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)

The competitive inhibitory effects of NK4 (a specific hepatocyte growth factor (HGF)-antagonist) on the interaction between HGF and the c-Met/HGF receptor has been shown in HGF-mediated invasion of some distinct types of human cancer cells. Furthermore, NK4 has inhibitory effects on the angiogenic pathways driven by basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), as well as by HGF. In this study, to evaluate the therapeutic efficacy of adenoviral-mediated NK4 gene treatment, we employed animal models of peritoneal metastasis using two gastric cancer cell lines, the strongly c-Met expressing MKN45 cell line and the weakly c-Met-expressing cell line, TMK1. In both models, the total number and weight of peritoneal tumours per mouse and ascites treated early with AxCANK4 (administered 3 times 2, 7 and 12 days after the tumour inoculation) were significantly reduced compared with those treated with phosphate-buffered solution (PBS) and AxCALacZ (P < 0.05). In Factor-VIII-related-antigen-stained sections from peritoneal metastatic tumours, the inhibition of intratumour vessels was observed in tissues from tumours of MKN45 and TMK1 treated with AxCANK4. We also compared the therapeutic effect of early AxCANK4 treatment with that of late treatment (at 7, 12 and 17 days). Peritoneal metastases and ascites treated late with AxCANK4 showed less of an improvement than those treated early with AxCANK4 in both models. In addition, the inhibitory effect of cisplatin (CDDP) on peritoneal metastasis was significantly enhanced by AxCANK4, suggesting that the combination of intraperitoneal (i.p.) chemotherapy with NK4 gene therapy might be effective, even in cases of advanced peritoneal metastasis from gastric cancer. To conclude, these results show clearly that NK4 gene therapy inhibits peritoneal metastases from gastric cancer, regardless of the level of c-Met/HGF receptor expression in the tumour cells, and especially in the early stages of peritoneal metastasis.
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PMID:Adenoviral-mediated gene transduction of the hepatocyte growth factor (HGF) antagonist, NK4, suppresses peritoneal metastases of gastric cancer in nude mice. 1534 89

Lymph node metastasis is one of the most important prognostic factors in malignant tumors. In this study, we investigated vascular endothelial growth factor (VEGF)-C expression in human gastric cancer using immunohistochemical techniques and determined the number of microvessels in peritumoral tissue. VEGF-C expression was positive in 22 of 79 cases (27.8%), and correlated with the presence of lymphatic invasion and lymph node metastasis. We confirmed by reverse transcription-polymerase chain reaction (RT-PCR) that VEGF-C mRNA expression is observed more commonly in cancer tissues than normal tissues. For 59 gastric tumors, we examined lymphatic vessel density (LVD) using the specific lymphatic vessel endothelial hyaluronan receptor (LYVE) -1 antibody. VEGF-C expression was observed in 10 of 25 cases (40%) that exhibited a high LVD. Furthermore, high LVD exhibited a significant correlation with VEGF-C expression. Our findings suggest that VEGF-C plays a pivotal role for lymphangiogenesis and tumor growth in gastric cancer.
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PMID:High lymphatic vessel density correlates with overexpression of VEGF-C in gastric cancer. 1575 50

Invasion and metastasis are critical determinants of cancer morbidity. Genes and molecules participating in these steps must be regarded as potential prognostic factors. Growth factors and their receptors, cell-cycle regulators, cell-adhesion molecules and matrix-degrading enzymes are those to be used as prognostic factors, including epidermal growth factor (EGF), EGF receptor, K-sam, HER-2, interleukin (IL)-8, vascular endothelial growth factor (VEGF), cyclin E, p27, E-cadherin, CD44v6, matrix metalloproteinase-1 (MMP-1), and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1). Alterations in epigenetics, such as aberrant DNA methylation and histone modification that are, in part, associated with the tumor progression of gastric cancer, can be candidate prognostic factors. The number of methylated genes may serve as a marker of tumor progression. Genetic polymorphism not only affects cancer susceptibility but also influences malignant phenotype; examples include single-nucleotide polymorphism in the HER-2 and MMP-9 genes. Comprehensive gene expression analyses are useful to search for novel genes related to invasion and metastasis and potential prognostic factors. Serial analysis of gene expression (SAGE) has identified several these genes, such as CDH17, APOE, FUS, COL1A1, COL1A2, GW112, and MIA. Overexpression of MIA is found to be associated with poor prognosis. Microarray analysis has great potential for identifying the characteristics of individual cancers, from the view point of gene expression profiles. A combination of these examinations can not only foretell a patient's prognosis but can also give information directly connected with personalized cancer medicine and prevention.
Gastric Cancer 2005
PMID:Molecular-pathological prognostic factors of gastric cancer: a review. 1586 15

