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)

Dietary factors play essential roles in gastric carcinogenesis. We recently found that dietary supplementation with NaHCO(3) significantly increased the development of gastric cancer in a rat gastric stump model. Here, we analysed nontransformed gastric mucosa for expression of the cancer-related proteins cyclooxygenase-2 (COX-2) and ornithine decarboxylase (ODC), and we examined the relationship between expression levels of those proteins and mucosal proliferation. Research has shown that COX-2 is upregulated in gastric mucosal inflammation and is strongly associated with gastrointestinal cancer. ODC is the key enzyme in polyamine synthesis and a regulator of cell proliferation. We performed gastric resections on 48 Wistar rats to induce spontaneous gastric cancer; half of these animals were given a normal diet, and the other half received a diet supplemented with NaHCO(3). Twenty-four unoperated rats served as a control group. The surgical procedure per se led to a significant rise in mucosal expression of COX-2 and an associated increase in cell proliferation. However, the COX-2 level in gastric mucosa was not further affected by dietary supplementation of carbonate. Interestingly, nontransformed gastric mucosa in the operated rats receiving a carbonate-supplemented diet showed a pronounced increase in ODC expression that was strongly correlated with a further enhanced cell proliferation. These results indicate that carbonate ions, which represent a major constituent of intestinal reflux into the stomach, increase the expression of ODC and thereby enhance cell proliferation in nontransformed mucosa, and consequently elevate the risk of gastric cancer.
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PMID:Dietary supplementation with carbonate increases expression of ornithine decarboxylase and proliferation in gastric mucosa in a rat model of gastric cancer. 1796 Jun 25

Angiopoietin-2 (Ang-2) and vascular endothelial growth factor (VEGF) contribute to gastric cancer aggressiveness by up-regulating the expression of proteases. We evaluated the expression and the prognostic significance of angiogenic factors and proteases in 148 patients with R0-resected gastric cancer. Expression of VEGF, Ang-2, cyclooxygenase-2 (COX-2), urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1, matrix metalloproteinases (MMP)-1 and -9 were assayed by immunohistochemistry. After a mean of 63 +/- 4 months, 81 out of 148 patients had died due to disease. The probability of being free of recurrence was 62, 48, and 42% at 2, 5, and 10 years, respectively. Single bivariate analysis identified VEGF, Ang-2, COX-2, PAI-1, and MMP-9 expression, along with several clinicopathological parameters (grade of curability, lymph node ratio, pTNM, pT, pN), as variables associated with both decreased disease-specific survival and recurrence. On multivariate analysis, after adjusting for significant clinical covariables, positive VEGF immunostaining was the primary prognostic factor, and no other tumor marker variable could add any significant improvement for the prediction, for both disease-specific survival (p = 0.001; HR, 3.27; 95% CI, 1.76 to 6.10) and tumor recurrence (p = 0.002; HR, 2.81; 95% CI, 1.48 to 5.35). Our study suggests that VEGF alone may be clinically useful for establishing therapeutic decisions in gastric cancer patients.
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PMID:Positive VEGF immunostaining independently predicts poor prognosis in curatively resected gastric cancer patients: results of a study assessing a panel of angiogenic markers. 1797 43

Although selective cyclooxygenase-2 (COX-2) inhibitors suppress cell proliferation in gastric cancer, it remains debatable whether their effect is mediated through COX-2 dependent or independent pathways. We investigated the effects of the targeted inhibition of COX-2 expression by small interfering RNA (siRNA) in human gastric cancer cells and compared it to the effects of treatment with a specific COX-2 inhibitor. COX-2 mRNA and proteins were significantly reduced by up to 80% on day 2 after COX-2 siRNA transfection to the gastric cancer cell line MKN45. Concentrations of prostaglandins E2 (PGE2) in the condition medium were also reduced to 30% after siRNA transfection. Transfection of COX-2 siRNA exhibited a more potent anti-proliferative effect on MKN45 cells than treatment with high-dose (100 microM) NS398. COX-2 siRNA also significantly reduced tumor growth in nude mice. While COX-2 siRNA transfection alone had no obvious pro-apoptotic effects, unlike low-dose (10 microM) NS398 it enhanced the apoptotic reaction of MKN45 cells to cisplatin therapy. In conclusion, our results demonstrate for the first time that COX-2 siRNA inhibits cell growth and enhances the chemosensitivity of gastric cancer cells. RNA interference may be a promising alternative to specific COX-2 inhibitors in the prevention and treatment of gastric cancer.
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PMID:Targeted inhibition of COX-2 expression by RNA interference suppresses tumor growth and potentiates chemosensitivity to cisplatin in human gastric cancer cells. 1798 44

