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 effect of L-glutamine and L-asparagine depletion by Acinetobacter L-glutaminase-L-asparaginase on the toxicity and antitumor activity of L-(alphaS,5S)-alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid (NSC-163501) was tested in mice. The LD50 of six daily doses of NSC-163501 in BDF1 female mice decreased from 7.5 to 0.3 mg/kg/day by combination treatment with the enzyme. Enzyme therapy also decreased the dose of NSC-163501 needed for maximal prolongation of survival in these mice inoculated with L1210 leukemia. Nevertheless, the combination did not prolong survival in L1210-bearing mice beyond that of higher doses of NSC-163501 alone. In contrast, the combination of enzyme plus NSC-163501 inhibited the growth of established sc implanted Ehrlich ascites carcinoma in ICRf male mice much more than either agent alone. Treatment with Acinetobacter L-glutaminase-L-asparaginase decreased the L-asparagine and L-glutamine levels in acid extracts of the Ehrlich tumor. NSC-163501 did not affect the amide levels or alter the decrease produced by enzyme therapy.
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PMID:Enhanced effect of an L-glutamine antagonist, L-(alphaS,5S)-alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid, by Acinetobacter L-glutaminase-L-asparaginase. 46 50

L-Asparaginase sensitivity and asparagin-deficiency of 5 tumor cell populations, i.e. mouse lymphoma L-1210, LI0-1, LTL, Berkitt lymphoma and human ovary cancer, line CaOv were studied. Radiometric estimation of 3H-thimidine incorporation into the cells of DNA served a criterion of cytotoxicity. "Krasnitin" (FDR) was used as L-asparaginase. The cells of leukemia L-1210, lymphosarcoma LIO-1 and line CaOv were asparagine-independent and non-sensitive to L-asparaginase. The cells of mouse lympholeukemia LTL and the cultures of Berkitt human lymphoma proved to be asparagin-dependent and highly sensitive to L-asparaginase. In concentration of 50 IU/ml the drug inhibited incorporation of 3H-thimidine in the cells of LTL and Berkitt lymphoma by 97-98 and 75-80 per cent respectively. Inhibition of 3H-thimidine incorporation in the cells of LTL and Berkitt lymphoma was more pronounced after incubation with the drug for 8 and 24 hours respectively. Two out of the 5 tumor cell populations were chosen as a result of the study. One of these 2 populations, i.e. the cells of Berkitt lymphoma was asparagin-dependent and highly sensitive to L-asparaginase, the other, i.e. the cells of line CaOv was asparagin-independent and resistant to the specific antitumor effect of the enzyme. The use of a system of these two cell lines provided estimation of the ratio of the specific cytostatic (antitumor activity) and non-specific cytostatic properties in the preparations with L-asparaginase activity.
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PMID:[Cellular test system for studying the biological properties of preparations with L-asparaginase activity]. 59 48

We have reviewed the neurological complications not directly attributable to leukaemic infiltration in a group of 438 children with leukaemia or lymphoma. 61 children had one or more complications due chiefly to bleeding, infection, or drug toxicity. Early death from intracranial haemorrhage occurred in 1% of children with lymphoblastic leukaemia and 7% of children with myeloblastic leukaemia. Measles and chicken pox were the most serious infective complications; one child remains severely retarded after presumed measles encephalitis, one child with chicken pox died, and a second remains disabled. 2 additional cases of measles encephalitis and one of progressive multifocal leucoencephalopathy are described. Drugs which caused neurotoxicity included vincristine, cytosine arabinoside, L-asparaginase, and phenothiazines, but most problems were caused by methotrexate. Methotrexate toxicity was more prevalent and more serious in children who had had previous central nervous system leukaemia. We conclude that viral infections and methotrexate pose the greatest neurological hazards to children with leukaemia.
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PMID:Neurological complications of childhood leukaemia. 59 22

A glutaminase-asparaginase enzyme from Achromobacter sp has antitumour activity in vitro and in animals. Glutaminase was administered in doses of 3500-20 000 IU/m2 body surface area/day to six patients with acute lymphoblastic leukaemia (ALL) and three patients with acute myeloid leukaemia (AML). The enzyme had a blood half life of 80 minutes but depletion of blood glutamine persisted for 12 hours after single doses. Seven patients, including four (two with AML and two with ALL) resistant to asparaginase, received repeated doses of glutaminase. Antileukaemic effects were observed in all seven; one elderly patient developed metabolic acidosis. Study of this new antileukaemic agent in patients with acute leukaemia at an earlier stage of their disease is now justified.
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PMID:Bacterial glutaminase in treatment of acute leukaemia. 77 14

