several GPCRs in primary tumor cells, including chemokine receptors and protease-activated receptors that were shown to be important for tumorigenesis by previous studies. In addition, we have uncovered several GPCRs, such as neuropeptide receptors, adenosine A2B receptor, P2Y purinoceptor, calcium-sensing receptor and metabotropic glutamate receptors, that are expressed at a significantly higher level in some cancer tissue and may play a role in cancer progression. Analysis of cancer samples in different disease stages also suggests that some GPCRs, such as endothelin receptor A, may be involved in early tumor progression and others, such as CXCR4, may play a critical role in tumor invasion and metastasis. The present study demonstrates the value of publicly available microarray data as a resource to gain more understanding of cancer biology, to validate previous findings from in vitro experiments, and to identify potential novel anticancer targets and biomarkers.
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PMID:Overexpression of G protein-coupled receptors in cancer cells: involvement in tumor progression. 1621 Dec 29

Helicobacter pylori causes various gastroduodenal diseases including gastric MALT lymphoma, but the mechanism underlying H. pylori-induced carcinogenesis is not known. The alternative pathway for NF-kappaB activation, which involves the processing of NF-kappaB2/p100 to p52, has been implicated in lymphocyte survival, attenuated apoptosis, and secondary lymphoid tissue development. In this study, we investigated H. pylori-induced activation of NF-kappaB through the alternative pathway in B lymphocytes. In immunoblot and EMSA, H. pylori induced NF-kappaB2/p100 processing to p52 and subsequent nuclear accumulation in IM-9 (human B cell line) cells and human peripheral blood B cells, but not in AGS (human gastric cancer cell line) cells. The activation of the alternative pathway was LPS-dependent but not cag pathogenicity island-dependent. Alternative pathway activation by H. pylori was associated with attenuated apoptosis. The expression levels of B lymphocyte chemoattractant, EBI-1 ligand chemokine, and stromal cell-derived factor-1alpha mRNAs were up-regulated in cocultured human B cells and in infected human gastric mucosa. In the infected mucosa, NF-kappaB2/p100 and p52 were detected immunohistochemically in the cytoplasm and nuclear compartments of lymphocytes, but not in epithelial cells. In summary, H. pylori activates the alternative NF-kappaB pathway in B lymphocytes. The effects on chemokine production and antiapoptosis mediated by H. pylori-induced processing of NF-kappaB2/p100 to p52 may drive lymphocytes to acquire malignant potential.
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PMID:Helicobacter pylori activates NF-kappaB via the alternative pathway in B lymphocytes. 1630 19

To compare the gene expression profiling between intestinal-type gastric cancer (IGC) and diffuse-type gastric cancer (DGC), cDNA microarray containing 7334 gene elements was performed on 12 paired IGC specimens/its' normal epithelial tissue and 11 paired DGC specimens/its' normal epithelial tissue. Twenty-seven genes were co-overexpressed in IGC and DGC. These overexpressed genes were related to transcription and translation, DNA replications and mitosis, calcium binding, apoptosis and mitochondria protein. Twelve genes were co-underexpressed in IGC and DGC. These underexpressed genes were associated with cell adhesion and migration, organelle movement and intracellular transport, and matrix metalloproteinase. A clustering dendrogram of IGC and DGC with 27 genes significantly differed between IGC and DGC. Nineteen genes were more overexpressed in DGC than in IGC, including annexin A1 (ANXA1), chemokine ligand 7 (CCL7), and chemokine ligand 8 (CCL8). Eight genes were more overexpressed in IGC than in DGC, including claudin 4 (CLDN4). The results of quantitative real-time PCR and immunohistochemical staining confirmed the microarray finding. The gene expression profiling between IGC and DGC suggested that they might have unique genetic pathways which share some of the same and some different genetic alterations.
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PMID:Identification of differential gene expression between intestinal and diffuse gastric cancer using cDNA microarray. 1632 34