To explore the proteins regulated by cyclooxygenase-2 (COX-2) in gastric cancer, the expression plasmid of COX-2siRNA was constructed and transfected into gastric cancer cell line SGC7901. Then, two-dimensional electrophoresis and the PDQuest software analysis were applied to discover the differentially expressed proteins. The differential protein spots were analyzed by matrix-assisted laser desorption/ionization time of flight mass spectrometry. Fourteen differentially expressed proteins between the two cell lines were identified. 15-Hydroxyprostaglandin dehydrogenase [NAD(+)] (15-PGDH), a key enzyme in prostaglandin degradation, was identified as an upregulated protein in SGC7901 cells transfected with the COX-2siRNA plasmid. To further explore whether the 15-PGDH is regulated by COX-2, western blotting and immunocytochemical assay were performed to detect the expression of 15-PGDH in different cell lines with different expression level of COX-2. The results showed that the expression of 15-PGDH was upregulated (128.57%) as COX-2 was suppressed by small interfering RNA and downregulated (51.72%) as COX-2 was enhanced by COX-2 cDNA transfection in gastric cancer cells. In tissue specimens with gastric cancer, there was a decreased expression of 15-PGDH and an increased expression of COX-2 simultaneously. A significantly negative correlation of 15-PGDH expression was found to COX-2 level, tumor differentiation, tumor, lymph node, metastasis (TNM) staging and lymph node metastasis of gastric cancer. All the results suggest that 15-PGDH is downregulated by COX-2 in human gastric cancer and may contribute to the carcinogenesis and development of human gastric cancer in combination with COX-2.
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PMID:Expression of 15-PGDH is downregulated by COX-2 in gastric cancer. 1817 34

Osteopontin (OPN), cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) are overexpressed in various experimental models of malignancy. However, the correlation and role of the three molecules in gastric cancer is unclear. In the present study, we found that OPN, COX-2 and VEGF were overexpressed in 53 cancerous tissues with gastric cancer compared with 40 normal mucosa tissues by immunohistochemistry method. Moreover, the results indicated co-expression of OPN, COX-2, and VEGF in gastric cancer. Levels of OPN, COX-2, and VEGF were all significantly correlated with TNM stage, lymph node metastasis and distant metastasis (P < 0.05), while not related to prognosis of patients. In addition, individual levels of OPN, COX-2, and VEGF were all significantly correlated with microvessel density (MVD), valued by CD34 staining directly with r-values of 0.416, 0.400, and 0.566, respectively (P < 0.01). Both OPN and COX-2 levels showed a positive correlation with VEGF (P < 0.05). Meanwhile, expression of COX-2 is in relation to OPN (P < 0.01). Overall, survival for patients with high MVD was significantly lower than for patients with low MVD (P < 0.05). Our findings indicate that OPN, COX-2, and VEGF synergically promote angiogenesis and metastasis in gastric cancer. It may be an important and useful strategy to target these molecules for prevention and therapy of tumor.
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PMID:Positive correlation of osteopontin, cyclooxygenase-2 and vascular endothelial growth factor in gastric cancer. 1818 Oct 47

Gastrin and cyclooxygenase-2 (COX-2) play important roles in the carcinogenesis and progression of gastric cancer. However, it remains unknown whether the combination of cholecystokinin-2 (CCK-2) receptor antagonist plus COX-2 inhibitor exerts synergistic anti-tumor effects on human gastric cancer. Here, we demonstrated that the combination of AG-041R (a CCK-2 receptor antagonist) plus NS-398 (a selective COX-2 inhibitor) treatment had synergistic effects on proliferation inhibition, apoptosis induction, down-regulation of Bcl-2 and up-regulation of Bax expression in MKN-45 cells. These results indicate that simultaneous targeting of CCK-2 receptor and COX-2 may inhibit gastric cancer development more effectively than targeting either molecule alone.
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PMID:Blockade of cholecystokinin-2 receptor and cyclooxygenase-2 synergistically induces cell apoptosis, and inhibits the proliferation of human gastric cancer cells in vitro. 1825 54

