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 therapeutic activity of the narcissus residual alkaloid A-2 against Rauscher leukemia has been compared with 10 standard anticancer drugs, and synergistic or additive combination pairs have been selected using a viral leukemia and two transplantable tumor systems. An increased beneficial effect has been demonstrated by a combination of the alkylating and DNA-binding agents and the alkaloid against the three malignant tumors, while a beneficial effect by combining the alkaloid and the antimetabolites (either 6-MP or 5-azacytidine) was seen only against the viral leukemia. The alkaloid has no suppressive activity against cellular immunity as tested by PHA reactivity and allogeneic tumor rejection systems.
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PMID:Combination chemotherapy of Rauscher leukemia and ascites tumors by narcissus alkaloid with standard drugs and effect on cellular immunity. 4 97

The Sendai virus-induced interferon (IF) production by partially purified human leucocyte suspensions of normal donors and of leukaemic patients have been investigated in vitro. (i) An increased production was observed with leucocytes taken from patients suffering from chronic myelogenous leukaemia (CML) during exacerbation, but the production was approximately normal with cells taken during remission. (ii) IF production was not influenced by large doses of cytostatics (DBM, 5-FU, FUDR, 5-HU, 6-MP, cyclophosphamide) irrespective of whether normal or CML leucocytes were used. (iii) In contrast, production was inhibited in both systems by inhibitors of RNA or protein synthesis (actinomycin D, puromycin, cycloheximide). (iv) CML leucocytes produced IF for a prolonged period of time as compared to normal leucocytes. (v) Leucocytes from children with acute blastic leukaemia and those from adults with chronic lymphoid or acute paramyeloblastic leukaemia produce, in contrast to normal leukocytes, approximately as much IF in the absence as in the presence of serum. It is concluded that the Sendai virus-induced IF synthesis in CML leucocytes requires de novo protein synthesis.
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PMID:Interferon production by human leukaemic leucocytes. 18 Jul 56

L-Asparaginase, in the dose of greater than or equal to 6000 IU/sq m three times weekly, was demonstrated to be an effective agent in reinduction of remissions in childhood leukemia. Four hundred thirteen children with acute lymphocytic leukemia were treated with L-asparaginase. Doses i.m. ranged from 300 to 12,000 IU/sq m. None of the patients had received prior asparaginase therapy. 6-Mercaptopurine was given p.o. concurrently. All of the patients had experienced several previous relapses, and their disease was not responsive to 6-mercaptopurine. L-Asparaginase was found to be effective in reinducing remissions at the following rates: 9.5% for 300 IU/sq m; 35.1% for 3,000 IU/sq m; 53.5% for 6,000 IU/sq m; and 62.5% for 12,000 IU/sq m. The drug was given three times weekly for four weeks. Hypersensitivity reactions occurred in 6.5% of patients.
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PMID:Effective dose of L-asparaginase for induction of remission in previously treated children with acute lymphocytic leukemia: a report from Childrens Cancer Study Group. 38 78

Deoxyribonucleic acid synthesis requires adequate cellular concentrations of the four deoxyribonucleoside triphosphates. Using a sensitive enzymic assay, we have measured the concentrations (pools) of these compounds in human bone marrow cells and in lymphocytes. The mean concentrations (pmol/10(6) cells) in normal human bone marrow cells were: deoxyadenosine triphosphate (dATP) 1.5; deoxyguanosine triphosphate (dGTP) 0.4; thymidine triphosphate (dTTP) 1.4 and deoxycytidine triphosphate (dCTP) 0.6; and in normal phytohaemagglutinin (PHA)-stimulated lymphocytes (72 h cultures); dATP 3.7; dGTP 1.9; dTTP 9.4 and dCTP 2.9. The deoxyribonucleoside triphosphate concentrations were increased approximately threefold in the nucleated marrow cells from patients with leukaemia and myeloproliferative diseases. PHA-stimulation of lymphocytes caused a marked increase of the deoxyribonucleoside triphosphate concentrations, particularly of dTTP, between 24 and 48 h of culture. In PHA-stimulated lymphocytes, the antifolate drugs methotrexate, pyrimethamine and trimethoprim, all produced a fall in dTTP and a rise in dATP concentrations within 1 h. These effects could be reversed by folinic acid. 5-Fluorouracil caused a fall in dTTP and in dCTP but no consistent changes in dATP; hydroxyurea caused a fall in dATP with a rise in dTTP. BCNU caused a significant fall in dATP and dCTP. Dibutyryl cyclic 3', 5' adenosine monophosphate and theophylline had no consistent effect on the deoxyribonucleoside triphosphate concentrations. 6-Mercaptopurine caused a fall in dATP and dGTP, the fall in dATP being marked after 4 h incubation. It is concluded that measurement of the deoxyribonucleoside triphosphates in human cells provides a new method of studying DNA synthesis in human disease states and of analysing the action of antimetabolite drugs on normal and diseased cells.
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PMID:Deoxyribonucleoside triphosphates in human cells: changes in disease and following exposure to drugs. 114 80

