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)

A new polychemotherapy regimen has been developed for gastric cancer. Etoposide at the dose of 120 mg/m2 for three days, Epidoxorubicin at the dose of 30 mg/m2 on day 1 and Cisplatin at the dose of 40 mg/m2 on day 2 were administered to 26 advanced gastric patients every two weeks with the support of Granulocyte Colony Stimulating Factor from day 8 to day 12 of each cycle. The treatment was feasible with most cases (21/25) having received at least four cycles with a dose intensity > 85%, without life-threatening side effects. Toxicity was lower than that observed in the classical combinations of Etoposide-Anthracycline-Cisplatin.
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PMID:A new schedule for etoposide, epidoxorubicin and cisplatin with granulocyte colony stimulating factor for advanced gastric cancer: a feasibility study. 942 95

Telomerase, a ribonucleoprotein that adds telomeric repeats onto chromosome ends, is involved in telomere length maintenance and permits unlimited cell proliferation. We examined the possibility that higher telomerase activity is associated with the replicative phase of the cell cycle using gastric cancer cell lines treated with anticancer drugs. Telomerase activity increased at the time point of S-phase accumulation in NUGC-3 cells (5 x 10(5) cells/ml) incubated with CDDP (0.5 microgram/ml), paclitaxel (0.01 microM), or VP-16 (1 microM) and in MKN-28 cells incubated with CDDP. When these cell lines were incubated with 5-fluorouracil (10 microM) or CPT (0.1 microM), the increase of telomerase activity preceded the S-phase accumulation. Our results suggest that telomerase activity be regulated by the cell cycle.
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PMID:[Telomerase activity during the cell cycle in gastric cancer cell lines]. 961 22

To study drug resistance mechanism of gastrointestinal tumor, doxorubicin resistant cell line of human gastric cancer, we developed BGC-823/DOX, by increasing doses of doxorubicin. We completed chromosomal analysis, double time of cell grow, cell cycle distributions, drug resistance and cross-resistance, and studied reversing drug resistance. The results showed that chromosome of BGC-823/DOX was subtriploid karyotype. Cell morphology, double time, cell cycle distributions were different from its parent cells and 6.35 times more resistant to cytotoxic action of doxorubicin, cross-resistant to VP-16. Verapamil showed modified effect on doxorubicin resistance. BGC-823/DOX with doxorubicin resistance has many characteristics of gastrointestinal tumors.
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PMID:[Establishment and characterization of doxorubicin-resistant BGC-823/DOX of human gastric cancer cell line]. 1037 55

Gadd 153 gene is known as one of the growth arrest and DNA damage inducible genes that may play an important role in signal transduction pathway(s) in response to DNA damage. We have investigated whether the introduction of gadd153 gene into gastric cancer cells could modulate the sensitivity to anticancer agents in association with apoptosis. The transfection of gadd153 gene into MKN45 gastric cancer cells (MKN45gadd153) increased the sensitivity to a variety of anticancer agents, compared to that of neo gene-transfected cells (MKN45neo). The sensitivity to CDDP and VP-16 was increased to a greater extent, whereas the sensitivity to 5-FU and taxotere was increased to a lesser extent. The increase of sensitivity to these drugs was associated with the increase of the formation of internucleosomal DNA ladders in apoptosis. The basal level of gadd153 mRNA was overexpressed in MKN45gadd153 cells, and its induction following the treatment of VP-16 and taxotere was found to a greater extent than that of MKN45neo cells. The analysis of mRNA expression in drug resistance-related genes including mdr1, mrp, topoisomerase II alpha showed that the increase of drug-sensitivity in MKN45gadd153 cells was not due to the changes in expression of drug resistance genes. These results suggest that the introduction of gadd153 gene into gastric cancer cells may modulate the sensitivity to certain anticancer agents by activating AP-1-associated signal transduction pathway(s) leading to apoptosis.
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PMID:Introduction of gadd153 gene into gastric cancer cells can modulate sensitivity to anticancer agents in association with apoptosis. 1047 Jan 15

