Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Preoperative chemotherapy with CDDP, MMC, UFT and etoposide (PMUE) was performed on cases of far advanced gastric cancer whose curative resection was impossible. The therapy comprised 1-5 courses of either intravenous or arterial infusion, or intraperitoneal administration of CDDP 75 mg/m2, MMC 10 mg/body and Etoposide 50 X 3 mg/body at 3-week intervals in combined use of UFT 400 mg/body. The effect of the preoperative PMUE therapy was CR, PR, NC and PD in 0, 7, 1 and 0 cases, respectively, the rate of effectiveness being 88% (7/8). 5 of 7 cases with PR were operated on, 2 cases succeeded in curative resection, but 3 cases did not. Histological judgment of effects confirmed Grade II-a, II-b and III in 2, 2 and 1 cases, respectively; these 5 cases further received 1-4 courses of PMUE therapy as postoperative adjuvant chemotherapy and are still alive at P.S. 0-2, suggesting the great efficacy of this PMUE therapy as a neoadjuvant chemotherapy for improvement in prognosis in far advanced gastric cancer. Abnormally high values of the tumor marker were noted in 5 of 8 cases, 4 of which had tumor marker values lowered in exponential function by the preoperative chemotherapy, which constituted an effective index in determining chemotherapeutic effects and the determination of the operative timing.
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PMID:[Neoadjuvant chemotherapy of far advanced gastric cancer--effect of preoperative chemotherapy by PMUE (CDDP, MMC, UFT, etoposide]. 210 35

The subrenal capsule assay in normal mice has more advantages to evaluate sensitivities of anticancer agents than other assays in vivo. However, this method has difficulties because mice reject human tumor grafts by their immune reaction. We examined three methods of immunosuppression in mice; radiation, administration of cyclophosphamide and that of cyclosporin A. The administration of cyclosporin A suppressed host reactions most effectively among the three, and the human tumor grafts in subrenal capsules grew well. We also investigated the intervals of administration and the doses of cyclosporin A in order to evaluate drug response. The minimal dose of cyclosporin A which inhibited host reactions was revealed to be 50mg/kg/day administered subcutaneously to mice. Then the adequate dosage of each anticancer drug for this assay system was investigated so that the body weights of mice do not decrease more than 20%, and the following doses were determined; Mitomycin C: 5mg/kg; Cisplatinum: 4mg/kg; Cyclophosphamide: 100mg/kg and 5FU: 90 mg/kg.
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PMID:[Subrenal capsule assay in normal mice immunosuppressed by cyclosporin A]. 210 89

The tumor growth of Walker-256 implanted sc. on dorsum side of hindpaw of Wistar rat were suppressed by warmed (43 degrees C) water immersion. Antitumor effects of hyperthermia were increased by injection (a.i.) of saline mixed with noradrenaline (5 mcg). Although tumors in advanced stage group (D-8) are larger in size and more tumor vascularity than in early stage group (D-4), hyperthermic cytotoxicity were observed in D-8 but not observed in D-4. The hyperthermic energy injured the tumor vessels, which failed to flow the blood to the tumor cells and resulted in sever cytotoxic damage of Walker-256. Therefore, cytotoxic damage could be enhanced by injecting warmed water (43 degrees C) into tumor vessels after chemotherapy (MMC; 0.5 mg/kg) in D-8. Metastatic liver cancer was treated with thermochemotherapy. 5% of glucose warmed (43 degrees C) mixed with 0.1 mg of noradrenaline and heparin was administered into hepatic artery after chemotherapy (2 to 6 mg of MMC a.i.).
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PMID:[Enhancing hyperthermic cytotoxicity in Walker-256 by intraarterial injection of warmed saline]. 210 8