NF-kappaB is an important transcriptional factor that is involved in multiple cellular responses, such as inflammation and antiapoptosis. IkappaB kinase alpha (IKKalpha) and IKKbeta, which are critical regulators of NF-kappaB activity, possess various mechanisms for NF-kappaB activation. This variability in NF-kappaB signaling may be associated with distinct inflammatory responses in specific cell types. The gastric pathogen Helicobacter pylori is known to activate NF-kappaB. However, the role of IKK in H. pylori infection remains unclear. In this report, we show that H. pylori activates both IKKalpha and IKKbeta in gastric cancer cells and enhances NF-kappaB signaling in distinct manners. We found that IKKbeta acted as an IkappaBalpha kinase during H. pylori infection, whereas IKKalpha did not. H. pylori induced IKKalpha nuclear translocation in time-, multiplicity of infection-, and cag pathogenicity island-dependent manners. In contrast, p100 processing, which is a known IKKalpha activity induced by several cytokines, was not induced by H. pylori. Both IKKs were responsible for chemokine secretion by infected cells. However, the antiapoptotic effect of H. pylori was merely transduced by IKKbeta. Microarray analysis and real-time PCR indicated that both IKKs were involved in the transcriptional activation of genes associated with inflammation, antiapoptosis, and signal transduction. Our results indicate that H. pylori activates NF-kappaB via both IKKalpha and IKKbeta using distinct mechanisms. IKKalpha nuclear translocation induced by H. pylori is indispensable for appropriate inflammatory responses but not for antiapoptosis, which suggests a critical role for IKKalpha in gastritis development.
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PMID:Helicobacter pylori induces IkappaB kinase alpha nuclear translocation and chemokine production in gastric epithelial cells. 1649 15

Prostaglandin E(2) (PGE(2)) is thought to play an important role in both inflammatory and anti-inflammatory effects. The effect of PGE(2) on the proinflammatory chemokine interleukin-8 (IL-8) in the gastric epithelial cells has not been defined yet. A gastric cancer cell line (MKN45) and primary gastric fibroblasts were cocultured with Helicobacter pylori standard strain (NCTC11637). The expressions of IL-8 and cyclooxygenase 2 (COX-2) mRNA were examined by reverse transcription polymerase chain reaction (RT-PCR) amplification. The amount of IL-8 antigen secreted by the MKN45 cells and gastric fibroblasts was measured by enzyme-linked immunosorbent assay (ELISA). We examined the effects of H pylori stimulation on IL-8 and COX-2 expression levels and the effects of COX-2 inhibitor on H pylori-induced IL-8 production in the MKN45 cells and gastric fibroblasts. Furthermore, we examined the expressions of subtypes of PGE(2) receptors, the effects of arachidonic acid and PGE(2) on IL-8 production, and the effects of PGE(2) on the total cellular cyclic adenosine monophosphate (cAMP) in MKN45 cells. MKN45 cells and gastric fibroblasts expressed IL-8 and COX-2 mRNA under stimulation with H pylori. The MKN45 cells produced IL-8 and PGE(2) antigen into the culture medium with H pylori stimulation, and the production level of IL-8 and PGE(2) antigen decreased significantly with COX-2 inhibitor pretreatment (concentration: 50 muM). On the other hand, the gastric fibroblasts strongly produced IL-8 antigen even in the unstimulated condition, and the amount of IL-8 antigen was not affected by H pylori stimulation and/or COX-2 inhibitor pretreatment. The MKN45 cells expressed IL-8 mRNA and released IL-8 antigen slightly, and the expression level of IL-8 mRNA and the amount of IL-8 antigen increased significantly with PGE(2) treatment in a dose-dependent manner. PGE(2)-induced IL-8 production was inhibited by pretreatment with EP2 and EP4 antagonists. The MKN45 cells expressed EP2 and EP4 subtypes of PGE(2) receptors, and these expression levels were not affected by H pylori stimulation or PGE(2) treatment. The amount of IL-8 antigen increased slightly, but not significantly, with arachidonic acid treatment. PGE(2) treatment for 15 minutes increased the total cellular cAMP in the MKN45 cells. These results suggest that the COX-2-PGE(2) pathway may be involved in IL-8 production in gastric epithelial cells.
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PMID:Involvement of cyclooxygenase-2--prostaglandin E2 pathway in interleukin-8 production in gastric cancer cells. 1707 3


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