Cyclooxygenase-2 (COX-2) is upregulated in gastric carcinoma, and its increased levels were found to have a prognostic significance in some studies. Both angiogenesis and Helicobacter pylori infection have been reported to be associated with COX-2 expression of gastric cancer in recent studies. In this study, COX-2 expression and its association with CD31 staining, H.-pylori infection, and well-known clinicopathological factors were investigated in 65 gastric cancer patients. COX-2 and CD31 expression assessment was done by immunohistochemical methods. Whartin Starry stain was performed for H.-pylori infection. Of 65 patients, 32 (49%) revealed intense COX-2 immunostaining. Among various clinicopathologic characteristics, COX-2 expression was inversely correlated with tumor size, TNM stage, and lymph node status. Thirty-two (49%) patients revealed intense CD31 immunostaining. Among various clinicopathologic characteristics, CD31 expression was associated only with lymph node metastasis. COX-2 expression was not correlated with CD31 staining and H.-pylori infection. Both COX-2 and CD31 staining had no prognostic significance. In conclusion, we found that COX-2 expression was significantly higher in earlier stages of gastric cancer. It can be suggested that COX-2 expression may be important in the initial development of gastric cancer but not in progression of the disease. Other factors which may be associated with COX-2 in gastric cancer, including angiogenesis and H.-pylori infection, should be investigated in further studies.
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PMID:Cyclooxygenase-2 expression and its association with angiogenesis, Helicobacter pylori, and clinicopathologic characteristics of gastric carcinoma. 1846 90

Seaweed extracts have recently been found to have antioxidant and antitumor activities. Capsosiphon fulvescens (Cf) is a green alga and nutrient-dense food source. In a previous study, we extracted polysaccharide from Cf (Cf-PS) and demonstrated its antitumor effect in gastric cancer cells. In this report, we describe the protective effect of Cf-PS against alcohol-induced gastric injury in rats and adenocarcinoma (AGS) cells. In vivo assay revealed stomach damage in rats treated with alcohol alone; however, the stomach condition of rats co-treated with Cf-PS and alcohol matched that of the control group. Cf-PS also inhibited alcohol-induced cell death in AGS cells. Compared with alcohol treatment alone, Cf-PS and alcohol co-treatment increased phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt but inhibited poly-ADP-ribose polymerase (PARP) cleavage. Thus, ERK1/2 and Akt activation are instrumental in the protective effect of Cf-PS against alcohol-induced cell death in AGS cells. Moreover, Cf-PS treatment reduced the expressions of cyclooxygenase-2 (COX-2) and the inducible form of nitric oxide (iNOS), proteins related to ulcers. These results suggest that Cf-PS could help protect against alcohol-induced peptic ulcers.
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PMID:The effect of polysaccharide extracted from the marine alga Capsosiphon fulvescens on ethanol administration. 1852 46

Hyperphosphorylation of extracellular signal-regulated protein kinases-1/2 (ERK1/2) is known to promote cancer cell proliferation. We therefore investigated the constitutive phosphorylation levels of ERK1/2 and the expression of its downstream targets c-Fos, c-Jun, and cyclooxygenase-2 (COX-2) in biopsied human gastric cancer tissues. Results showed that ERK1/2 phosphorylation and c-Jun expression were significantly lowered in gastric cancer compared with the non-cancer adjacent tissues. The expression of c-Fos, however, was not altered while COX-2 was significantly up-regulated. To conclude, we demonstrate that hypophosphorylation of ERK1/2 may occur in gastric cancer. Such discovery may have implication in the application of pathway-directed therapy for this malignant disease.
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PMID:Constitutive hypophosphorylation of extracellular signal-regulated kinases-1/2 and down-regulation of c-Jun in human gastric adenocarcinoma. 1857 Aug 90

The caudal-related homeobox gene, CDX1, encodes for an intestinal-specific transcription factor and is involved in the induction of intestinal metaplasia (IM) of the stomach in gastric cancer. Gastric IM induced by bile reflux is a precancerous gastric adenocarcinomal lesion and has been associated with the induction of cyclooxygenase-2 (COX-2). In this study, we demonstrate the molecular mechanisms underlying the transcriptional regulation of COX-2 by bile acid in gastric cells. We noted that the ectopic expression of CDX1 enhanced COX-2 gene expression and that bile acid was associated with the induction of CDX1 expression. Furthermore, the induction of CDX1 by bile acid was mediated by the orphan nuclear receptor, small heterodimer partner (SHP). Finally, it was verified that the expression of COX-2, CDX1, SHP and CCAAT element-binding protein beta messenger RNA in human IM lesions were significantly higher than in lesions associated with gastritis. Collectively, these results reveal that bile acid induces an increase in the gene expression of COX-2 via the sequential transcriptional induction of SHP and CDX1 in precancerous lesions of human gastric cancer.
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PMID:Bile acid induces expression of COX-2 through the homeodomain transcription factor CDX1 and orphan nuclear receptor SHP in human gastric cancer cells. 1877 15


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