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)

The effects of Ara-C derivatives, 5-FU derivatives and water-soluble nitrosoureas on L1210 leukemia implanted intracerebrally have been evaluated. Daily treatment with BH-AC showed a similar effect to that of Ara-C and intermittent treatment with BH-AC showed a marked effect. Daily treatment with FT-207, UFT and HCFU, 5-FU derivatives, resulted in more than 50% ILS but the effects of these compounds were inferior to those of ACNU and BH-AC. MCNU, a water-soluble nitrosourea, was effective, but less so than ACNU.
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PMID:[Effects of derivatives of Ara-C, 5-fluorouracil and nitrosourea against intracerebral implanted L1210 leukemia]. 294 3

In this article, the clinical effects of rH-TNF on various cancer patients and the mechanism of self-induction of defense against rH-TNF cytotoxicity in tumor cells and the counter measures against this are reviewed. 1) Clinical effects of rH-TNF Intratumoral administration of rH-TNF was performed in 7 patients and clinical efficacy (PR + MR) was observed in 3/7 (42.9%). Also a reduction of leukemia cells in peripheral blood was observed in all 4 leukemia patients following intravenous (i.v.) administration of rH-TNF. Furthermore, in 2 multiple myeloma patients, the myeloma protein and plasma cells in bone marrow were reduced by i.v. administration of rH-TNF. 2) Self-induction of defense against rH-TNF cytotoxicity Investigation of the effect of TNF on RNA and protein synthesis by tumorigenic and normal cell lines showed that their synthesis in tumor cells was increased at 12 h and peaked at 24 h of incubation with TNF, while that in normal diploid fibroblast (HEL) cells was apparently unaffected by the presence of TNF. Artificial inhibition of either RNA or protein synthesis by L-M cells, upon addition of Act D or CHI increased the cytotoxic effect of TNF, thus suggesting that the elevated RNA and protein synthesis is related not to the cytotoxic reaction itself but rather to a defense mechanism. Similar incubation of HEL cells with TNF in the presence of either inhibitor resulted in the occurrence of cytotoxicity not observed with TNF alone, thus suggesting the existence of a defense mechanism in normal, TNF-resistant cells which is absent or greatly weakened in tumor cells. 3) Combination therapy of rH-TNF with various anticancer drugs. A synergistic increase in the cytotoxic effects of rH-TNF and anti-cancer drugs was demonstrated in vitro The cytotoxicity of rH-TNF against L-M cells in combination with MMC, ADM, Ara-C, ACD, DM, CDDP, VCR and 5-FU was 4 to 347 times as high as that of rH-TNF alone. These results suggest that combination therapy including rH-TNF and anti-cancer drugs may be of value in the treatment of malignancy in human patients.
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PMID:[Anti-tumor effect of human recombinant TNF]. 329 72

Deoxyspergualin, the 15-deoxy derivative of the antibiotic spergualin, is a novel guanidino analog structurally related to spermine. Deoxyspergualin has significant activity in selected experimental tumor models, and clinical trials have been initiated. Described here are in vivo evaluations of the therapeutic activity of deoxyspergualin against murine leukemia lines specifically resistant to eight clinically useful antitumor drugs. These were P388 lines resistant to doxorubicin, vincristine, L-phenylalanine mustard, cisplatin, ara-C, and methotrexate and L1210 lines resistant to 5-FU, L-phenylalanine mustard, and cyclophosphamide. Sensitivity to deoxyspergualin was evaluated in parallel comparisons of each resistant leukemia to the sensitive line from which it had been derived. All experiments were repeated at least once for confirmation of results. Responses were quantitated in terms of the change in tumor cell numbers from the beginning of treatment to the end of treatment as estimated from the median survival times of dying mice. The results indicated that P388 leukemia resistant to cisplatin (P388/DDPt) was cross-resistant to deoxyspergualin. No cross-resistance was observed in leukemias resistant to doxorubicin, vincristine, ara-C, methotrexate, or cyclophosphamide. L1210 resistant to 5-FU (L1210/5-FU) was collaterally sensitive to deoxyspergualin. Although cross-resistance was also observed in P388/L-PAM, L1210/L-PAM retained sensitivity to deoxyspergualin. Total glutathione concentrations in P388/L-PAM and L1210/L-PAM provided no apparent explanation for this unexpected result. It may be tentatively concluded that resistance to cisplatin, L-PAM, or other DNA alkylators or cross-linkers may increase the potential for cross-resistance to deoxyspergualin. This conclusion requires verification with additional alkylating agents, with drug-resistant human tumor cell lines, and with prospective clinical studies.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cross-resistance of drug-resistant murine leukemias to deoxyspergualin (NSC 356894) in vivo. 343 39

