Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.1.1 (asparaginase)
 2,695 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thirty-four children with acute lymphoblastic leukaemia (ALL) in relapse or resistant to initial induction received combination chemotherapy with prednisolone, vincristine, l-asparaginase, and daunorubicin. L-asparaginase was given subcutaneously on alternate days for four weeks and was well tolerated. A complete remission was achieved in 96% of children in relapse and in five out of six children resistant to induction. Remission was achieved without hospitalisation in over 60% of patients. The median duration of subsequent remission was only 13 weeks, but six out of eight children receiving a second course of the drug combination achieved a further remission. We conclude that prolonged l-asparaginase therapy in combination with an anthracycline might well be used in initial or consolidation therapy for childhood ALL.
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PMID:Combination chemotherapy for bone marrow relapse in childhood lymphoblastic leukaemia (ALL). 28 4

In 49 children with acute lymphoblastic leukemia serial EEGs were performed during the course of treatment. Therapy in the first four weeks consisted of: Prednisone, vincristine, daunorubicine and L-asparaginase. In the second month 6-mercaptopurine, cytosin-arabinoside, cyclophosphamide, methotrexate-i. th. and cranial irradiation were administered. Maintenance-therapy consisted of 6-mercaptopurine, cyclophosphamide and methotrexate i.v. Before treatment only 24% of patients showed normal EEG-findings, whereas 57% presented sly induced by leukemic infiltrations and partly due to the impaired clinical state. At the end of the first phase of therapy, the combined toxicity of vincristine and L-asparaginase led to the finding of 23% severely and 37% moderately slowed EEGs. Slightly disturbed EEGs were found in 29% and normal ones in 11% of children. Regression occurred duirng the phase of CNS-prophylaxis. At its end 37% of recordings were normal and 57% slightly abnormal. After maintenance-therapy of 1/2 to 1 year duration, there were 65% normal findings. Moderate and severe disorders were no longer demonstrated. Paroxysmal activity developed twice, each during the first phase of therapy and accompnaying convulsions. In both cases we saw slowing of background-activity and signs of increased excitability still months after. In one of these patients, the probable cause was a vincristin-encephalopathy, the cause of the second case remained unknown. EEGs of two furtehr patients with rubella-encephalitis and subarachnoideal hemorrhage exhibited severe unspecific changes.
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PMID:EEG-changes during intensified induction-therapy of acute lymphoblastic leukemia. 29 91

Serum complement studies were carried out in five children with acute lymphocytic leukemia. During therapy with L-asparaginase, prednisone and vincristine, hypocomplementemia developed in all patients, and disappeared within 2 weeks after the discontinuation of L-asparaginase. Complement breakdown products were not present in plasma. The changes of serum complement levels paralleled those of plasma fibrinogen. These findings suggest that the hypocomplementemia observed in these patients may be related to impaired protein synthesis induced by L-asparaginase.
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PMID:L-asparaginase-induced hypocomplementemia in acute lymphocytic leukemia (ALL) of childhood. 29 75

A study was done to evaluate intramuscular versus intravenous administration of L-asparaginase in childhood leukemia. The results of this study demonstrate that the intramuscular method of administering L-asparaginase is as effective, but less toxic, than the intravenous method for children with advanced leukemia. The utilization of L-asparaginase in the initial induction of children with lymphoblastic and undifferentiated leukemia should be investigated. Its addition to the standard inducing agents may increase the percentage and ease of remission without significantly increasing toxicity.
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PMID:Evaluation of intramuscular versus intravenous administration of L-asparaginase in childhood leukemia. 29 76

An 18-year-old primagravida received combination chemotherapy with vincristine, prednisone, L-asparaginase, cyclophosphamide, daunomycin, 6-mercaptopurine and central nervous system (CNS) prophylaxis with intrathecal methotrexate and whole-brain irradiation for acute lymphoblastic leukemia (ALL) beginning in the 12th week of pregnancy. Therapy resulted in sustained complete remission of the leukemia and delivery of a normally developed female infant whose immediate neonatal course was complicated by transient severe bone marrow hypoplasia. Our experience confirms the reports of others that intensive chemotherapy can be administered in the last two trimesters of pregnancy without serious teratogenic complications. However, we conclude that such therapy may cause significant myelosuppression in the newborn.
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PMID:Acute leukemia in pregnancy: transient neonatal myelosuppression after combination chemotherapy in the mother. 29 85

The effect of L-asparaginase (L-asp) therapy on circulating antithrombin-III (AT-III) was monitored in three patients with acute lymphoblastic leukemia. Serial determination for AT-III by both a functional assay and an immunologic assay demonstrated a rapid decrease in serum AT-III levels, followed by a protracted recovery beyond the period of L-asp exposure. One of the three patients developed a reversible venous thrombosis of the arm. The mechanism of the L-asparaginase effect may be related to peripheral degradation of AT-III or to inhibition of production.
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PMID:L-asparaginase effect on antithrombin-III levels. 29 86

The characterization of two human T-lymphocyte lines revealed that they required exogenous L-asparagine for cell growth, whereas all four B-cell lines studied were L-asparagine independent. T-cells were 800-2,000 times more sensitive to Escherichia coli L-asparaginase than were B-cells. The cytotoxic effects of a high concentration of L-asparaginase on B-cells were not related to the hydrolysis of L-asparagine but were due to heat-labile and heat-resistant substances in the enzyme. The findings were consistent with reports that L-asparaginase is effective in suppressing cellular immunity and inducing remission in patients with acute lymphocytic leukemia, mainly a non-B-cell disease. Thus these cell lines provide in vitro models for the study of a nutritional approach to chemotherapy or immunotherapy.
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PMID:L-asparagine requirements of human T-lymphocytes and B-lymphocytes in culture. 30 63

Ten patients with late-stage acute lymphocytic leukemia were treated with L-asparaginase and cytosine arabinoside. Complete remission was achieved in 8 patients including 5 of 5 patients with T-cell leukemia. Major toxicity included anaphylactic reactions in 3 of the 10 patients.
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PMID:Use of L-asparaginase and cytosine arabinoside for refractory acute lymphocytic leukemia with particular reference to T-cell leukemia. 31 13

The sensitivity of the neoplastic cell to amino acid deprivation shows considerable variation. The responsiveness of human leukemic cell cultures to L-asparaginase indicates that those of T cell origin are much more sensitive to the action of this L-asparagine-depleting enzyme than those of B cell origin. A cautionary note is raised concerning amino acid analogs. Minor changes such as substituting selenium for sulfur to make seleno-L-methionine rather than L-methionine may lead to considerable differences in their respective metabolic polls in vivo. A systemic survey of amino acid requirements of human neoplasms is desirable before designing new analogs.
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PMID:Lessons from the study of induced alterations in amino acids in patients with cancer. 31 38

The antitumour activity of the preparations of L-asparaginase from E. coli and Erw. carotovora with respect to lymphadenosis L-5178 and Yorker's carcinosarcoma (ascitic cariants) has been established. No difference in antitumour efficacy of the preparation of L-asparaginase obtained from E. coli and Erw. carotovora was noted.
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PMID:[Results of an experimental study of the antitumor activity of 1-asparaginase from E. coli and Erw. carotovora]. 32 Sep 35


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