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)

Previous studies have suggested that cyclooxygenase-2 (COX-2) over-expression is associated with angiogenesis in gastric cancer. However, the relationship between COX-2 and lymphangiogenesis is still unclear. The aim of this study was to determine the relationship between COX-2 expression and lymphangiogenic factor, vascular endothelial growth factor-C (VEGF-C), in human gastric cancer, as well as to correlate with clinicopathological parameters. Sixty-three gastric cancer patients underwent radical gastrectomy (D2 or D3) were enrolled in this study. The expression of COX-2 and VEGF-C were detected by immunohistochemistry, and the small lymphatic vessels were immunohistochemically stained by LYVE-1 antibody. The association between COX-2 and VEGF-C expressions and clinicopathological parameters (such as gender, tumor location, lymph node status and Lauren classification) were determined. VEGF-C over-expression was observed in 33 of 63 patients (52%), while COX-2 over-expression occurred in 42 of 63 tumor samples (67%). Presence of microlymphatic vessels with LYVE-1 staining was found in 35 cases. COX-2 over-expression was highly correlated with VEGF-C over-expression (P = 0.032), microlymphatic vessels (P = 0.002) as well as presence of metastatic lymph nodes (P = 0.007). However, no significant correlation was found between COX-2 expression and other clinicopathological parameters. Our data suggest that COX-2 expression is associated with lymphangiogenesis and lymph node metastasis in human gastric carcinoma. This raises the possibility that COX-2-mediated VEGF-C over-expression might promote lymph node metastasis via lymphangiogenesis pathway in patients with gastric cancer.
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PMID:Cyclooxygenase-2 expression is associated with VEGF-C and lymph node metastases in gastric cancer patients. 1650 94

Many researches have confirmed the tumor-prophylactic effects of cyclooxygenase-2 (COX-2) inhibitors. We previously observed their anti-cancer effects in vivo in nude mice and found that sulindac, a traditional non-steroidal anti-inflammatory drug (NSAID), and celecoxib, a selective COX-2 inhibitor, depressed the growth of SGC7901 xenografts via altering cell kinetics. Then we deeply studied the relationship between the two drugs and angiogenesis in gastric cancer. The results showed both sulindac and celecoxib decreased the micro-vessel density (MVD), which was labeled by either CD34 or VWF staining, within xenografts. Expression of both vascular endothelial growth factor (VEGF) and FGF-1 was suppressed. In addition, a positive correlation between MVD and the volume of SGC7901 xenografts was found. The effect of selective COX-2 inhibitor was stronger than non-special one despite of the insignificant difference. These results demonstrate that COX-2 plays an important role in angiogenesis of cancer. Apart from interfering cell kinetics, decreasing the expression of angiogenic factors and then inhibiting tumor angiogenesis could also be one of the mechanisms that COX-2 inhibitors suppress the growth of gastric cancer. These findings offer another theory basis for the future clinical application of NSAIDs against cancer.
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PMID:Cyclooxygenase-2 inhibitors suppress angiogenesis and growth of gastric cancer xenografts. 1650 95

