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 relationship was analyzed between drug resistance and MDR1 (with MDR signifying multiple drug resistance) and glutathione S transferase-pi (GST-pi) gene expression in four stomach and four colon cancer cell lines. Northern blot analysis by pmdr1 probe showed that stomach cancer cell lines had no detectable level of MDR1 mRNA expression. By contrast, some levels of MDR1 mRNA expression were found in two colon cancer cell lines, indicating doxorubicin resistance. To examine the MDR1 mRNA in each cell level, in situ hybridization was used. It was found that all colon cell lines and two stomach cell lines had more silver grains per cell than KB cells (a human KB kidney epidermoid carcinoma cell line). However, the number of silver grains in each cell was heterogeneous in the colon and stomach cell lines. Low-level MDR1 mRNA expression could be detected even in cell lines without MDR1 mRNA expression by northern blot hybridization. These results suggest the possibility that all gastrointestinal cell lines can acquire multiple drug resistance. In addition, all examined gastrointestinal cell lines had high GST-pi mRNA expression. This GST-pi gene expression shows cisplatin resistance in the examined cell lines. Heterogeneity of GST-pi mRNA expression also was shown at the cellular level.
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PMID:Expression of MDR1 and glutathione S transferase-pi genes and chemosensitivities in human gastrointestinal cancer. 173 85

The mechanism of drug resistance of gastric cancer cells has rarely been investigated. We specifically examine the magnitude and the biologic significance of multidrug resistance-1 (MDR-1) expression in human gastric cancer. All patients had previously been treated in prospective clinical trials for advanced gastric cancer in our institution. Patients with adequate prechemotherapy gastric cancer tissues for immunohistochemical studies by a C219 monoclonal antibody were selected for the determination of the expression rate of MDR-1. The results were designated as negative or positive by the independent interpretation of two pathologists. A subgroup of patients who had been treated with doxorubicin- or etoposide-containing regimens were selected for further correlation with drug sensitivity. Between 1990 and 1996, a total of 60 patients, 38 men and 22 women with a median age of 55 years, were studied. Eight (13.3%; 95% confidence interval, 6%-25%) of them had MDR-1 expression. None of the pertinent clinicopathologic features, including the histopathologic types of the tumors and the extent of the diseases, correlated with the expression of MDR-1. Among the 30 patients who had received doxorubicin- or etoposide-containing combination chemotherapy, 3 (10%; 95% confidence interval, 3%-27%) were designated positive for MDR-1 expression. None of the 3 patients responded to chemotherapy, whereas 19 (70.4%) of the 27 patients who had not expressed MDR-1 did respond (p=0.041 by Fisher's exact test). We conclude that the expression of MDR-1 in gastric cancer is relatively low. Its expression, however, is clinically relevant and is useful in predicting the chemoresistance of patients with gastric cancer receiving doxorubicin- or etoposide-containing combination chemotherapy.
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PMID:Relatively low expression of multidrug resistance-1 (MDR-1) and its possible clinical implication in gastric cancers. 964 10

It was determined whether the expression level of several genes that regulate different steps of metastasis in formalin-fixed paraffin-embedded archival specimens of human gastric cancers correlated with disease recurrence and metastasis. The steady-state mRNA expression level for epidermal growth factor receptor (EGF-R), basic fibroblast growth factor (bFGF), E-cadherin, type IV collagenase and multidrug resistance (MDR-1) were examined by a colorimetric in situ hybridisation (ISH) technique, concentrating on reactivity at the periphery of the lesions. All patients were operated on for cure. 15 cases were disease-free and 10 had disease recurrence by 4.5 years after resection of the primary tumours. The expression of EGF-R and bFGF type IV collagenase was higher and expression of E-cadherin was lower in the disease-recurrence cases than in the disease-free cases. The ratio between the expression level of collagenase type IV and E-cadherin at the periphery of the surgical specimens differed significantly between the disease-free cases and the recurrent-metastatic cases. These data show that multiparametric ISH analysis for several metastasis-related genes may allow prediction of disease recurrence of gastric cancer.
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PMID:Expression of metastasis-related genes in surgical specimens of human gastric cancer can predict disease recurrence. 971 9