For the purpose to establish the reliability of SRCA using clinical materials, a histological assessment under the suppression of host reaction was introduced; 1) for the immune suppression cyclosporin A (CsA) was used, 2) to overcome the heterogeneity of fragments, the numbers of implants were increased to ten per group (two pieces/kidney), 3) time flame was 6 days as original, 4) the amounts of drugs were essentially similar to those of Bogden's original method. Drugs solely enough to induce immunosuppression such as 5-FU, CPA and MTX were administered by themselves and those not enough such as MMC, ADM and CDDP were done with least enough usage of CsA, 5) histological changes were analysed from three factors such as grade of degeneration (5 grades), tumor cell amounts (3 grades) and numbers of mitosis (3 grades). The histological analysis form representing the numbers of implants of each group on the indicated places by the individual grades of those 3 factors was devised. With this form, chemosensitivity results were expressed as ++, +, +/- and -. In a panel of more than one +/- results a sensitivity ranking was put on. 5) Macroscopic assessment was made by the measurement of height of the implants at day 6 for simplicity only for future relevance. This method of histological SRCA was applied on one parotid, one pancreas and ten colon cancers where viable tumor cells with frequent mitosis were seen in the CsA treated control groups and, on the other hand, occasional apparent degenerations were observed in some of drug treated groups. These facts verified that this histological assessment was practical and rational and covers the disadvantage of macroscopic findings.
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PMID:[Methodological aspects on the histological evaluation of subrenal capsule assay (SRCA)]. 210 10

In an effort to develop effective combination treatments for use with radiation against solid tumors, the cytotoxic effects of the addition of mitomycin C or porfiromycin on treatment with Fluosol-DA/carbogen (95% O2/5% CO2) breathing and radiation in the FSaIIC tumor system were studied. In vitro mitomycin C and porfiromycin were both preferentially cytotoxic toward hypoxic FSaIIC cells. After in vivo exposure, however, the cytotoxicity of mitomycin C toward single cell tumor suspensions obtained from whole tumors was exponential over the dose range studied, but for porfiromycin a plateau in cell killing was observed. With Fluosol-DA/carbogen breathing and single dose radiation, addition of either mitomycin C or porfiromycin increased the tumor cell kill achieved at 5 Gy by approximately 1.2 and 1.0 logs, respectively. Less effect was seen with addition of the drugs at the 10 and 15 Gy radiation doses. In tumor growth delay experiments, the addition of either mitomycin C or porfiromycin to Fluosol-DA/carbogen breathing and radiation resulted in primarily an additive increase in tumor growth delay. The survival of Hoechst 33342 dye-selected tumor cell subpopulations indicated that Fluosol-DA/carbogen breathing increased the cytotoxicity of radiation (10 Gy) more in the bright cell subpopulation (4-fold) than in the dim cell subpopulation (2-fold) resulting in an overall 4-fold sparing of the dim subpopulation. Mitomycin C and porfiromycin were both more toxic toward the dim cell subpopulations. Addition of mitomycin C or porfiromycin to Fluosol-DA/carbogen breathing and radiation (10 Gy) resulted in a primarily additive effect of the drugs and radiation killing in both tumor cell subpopulations. Thus, with mitomycin C/Fluosol-DA/carbogen and radiation there was a 2-fold sparing of dim cells and with porfiromycin in the combined treatment a 1.6-fold sparing of the dim cell population. Our results indicate that treatment strategies directed against both oxic and hypoxic tumor subpopulations can markedly increase the tumor cell kill achieved by radiation.
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PMID:Addition of a hypoxic cell selective cytotoxic agent (mitomycin C or porfiromycin) to Fluosol-DA/carbogen/radiation. 211 98

