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)

In order to identify reliable molecular markers for prognostic prediction in gastric carcinoma, we evaluated the expression of six molecular markers, namely bFGF, IGF-2, HGF, MMP-9, integrin beta3 and uPA in gastric cancer. There was a significant correlation between the expression of these markers and the depth of tumor invasion, vessel invasion, lymph node and distant metastasis, TNM stage and microvessel density. The average survival time and 5-year survival rate of patients with positive expression of molecular markers was higher than those with negative expression. Multivariate analysis showed that abnormal expression of bFGF, MMP-9 and uPA, as well as depth of invasion, lymph node and distant metastasis and TNM stage were independently related to poor prognosis of gastric cancer. MMP-9, bFGF and uPA are potential candidates for development as clinically applicable molecular prognostic markers for gastric carcinoma, and may be effective therapeutic targets for the disease in the future.
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PMID:Prognostic value of tumor-related molecular expression in gastric carcinoma. 1929 33

Immunohistochemical analysis of the expression and distribution of nm23 protein and biochemical analysis of the main components of plasminogen activation system in tumors were carried out in stomach cancer patients. The data indicate that the expression of nm23 protein in malignant epithelial gastric tumors is heterogeneous, characterized by cytoplasmic and nuclear immunoreactivity. Reduced expression of the marker is more typical of poorly or undifferentiated tumors. The expression of nm23 protein positively correlated with tPA level (r(s)=0.4; p=0.01) and did not correlate with the content of uPA and PAI-1 in tumors. High PAI-1 values in tumors (>0.5 ng/mg protein) significantly correlated with lower 3-year overall survival of stomach cancer patients. These data confirm the role of the studied proteins in invasion and metastases of malignant tumors and suggest a relationship between changes in the expression of nm23 protein and mechanisms of stomach cancer progress.
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PMID:Analysis of NM23 protein and components of plasminogen activation system in tumors of patients with stomach cancer with consideration for disease clinical picture and morphology. 1951 84

Gene associated with retinoid-IFN-induced mortality 19 (GRIM-19), as a novel IFN-beta/RA-inducible gene product, was identified as a potential tumor suppressor associated with growth inhibition and cell apoptosis. Recently, it has been reported that the apoptotic effects and apoptosis-related gene induction of GRIM-19 can be attenuated by GW112, indicating that GRIM-19 and GW112 are involved in a common signal transduction pathway. To investigate the signaling mechanisms that link GRIM-19 to GW112 and their functional role in tumor cell invasion and metastasis, we utilized adenovirus-mediated overexpression of GRIM-19 in the gastric cancer SGC-7901 cell line. We observed that enhanced expression of GRIM-19 not only downregulated GW112 but also decreased NF-small ka, CyrillicB binding activity. As a result, we found that tumor cell adhesion, migration, invasion and liver metastasis were inhibited. Additionally, upregulation of GRIM-19 also suppressed secretion of urokinase-type plasminogen activator (u-PA), matrix metalloproteinase (MMP)-2, 9 and vascular endothelial growth factor (VEGF). These results indicate that GRIM-19 acts as an upstream regulator of GW112 to block NF-small ka, CyrillicB binding activity, thereby inhibiting gastric cancer cell migration, invasion and metastasis. We conclude that adenoviral transfer of the GRIM-19 gene may be an efficacious approach to controlling the invasion and metastasis of human gastric cancer.
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PMID:Upregulation of the GRIM-19 gene suppresses invasion and metastasis of human gastric cancer SGC-7901 cell line. 2047 5