Drug resistance remains a major problem in the treatment of gastric cancer. In Turkey, gastric carcinoma is the second most common cancer and, because the rate of early diagnosis is low, chemotherapy plays an important role in the treatment of the disease. We aimed to investigate expression of the multidrug resistance-1 gene (MDR-1) and its relationship with multiple prognostic factors in gastric cancers. Between 1996 and 1998, a total of 55 patients (37 men and 19 women; median age 55 years) were studied. Sections from specimens of gastric carcinomas were immunohistochemically stained to detect P-glycoprotein (which is associated with MDR-1 expression). We found MDR-1 expression in 48 (87%) of the patients. None of the multiple prognostic factors, including histological type of tumour, correlated with expression of MDR-1. Patients who had low MDR-1 expression had better survival. We conclude that the expression of MDR-1 in gastric cancer is high in Turkey, and this may be related to poor prognosis.
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PMID:High expression of multidrug resistance-1 (MDR-1) and its relationship with multiple prognostic factors in gastric carcinomas in patients in Turkey. 1044 94

AIM:To compare the expression level of Fas gene and Bcl-2 gene in gastric cancer cells SGC7901 and gastric cancer MDR (multidrug resistant) cells SGC7901/VCR,to transduce Fas cDNA and Bcl-2 antisense nucleic acid into SGC7901/VCR cells respectively, and to observe the expression of two genes in transfectants and non-transfectants as well as their drug sensitivity.METHODS:Eukaryotic expression vector pBK-Fas cDNA and pDOR-anti Bcl-2 were constructed and transfected into SGC7901/VCR cells by lipofectamine,respectively.Northern blot and Western blot were used to detect the expression of mRNA and protein in SGC7901/VCR and SGC7901 cells and transfectants, and drug sensitivity of transfectants for VCR, CDDP and 5-FU was analyzed with MTT assay.RESULTS:After gene transfection, 80 for Fas and 120 for antisense Bcl-2 drug-resistant clones were selected from 2 X10(5) cells, transfection rate being 0.04% and 0.06%. Two clones of SGC7901 Fas/VCR cells and SGC7901 anti Bcl-2/VCR cells were randomly selected for further incubation. Hybridization results showed that the expression level of Fas mRNA and protein in SGC7901/VCR cells was much lower,but that of Bcl-2 mRNA and protein was higher than that in SGC7901 cells. The expression of Fas mRNA and protein in SGC7901 Fas/VCR cells was higher,and of Bcl-2 mRNA and protein was lower in SGC7901 anti Bcl-2/VCR cells than that in non-transfectants. MTT assay showed that transfectants were more sensitive to VCR, CDDP, 5-FU than non-transfectants. CONCLUSION:Bcl-2 gene displayed high expression while Fas gene had low expression in drug resistant gastric cancer cells. Expression of Bcl-2 protein was effectively blocked in SGC7901 anti Bcl-2/VCR cells by gene transfection. In contrast, the expression of Fas mRNA and protein in SGC7901 Fas/VCR cells increased. Fas gene and Bcl-2 antisense nucleic acid transfection sensitized drug resistant gastric cancer cells to chemotherapeutic drugs. These results suggest cell apoptosis plays an important role in the mechanism of MDR, and enhancing apoptosis might reverse MDR.
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PMID:Transduction of Fas gene or Bcl-2 antisense RNA sensitizes cultured drug resistant gastric cancer cells to chemotherapeutic drugs. 1181 36