Of 4 lines of myelogenous rat leukemias induced by N-nitrosobutylurea (NBU), DBLA-6 was selected as a screening model for antileukemic agents because of the following characteristics: a) High transplantability either by intravenous (i.v.) or intraperitoneal (i.p.) inoculation; b) linear relationship between inoculum size and survival time; c) marked increase of leucocyte counts in the peripheral blood as the tumor progresses after intravenous inoculation. To investigate reliability in its predicting clinical efficacy, its sensitivity to known antileukemics was studied. To determine the effects, a change of leucocyte counts in the peripheral blood together with the prolongation of life span was checked in the following systems; i.v.-i.v. (i.v.-inoculation, i.v.-injection), i.v.-i.p., i.p.-i.p., i.p.-i.v. Fifty percent cure was obtained with Vincristine, Vinblastine, Daunorubicin, 6-Mercaptopurine, and alkylating agent 838D or 864T. The success of treatment was measured by decrease of leucocytes. Methotrexate, cytosine arabinoside (Ara-C), and cyclophosphamide showed only poor effects, and Mitomycin C, L-asparaginase, and Bleomycin were ineffective. In addition, the chemotherapeutic effects of Vincristine and 864 on this leukemia were quite dependend both on the route of drug injection and on the site of tumor inoculation. Subsequently, our studies are being extended to cover the correlation between drug distribution and tumor localization or dissemination.
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PMID:Sensitivity of DBLA-6 leukemia of rats to known antitumor agents in relation to their clinical effects. 116 99

Inversion of chromosome 16 was found in a 73-year-old female with acute myeloblastic leukemia (FAB:M2). Complete remission was achieved by combined chemotherapy (DNR, Ara-C, 6-MP, Prednisolone), but she relapsed 6 months later without CNS involvement and died of respiratory failure presumably due to cerebrovascular accident during remission reinduction chemotherapy. Biphenotypic surface markers (CD2+ and CD13+) were observed on relapse. Eosinophilia was not observed throughout. Our patient and the other reported case suggest that biphenotypism and the lack of eosinophilia and monocytosis in inv (16) leukemia may be correlated with a poor prognosis.
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PMID:[Inversion of chromosome 16 observed in acute myeloblastic leukemia (M2) with biphenotypic surface markers lacking monocytosis and eosinophilia]. 135 70

The distribution of T-lymphocyte subsets of 18 patients with lymphocytic leukaemia tested with monoclonal antibodies as well as E-rosettes formations and EAC-rosettes formations were studied. The patients classified according to RAI (stages 0-II. and III-IV.) a proportional decrease of T-lymphocytes was observed only, whereas their absolute number increased. T-lymphocyte subsets also changed: the ratio of CD4 positive lymphocytes reduce, while the proportion of CD-8 positive lymphocytes increased. The ratio of the two cell groups was below the normal value (1.8 and 1.0, respectively). This value is lower in stages III-IV., and refers to a serious immune imbalance, the latter being responsible for acute infections. The four weeks medication with Leukeran and COP resulted in unchanged rates of pathological cells with a decrease in the number of lymphocytes. These phenomena primarily refer to clonal damage of the cell line, resulting in pathological T-helper and T-suppressor functions. Owing to the relatively long lifespan of the lymphocytes, only a prolonged cytostatic treatment can yield favorable results in therapy.
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PMID:Changes of T-lymphocyte-subsets and their consequences in B-CLL. 169 65