Mature dendritic cells (DCs) play an important role as antigen-presenting cells in tumor immunity. The angiogenic factor, vascular endothelial growth factor (VEGF), inhibits DC maturation. In this study, 174 gastric cancer patients were assessed by immunohistochemistry using anti-S-100 antibody for total DCs, anti-CD83 antibody for mature DCs and anti-VEGF antibody for VEGF expression, and the relationships between total DC density (TDD), mature DC density (MDD), clinicopathological factors, VEGF expression and prognosis were examined. The MDD (count/cm(2)) was significantly lower in gastric cancer tissue (2.07, median value) than in normal gastric tissue (8.06) (p=0.0067), and also significantly lower in advanced stage gastric cancer tissue (1.55) than in early stage gastric cancer tissue (2.22) (p=0.0374). Among the 104 advanced gastric cancer patients, the MDD was significantly lower in older patients, and in those with a larger or histologically differentiated-type tumor or strong VEGF expression (p<0.05). The 5-year survival rate was significantly higher in the high TDD group than the low TDD group, and also significantly higher in the high MDD group than the low MDD group (p<0.05). By multivariate analysis, blood vessel invasion (p=0.0001, hazard ratio =3.464) and MDD (p=0.0171, hazard ratio =2.179) were revealed to be independent prognostic factors in advanced gastric cancer. These results suggest that the maintenance of MDD could prolong the survival of patients with advanced gastric cancer.
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PMID:Prognostic value of CD83-positive mature dendritic cells and their relation to vascular endothelial growth factor in advanced human gastric cancer. 1601 17

Autocrine motility factor (AMF) is a cytokine known to regulate tumor cell motility. Recent studies have extended its role to many other aspects of cancer biology. In the present study, we examined the level of AMF expression and its relationship with vascular endothelial growth factor (VEGF) expression and the angiogenic phenotype in human gastric cancer and their effect on survival. The AMF and VEGF expression level and tumor microvessel density (MVD) status in archived tissue specimens from 86 resected gastric cancer cases were determined. AMF expression was significantly higher in both primary tumors and lymph node metastases than in adjacent normal gastric mucosa and normal gastric mucosa from individuals without gastric cancer. In univariate survival analyses, strong AMF expression was associated with inferior survival (P = 0.028). In a Cox proportional hazards model, strong AMF expression (P = 0.019) was independently prognostic of poor survival. Strong AMF expression in the lymph node metastases was associated with poor survival (P = 0.011). Furthermore, AMF expression in the primary tumors was directly correlated with VEGF expression and MVD status. We found the first clinical evidence that AMF expression is directly correlated with VEGF expression and MVD status and predicts clinical outcome in patients with gastric cancer, supporting the hypothesis that the AMF/AMF receptor pathway plays an important role in multiple aspects of cancer biology.
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PMID:Expression of autocrine motility factor correlates with the angiogenic phenotype of and poor prognosis for human gastric cancer. 1611 16

Cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF)-C are closely related with the development and metastasis of tumors. The gene expression of COX-2 and VEGF-C in gastric cancer and the correlation between them were investigated; 64 paraffin-embedded gastric cancer samples and 22 flesh gastric cancer samples were tested by using immunohistochemistry and the reverse transcription polymerase chain reaction (RT-PCR) technology, respectively. The mean expressive density of COX-2 and VEGF-C mRNA in gastric cancer, with beta-actin coamplified as an internal standard, were both significantly higher than those in non-cancerous gastric mucosa (1.363 +/- 0.351 vs 0.763 +/- 0.304, 0.972 +/- 0.331 vs 0.314 +/- 0.215, p < 0.001). The positive rates of COX-2 and VEGF-C in 64 gastric cancer samples were 72% and 64% respectively. Their expression in the lymph-node metastasis groups were higher than that of the non-lymph-node metastasis groups (p < 0.05). Moreover, there was a close correlation between COX-2 and VEGF-C expression levels (p < 0.05). The study indicates gastric tumor tissues that produce COX-2 and VEGF-C may have a higher lymphatic invasion and metastatic potential. COX-2 may participate in VEGF-C lymphangiogenic pathway and the high expression of them may play an important role in the lymphatic proliferation and spread in gastric cancer.
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PMID:Overexpression of cyclooxygenase-2 in gastric cancer correlates with the high abundance of vascular endothelial growth factor-C and lymphatic metastasis. 1626 Aug 57

In this study the expression levels of reversion-inducing-cysteine-rich protein with Kazal motifs (RECK) in gastric cancer cell lines and tissues have been analysed in order to assess their value as a prognostic indicator. The expressions of RECK, activated matrix metalloproteinase (MMP)-7, and vascular endothelial growth factor (VEGF) in gastric cancer tissues and cell lines were evaluated by Western blot analysis; and MMP-2 and MMP-9 were evaluated by gelatin zymography. RECK expression in the context of gastric cancer was also compared with various clinicopathologic parameters and compared to the expression of activated MMP-7, MMP-2, and MMP-9. Fifty-two percent of the 102 gastric cancer tissues and 81.8% of the 11 gastric cancer cell lines exhibited reduced RECK expression. We also detected a significant inverse correlation between RECK expression and macroscopic tumour growth (P=0.018), lymphatic invasion (P=0.018), lymph node metastasis (P=0.000), stage (P=0.000), and MMP-9 (P=0.039). No correlation between RECK expression and MMP-7 and MMP-2, VEGF were detected. Our data strongly supports the hypothesis that RECK is a suppressor of malignancy, and constitutes a good prognostic indicator in gastric cancer.
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PMID:Expression of reversion-inducing-cysteine-rich protein with Kazal motifs (RECK) as a prognostic indicator in gastric cancer. 1632 34

Low oxygen tension can influence tumor progression by enhancing angiogenesis, a process that may involve Rho GTPases whose activities have been implicated in tumorigenesis and metastasis. In the present study, we show that hypoxia can increase the mRNA levels and intracellular activities of Rac1 and Cdc42 in a time-dependent manner. The hypoxia-stimulated activities of Rac1 and Cdc42 could be blocked by the phosphatidylinositol 3'-kinase (PI3K) inhibitor LY294002 and the protein tyrosine kinase (PTK) inhibitor genistein but were not affected by the p38MAPK inhibitor SB203580 or the MEK-1 inhibitor PD98059, suggesting that the hypoxia-mediated signals were through PI3K and PTK. Correlating with the increased activities of Rac1 and Cdc42, the expression of the pro-angiogenesis factors HIF-1alpha and vascular endothelial growth factor (VEGF) was upregulated by hypoxia, whereas the expression of the tumor suppressors von Hippel-Lindau and p53 was down-regulated. Dominant negative N17Rac1 and N17Cdc42 could upregulate the expression of p53 and pVHL but downregulate that of HIF-1alpha and VEGF under hypoxia. Furthermore, the preconditioned medium from N17Rac1 or N17Cdc42-expressing gastric cancer cells was able to inhibit the proliferation of HUVECs. Our results indicate that PI3K and PTK-mediated activations of Rac1 and Cdc42 are involved in the hypoxia-induced production of angiogenesis-promoting factors and tumor suppressors, and suggest that the Rho family GTPases Rac1 and Cdc42 may contribute to the hypoxia-mediated angiogenesis.
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PMID:Role of Rac1 and Cdc42 in hypoxia induced p53 and von Hippel-Lindau suppression and HIF1alpha activation. 1639 16

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


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