UMLS:C0024623 - FACTA Search

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Query: UMLS:C0024623 (gastric cancer)
36,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

AIM:To study the effects of arsenic trioxide and HCPT on dif ferent degrees of differentiated gastric cancer cells (SGC-7901, MKN-45, MKN-28) with respect to both cytotoxicity and induction of apoptosis in vitro.METHODS:The cytotoxicity of As(2)O(3) and HCPT on gastric cancer cells was det ermined by MTT assay.Morphologic changes of apoptosis of gastric cancer cells were observed by light microscopy and transmission electron microscopy.Apoptosis and cell cycle changes of gastric cancer cells induced by HCPT and As(2)O(3) we re investigated by TUNEL method and flow cytometry.RESULTS:As(2)O(3) and HCPT had remarkable cytotoxic effects on different degrees of differentiated gastric cancer cells. The IC(50) of As(2)O(3) on well differentiated gastric cancer cell MKN-28, moderately differentiated gastric cancer cell SGC-7901, and poorly differentiated gastric cancer cell MKN-28 were 8.91 &mgr;mol/L, 10.57 &mgr;mol/L, and 11.65&mgr;mol/L, respectively. The IC(50) of HCP T on MKN-28, SGC-7901, and MKN-45 were 9.35 mg/L, 10.21 mg/L,and 12.63 mg/L respectively after 48 h treatment. After 12 h of exposure to both drugs, gastric cancer cells exhibited morphologic features of apoptosis, includ ing cell shrinkage,nuclear condensation, and formation of apoptotic bodies. A ty pical subdiploid peak before G(0)/G(1) phase was observed by flow cytometry. The apoptotic rates of SGC-7901, MKN-45, and MKN-28 were 13.84%, 22.52%, and 9.68%, respectively after48 h exposure to 10&mgr;mol/L As(2)O(3). The apoptotic ra tes of SGC-7901, MKN-45, and MKN-28 were 21.88%, 12.35%, and 30.26%, resp ectively after 48 h exposure to 10 mg/L HCPT. The apoptotic indice were 7%-15% a s assessed by TUNEL method. The effect of As(2)O(3) on SGC-7901 showed remarkab le cell cycle specificity, which induced cell death in G(1) phase, and blocked G(2)/M phase.HCPT also showed a remarkable cell cycle specificity, by inducing cell death and apoptosis in G(1) phase and arrest of proliferation at Sphase.CONCLUSION:As(2)O(3) and HCPT exhibit significant cytotoxicity on gastric canc er cells by induction of apoptosis. As(2)O(3) and HCPT might have a promising pr ospect in the treatment of gastric cancer, which needs to be further studied.
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PMID:Induction of apoptosis by arsenic trioxide and hydroxy camptothecin in gastriccancer cells in vitro. 1181 42

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

AIM:To evaluate the potential of RA-538 gene therapy for gastric carcinoma.METHODS:Human gastric carcinoma cell line SGC7901 treated with Ad-RA538 or Ad-LacZ were analysed by X-gal stain, MTT, DNA ladder, Tunel, flow cytometric analysis, PCR, and Western Blot in vitro. The tumorigenicity and experimental therapy in nude mice model were assessed in vivo.RESULTS:Ad-LacZ could efficiently transfer the LacZ gene into SGC7901 cells. X-gal-positive cells at MOI 25, 50, 100, and 200 were 90%, 100%, 100%, and 100% respectively. Ad-RA538 could strongly inhibit cell growth and induced apoptosis in SGC7901 cells.The proliferation of the Ad-RA538-infected SGC7901 cells was reduced by 76.3%.The mechanism of killing of gastric carcinoma cells by Ad-RA538 was found to be apoptosis by DNA ladder,Tunel and flow cytometric analysis.The tumorigenicity in nude mice using Ad-RA538 showed that all three mice failed to form tumor from 7 to 30 days compared with Ad-LacZ and parent SGC7901 cells. Experimental therapy on the nude mice model bearing subcutaneous tumor of SGC7901 cells showed that intratumor instillation of Ad-RA538 inhibited the growth of the tumors. Ad-RA538-treated tumors were inhibited by 60.66%, compared with that of the tumor injected with Ad-LacZ and mock.CONCLUSION: The expression of Ad RA538 can inhibit growth and induce apoptosis of gastric cancer cell in vitro and in vivo. Ad RA538 can be used potentially in gene therapy for gastric carcinoma.
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PMID:The therapeutic effects of recombinant adenovirus RA538 on human gastric carcinoma cells in vitro and in vivo. 1181 8