Cytidine 5'-monophosphate and 5'-ara-CMP conjugates of 2,7-diaminomitosene, with the phosphate groups linked to C-1, were prepared by treating mitomycin C with the appropriate nucleotides. 5'-UMP conjugates were prepared from mitomycin A, 7 (M-83), and 8 (BMY-25282) by similar procedures. A conjugate could not be prepared from mitomycin C and 6-MPRP, but a sulfur-linked derivative was made with 6-MP ribonucleoside. The corresponding 1-hydroxy-2-aminomitosenes were prepared from the parent mitomycin analogues for structure-activity comparisons. All compounds were tested against L1210 murine leukemia in the MTT tetrazolium dye assay. In general, the conjugates were less potent than the parent mitomycins; however 5'-ara-CMP conjugate 14 derived from mitomycin C was more potent than the parent compound or any mitomycin tested except mitomycin A. It also was more potent than ara-C. This result establishes the value of this approach to prodrugs, at least in cell culture. Against a multi-drug-resistant L1210 cell line, all of the conjugates derived from mitomycin C were more potent than the parent compound. 6-Mercaptopurine ribonucleoside conjugate 15 was more active against the resistant cells than it was against the parental cell line.
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PMID:Additional nucleotide derivatives of mitosenes. Synthesis and activity against parental and multidrug resistant L1210 leukemia. 190 7

Cancer and Leukemia Group B undertook a randomized trial of intensification treatment in adults aged 15 to 79 years with acute lymphocytic leukemia (ALL) in complete remission (CR). Daunorubicin (DNR), prednisone, vincristine (VCR), intrathecal (IT) methotrexate (MTX), and asparaginase produced 177 CRs in 277 patients. One hundred fifty-one patients were randomly assigned to receive treatment as follows: 74 received intensive cytarabine and DNR, and 77 received cycles of mercaptopurine (6-MP) and MTX, followed by 6MP, MTX, VCR, and prednisone for 3 years in all. One hundred twelve patients received CNS prophylaxis. Intensification produced major myelosuppression but did not improve remission duration (median, 21 months). Of the 151 patients with CRs who entered the intensification phase, 29% remain in continuous CR (43 to 117 months); in 19 patients, CRs have lasted for longer than 7 years. No relapses occurred after 60 months. Median survival from the time of randomization was 30 months. Those under 30 years of age responded more frequently, with longer CR and survival. While 53% of those aged 15 to 19 years remain in continuous CR, 92% of patients over 59 years have relapsed. The presence of a myeloid antigen on the leukemic cells was adversely prognostic for CR achievement and for survival. Pretreatment WBC and platelet levels independently affected CR duration and survival. Early M1 marrow development presaged longer remissions. CNS relapse occurred in 47 of 256 patients with normal CSF before treatment, in 29 before CNS prophylaxis. CNS disease occurred after CNS prophylaxis in 18 patients: 13 of 61 who had received standard premaintenance and five of 51 who received intensification. No advantage in CR duration or survival resulted from intensive treatment with DNR and cytarabine following induction of CR.
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PMID:The effects of postinduction intensification treatment with cytarabine and daunorubicin in adult acute lymphocytic leukemia: a prospective randomized clinical trial by Cancer and Leukemia Group B. 194 Oct 59

Effects of amsacrine in combination with other anticancer agents at ID80 were evaluated by cell growth assay using a human T-cell leukemia cell line (MOLT-3). The data were analyzed with the aid of an improved isobologram, using the concept of an envelope of additivity. A supra-additive effect was observed for amsacrine in combination with cytosine arabinoside and mitoxantrone. An additive effect was observed in its combinations with bleomycin, CPT-11, cisplatin, daunorubicin, doxorubicin, etoposide, 5-fluorouracil, homoharringtonine, mitomycin C, or vincristine. 6-Mercaptopurine had an additive effect with amsacrine at ID80 but a sub-additive to protective effect at ID90. A sub-additive to protective effect was shown for amsacrine in combination with methotrexate. These data suggest that cytosine arabinoside and mitoxantrone are the best of the anticancer agents we studied for use in combination with amsacrine. Bleomycin, cisplatin, CPT-11, doxorubicin, cytosine arabinoside, homoharringtonine, mitomycin C, and vincristine also yielded favorable results when administrated simultaneously with amsacrine. Simultaneous administration of amsacrine with 6-mercaptopurine and methotrexate is not appropriate. If amsacrine is combined with 6-mercaptopurine and methotrexate, other suitable schedules should be explored. These results may provide a rationale for the design of clinical protocols combining amsacrine with other anticancer agents.
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PMID:Effects of amsacrine in combination with other anticancer agents in human acute lymphoblastic leukemia cells in culture. 196 Oct 9


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