Cytarabine (ara-C) is the first line agent with its excellent activity for acute myelogenous leukemia. Combination therapy of MFC (mitomycin C, 5-FU, ara-C) has been used for GI tract cancer with a synergistic effect on L-1210 mouse leukemia. In the results of research on the administration, a high dose ara-C is an effective agent in the refractory cases to the standard dose ara-C and the combination with daunorubicin is applied to a remission consolidation therapy. A small dose ara-C is used against an atypical leukemia with its mechanism of induction of differenciation. On the other hand, in the development of its derivertive compounds ancitabine or enocitabine (BH-AC) were induced to a treatment of acute myelogenous leukemia. Especially BH-AC is the first choice agent for acute myelogenous leukemia combined with other agents.
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PMID:[Cytarabine]. 347 3

Ubenimex (Bestatin) was discovered by Umezawa et al. in 1976 from the culture broth of Streptomyces olivoreticuli. Bestatin is a compound of low-molecular weight peptide and inhibits leucine aminopeptidase and aminopeptidase B which localized in cell membrane. Bestatin exhibited antitumor effect against murine syngeneic tumors including mouse colon 26 and C1498 leukemia, and also it was active against MNNG-induced rat tumor by oral administration. Combination treatment of mouse colon 26 with bestatin and mitomycin C, 5-FU or CDDP was effective for the life prolongation of the treated mice compared to mono-therapy alone. Bestatin was found to exhibit the antitumor effect through T lymphocyte stimulation, macrophage activation and bone marrow stem cell stimulation were also observed by bestatin treatment experimentally. Values of T cell subsets in cancer patients recovered to the normal levels by Bestatin treatment. Release of Interleukin-1 and -2 was enhanced by Bestatin treatment in vitro. In the phase I study, clinical optimal daily dose was estimated as 10-100 mg to give 2-3 times weekly or daily continuously. In the comparative clinical trials, Bestatin was found to be effective for the prolongation of survival time of the patients with acute non-lymphocytic leukemia after induction of complete remission in combination with maintenance chemotherapy. Minimal side effects were noted.
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PMID:[A new antitumor drug with immunomodulating activity, ubenimex (bestatin)]. 349 57

In a prospective, randomized trial Cancer and Leukemia Group B (CALGB) evaluated CAF chemotherapy (cyclophosphamide + doxorubicin + 5-fluorouracil [5-FU]) v CAF plus tamoxifen (TCAF) in advanced breast cancer. Patients were stratified by estrogen receptor (ER) status, dominant site of metastatic disease, menopausal status, and prior adjuvant therapy. Regardless of ER status or menopausal status, the addition of tamoxifen conferred no significant advantage in response rate, response duration, time to treatment failure (TTF) or survival over CAF alone. A secondary objective was to compare the response to CAF of ER positive (ER+) and ER negative (ER-) patients to determine if there was a differential response to cytotoxic chemotherapy. Response rates of ER+ and ER- patients to CAF were identical (56%), but the response duration, time to treatment failure, and survival of ER+ patients were significantly longer than ER- patients. This lack of differential response implies that chemotherapy and hormonal therapy may compete for the same pool of ER+ cells. It also suggests that chemotherapy kills breast cancer cells indiscriminately, regardless of ER status.
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PMID:Chemohormonal therapy in advanced carcinoma of the breast: Cancer and Leukemia Group B protocol 8081. 365 56

5-Fluorouracil (5-FU), an effective pyrimidine antimetabolite was evaluated in the BNML rat model of human acute myeloid leukemia. Single injections of 5-FU, 15-50 mg/kg i.p., caused a sharply dose-related reduction of leukemic growth as measured by liver and spleen weights and leucocyte counts. Similar results were obtained with three doses of 5-FU over a period of 10 days. No apparent toxicity was observed in these experiments. A schedule of 25 mg/kg every 5 days extended the survival time of leukemic rats to 156%, as compared to untreated controls. In the BNML model such an increase in lifespan is equivalent to a 10,000 fold reduction of the tumor mass. These results indicate a potential value of 5-FU treatment in human myeloid leukemia. 5-FU, however, is not used in the clinical treatment of leukemia. A review of the literature revealed that there have been very few relevant studies of this application of 5-FU, while the more unique activity of this drug against some solid tumors has been investigated extensively. Therefore, it can be concluded that there is no clear evidence of the ineffectiveness of 5-FU against leukemia, and that further investigations should find out whether the disregard of 5-FU in this respect is justified.
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PMID:5-Fluorouracil treatment of rat leukemia and a reappraisal of its application in human leukemia. 375 59

