Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cisplatin plus 5-FU appears to have significant additive activity in various tumors, such as head and neck carcinoma and esophageal cancer. A partial explanation for this may be drug synergism, which has been noted in the L1210 leukemia model. Based on these data, a prospective trial of weekly bolus 5-FU (15 mg/kg) and cisplatin (60 mg/m2) given every 3 weeks was initiated at Indiana University. Forty-one patients, of whom 38 are fully evaluable for response, were treated with these two drugs. Ten partial and one complete response (complete + partial response rate = 29%) were observed in the 38 evaluable patients. Thirteen additional patients had stable disease for greater than or equal to 3 months. The median durations of remission and survival time were 6 and 10.3 months, respectively. Myelosuppression was unusually severe, with granulocyte counts less than 1000/mm3 in 65% of patients, including four patients with granulocyte count nadirs less than 100/mm3. Three patients developed granulocytopenic fever, with two drug-related deaths (sepsis, hyperosmolar coma). Nearly all patients had nausea and vomiting, but this was not a treatment-limiting toxic effect in any patient. Although this combination suggests a higher response rate than usually seen with bolus iv 5-FU in colon cancer, a trial comparing 5-FU alone or with cisplatin to determine whether true synergy exists is currently underway.
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PMID:Cisplatin plus 5-FU for the treatment of adenocarcinoma of the colon. 407 11

The cytotoxic activity of 5'-deoxy-5-fluorouridine (5'-ddFUrd) was established in six cultured human tumor lines: 47-DN and MCF-7 breast carcinomas, MG-63 osteosarcoma, HCT-8 colon carcinoma, Colo-357 pancreatic carcinoma, and HL-60 promyelocytic leukemia. Cells were exposed to a wide range of 5'-dFUrd concentrations (from 0.1 microM to 1.0 mM) for 3, 6, or 24 hrs, and then cloned using standard in vitro clonogenic assays. 5'-dFUrd exhibited its best activity in the 47-DN and MCF-7 breast cell lines and in the MG-63 osteosarcoma line (3-hr LD50 values of 32, 34, and 38 microM, respectively). Less activity was observed in the HCT-8 colon (LD50 = 195 microM) and Colo-357 pancreatic (LD50 = 155 microM) tumor lines, and ver poor activity was noted in the HL-60 leukemia cell line (LD50 = 465 microM). The metabolism of 5'-dFUrd to 5-FU (FUra) and FUra-nucleotides was determined and found to directly correlate with the potency of 5'-FUrd in these cell lines. These results suggest that: (a) there is a marked variation in sensitivity of human cancer cells of different tissue origin to 5'-dFUrd, (b) there is a direct relationship between the sensitivity of human cells to 5'-dFUrd and the ability of the cell to metabolize 5'-dFUrd to FUra, and (c) increasing exposure period of cells to 5'-dFUrd did not markedly alter 5'-dFUrd potency in all human cancer cells examined, with the exception of the 47-DN breast cancer cells.
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PMID:Cytotoxic activity of 5'-deoxy-5-fluorouridine in cultured human tumors. 622 89

The present study was designed to elucidate the cytotoxic potential of 8 possible substituted uracilic metabolites of methylxanthines. 5-Fluorouracil (5-FU) was used as a reference uracil analogue with cytotoxic activity. Substituted uracil derivatives examined in this study did not affect the proliferative capacity of PHA-stimulated rat lymphocytes, murine L1210 leukaemia and rat chondrocytes. Caffeine had some growth inhibitory activity of extremely high concentrations (greater than 100 micrograms/ml). In vivo administration of 6-amino-5[N-methyl-formylamino]1,3-dimethyluracil (1,3,7-TAU) and 6-amino-5[N-acetylamino]3-methyluracil (7-A3-MAU) caused a transient short-lived reduction of L1210 tumour cell numbers. These observations do not appear to support the hypothesis that substituted uracils are involved in the toxicity of high doses of caffeine in rats.
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PMID:In vitro and in vivo cytotoxicity of possible uracil metabolites of methylxanthines. 662 37