Mitomycin C (MMC) is regarded as the prototype bioreductive alkylating agent in clinical use. To elucidate the biochemical basis of MMC resistance, we isolated a drug resistant derivative (designated CHO-MMC) of a Chinese hamster ovary cell line (CHO-K1) by exposure to progressively higher concentrations of MMC. CHO-MMC cells exhibited a 17-fold increase in resistance to MMC and were 33-fold cross-resistant to the monofunctional derivative, decarbamoyl mitomycin C. In contrast, CHO-MMC cells showed only a 2-fold level of resistance to BMY 25282, a more easily activated analogue of MMC, and exhibited parental sensitivity to MMC under radiobiologically hypoxic conditions. CHO-MMC cells showed no increased resistance to a range of DNA damaging agents including several other alkylating agents (e.g., melphalan and methyl methanesulfonate). Cross-resistance to drugs associated with the multidrug resistant phenotype (e.g., Adriamycin and vincristine) was present only at very low levels. Using a specific high performance liquid chromatography technique, we examined the rates of reduction of MMC and BMY 25282 in cell extracts from CHO-K1 and CHO-MMC cells under both aerobic (air) and hypoxic (N2) conditions. Reduction rates for both drugs were at least 30-fold faster under nitrogen than in air. Metabolism of MMC was undetectable in air but was readily detectable under nitrogen and was 2- 3-fold slower in CHO-MMC cell extracts than in CHO-K1 cell extracts. Although BMY 25282 was more readily reduced under nitrogen, no difference was detected between extracts from CHO-K1 or CHO-MMC cells in the rate of reduction of BMY 25282 under either air or nitrogen. The activity of NADPH:cytochrome P-450 (cytochrome c) reductase, an enzyme implicated in the bioreductive activation of MMC, was 3-4-fold lower in CHO-MMC cells than in the parental line. These findings suggest that the resistance of CHO-MMC cells to MMC under aerobic conditions may be due to impaired metabolic activation of the drug as a result of a decrease in NADPH:cytochrome P-450 reductase activity. This supports the view that decreased bioreductive enzyme activity may be a significant mechanism for acquired resistance to MMC in tumor cells in vivo and that more readily activated analogues may be potentially useful in overcoming this specific form of resistance.
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PMID:Decreased NADPH:cytochrome P-450 reductase activity and impaired drug activation in a mammalian cell line resistant to mitomycin C under aerobic but not hypoxic conditions. 211 46

The approach that I have followed for patients with recurrent superficial transitional cell carcinoma of the urinary bladder has generally been to perform a thorough endoscopic evaluation of the bladder with appropriate evaluation of the prostatic urethra as well as the upper urinary tract, and if it is felt that the neoplasm is confined to the bladder (and possibly the mucosa of the prostatic urethra), then all obvious tumor should be resected and a three-month trial of intravesical therapy instituted. Based upon the results presented, the response at the first three-month evaluation has major prognostic importance. Those patients who had no evidence of tumor at this first three-month evaluation were less likely to have a subsequent cystectomy or die of bladder cancer than those who had evidence of persistent tumor. Among the 80 patients who received a treatment course of MMC, 13% of the complete responders compared to 34% of those who failed had a subsequent cystectomy, and among the 55 patients who received BCG, 6% of the complete responders compared to 25% of the failures had a subsequent cystectomy during the follow up interval. Indeed, part of this difference can be explained by the gradual adherence to the philosophy that if there is persistent high grade tumor or a high grade tumor develops following an adequate treatment course of MMC or BCG, cystectomy is indicated in order to avoid the development of a tumor which invades into the muscle.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Follow up of patients receiving treatment for superficial bladder cancer with mitomycin C and BCG. 211 89