This paper is an extension of a previous report (Yaqub 1975). Our interest in L-asparaginase is increasing due to the recognition of the fact that it is a best tool against leukemia. In this paper we have tried to discuss (in view of research work, 1973-75) its basic characteristics and its practicability of successfully being used as an antitumour agent.
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PMID:L-asparaginase--antileukemia agent. 82 75

This paper is an extension of a previous report (Yaqub 1975). Our interest in L-asparaginase is increasing due to the recognition of the fact that it is a best tool against leukemia. In this paper we have tried to discuss (in view of research work, 1973-75) its basic characteristics and its practicability of successfully being used as an antitumour agent.
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PMID:L-asparaginase-antileukemia agent. 82 61

Twenty-one children with acute nonlymphoblastic leukemia (ANLL) were treated with a combination regimen consisting of arabinosyl cytosine (Ara-C), 6-thioguanine (TG), and Adriamycin, The incidence of complete remission was 74%. For consolidation, addition courses of Ara-C and TG were given, followed by L-asparaginase. The maintenance program was the same as that for the lymphoblastic type (L-2) including intrathecal methotrexate for prophylaxis of meningeal leukemia. Of the 16 who were evaluable for the duration of complete remission, six developed bone marrow relapse, one meningeal leukemia within 3-14 months after entering complete remission and one was lost to follow-up. Eight remain in complete remission for 9-72 months. In five of eight, chemotherapy has been terminated after 3 years, and all continue in remission for 11-32 months post-treatment. Although the results do not compare well to those of the lymphoblastic morphology, long-term disease-free survival can be achieved with multiple-drug intensive treatment in childhood ANLL.
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PMID:Treatment of acute nonlymphoblastic leukemia in children with a multiple-drug protocol. 90 61

The authors analysed 58 consecutive cases of acute leukaemia treated during 3.5 years. The material included 35 patients with myeloblastic leukaemia, 2 with pyomyelocytic leukaemia, 3 with monocytic leukaemia, 2 with erythroleukaemia, 7 with lymphoblastic leukaemia, and 8 with myeloblastic exacerbations of chronic myelocytic leukaemia. Most patients were treated by the VAMP schedule, in some cases L asparaginase, in other rubidomycin and cytosine arabinoside were used for obtaining remissions. Fourteen patients died within 14 days after admission to hospital. In 15 cases partial remissions, rather short-lasting, were achieved. In 4 cases the remissions were complete and in 3 of them the survival exceeds now 3 years. All patients in whom long-lasting remissions were obtained belonged to the youngest age group and 3 had lymphoblastic leukaemia. The authors suggest the need of rapid institution of treatment and systematic continuation.
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PMID:[Results of treatment of acute luekemia in adults according to our records]. 105 3

77 unselected adult patients with acute myeloblastic leukaemia (AML), including practically all AML patients from an area with 1.9 million inhabitants, were randomized for either (1) 5 days pretreatment with 1-asparaginase and prednisolone followed by a combination of rubidomycin and cytosine arabinoside (ARAP), or (2) treatment with a combination of rubidomycin, cytosine arabinoside and prednisolone without 1-asparaginase pretreatment (RAP). Complete remission was induced with ARAP in 12 patients (31%) and with RAP in 13 patients (34%). Thus pretreatment with 1-asparaginase did not improve the therapeutic response. The overall remission frequency was significantly higher below the age of 60; 50% compared to 13% above this age. Side-effects such as liver dysfunction, nausea and vomiting were more common in patients pretreated with 1-asparaginase. Sterilization of the gut did not improve the remission frequency with either regime.
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PMID:L-asparaginase and prednisolone pretreatment followed by rubidomycin and cytosine arabinoside for induction of remission in adult patients with acute myeloblastic leukaemia. 105 27

A remission-induction regimen for childhood leukemia using cyclophosphamide, asparaginase, vincristine, and prednisone (CAVP) was compared to standard vincristine-prednisone (VP) induction. The more intensive regimen was associated with a lower complete remission rate (81% vs 93%) and a higher early death rate from infection (15% vs 5%) for acute lymphocytic leukemia. In contrast, complete remission was achieved in 58% of children with acute nonlymphocytic leukemia treated with CAVP compared to 18% for VP. Early death rates were similar (27% vs 25%). These observations corroborate previous studies in childhood nonlymphocytic leukemia showing activity for asparaginase. Preliminary analysis of remission duration and survival for responders shows no advantage for those who survived the more intensive induction.
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PMID:Cyclophosphamide-asparaginase- vincristine-prednisone induction therapy in childhood acute lymphocytic and nonlymphocytic leukemia. 106 49


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