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 synergistic antitumor activity of mitomycin C (MMC) and cisplatin (DDP) against the gastric cancer cell lines MKN-28 and MKN-45 was assessed in vitro using the MTT assay. The synergism of the two agents was evaluated in terms of the interaction index (I.I.). The sequence of MMC followed by DDP showed higher antitumor activity than the reverse sequence against MKN-28 and MKN-45, and the intracellular concentration of platinum was significantly increased in MKN-45 by preincubation with MMC, suggesting that MMC modulates cellular permeability to DDP or the ability of DDP to intercalate DNA. Since these two antitumor agents show different types of toxicity clinically, i.e., myelotoxicity by MMC and nephrotoxicity by DDP, this combination chemotherapy could be advantageous by providing synergistic antitumor activity without increased toxicity.
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PMID:Synergistic antitumor activity of mitomycin C and cisplatin against gastric cancer cells in vitro. 841 67

Cisplatin, mitomycin C and 5-fluorouracil were given a 55-year-old woman for an unresectable gastric cancer, and successful radical gastrectomy was performed. Postoperative adjuvant immunochemotherapy using UFT and PSK was continued for about 4 years and 4 months. Pancytopenia was observed at 5 years after the treatment and then marked leucocytosis was noted. She also showed complications of general fatigue, appetite loss etc. A secondary acute leukemia associated with eosinophilia was diagnosed by peripheral blood examinations, showing WBC, 122,400: blast, 37.5 % and eosinophil, 41%. Results also showed atypia and pseudo-Pelger nuclear abnormality of eosinophil, high positive stain of cell myelogenic cell surface marker, many numeral and structural abnormalities of chromosomal analysis, etc. From the above results, it was suggested that the leukemia might be induced by previously performed chemotherapy. The patient died about 2 months following its onset.
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PMID:[A case of secondary leukemia induced by chemotherapy with a CDDP-based regimen for gastric cancer 5 years following radical resection]. 842 78

A pharmacodynamic study of cisplatin (DDP) was conducted using the gastric cancer cell lines MKN-45 and MKN-74 in vitro. Ten thousand tumor cells were incubated with 0.4-500 micrograms/ml DDP for 1-25 h, followed by recovery culture for a further 48 h. At the end of incubation, cell viability was detected by the MTT end-point, and the inhibition rate was compared in relation to the incubation time, DDP concentration, and the time X concentration product (area under the curve in vitro: AUC vitro). In both of the cell lines, the IC50 and IC90 values decreased as the exposure time increased, going a linear curve with a slope of almost -1, and showing a typical log-log AUC vitro-dependent curve. These results indicate that the antitumor activity of DDP is dependent on its AUC vitro, suggesting the clinical usefulness of this drug when administered daily in small divided doses.
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PMID:Antitumor activity of cis-diamminedichloroplatinum (II) depends on its time x concentration product against human gastric cancer cell lines in vitro. 855 32

A pharmacodynamic analysis of cis-diamminedichloroplatinum(II) (DDP) was conducted using two human gastric cancer xenografts, SC-1-NU and MKN-45, and one human breast cancer xenograft, MX-1, grown serially in BALB/c nu/nu mice. DDP was administered intraperitoneally (i.p.) at a total dose of 5, 10, or 20 mg/kg in a schedule of q7d x 3 or (qd x 5) x 3. DDP was also administered i.p. to BALB/c +/? mice, whose plasma was used for the assay of total and free platinum by the atomic absorption method. A total dose of 20 mg/kg DDP seemed to be the maximum tolerated dose that was effective on MX-1 and SC-1-NU. When the totally administered doses were equivalent, the antitumor effects of the q7d x 3 and (qd x 5) x 3 schedules were similar to each other. The antitumor activity of DDP against MKN-45 was dependent on the total administered dose as well as the area under the curve of free and total platinum in the plasma. Side effects were significantly reduced using a schedule of (qd x 5) x 3 in terms of body and spleen weight loss when a total of 10 or 20 mg of DDP per kg was administered. These results suggest that DDP would be useful when administered using a daily schedule for obtaining the same antitumor activity as that of bolus injection but with reduced adverse effects.
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PMID:Antitumour activity of cis-diamminedichloroplatinum (II) against human tumour xenografts depends on its area under the curve in nude mice. 860 46