AIM:To construct Hsp90 antisense RNA eukaryotic expression vector, transfect it into SGC7901 and SGC7901/VCR of MDR-type human gastric cancer cell lines, HCC7402 of human hepatic cancer and Ec109 of human esophageal cancer cell lines, and to study the cell cycle distribution of the gene transected cells and their response to chemotherapeutic drugs.METHODS:A 1.03kb cDNA sequence of Hsp90beta was obtained from the primary plasmid phHSP90 by EcoR I and BamH I nuclease digestion and was cloned to the EcoR I and BamH I site of the pcDNA by T4DNA ligase and an antisense orientation of Hsp90beta expression vector was constructed. The constructs were transfected with lipofectamine and positive clones were selected with G418. The expression of RNA was determined with dot blotting and RNase protection assay, and the expression of Hsp90 protein determined with western blot. Cell cycle distribution of the transfectants was analyzed with flow cytometry, and the drug sensitivity of the transfectants to Adriamycin (ADR), vincrinstine (VCR), mitomycin (MMC) and cyclophosphamide (CTX) with MTT and intracellular drug concentration of the transfectants was determined with flow cytometry.RESULTS:In EcoR I and BamH I restriction analysis, the size and the direction of the cloned sequence of Hsp90beta remained what had been designed and the gene constructs were named pcDNA-Hsp90.AH-SGC7901, AH-SGC7901/VCR, AH-HCC7402 and AH-Ec109 cell clones all expressed Hsp90 anti-sense RNA. The expression of Hsp90 was down-regulated in AH-SGC7901, AH-SGC7901/VCR, AH-HCC7402 and AH-Ec109 cell clones. Cell cycle distribution was changed differently. In AH-SGC7901/VCR and AH-Ec109 cells, G(1) phase cells were increased; S phase and G(2) phase cells were decreased as compared with their parental cell lines. In AH-SGC7901 cell, G(1)phase cells were decreased, G(2) phase cells increased and S phase cells were not changed, and in AH-HCC7402 cells G(1), S and G(2) phase cells remained unchanged as compared with their parental cell lines. The sensitivity of AH-SGC7901, AH-SGC7901/VCR, AH-HCC7402 and AH-Ec109 to chemotherapeutic drugs, the sensitivity of AH-SGC7901/VCR to ADR, VCR, MMC and CTX the sensitivity of AH-HCC7402 to ADR and VCR, and the sensitivity of Ec109 to ADR, VCR and CTX all increased as compared with their parental cell lines. The mean fluorescence intensity of ADR in AH-SGC7901, AH-SGC7901/VCR, AH-HCC7402 and AH-Ec109 was also significantly elevated (P < 0.05).CONCLUSION: Down-regulation of Hsp90 could change cell cycle distribution and increase the drug sensitivity of tumor cells.
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PMID:Down-regulation of Hsp90 could change cell cycle distribution and increase drug sensitivity of tumor cells. 1181 30

AIM:To observe the drug sensitizing effect and related mechanisms of fas gene transduction on human drug-resistant gastric cancer cell SGC7901/VCR (resistant to Vincristine).METHODS:The cell cycle alteration was observed by FACS. The sensitivity of gastric cancer cells to apoptosis was determined by in vitro apoptosis assay. The drug sensitization of cells to several anti-tumor drugs was observed by MTT assay. Immunochemical method was used to show expression of P-gp and Topo II in gastric cancer cells.RESULTS:Comparing to SGC7901 and pBK-SGC7901/VCR, fas-SGC7901/VCR showed decreasing G2 cells and increasing S cells, the G2 phase fraction of pBK-SGC7901/VCR was about 3.0 times that of fas -SGC7901/VCR but S phase fraction of fas -SGC7901/VCR was about 1.9 times that of pBK-SGC7901/VCR, indicating S phase arrest of fas-SGC7901/VCR. FACS also suggested apoptosis of fas-SGC7901/VCR.fas-SGC7901/VCR was more sensitive to apoptosis inducing agent VM-26 than pBK-SGC7901/VCR. MTT assay showed increased sensitization of fas-SGC7901/VCR to DDP, MMC and 5-FU, but same sensitization to VCR according to pBK-SGC7901/VCR. SGC7901, PBK-SGC7901/VCR and fas -SGC7901/VCR had positively stained Topo II equally. P-gp staining in pBK-SGC7901/VCR was stronger than in SGC7901, but there was little staining of P-gp in fas-SGC7901/VCR.CONCLUSION:fas gene transduction could reverse the MDR of human drug-resistant gastric cancer cell SGC7901/VCR to a degree, possibly because of higher sensitization to apoptosis and decreased expression of P-gp.
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PMID:Suppression of P-gp induced multiple drug resistance in a drug resistant gastric cancer cell line by overexpression of Fas. 1181 71