Cultured leukemic lymphocytes originating from patients with T, B and non-T, non-B (null) leukemia were tested for their sensitivity to thymidine and 5-fluorouracil. T cells were found to be 5-7 fold more sensitive to thymidine growth inhibition than B-cells. At 10(-3) M concentration of thymidine, T cells showed a progressive (up to 75%) decline in the populating trypan blue-excluding cells, after 72 h. At this concentration of thymidine B cells showed slight inhibition at 24 and 48 h, then at 72 h the surviving cell level returned almost to the level of unperturbed cells. Thymidine at 10(-5) M concentration, caused 40% cell growth inhibition of T cells, however, at this concentration it had little or no effect on B cells. 5-fluorouracil effects on B and T lymphocytes are opposite to that of thymidine. B cells were on an average 5-7 times more sensitive to 5-FU than T cells. 5-FU at 10(-6) M caused up to 45% inhibition of B-cell growth but at this concentration it had no effect on the growth of T cells. B-, T- and null-lymphocytes sensitivity to thymidine and 5-FU was correlated with the level of the catabolic enzyme thymidine phosphorylase. B cells had, on average, 5-fold more thymidine phosphorylase than T or null cells. Furthermore, the enzyme from the B-cell line (HR1K) chromatographed differently on DEAE-Sephadex than the normal peripheral blood lymphocytes enzyme. The normal enzyme from peripheral blood lymphocytes when adsorbed to DEAE-Sephadex was eluted at a salt concentration of 0.3 M KCI, Enzyme activities of HR1K did not adsorb to the DEAE-Sephadex column but were adsorbed to a phosphocellulose column. Enzyme from normal and leukemic lymphocytes showed similar molecular weights of 130,000 dalton as determined by gel filtration.
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PMID:The molecular basis for the differential sensitivity of B and T lymphocytes to growth inhibition by thymidine and 5-fluorouracil. 387 86

Between February 1980 and August 1982, the Cancer and Leukemia Group B (CALGB) performed a randomized study aimed to compare chemotherapy with CAF (Cyclophosphamide, Adriamycin, 5-Fluorouracil) versus the same chemotherapeutic regimen plus tamoxifen (T-CAF) in stage IV breast cancer patients. Patients were stratified on the basis of menopausal status, estrogen receptors (ER) status, dominant site of metastasis and prior adjuvant treatment. Overall 474 patients were entered into the study of whom 433 were assessable for response. 314 patients were postmenopausal, 85 premenopausal and 34 patients were unknown as far menopausal status was concerned. No difference was evident among postmenopausal patients in overall response rate and duration of responses between T-CAF and CAF (52% vs 50% respectively). Similarly no difference was shown among premenopausal patients, response rates being 63% with T-CAF and 60% with CAF. Lack of benefit from adding T to chemotherapy was seen also according to the different strata, including patients with ER positive tumors. The failure for this combination to be synergistic might reflect an effect of T on tumor kinetics interfering with the activity of chemotherapy.
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PMID:Chemotherapy with cyclophosphamide, adriamycin, and 5-fluorouracil compared to chemotherapy plus hormonal therapy with tamoxifen in the treatment of advanced breast cancer: an interim analysis. 391 18

Combination chemotherapy using the water-soluble nitrosourea MCNU with various anti-cancer agents was studied using L1210 leukemia and P388 leukemia. In titration experiments MCNU showed remarkable antitumor effects at doses from 5 mg/kg to 80 mg/kg, producing numbers of 60-day survivors with L1210 leukemia. In L1210 leukemia, respective combinations of MCNU with the antimetabolites, MTX, 6-MP, 6-TG, MCNU, 5-FU and Cyclo-C showed enhanced antitumor effects. MCNU combined with each of ADR, MMC and CPM also showed marked anti-tumor effects with 60-day survivors. In P388 leukemia MCNU combined with each of ADR, MMC, VDS and CPM produced strong anti-tumor effects with numbers of 60-day survivors. In the results of these combinations, especially the combinations of MCNU + 5-FU in L1210 leukemia and MCNU + CPM in both L1210 and P388 leukemia, a significant increase in mean survival time was achieved. These combinations also produced many 60-day survivors which were considered to be due to the synergistic antitumor effects of the combined drugs.
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PMID:[Effects of combination chemotherapy of MCNU with various anti-cancer agents]. 391 6


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