A series of acridine monosubstituted derivatives of the antitumour agent amsacrine [4'-(9-acridinylamino)methanesulphon-m-anisidide] has been tested for activity against intraperitoneally inoculated P388 leukaemia and intravenously inoculated Lewis lung carcinoma growing in DBA/2J X C57BL/6J mice, and treated using a q4d X 3 intraperitoneal injection schedule. Whereas all derivatives tested exhibited moderate to high activity towards the leukaemia, activity against the lung tumour varied from inactive to curative. Amsacrine itself displayed low but statistically significant activity. Cyclophosphamide and 2-beta-D-ribofuranosylthiazole-4-carboxamide (tiazofurin) were highly active. 5-Fluorouracil was active but doxorubicin, daunorubicin, ametantrone and mitoxantrone showed no significant activity. Since the Lewis lung carcinoma is responsive to a high proportion of agents active against solid tumours in the clinic, it is concluded that some derivatives of amsacrine could be considerably more active than amsacrine itself against human solid tumours.
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PMID:Divergent activity of derivatives of amsacrine (m-AMSA) towards Lewis lung carcinoma and P388 leukaemia in mice. 668 94

The effects of thymidine (TdR) on the toxicity and antitumor activity of ftorafur (FT), a 5-FU analog, were determined. The LD10 of FT was 130, 430, and 680 mg/kg, respectively, when FT was administered ip in the following treatment schedules: (a) daily for 9 days, (b) every 4th day for three treatments, and (c) 1 day only. When FT was administered simultaneously with 250 mg/kg of TdR, the LD10 was 13, 62, and 630 mg/kg in the respective treatment schedules. Lethargy was observed in mice when the daily dose of FT was greater than or equal to 150 mg/kg. FT alone was active (% treated/control [T/C] = 153) against ascites P388 murine leukemia only at high, single doses. Simultaneous administration of FT and 250 mg/kg of TdR at or below the LD10 dose of FT resulted in an increase in the antitumor activity to a % T/C of 217 (daily, Days 1-9) and 188 (daily, Days 1, 5, and 9). The activity of FT administered simultaneously with TdR on Day 1 only (%T/C = 142) was lower than that for FT alone. Using a treatment schedule of Days 1, 5, and 9, a TdR/FT mol ratio of greater than or equal to 2.0 seems necessary to achieve an increase in therapeutic value against P388 murine leukemia. This may explain the lack of increase in activity against P388 when 250 mg/kg of TdR was coadministered with FT on Day 1 only. FT alone or coadministered with 250 mg/kg of TdR was equally active against L1210 ascites tumor at doses up to the LD10 with daily treatments on Days 1, 5, and 9 and on Days 1-9; the doses of FT, however, were below those which cause lethargy.
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PMID:Effect of thymidine on the toxicity and antitumor activity of ftorafur. 679 8

The antitumor activity of cyclophosphamide (CP) in combination with ftorafur (FT) against advanced L1210 murine leukemia was investigated and compared with the activity of the combination of CP and 5-FU. CP at doses of 200--350 mg/kg was highly active, the most effective dose (% treated/control = 327) being 300 mg/kg. The activity of FT up to the LD10 dose and of 5-FU at 50 mg/kg was minimal (% treated/control less than or equal to 142). Coadministration of 200 mg/kg of FT with 100 mg/kg of CP resulted in an increase in activity as compared with the respective dose of CP alone as did the coadministration of 400 mg/kg of FT with 200 mg/kg of CP; the activities, however, were no better than that resulting from treatment with 300 mg/kg of CP alone. The coadministration of CP and 600 mg/kg of FT resulted in an increase in host toxic reactions and loss of antitumor activity, as did the coadministration of 400 mg/kg of FT with 300 mg/kg of CP. Treatment with FT at 400 or 600 mg/kg 24 hours before or after administration of CP at 200 or 300 mg/kg did not increase the activity over that occurring when the respective combinations of the drugs were coadministered. The activity of the combination of CP with 5-FU at doses previously reported to be synergistic was equal to that observed when mice were treated with 300 mg/kg of CP alone. These data suggest that FT increases the cytotoxicity of CP but that the combination is not synergistic.
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PMID:Combination chemotherapy with cyclophosphamide and ftorafur against advanced L1210 murine leukemia. 680 29