Helicobacter pylori is an important risk factor of gastric cancer (GC). Although many H. pylori virulence factors have been reported, the pathogenic mechanism by which H. pylori infection causes GC remains unclear. The aims of this study were to identify GC-related antigens from H. pylori and characterize their roles in the development of GC. As GC and duodenal ulcer (DU) are considered clinically divergent, we compared two-dimensional immunoblots of an acid-glycine extract of H. pylori probed with serum samples from 15 patients with GC and 15 with DU to find GC-related antigens, which were subsequently identified by mass spectrometry. Many protein spots were recognized by more than one serum, and 24 of these were better recognized by GC sera. The proteins showing higher frequency of recognition in GC group are threonine synthase, rod shape-determining protein, S-adenosylmethionine synthetase, peptide chain release factor 1, DNA-directed RNA polymerase alpha subunit, co-chaperonin GroES (monomeric and dimeric forms), response regulator OmpR, and membrane fusion protein. Of these proteins, GroES was identified as a dominant GC-related antigen with a much higher seropositivity of GC samples (64.2%, n = 95) compared with 30.9% for gastritis (n = 94) and 35.5% for DU (n = 124). GroES seropositivity was more commonly associated with antral GC than with non-antral GC (odds ratio = 2.7; 95% confidence interval, 1.1-6.7). In peripheral blood mononuclear cells, GroES stimulated production of interleukin (IL)-8, IL-6, granulocyte macrophage colony-stimulating factor, IL-1beta, tumor necrosis factor-alpha, cyclooxygenase-2, and prostaglandin E(2). Moreover when incubated with gastric epithelial cells, GroES induced expression of IL-8, cell proliferation, and up-regulation of c-jun, c-fos, and cyclin D1 but caused down-regulation of p27(Kip1). We conclude that GroES of H. pylori is a novel GC-associated virulence factor and may contribute to gastric carcinogenesis via induction of inflammation and promotion of cell proliferation.
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PMID:Comparative immunoproteomics of identification and characterization of virulence factors from Helicobacter pylori related to gastric cancer. 1676 9

Gastric cancer is the second commonest cause of cancer-associated death in the world. The high mortality is largely attributed to the huge number of at-risk individuals as well as the delay in presentation. Hence, chemoprevention of gastric cancer appears to be the most promising approach in reducing the incidence and mortality related to this cancer. Among various chemoprevention strategies, Helicobacter pylori eradication is the one being most extensively examined. Results from several large-scale prospective randomized studies, however, showed marginal benefits of H. pylori eradication on regression of premalignant gastric lesions. Moreover, there is no significant reduction in gastric cancer incidence. Similarly, ascorbic acid and/or beta-carotene supplementation have borderline effects on premalignant gastric lesions. Based on epidemiological data, the use of non-steroidal anti-inflammatory drugs is associated with a reduced risk of stomach cancer. Future studies should evaluate the role of other chemopreventive agents, particularly specific cyclooxygenase-2 inhibitors, in reducing the risk of gastric cancer.
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PMID:Chemoprevention of gastric cancer. 1682 3

The DNA repair protein Ku acts as a heterodimer of Ku70 and Ku80 that binds to the DNA ends, nicks, or single-to-double-strand transition. It has a crucial role for DNA double-strand-break repair. Either Ku70 or Ku80 itself may have a unique function that is independent of the other Ku subunit. In this review, the role of Ku on cell proliferation and apoptosis will be discussed. Ku acts as a regulator of transcription by interacting with the recombination signal binding protein Jkappa and the NF-kappaB p50 homodimer to up-regulate p50 expression, which may regulate the proliferation of gastric cancer cells. Both Ku70 and Ku80 expressions are mediated by constitutively activated NF-kappaB and constitutively expressed cyclooxygenase-2 in gastric cancer cells, which may be related to gastric cell proliferation and carcinogenesis. In addition, nuclear loss of Ku may underlie the mechanism of apoptosis in pancreatic acinar cells after oxidative stress.
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PMID:DNA repair Ku proteins in gastric cancer cells and pancreatic acinar cells. 1703 78

The Nobel prize in Physiology and Medicine in 2005 was presented to Barry Marshall and Robin Warren for their discovery of Helicobacter pylori (Hp), but only the involvement of this germ in gastritis and peptic ulcer has been mentioned in the award sentence, while numerous epidemiological, clinical and experimental studies and reports emphasized the crucial role of Hp in pathogenesis of gastric cancer (GC). This review is based on the old concept proposed by P. Correa much before the discovery of spiral bacteria in the stomach, postulating the cascade of mucosal changes from acute/chronic gastritis into the atrophic gastritis with intestinal metaplasia and finally to dysplasia and GC. It is now widely accepted view that Hp infection is the major initiator of the inflammatory and atrophic changes in gastric mucosa accompanied by an over-expression of certain growth factors such as gastrin as well as of cyclooxygenase-2 (COX-2) and anti-apoptotic proteins including survivin and B-cl(2), leading to proliferation of mutated atrophic cells, excessive angiogenesis, inhibition of apoptosis and formation of gastric tumour. All the morphological and biochemical changes associated with the transformation of mucosal cells into the cancer cells can be traced in excellent experimental model of gastric cancerogenesis induced by infection of Hp in Mongolian gerbils. Since the eradication therapy was proved in several prospective clinical trials to greatly reduce the incidence of GC and this was confirmed on the gerbil model of Hp-induced GC, it has been postulated; a) that Hp is the major causal factor in pathogenesis of GC and b) that the only rational approach in attempt to reduce the occurrence of GC is the global eradication of Hp.
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PMID:Gastric cancer and Helicobacter pylori infection. 1703 5