Taxotere (Docetaxel) is a novel microtubulin inhibitor which is currently in phase II/III clinical trial. We found that the sensitivity to taxotere was correlated with apoptotic cell death determined by the internucleosomal DNA ladders in gastric cancer cell lines. The treatment of taxotere activated proapoptotic genes such as bcl-Xs and bax genes. The relationship between the mRNA induction of bcl-Xs and bax genes and the internucleosomal DNA ladders by taxotere was significant, respectively (p<0.05). The introduction of bcl-Xs gene into MKN45 gastric cancer cells increased the sensitivity to VP-16 and taxotere 2-3-fold in the IC50 values, whereas the introduction of bax gene increased the sensitivity to CDDP, VP-16 and taxotere 2-5-fold in the IC50 values, as compared to that of the Neo-transfected MKN45 cells. The mRNA overexpression of bax gene was found in the bcl-Xs-transfected cells. Likewise, the mRNA overexpression of bcl-Xs gene was also found in the bax-transfected cells. These results indicate that the activation of bcl-2 family genes such as bcl-Xs and bax plays a crucial role in modulating apoptotic cell death in the sensitivity to anticancer drugs, and suggest that these proapoptotic genes might interact in the up-regulation for activating downstream signals leading to apoptosis in gastric cancer cells.
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PMID:Activation and the interaction of proapoptotic genes in modulating sensitivity to anticancer drugs in gastric cancer cells. 1049 58

Apoptois is an important determinant in the sensitivity to chemotherapeutic agents in gastric cancer cells. In this study, we examined whether the introduction of the bax gene into MKN45 gastric cancer cells could enhance the sensitivity to chemotherapeutic agents in association with apoptosis. Apoptosis in the bax-transfected gastric cancer cells was enhanced following the treatment of various chemotherapeutic agents including adriamycin (ADM), cisplatin (CDDP), etoposide (VP-16) and taxotere (TXT) as compared to those of neo gene-transfected cells. The enhancement of apoptosis was coincident with the increase of sensitivity in the ratio of IC50 value, that was 1.3-fold in ADM, 4.4-fold in CDDP, 4.6-fold in VP-16 and 2.5-fold in TXT, respectively. Further, the enhancement of apoptosis in the bax-transfected gastric cancer cells was associated with the activation of c-Jun N-terminal kinase 1 (JNK 1) and caspase 3 (CPP32). The increases of sensitivities to these agents in the bax-transfected cells were also demonstrated in in vivo experiments using the tumor cells transplanted into nude mice. The tumor growth in the bax-transfected cells was significantly suppressed following the treatment of CDDP or VP-16 compared to that of neo-transfected cells (p < 0.05). These results indicated that, the bax gene might play a critical role in determination of sensitivity to chemotherapeutic agent in gastric cancer cells in vivo, and that the activation of JNK 1 and CPP32 might be involved in the signal transduction pathways leading to apoptosis.
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PMID:Enhancement of chemotherapeutic agents induced-apoptosis associated with activation of c-Jun N-terminal kinase 1 and caspase 3 (CPP32) in bax-transfected gastric cancer cells. 1076 93

Gastric cancer usually shows poor sensitivity to chemotherapy, and the presence of lymph node metastases is associated with extremely poor prognosis, especially when the number of such nodes is more than 10. We report here a case of advanced gastric cancer with histopathologically confirmed metastases in 15 regional lymph nodes, in which the recurrent tumor was sensitive to combination chemotherapy. Distal gastrectomy with lymphadenectomy was performed for the primary tumor. A hard (recurrent) tumor was detected in the upper abdomen 5 months postoperatively. Abdominal CT revealed two tumors measuring 3.5 x 1.8 and 3.3 x 2 cm in diameter at the front of the pancreatic head, which suggested recurrence. Etoposide, adriamycin and cisplatin (EAP) chemotherapy (20 mg/kg adriamycin, 100 mg/kg etoposide and 50 mg/kg cisplatin (CDDP)) was administered every 6 weeks. The tumors regressed and became undetectable on CT after four cycles. At that stage, CDDP was replaced with 400 mg/kg carboplatin, which was administered every 1 or 2 months. The patient had no recurrence 8 years after surgery. For treatment of advanced gastric cancer with multiple lymph node metastases, a wide resection of the tumor should be performed followed by treatment of the residual tumor cells with a suitable combination chemotherapy taking into consideration the characteristics of the tumor and the condition of the host. We present a patient with gastric cancer and histopathologically confirmed metastases in 15 regional lymph nodes, who was successfully treated by surgery followed by EAP adjuvant chemotherapy. The patient remains alive and well at 8 years after surgery.
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PMID:Advanced gastric cancer with multiple lymph node metastasis successfully treated with etoposide, adriamycin and cisplatin. 1135 May 60