Recombinant interferon-beta (IFN-beta) shows a high anti-tumor effect on cancerous ascites, has little local irritative action and can safely be administered intraperitoneally. A randomized trial was conducted to evaluate the efficacy of intraperitoneal administration of IFN-beta for the purpose of preventing peritoneal metastasis of gastric cancer. The subjects selected were patients under 75 years of age who were macroscopically positive for serosal invasion and had undergone curative operation. Comparison was made by the envelope method between the cases given IFN-beta i.v. at 6 x 10(6) units continuously for 14 days from the day of operation and from 1 week after operation. MMC, 20 mg (i.v.) on the day of operation and 5-FU, 200 mg (p.o.) for 1 year from 2 weeks after operation were administered, respectively, in the two groups. The number of cases registered from March, 1987 to September, 1988 was 33, with 17 in the administration group and 16 in the control group. No difference was noted between the two groups in 3-year survival rate and disease free survival rate. As to the recurrence involving the peritoneum, however, there was a difference between the two groups, with 1 out of 6 cases in administration group and 3 out 4 cases in control group. Intraperitoneal chemotherapy can be an effective adjuvant therapy for gastric cancer, if cases are selected.
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PMID:[Intraperitoneal administration of recombinant interferon-beta for prevention in peritoneal metastasis of gastric cancer]. 211 91

A study of hyperthermia was performed after injection of 0.5 mg/kg of MMC into feeding artery of Walker 256 implanted 4 days (early stage) or 8 days (advanced stage) earlier into the s.c. dorsum side of hindpaw of Wistar rats. The tumor growth curves on 6 days after treatment by warming tumor in hot water (44 degrees C) for 60 minutes were inhibited in advanced stage group which formed tumor vessels, but not in the early stage which had not still formed them. An intraarterial injection of warmed 0.01 to 0.05% Noradrenaline solution (44 degrees C, 10 ml) after chemotherapy (0.5 mg/kg of MMC a.i.), by which the temperature did not rise in the tumor tissue but rose to 40 degrees C for 5 to 10 minutes in the tumor vessels, showed severe cytotoxic damage in advanced stage group. The warming target of the tumor for hyperthermia can be considered to be the tumor vessels. Warmed 5% glucose using 0.1 mg of Noradrenaline (500 ml, 44 degrees C) injected into the tumor feeding artery after chemotherapy (2 to 6 mg of MMC or 250 mg of 5-FU a.i.) was tried in advanced cancer patients (liver tumor 4 cases, pancreas tumor 1 case, metastatic bone tumor 1 case, and multicentric tumor in liver, gall bladder and pancreas 3 cases). Efficacy was noted in 8 cases at the rate of 72.7% (8/11). It was concluded that warmed Noradrenaline solution delivered to the tumor vessels after chemotherapy for advanced cancer resulted in good efficacy rate as a from of chemo-thermotherapy.
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PMID:[Warm drug solution injected into tumor vessel may enhance antitumor effect]. 211 3

Continuous hepatic arterial infusion chemotherapy using implantable reservoir was performed for liver metastases from colorectal cancer, and the therapeutic effects, side effects, and complications were evaluated. 9 patients with unresectable liver metastases were as follows, 1. Group A; 3 patients, MMC 2 mg.one shot + 5-FU 250 mg/day.continuous infusion x 14 days, and then 5-FU tablets 150 mg/day.p.o. x 14 days, 2. Group B; 4 patients, MMC 2 mg.one shot + 5-FU 500 mg/day.continuous infusion x 7 days, and then 5-FU tablets 150 mg/day.p.o. x 14 days, 3. Group C; 2 patients, 5-FU 500 mg/day.continuous infusion x 14 days, and then free from agents for 14 days. In 2 of 3 group A patients, the catheters became dislocated and one died of perforation of duodenum. In group A and group B, no severe side effects were noted. But both of group C patients showed nausea, vomiting and diarrhea. In 8 of 9 patients (89%), serum CEA level fell below the preoperative level. In 4 of 7 patients who underwent CT scan, the size of the tumor regressed. Total infused dose of 5-FU was 8.17 +/- 7.56 g in group A, 16.9 +/- 2.88 g in group B, and 21.0 +/- 9.90 g in group C on average. In 2 patients of group B, therapy was repeated seven times.
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PMID:[Continuous hepatic arterial infusion chemotherapy using implantable reservoir in liver metastases from colorectal cancer]. 211 7


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