A pharmacokinetic analysis of cis-diamminedichloroplatinum (II) (DDP) was conducted comparing low-dose daily bolus infusions, and high-dose drip infusions. Eight patients with gastric cancer were treated with low-dose daily bolus infusions of DDP to a total daily dose of 75 mg/m2 bid for 5 days. Four patients with esophageal cancer and one patient with gastric cancer were treated with high-dose drip infusions of DDP to a total daily dose of 70-80 mg/m2. Side effects were assessed in all the patients, and the platinum concentration in plasma was determined by an atomic absorption method. The peak plasma concentration (Cmax) and area under the curve (AUC) were calculated in four cases of the low-dose therapy, and three cases of the high-dose therapy. The side effects of DDP were evaluated according to the World Health Organization (WHO) grading, paying particular attention to nausea/vomiting, appetite loss, renal toxicity, and bone marrow suppression. The incidence of nausea/vomiting and appetite loss was significantly reduced with low-dose daily bolus infusions when compared to the high-dose drip infusions. Bone marrow toxicity and renal toxicity were similar with both administration methods, although hydration was required for the high-dose drip infusions to prevent renal toxicity. The peak plasma concentration (Cmax) of total and free platinum, and the area under the curve (AUC) of total platinum, were similar with both administration methods, while the AUC of free platinum was higher with the low-dose daily bolus infusions compared to the high-dose drip infusions. The time when the concentration of total platinum was > 1 microgram per ml (holding time) was significantly longer with the high-dose drip infusions than with the low-dose daily bolus infusions. The present study suggests that low-dose daily bolus infusions of DDP would be useful in reducing gastrointestinal toxicity, without reducing the area under the curve which is important for antitumor activity.
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PMID:Pharmacokinetics of cis-diamminedichloroplatinum (II) given as low-dose and high-dose infusions. 864 40

Previous studies have demonstrated the immunomodulatory effects of cisplatin under certain conditions. The present study was designed to clarify whether cisplatin modulates the expression of surface antigens, especially human leukocyte antigen (HLA), on human tumor cell lines and/or augments the susceptibility and binding of tumor cells to cytotoxic effector cells. A human gastric cancer cell line, KATO-3, was employed. The expression of HLA and other tumor-associated antigens was analyzed by flow cytometry using FITC-conjugated monoclonal antibodies. The cytotoxicity of effector cells was determined by 51Cr release assay. The expression of HLA class I antigen, beta2-microglobulin, leukocyte function-associated antigen-1, and AC-81 adenocarcinoma-associated antigen on KATO-3 increased after exposure to cisplatin at 10 micrograms/ml for 3-6 hr; augmentation of HLA class I subtypes -B2 and -B27 was particularly prominent. Furthermore, the susceptibility and binding of KATO-3 to both lymphokine-activated killer cells and KATO-3-specific cytotoxic T lymphocytes significantly increased after cisplatin treatment. Cisplatin may modulate the expression of tumor-associated antigens on some human tumor cells. Tumor regression by cisplatin administration may depend on its direct cytotoxicity as well as on its modulating effects on the expression of tumor-associated antigens, subsequently leading to the activation of the immune surveillance system against the tumor.
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PMID:Cis-diamminedichloroplatinum(II) augments expression of tumor-associated antigens on human gastric cancer cell line KATO-3 and increases susceptibility and binding of tumor cells to various cytotoxic effector cells. 866 22

The effects of shock waves in combination with various anti-cancer agents i.e. Bleomycin (BLM), Cisplatin (CDDP) and 5-fluorouracil (5-FU) on tumor cells suspended in media containing these agents were examined. GCIY cells derived from human gastric cancer and LS 174T and SW480 cells derived from human colon cancers were used for in vitro experiments; GCIY and SW480 cells were also transplanted into nude mice for in vivo study. It was only with BLM that enhancement was evident in all three cell lines, with a degree of chemotherapeutic enhancement proportional to the amount of shock wave energy applied. Ladder formation of DNA in GCIY cells was observed only when treated with both BLM and shock waves in combination. When SW480 and GCIY cells transplanted into the backs of nude mice were treated with a combination of intravenously (i.v.) injected BLM and regional exposure to shock waves, a significant enhancement of chemotherapeutic effects was observed in terms of the tumor growth curve.
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PMID:Enhancement of chemotherapeutic effects with focused shock waves: extracorporeal shock wave chemotherapy (ESWC). 879 42