Activation of proteases can play an important role in apoptotic cell death induced by anticancer drugs. To assess involvement of activation of cysteine and serine proteases in anticancer drug-induced apoptosis, we tested effect of inhibitors of cysteine and serine proteases on sensitivity to anticancer drugs in MKN45 gastric cancer cells. Cytotoxic effect by adriamycin (ADM), SN-38 (active form of irrinotecan) and cisplatin (CDDP) was significantly prevented by cotreatment with Z-Val-Ala-Asp-fluoromethylketone (Z-VAD-fmk) (p<0.01), a pancaspase inhibitor compared with drug alone using MTT assay. In contrast, cotreatment with N-acetyl-Tyr-Val-Ala-Asp aldehyde (AC-YVAD-CHO), a caspase 1 inhibitor did not prevent any cytotoxic effect of these drugs. Cotreatment of N-acetyl-Asp-Glu-Val-Asp aldehyde (AC-DEVD-CHO), a caspase 3 inhibitor prevented cytotoxic effect of VP-16 and SN-38 (p<0.01). Prevention of these cytotoxic effects by caspase inhibitors was not dose-dependent. Cotreatment of N-tosyl-L-lysyl chloromethylketone (TLCK), a serine protease inhibitor significantly prevented cytotoxic effect of ADM, SN-38, 5-fluorouracil (5-FU) and CDDP in a slight dose-dependent manner (p<0.01) except for etoposide (VP-16) and docetaxel (TXT), while an other serine protease inhibitor, N-tosyl-L-phenylalanyl chloromethylketone (TPCK) did not prevent any anticancer drug-induced cytotoxic effect. These effects were associated with prevention of internucleosomal DNA ladder formation in apoptosis. Further, protease inhibitors did not block induction of cytochrome c, that can explain the partial effect of prevention by anticancer-induced cell death. These results suggest that anticancer drug-induced cytotoxic effect is mediated by activation of serine protease (caspase-independent) as well as caspase-dependent pathway leading to apoptotic cell death, and that protease-independent pathway may also be involved in apoptotic pathways. The involvement of protease in signal transduction pathways may differ in cytotoxic action of drugs in gastric cancer cells.
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PMID:Effect of inhibitors of cysteine and serine proteases in anticancer drug-induced apoptosis in gastric cancer cells. 1135 Dec 55

A complete surgical resection currently represents the only curative treatment option for gastric carcinoma, but as regards locally advanced cancer the possibility of local or distant recurrence remains extremely high even following a R0 resection. As far as T3-4/N+ tumors are concerned, unsatisfying results of surgery alone have stressed the need for multimodal treatments: in the recent past adjuvant chemotherapy has represented a common complementary treatment for locally advanced gastric cancer, but conclusive results of most randomized trials did not show a significant impact on long term survival. Literature review shows a growing trend throughout the 90's towards the adoption of a preoperative chemotherapy, initially evaluated as a form of "salvage" palliative treatment for unresectable patients. To date a number of phase II study suggests the efficacy of neo-adjuvant treatment administered to resectable patients with the purpose of inducing tumor downstaging, increasing the rate of R0 resections and controlling recurrencies. From March 1996 the Authors have started a controlled study on neo-adjuvant therapy for locally advanced gastric cancer. Accurate staging and patients selection were based upon immediately preoperative laparoscopy. In this ongoing study, patients are administered two preoperative cycles of EEP chemotherapy (Etoposide, Epirubicin, cis-Platin). Preliminary data have been evaluated on the first 15 cases. Grade I myelosuppression has been observed in 12/15 cases and grade II/III in 3/15 cases; 1 patient died by septic complications. Restaging has not shown progression of the disease in 13/14 cases; a macroscopic response was evidenced in 7/14 patients; 14/14 patients could undergo a successful D2 surgical resection following neo-adjuvant therapy. Pathological staging confirmed tumor downstaging in 7 out of 14 cases; 12/14 patients in this group (85.7%) could benefit a R0 resection. These preliminary data encourage us to proceed in our prospective investigation.
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PMID:[Neoadjuvant chemotherapy in gastric carcinoma]. 1146 95

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


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