Helicobacter pylori up-regulates cyclo-oxygenase-2 (COX-2) expression, which in turn is involved in tumourigenesis. Recently, a causal link between COX-2 and multidrug resistance 1 (MDR-1) gene expression, implicated in cancer chemoresistance, has been demonstrated. Thus, the expression of COX-2 and the downstream enzyme involved in PGE2 biosynthesis, microsomal PGE-synthase1 (mPGES1), was correlated with P-gp, the product of MDR-1, and the anti-apoptotic protein, Bcl-xL, in gastric biopsies from patients with H pylori infection and in patients with gastric cancer. In a retrospective analysis of endoscopic and pathology files, 40 H pylori-negative patients (Hp-), 50 H pylori-positive patients who responded to eradication therapy (Hp+R), 84 H pylori-positive patients who did not respond to eradication therapy (Hp+NR), and 30 patients with gastric cancer (18 intestinal and 12 diffuse types) were selected. COX-2, mPGES1, P-gp, and Bcl-xL were detected by immunohistochemistry. COX-2, mPGES1, P-gp, and Bcl-xL expression was undetectable in gastric mucosa from Hp- patients. By contrast, COX-2 and mPGES1 expression was detected in 42% and 44% of Hp+R patients, respectively, and in up to 66% (range 63-66%) of Hp+NR patients (p < 0.05). The expression of COX-2 and mPGES1 correlated significantly (p < 0.0001) with that of P-gp and Bcl-xL. High levels of COX-2, mPGES1, P-gp, and Bcl-xL expression were found in intestinal-type gastric cancer samples. In conclusion, H pylori-dependent induction of COX-2 and mPGES1 is associated with enhanced production of P-gp and Bcl-xL that may contribute to gastric tumourigenesis and resistance to therapy.
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PMID:Expression of COX-2, mPGE-synthase1, MDR-1 (P-gp), and Bcl-xL: a molecular pathway of H pylori-related gastric carcinogenesis. 1499 95

The Runx3 gene is a member of the runt domain family transcription factors, key regulators of development and differentiation in metazoan. Recently, Runx3 was identified as a tumor suppressor gene. Loss of Runx3 was found to be associated with genesis and progression of gastric cancer. In this study, we transfected the gastric cancer cell line SGC7901 with eukaryotic expression vector of Runx3. In vitro drug sensitivity assay suggested that SGC7901/Runx3 cells were more sensitive to various chemotherapeutic drugs. Blocking Runx3 expression in immortalized stomach mucosal cells (GES-1) or gastric cancer cells (SGC7901) by Runx3-specific small interfering RNA conferred the cells resistance to chemotherapeutic drugs. Flow cytometry examination suggested that expression of Runx3 in gastric cancer cells increased the intracellular accumulation and retention of adriamycin. Semiquantitative RT-PCR and Western blot suggested that Runx3 downregulated expression of Bcl-2, MDR-1 (P-gp) and MRP-1. Binding of Runx3 to promoter sequences of Bcl-2, MDR-1 and MRP-1 gene was detected by eletrophoretic mobility shift assay (EMSA) and supershift EMSA. We cloned the MDR-1 and MRP-1 gene promoters containing Runx binding sites and constructed the luciferase reporter vectors of these 2 promoters. Luciferase reporter assay suggested that Runx3 inhibited the promoter activity of the MDR-1 and MRP-1 promoter in SGC7901 cells. Taken together, our findings suggested that overexpression of Runx3 could sensitize gastric cancer cells to chemotherapeutic drugs by downregulating the Bcl-2, MDR-1 and MRP-1.
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PMID:Tumor suppressor gene Runx3 sensitizes gastric cancer cells to chemotherapeutic drugs by downregulating Bcl-2, MDR-1 and MRP-1. 1575 76

Cytokine-induced antiapoptosis inhibitor 1 (CIAPIN1) is a newly identified antiapoptosis molecule and a mediator of gastric MDR. We cloned cDNA of human CIAPIN1 by RT-PCR and constructed prokaryotic expression vectors of human CIAPIN1 by inserting human CIAPIN1 coding region into pET28-a(+) and pGEX- 4T-1, respectively. The fusion proteins were expressed in Escherichia coli and purified by affinity chromotography. Monoclonal antibody (MAb) against CIAPIN1 was obtained with standard cell fusion technique and ELISA screening. Immunohistochemistry and Western blot showed that the anti-CIAPIN1 MAb recognizes human and mouse CIAPIN1 protein in both native and denatured form. Western blotting confirmed that the expression of CIAPIN1 was upregulated in MDR gastric cancer cell lines. This MAb will be a useful tool for the detection of CIAPIN1 protein in future studies.
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PMID:Preparation and characterization of a specific monoclonal antibody against CIAPIN1. 1594 61


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