It has been reported that the 67-kDa laminin receptor (67LR) is implicated in cancer metastasis. We recently showed that 37LRP, the 67LR precursor, is a hypoxia-inducible factor 1 (HIF-1) target gene exposed to hypoxia in gastric cancer. Here, we investigated the role of 67LR in hypoxic metastasis and invasion in gastric cancer. Immunohistochemical analysis, western blotting, and RT-PCR assays revealed that 67LR was highly expressed in metastatic gastric cancers in vivo. Knockdown of the 67LR protein by RNA interference significantly decreased the adhesive, invasive, and in vivo metastatic abilities of the gastric cancer cell lines SGC7901 and MKN-45. Western blot analysis showed that 67LR increased the expression of urokinase-type plasminogen activator (uPA) and matrix metalloproteinase (MMP)-9, and decreased tissue inhibitor of matrix metalloproteinase (TIMP)-1 protein. We further showed that hypoxia induced 67LR expression in a time-dependent manner and this induction was inhibited by HIF-1 small-interfering (si) RNA. Both ERK and JNK inhibitors significantly inhibited hypoxia-induced expression of 67LR and the subsequent expression of uPA and MMP 9. SiRNA against 67LR or antibody against MMP9 and uPA significantly inhibited hypoxia-induced in vitro invasive ability. Taken together, these results reveal that 67LR promotes the invasive and metastatic ability of the gastric cancer cells through increasing uPA and MMP 9 expression, with involvement of the ERK and JNK signal pathway in hypoxia-induced 67 LR expressions and subsequent uPA and MMP9 expression.
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PMID:Hypoxia promotes metastasis in human gastric cancer by up-regulating the 67-kDa laminin receptor. 2049 81

Cell motility involves metastasis suppressors and other regulators that play an important role in tumor invasion and metastasis. Phenethyl isothiocyanate (PEITC), found in dietary cruciferous vegetables, has been found to exhibit antitumor properties and therefore is of special interest for the development of chemopreventive and chemotherapeutic agent for human cancers. Here, we report that in addition to its function as an anticancer agent, and PEITC can inhibit migration and invasion through the extracellular signal-regulated kinases 1/2 (ERK1/2), protein kinase C (PKC) and nuclear factor-kappaB (NF-kappaB) signaling pathways in human gastric cells. The results from wound healing and Boyden chamber assays (migration and invasion) assay indicated that PEITC exhibited an inhibitory effect on the migration and invasion of AGS cells. Results from Western blotting examination demonstrated that PEITC exerted an inhibitory effect on the ERK1/2, mitogen-activated protein kinase kinase 7 (MKK7), MAP kinase kinase kinase 3 (MEKK3), son of sevenless 1 (SOS1), PKC, Ras homolog gene family, member A (Rho A) and urokinase-type plasminogen activator (uPA), causing the inhibition of matrix metallopeptidase-2 (MMP-2) and -9 then followed by the inhibition of invasion and migration of GAS cells in vitro. PEITC also inhibited Ras, growth factor receptor-bound protein 2 (GRB2), vascular endothelial growth factor (VEGF), focal adhesion kinase (FAK), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), causing inhibition of cell proliferation of AGS cells. Results from real-time PCR showed that PEITC inhibited the gene expressions of MMP-2, -7 and -9, FAK and RhoA after PEITC treatment for 24 and 48 h of AGS cells. Taken together, these findings may provide insight into a new mechanisms and functions of PEITC in migration and invasion of human gastric cancer AGS cells. Our data imply that molecular targeting of PKC leading to the inhibition of MMP-2 and -9 might be a useful strategy for the inhibition of migration and invasion of human gastric cancer.
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PMID:Phenethyl isothiocyanate inhibits migration and invasion of human gastric cancer AGS cells through suppressing MAPK and NF-kappaB signal pathways. 2065 62

In a search for proteins involved in cancer metastasis, we analyzed proteomes of the human gastric cancer cell OCUM-2M and its metastatic subline OCUM-2MLN. We observed that aspartate aminotransferase (AAT), D-site binding protein (DBP), and anterior gradient protein 2 (AGR2) are differentially expressed in metastatic OCUM-2MLN cells. Measurement of protein expression in clinical samples indicated that DBP and AAT are also down-regulated in metastatic adenocarcinoma. Additionally, urokinase-type tissue plasminogen activator is up-regulated in OCUM-2MLN cells and also in metastatic gastric cancer samples. Collectively, these results raise a possibility that AAT, DBP and AGR2 are functionally implicated in the invasiveness of gastric cancer cells.
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PMID:Identification of proteins differentially expressed in gastric cancer cells with high metastatic potential for invasion to lymph nodes. 2153 48