The importance of cancer-mesenchymal interactions in the aggressive behavior of scirrhous gastric cancer is supported by experimental and clinical evidences. We have previously reported that gastric fibroblasts secretion of keratinocyte growth factor (KGF) underline the remarkable proliferation of scirrhous gastric cancer cells. Cyclooxygenase-2 (COX-2) is not only expressed in cancer cells, but also in interstitial fibroblasts in gastric carcinoma. To clarify the mechanisms responsible for the antiproliferation effect of COX-2 inhibitors, effect of COX-2 inhibitor on the paracrine epithelial-mesenchymal interactions of growth was examined. Scirrhous gastric cancer cell line, OCUM-2M, gastric fibroblasts, NF-21, and COX-2 inhibitor, JTE-522, were used. Growth-interaction was examined by calculating the number of cancer cells or by measuring [(3)H] thymidine incorporation of cancer cells. Effect of JTE-522 on KGF expression from NF-21 cells and OCUM-2M cells was analyzed by ELISA and RT-PCR. The conditioned medium from gastric fibroblasts significantly stimulated the growth of scirrhous gastric cancer cells. JTE-522 at the concentrations of 10(-5) and 10(-6) M significantly decreased the growth-stimulating activity of gastric fibroblasts. JTE-522 reduced the expression of KGF mRNA and the production of KGF from gastric fibroblasts. Oral administration of JTE-522 significantly decreased the size of xenografted tumor coinoculated with OCUM-2M cells and NF-21 cells in nude mice. JTE-522 decreased COX-2 expression and Ki67 labeling index within the coinoculated tumor. These findings suggested that a selective COX-2 inhibitor, JTE-522, downregulates KGF production from gastric fibroblasts, resulting in the inhibition of paracrine epithelial-mesenchymal interactions of proliferation between scirrhous gastric cancer cells and gastric fibroblasts.
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PMID:Selective cyclooxygenase-2 inhibitor downregulates the paracrine epithelial-mesenchymal interactions of growth in scirrhous gastric carcinoma. 1709 55

Cyclooxygenase-2 (COX-2) plays a crucial role in the development and invasion of gastric cancer. COX-2 inhibitors have been shown to be chemopreventive against gastrointestinal cancers. In vitro studies have suggested that the mechanisms may be related to induction of apoptosis and inhibition of angiogenesis. COX-2 may also have impact on E-cadherin. In our study we investigate the effect of Celecoxib on expression of E-cadherin and serum soluble E-cadherin, as well as on apoptosis and angiogenesis in patients with gastric cancer. Fifty nine gastric cancer patients were randomly divided into two groups: Surgery group (n = 22), in which patients underwent surgical resection after diagnosis, and Celecoxib + Surgery group (n = 37), in which patients received oral Celecoxib 200 mg twice daily for 7 days before curative resection. Twenty healthy subjects (Healthy controls) were recruited as normal controls. After curative resection, COX-2, E-cadherin, VEGF, and MVD were detected by immunohistochemistry. Serum soluble E-cadherin was quantitatively measured using a commercially available enzyme-linked immunosorbent assay kit. Apoptosis was determined by TUNEL assay. Significantly decreased expression of COX-2, increased E-cadherin and apoptosis, decreased VEGF and MVD were observed in gastric cancer tissues from patients receiving Celecoxib compared to Surgery group. Compared to Healthy controls, the serum soluble E cadherin levels were higher in gastric cancer patients which were decreased by Celecoxib. This in vivo study demonstrated that Celecoxib induces apoptosis and inhibit angiogenesis of gastric cancer. Its impact on E-cadherin may suggest that this agent may suppress the invasion of advanced gastric cancer.
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PMID:Effect of celecoxib on E-cadherin, VEGF, Microvessel density and apoptosis in gastric cancer. 1742 34