We investigated supra-additive cytotoxic effects of 5-fluorouracil (5FU) on gastric and colon cancer cells with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in vitro. p53 wild- and mutant-type gastric and colon cancer cell lines were treated by 5FU alone, TRAIL alone, and a combination of 5FU and TRAIL, and cell viability after each treatment was determined by MTT assay. The p53 wild-type cells were more sensitive to 5FU alone or to TRAIL alone than p53 mutant-type cells. The cell growth inhibitory effects of the combined treatment were supra-additive and more significant in proportion to the increasing concentrations of TRAIL as compared with 5FU alone both in p53 wild- and mutant-type cells. Furthermore, TRAIL could cause a decrease in 5FU IC(50) to within the range of clinically relevant doses, particularly in p53 wild-type cells. This is the first demonstration of the supra-additive antitumor activity of 5FU with TRAIL on gastric cancer cells, giving evidence that TRAIL can reduce the requirement for 5FU that ultimately results in minimizing risks for systemic side effects while increasing the antitumor activity of 5FU, suggesting the clinical applicability of this combination for gastric and colon cancers.
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PMID:Supra-additive antitumor activity of 5FU with tumor necrosis factor-related apoptosis-inducing ligand on gastric and colon cancers in vitro. 1216 12

To evaluate the clinical usefulness of 7-hydroxystaurosporine (UCN-01), we compared the antitumor spectrum of UCN-01 with those of conventional antitumor agents against 40 fresh gastric and 40 fresh colorectal cancer specimens using the MTT assay. At a cut-off concentration of 30 micrograms/ml, UCN-01 showed a higher efficacy rate than mitomycin C (MMC), cisplatin, and 5-fluorouracil (5-FU) against both gastric and colorectal cancers. With respect to the gastric cancer specimens, the antitumor spectrum of UCN-01 was independent from those of the other agents, while the patterns of antitumor effects of the conventional agents all correlated significantly with each other. For the colorectal cancer specimens, the pattern of UCN-01-sensitivity did not correlate with the patterns for 5-FU or MMC. In conclusion, UCN-01 may be useful for clinical application against gastric and colorectal cancer due to its different antitumor spectrum from conventionally available agents.
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PMID:Independent antitumor spectrum of UCN-01 (7-hydroxystaurosporine) against gastric and colorectal cancers as detected by MTT assay. 1255 63

After incubation with 2-butylamino-2-demethoxy-hypocrellin A (2-BA-2-DMHA), photodynamically induced change in the cytoplasmic free calcium concentration ([Ca(2+)](i)) and its effect on cell damage were investigated in human gastric cancer (MGC-803). Fluorescence spectrophotometry measurement indicated that the photosensitization of MGC-803 by 2-BA-2-DMHA caused an increase in intracellular calcium [Ca(2+)](i), and this increase in [Ca(2+)](i) showed a dependence on the concentration of 2-BA-2-DMHA, light dose and extracellular [Ca(2+)](e). This phenomenon of intracellular calcium accumulation was further confirmed by using laser scanning confocal microscopy (LSCM). Furthermore, the results from MTT assay and flow cytometry analysis suggested that chelation of extracellular calcium by EGTA or intracellular calcium by BAPTA could inhibit photodynamically induced cell killing, while increase of [Ca(2+)](i) by thapsigargin (TG), a highly specific inhibitor of the Ca(2+)-ATPase, or by A23187, a calcium ionophore could enhance this action. Meanwhile, the nucleus morphology was also investigated by fluorescence microscopy. The results indicated that the increase in intracellular Ca(2+) concentration was responsible for 2-BA-2-DMHA photodynamically induced damage to MGC-803.
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PMID:Role of calcium in phototoxicity of 2-butylamino-2-demethoxy-hypocrellin A to human gastric cancer MGC-803 cells. 1258 63

Human thymidine phosphorylase (dThdPase) is an angiogenic factor identical to platelet-derived endothelial cell growth factor (PD-ECGF). Thymidine phosphorylase is also a converting enzyme of the prodrug 5'-deoxy-5-fluorouridine (5'-DFUR) to 5-fluorouracil (5-FU) in tumors. To assess the role of dThdPase in targeting chemotherapy, we examined the relationship between the expression of dThdPase and the sensitivity of 5'-DFUR in cancer cell lines, and also examined whether transfection of dThdPase cDNA enhanced the drug-sensitivity to 5'-DFUR with or without angiogenesis in breast cancer cells. Thirteen human cancer cell lines consisting of 4 breast cancer, 6 gastric cancer, and 3 colon cancer cell lines were used. Expression of dThdPase was assessed by reverse transcriptase-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). In vitro drug-sensitivity was assessed by MTT assay, and anti-tumor effect in vivo was assessed using nude mouse xenografts. Intratumoral microvessel density was evaluated by immunohistochemical staining to factor VIII related antigen. Transfection of dThdPase cDNA was performed using pcDNA3 expression vector encoding its cDNA by the lipofection method. An inverse relationship between the expression of dThdPase and the IC50 values of 5'-DFUR was observed (p=0.1278, rho=-0.440) in the 13 cancer cell lines. Transfection of dThdPase cDNA into MCF-7 breast cancer cells resulted in an approximately 2.6- and 10-fold increase of the expression of dThdPase mRNA and its enzyme activity, respectively, compared to the control vector alone. The sensitivity to 5'-DFUR in the transfected cells was increased approximately 20-fold compared to the parent cells and control vector alone, and the sensitivity to 5-FU was also somewhat increased. In contrast, the sensitivity to ADM, CDDP, and VP-16 was not different between the transfected and control cells. In nude mice xenografts of the transfected cells, treatment with 5'-DFUR had a significant anti-tumor effect compared to those of the untreated transfected cells and control vector alone treated with 5'-DFUR (p<0.01). Intratumoral microvessel density in the transfected cells was not significantly increased with or without treatment with 5'-DFUR compared to control vector alone. The high expression of dThdPase was correlated with an increase in the sensitivity to 5'-DFUR in gastrointestinal and breast cancer cell lines. The introduction of dThdPase cDNA in breast cancer cells enhanced the sensitivity to 5'-DFUR without an increase of tumor angiogenesis, and targeting chemotherapy of dThdPase may be a good tumor-specific and personalized therapy for improving the poor prognosis of cancer patients who show high expressions of dThdPase.
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PMID:Effects of introduction of dThdPase cDNA on sensitivity to 5'-deoxy-5-fluorouridine and tumor angiogenesis. 1263 76