The gene expressions of urokinase-type plasminogen activator (u-PA), u-PA receptor (u-PR), and plasminogen activator inhibitor (PAI)-1 and -2 in human tumor cell lines and human gastric cancer tissues were analyzed using the reverse transcription (RT)-PCR. The expression patterns were compared with experimental metastatic ability in chick embryo or clinicopathological findings. The results indicate that the function of u-PA binding to u-PR and the diminished expression of PAI-2 are significantly involved in the process of cancer metastasis and PAI-2 may be more effective in regulating u-PA activity than PAI-1.
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PMID:Relationship between expression of plasminogen activator system and metastatic ability in human cancers. 2154 36

Urokinase-type plasminogen activator (UPA) is a serine protease implicated in cancer invasion and metastasis. There are at least two kinds of specific inhibitor which act on UPA: plasminogen activator inhibitor-1 (PAI-1) and plasminogen activator inhibitor-2 (PAI-2). It has been reported that both UPA and PAI-1 antigen levels are associated with short survival in patients with breast cancer. In this study, we investigated the correlation between the expression of UPA, PAI-2 and prognosis in gastric carcinoma. One hundred and twenty specimens resected from patients with gastric carcinoma were investigated by staining with monoclonal antibodies against UPA and PAI-2. UPA positive rate was significantly higher in patients with liver metastases than in those without such metastases, There was no significant association between PAI-2 expression and clinicopathologic factors. However, patients with UPA-positive and PAI-2-negative tumors had more advanced cancer than other patients. According to the prognosis, the patients with UPA-positive and PAI-2-negative tumors had a significantly poorer prognosis than other patients. In conclusion, the combined evaluation of UPA and PAI-2 expression is associated with tumor progression in gastric cancer.
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PMID:Combined evaluation of urokinase-type plasminogen activator and plasminogen activator inhibitor-2 expression in gastric carcinoma. 2154 88

To elucidate the relation between urokinase-type plasminogen activator (U-PA) and metastasis in gastric cancer, we examined U-PA tissue status immunohistochemically. Ninety-eight primary gastric cancer, prepared by AMeX method, were analyzed with anti-U-PA and anti-proliferating cell nuclear antigen (PCNA) monoclonal antibody. In addition, DNA ploidy patterns were determined by cytofluorometer after staining with propidium iodide. U-PA immunoreactivity can be observed as diffuse cytoplasmic staining, as intensely outlined luminal borders or in desquameted cells in the lumens. U-PA expression-positive tumors showed higher incidence of serosal invasion, lymph node involvement or larger tumors than did U-PA negative ones. There was no correlation between U-PA tissue status and PCNA labeling rates or DNA ploidy patterns. Patients with a U-PA positive tumor survived significantly shorter than those with U-PA negative ones. These results may indicate that U-PA tissue status is a useful biological prognostic indicator in gastric cancer. The high malignant potential of U-PA positive tumors may be associated with a rapid infiltrating capacity through gastric wall but not with a high proliferative activity.
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PMID:Prognostic value of urokinase-type plasminogen activators in gastric-cancer. 2160 38

We report a case of pulmonary carcinomatous lymphangitis and multiple pulmonary infarctions from gastric cancer. A 58-year-old housewife presented with a complaint of a worsening cough over the previous 6 weeks. Chest radiography and CT scans revealed infiltration and diffuse ground-glass opacities in both lung fields, and she was hospitalized for further examination. No specific findings were found upon screening examination, including bronchoscopy with bronchoalveolar lavage (BAL). However, a CT scan showed mediastinal, hilar and paraaortic lymph node swelling, and therefore we suspected the presence of a malignant tumor. On the 11th hospital day, she suddenly developed severe hypoxia and went into cardiogenic shock. Although there was no sign of a filling defect in the vessels on CT with an intravenous contrast, we diagnosed pulmonary thromboembolism based on other examination findings and began thrombolysis and anticoagulant therapy. Treatment with heparin and urokinase did not improve her condition, and she died on the 14th hospital day. The autopsy findings revealed widespread gastric cancer with pulmonary lymphangitis carcinomatosa and thrombus formation in arterioles throughout the pulmonary lobes: 'Trousseau syndrome'.
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PMID:[A case of pulmonary carcinomatous lymphangitis and multiple pulmonary infarctions from gastric cancer]. 2189 72


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