Helicobacter pylori infection leads to gastroduodenal inflammation, peptic ulceration, gastric lymphoma and gastric cancer. Certain herbal remedies have been used to treat gastric disease. In this study, we examined the anti-inflammatory effect of San-Huang-Xie-Xin-Tang (SHXT) and its main component baicalin on Helicobacter pylori-infected human gastric epithelial AGS cell. AGS cells were treated with Helicobacter pylori at a bacterium/cell ratio of 300:1. mRNA expression and protein levels were determined by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis and western blot analysis, respectively. Interleukin-8 (IL-8) level and the translocation of nuclear factor kappa B (NF-kappaB) were measured by enzyme-linked immunosorbent assay (ELISA) and enzyme-linked DNA-protein interaction assay (ELDIA), respectively. Nitric oxide production was measured by Griess reagent. We found that SHXT and baicalin inhibited Helicobacter pylori-induced cyclooxygenase-2 (COX-2) enhancement and IkappaBalpha degradation in both mRNA and protein levels. SHXT and baicalin also inhibited Helicobacter pylori-induced inducible nitric oxide synthase (iNOS) and IL-8 mRNA expression, and decreased NO and IL-8 production. Furthermore, SHXT and baicalin inhibited nuclear translocation of p50 subunit of NF-kappaB in Helicobacter pylori-infected AGS cells. Based on the above findings, SHXT and baicalin might exert anti-inflammatory and gastroprotective effects in Helicobacter pylori-induced gastric inflammation.
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PMID:San-Huang-Xie-Xin-Tang inhibits Helicobacter pylori-induced inflammation in human gastric epithelial AGS cells. 1753 3

Studies have linked microsomal prostaglandin E synthase (mPGES)-1 with gastric cancer. The purpose of this study was to determine mPGES-1, mPGES-2, and cytosolic PGES (cPGES) expression in gastric cancer and to evaluate the correlation between mPGES-1 and mPGES-2 expression and clinicopathological factors and cyclooxygenase-2 expression. PGES protein expression was examined by Western blot in gastric cancer cell lines and in biopsy samples from patients with gastric cancer. mPGES-1, mPGES-2, and cPGES protein localizations were examined immunohistochemically in 129 archival gastric cancer surgical resections. mPGES-1 protein expression was found in gastric cancer biopsies and cancer cell lines with differentiated or undifferentiated adenocarcinoma. There was no mPGES-1 expression in nonneoplastic biopsies. All cell lines and tissue samples expressed mPGES-2 and cPGES. Immunohistochemical analysis showed cancer cells expressed mPGES-1 in 47% of cases. mPGES-2 immunoreactivity was seen both in nonneoplastic glandular epithelium and cancer cells; however, cancer cell immunoreactivity was significantly more pronounced in 29% of cases. cPGES expression was constitutive both in nonneoplastic and neoplastic tissues, with no significant variation among cases. mPGES-1 and mPGES-2 expression correlated with cyclooxygenase-2 expression. mPGES-1 and mPGES-2 expression, and tumor-node-metastasis stage had independent prognostic significance under multivariate analysis in patients with gastric cancer overall and in patients with differentiated cancers. However, only tumor-node-metastasis stage and mPGES-2 expression retained independent prognostic significance in patients with poorly differentiated cancers. mPGES-1 and mPGES-2 correlate with clinicopathological factors and may be valuable prognostic factors in gastric cancer.
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PMID:Clinical significance of prostaglandin E synthase expression in gastric cancer tissue. 1786 74


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