To identify chemoresistance-related genes of gastric cancer, we utilized cDNA microarray technology. Thirty-five gastric cancer specimens surgically resected at our institute between 1998 and 1999 were studied for quantification of expression of 6300 genes by means of oligonucleotide microarray methods, and the results were evaluated in comparison with the chemoresistance of the specimens, which was determined by MTT (tetrazolium-based 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Inhibition rates (IR) were determined for cisplatin (DDP), 5-fluorouracil (5-FU), mitomycin C or doxorubicin. IR of 60% or more was regarded as sensitive to each agent, and IR of less than 40% was defined as resistant. Clustering was successfully completed for DDP, resulting in selection of 23 candidates as DDP-resistance-related genes, including vascular permeability factor, 2 membrane transporting subunits, and retinoblastoma-binding protein-1. In addition, further selection of DDP-resistance-related genes was performed according to these criteria: 1) Expression of the gene can be detected in more than 70% of resistant tumors. 2) Expression can be detected in less than 30% of sensitive tumors. 3) Expression in tumors is more than twice that of normal mucosa in more than 50% of specimens. Then, metallothionein-IG and heparin-binding epidermal growth factor-like growth factor (HB-EGF) were identified as candidate DDP-resistance-related genes. When known DDP-resistance-related genes were analyzed according to the MTT assay result, families of glutathione-S-transferase and cyclooxygenase-2 genes were also evaluated as resistance-related genes. For 5-FU resistance, dihydropyrimidine dehydrogenase and HB-EGF-like growth factor genes were also suggested to be resistance-related genes. The present study demonstrated that oligonucleotide microarrays can provide information regarding chemoresistance factors in cancer.
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PMID:Possible chemoresistance-related genes for gastric cancer detected by cDNA microarray. 1282 4

To evaluate the clinical usefulness of taxanes as antitumor agents, we compared the antitumor spectrum of taxanes with those of conventional antitumor agents against 88 fresh gastric cancer specimens by MTT assay. At cut-off concentrations of 100 micrograms/ml for taxotere (Docetaxel, DOC) and 300 micrograms/ml for taxol (Paclitaxel, PAC), both agents showed a higher efficacy rate than mitomycin C (MMC), cisplatin (CDDP) and 5-fluorouracil (5-FU) against the gastric cancer specimens. The patterns of antitumor activity of DOC and PAC were independent from those of the conventional agents, while the patterns of antitumor activity of the taxanes significantly correlated with each other. Conventional agent antitumor activity patterns tended to correlate with the patterns of other conventional agents. In conclusion, taxanes may be useful for clinical application against gastric cancer due to their different antitumor spectrum as compared to conventional agents.
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PMID:No cross-resistance of taxotere and taxol to conventional chemotherapeutic agents against gastric cancers as detected by MTT assay. 1292 47

COX-2 over-expression occurs in various cancers, but the role of COX-2 in cancer progression remains to be elucidated. We examined the inhibitory effects of a novel selective COX-2 inhibitor, JTE-522 (JT), against gastric cancer cell lines (TMK-1, MKN-45 and MKN-74) alone and in combination with cisplatin (CDDP). The antitumor activity of JTE-522 was evaluated by MTT assay, which revealed that JT alone elicits a dose-dependent antitumor activity in vitro. The JT/CDDP combination elicited a synergistic antitumor effect in MKN-45 cells and an additive effect in the other cell lines. In an in vivo study, 10 mg/kg JT and 12 mg/kg CDDP together elicited a synergistic antitumor activity against MKN-45 cells that were subcutaneously transplanted into nude mice. We conclude that JT is a potent antitumor agent in vitro and in vivo and that, in combination with CDDP, it might be a useful treatment strategy for gastric cancer.
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PMID:Combination chemotherapy with JTE-522, a novel selective cyclooxygenase-2 inhibitor, and cisplatin against gastric cancer cell lines in vitro and in vivo. 1292 71

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