The sub-cellular fractions from Group A streptococcus (Su-strain) were prepared, and their antitumor and biological activities were examined. The cell wall fraction (CWF) and the protoplast membrane fraction (PMF) were slightly effective in retarding the growth of Ehrlich ascites carcinoma in outbred ddY mice when either fraction was used in combination with 5-FU. The cytoplasmic particle fraction (CPF) and the cytoplasmic soluble fraction (CSF), however, were not effective. In the B6D2F1 mice-L 1210 leukemia system, none of the subcellular fractions were beneficial even when combined with 5-FU. Further, the antitumor effect of OK-432 was completely abolished by disruption of the preparation, indicating that antitumor activity of OK-432 may depend on the structural integrity of the cocci in the preparation. Despite the general lack of anti-tumor activity in the mouse systems, the subcellular fractions, including those of OK-432, inhibited the growth of Yoshida sarcoma cells in culture and the uptake of [2H]-UR and [3H]-TdR by L 1210 cells in vitro. The immunopotentiating activities of these fractions, however, were demonstrated to be markedly diminished as compared with those of OK-432 and heated Su-cocci (60 degrees C, 30 min). The present study, therefore, shows that the decreased antitumor activity of the subcellular fractions closely correlate to the decrease of their immunopotentiating activities.
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PMID:Reduced antitumor and immune-adjuvant activities of the sub-cellular fractions from Group A Streptococcus. 704 Jul 46

A pilot study was carried out among 21 patients with advanced solid tumors to establish appropriate dose levels of PALA and 5-FU given on a 5-day schedule to produce definite but tolerable clinical toxicity. While dermatitis, diarrhea, leukopenia, and thrombocytopenia were observed, stomatitis was the dose-limiting side effect. The recommended initial dose levels for further clinical trials are 625 mg/m2 of PALA daily x 5 and 250-300 mg/m2 of 5-FU daily x 5, with courses repeated at 4-week intervals. Studies were also conducted to establish the time course of anticipated increased incorporation of 5-FU into cellular RNA following treatment with PALA. In murine P388 leukemia, PALA increased tritiated 5-FU incorporation by as much as 70%, the effect being maximal within 1 hour and maintained up to 25 hours. It was not possible to demonstrate increased tritiated 5-FU uptake into normal human leukocyte RNA from patients receiving combination chemotherapy with PALA and 5-FU, perhaps because of low rates of RNA synthesis.
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PMID:Pilot study of PALA and 5-FU in patients with advanced cancer. 705 70

Uninfected DBA/2 mice and those infected 12 days previously with the polycythemia-inducing Friend murine leukemia virus were treated with 5-FU in doses of 18.75--200 mg/kg ip, and the effects on spleen weight, reticulocytosis, and hematopoietic stem cell compartments CFU-S, CFU-C, and CFU-E was studied. The CFU-E population of virus-infected mice, which had been completely independent of erythropoietin (Ep) in vitro before treatment, showed a considerable proportion of normal Ep-requiring CFU-E at Days 2--6 after doses less than or equal to 50 mg/kg, indicating a chemotherapy-induced remission. Later, Ep-independent growth was seen again, most probably due to a reinfection by the virus at the target cell level. The regeneration of all stem cell types was quicker in uninfected mice than in those infected with virus. These data are discussed in relation to results obtained with hydroxyurea treatment, where Ep-dependent CFU-E were also seen, and with respect to the effects of busulfan, carmustine, and dactinomycin, with their different modes of actin. The importance of effective antiviral therapy for the cure of such a virus-induced malignancy is emphasized.
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PMID:Hematopoietic stem cells in Friend murine leukemia virus-infected mice undergoing chemotherapy: effects of 5-FU. 713 39

The immunoprophylactic and immunotherapeutic effects of LAK cells transferred adoptively on L615-suffering mice were studied. The results showed that adoptive transfer of LAK cells could increase the survival rate of the mice and prolong the mean survival time of mice with advanced L615 leukemia. IL-2 in appropriate concentration was required in the adoptive immunotherapy, and the combined use of LAK cells with 5-FU or IFN-r had no additive immunotherapeutic effects. The results also revealed that the immunotherapeutic activity of the transferred LAK cells maintained a relatively long period of time in the host body.
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PMID:[Immunoprophylactic and immunotherapeutic effects of adoptively transferred LAK cells on L615 leukemia suffering mice]. 751 34


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