Hepatic arterial infusion chemotherapy (HAIC) using implantable reservoir was performed for liver metastases of gastric cancer and the therapeutic effects were evaluated. A catheter was placed in the hepatic artery via left subclavian artery or by direct insertion at laparotomy. Cisplatin, adriamycin and 5-FU were administered. The liver metastases of gastric cancer without unresectable primary tumors and hepatectomy were divided into two groups, 16 HAIC cases (11 synchronous, 5 metachronous metastases) and 23 systemic chemotherapeutic cases (10 synchronous, 13 metachronous metastases). As a result, HAIC revealed a 62.5% response rate. The 50% survival period was 395 days for HAIC, and it was significantly prolonged compared with 198 days for systemic chemotherapy (p < 0.01). But 4 among 10 cases responding to HAIC showed subsequent extrahepatic spread of the disease. Treatment of these extra-hepatic lesions is difficult.
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PMID:[Evaluation of hepatic arterial infusion chemotherapy for gastric cancer]. 893 89

A cis-diamminedichloroplatinum (CDDP)-resistant scirrhous gastric cancer cell line, OCUM-2M/DDP, was established by chronic exposure of cells of the parent scirrhous gastric cancer cell line, OCUM-2M, to CDDP at progressively increasing concentrations. The OCUM-2M/DDP cell line had an 11.3-fold higher level of resistance relative to its parent cell line as determined by a succinate dehydrogenase inhibition test. The biological and biochemical characteristics of the resistant and parent cell line were compared. There were differences in the modal chromosome number and DNA index, suggesting that some alterations of the DNA in the CDDP-resistant cells had occurred. Neither the parent nor resistant cell line expressed mdr-1 mRNA. After exposure to CDDP for 4 h, the intracellular platinum content of OCUM-2M cells was significantly higher than that of OCUM-2M/DDP cells (51.9 +/- 1.8 vs 16.4 plus 1.0 ng/mg protein, mean +/- SD, respectively). The GSH levels in OCUM-2M cells and OCUM-2M/DDP cells were 3.5 +/- 1.0 micrograms/mg protein and 16.8 +/- 1.2 micrograms/mg protein, respectively. These levels were also significantly different. These findings suggest that the possible mechanisms of acquired resistance to CDDP in OCUM-2M/DDP cells may be a decrease in intracellular CDDP accumulation and detoxication by GSH. This OCUM-2M/DDP cell line could be used in further investigations of the mechanism of CDDP resistance in gastric cancer.
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PMID:Establishment of a cisplatin-resistant gastric carcinoma cell line OCUM-2M/DDP. 913 37

Precise prediction of recurrence risks is of importance in the selection of adjuvant chemotherapy. A proportional hazards regression analysis was performed to seek objective criteria for 234 gastric cancer patients. The analysis showed that a high level of carcinoembryonic antigen (CEA) in peritoneal washing (100 ng/g protein) was an independent risk factor for peritoneal recurrence, and a high MMP9 (92 KD type IV collagenase) level in serum was a powerful indicator of hematogenous recurrence. In addition, the PHREG analysis in 1453 gastric cancer patients showed that MF therapy (mitomycin C i.v. + fluoropyrimidine derivatives) and PF therapy (Cisplatin i.p. + fluoropyrimidine derivatives) might be effective in the prevention of hematogenous and peritoneal recurrence after a curative operation, respectively. Based on these findings, a recurrence type-oriented adjuvant chemotherapy, i.e., PF therapy for high CEA group and MF therapy for high MMP9 group, was designed. The retrospective analysis showed significant survival benefit in stage III gastric cancer patients who underwent a curative operation. The 5-year survival rate was 67%, while that of the historical control was 46%. Prediction of recurrence type using CEA levels in peritoneal washings and MMP9 levels in sera may be of value in the selection of a proper population of patients for PE or MF therapy after gastrectomy. The selection system of adjuvant chemotherapy using such objective criteria may improve the prognosis of gastric cancer patients and keep their good quality of life through the selection of proper candidates and by eliminating patients in no need of therapy.
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PMID:Selection of adjuvant chemotherapy for gastric cancer using objective criteria. 921 Sep 3


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