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

Short courses of cytosine arabinoside (Ara-C), cyclophosphamide, and L-asparaginase were given to seven children with newly diagnosed acute lymphocytic leukemia, who had failed to remit on standard remission induction therapy. These 4-day courses of Ara-C and cyclophophamide followed by 4 days of L-asparaginase were repeated at 3- to 4-week intervals for two or four courses. Complete remission occurred in six patients. The median duration of remission was 94+ days, on various maintenance regimens. The most serious side effect was neutropenia. This combination of these three drugs appears to be effective remission-induction therapy for children with ALL with unfavorable prognostic features.
Cancer 1975 Oct
PMID:Combination chemotherapy for children with acute lymphocytic leukemia who fail to respond to standard remission-induction therapy. 105 44

One hundred and fourteen patients with acute leukemia, 57 children (10 AML and 47 ALL) and 57 adults (37 AML and 20 ALL) were treated with L-asparaginase (Asnase) 200 or 1000 IU/kg daily for 30 days unless withdrawn on account of side effects. Combinations with other cytotoxic drugs were used in all but eight patients. Hypersensitive reactions, decrease in Asnase activity in plasma, and bivalent antibodies to Asnase appeared more frequently in adults (28%, 46%, and 79%, respectively) than in children (16%, 17%, and 25% respectively). There was a clear association between these three parameters. Thus hypersensitive reactions generally developed at the time of or after the decrease in plasma Asnase activity. Antibodies were detected only where Asnase activity had disappeared from the plasma. This time sequence, and in vitro experiments, suggest the formation of antigen-antibody complexes which might be responsible for inactivation of Asnase and for the development of hypersensitive reactions. However in many cases antibodies were found without concomitant enzyme inactivation or hypersensitive reactions. Antibodies to Asnase of IgE type (reagins) were found in only 10 children and 6 adults. There was no correlation between hypersensitive reactions, decrease in Asnase activity, and IgE antibodies. The frequency of remission among patients developing bivalent antibodies to Asnase was 68% (13/19) in contrast to 27% (3/11) among patients whose sera contained no detectable antibodies to Asnase, but the difference was not statistically significant.
Cancer 1976 Jan
PMID:Hypersensitive reactions and antibody formation during L-asparaginase treatment of children and adults with acute leukemia. 106 36

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.
Cancer 1976 Mar
PMID:Cyclophosphamide-asparaginase- vincristine-prednisone induction therapy in childhood acute lymphocytic and nonlymphocytic leukemia. 106 49

Acinetobacter glutaminase-asparaginase (AGA) and Escherichia coli asparaginase were compared for their effects on plasma and tissue levels of amino acids, ammonia, and glutamyl transferase activity in the mouse. Free asparagine was depleted similarly in plasma and tissues by both enzymes. AGA treatment produced partial depletion of glutamine concentrations in muscle, spleen, small intestine, and liver. Brain and kidney glutamine concentrations actually rose with treatment. Despite over 100-fold increase in plasma glutamate, only the kidney showed a substantial increase in free glutamate levels during AGA treatment. Glutamine biosynthesis measured by glutamyl transferase activity showed an appreciable increase only in the kidney. Ammonia levels in tissues and plasma rose 1.3- to 4.3-fold. In general, E. coli asparaginase treatment had much less effect on these measurements than did AGA. The changes in these levels are discussed in relation to sites of possible toxicity and antitumor effects.
Cancer Res 1975 May
PMID:Effect of Acinetobacter glutaminase-asparaginase treatment on free amino acids in mouse tissues. 109 50

This study presents results of single-drug and combination chemotherapy of the transplantable acute leukemia L5222 in BD IX rats. In leukemia L5222 there is a direct relationship between the number of transplanted cells and mean life expectancy. After single-drug therapy with L-asparaginase, 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), cyclophosphamide, cytosine arabinoside, daunomycin, 6-mercaptopurine, methylglyoxal bis(guanylhydrazone) dihydrochloride, prednisolone, or vincristine, the best therapeutic effect was observed with BCNU and cyclophosphamide. A massive-dose therapy with BCNU repeated twice or a conbination of vincristine with cyclophosphamide or BCNU with cyclophosphamide yielded a high percentage of cures. Morever, leukemia L5222 seems to be suitable for studying the influence of drugs on the proliferation kinetics of leukemia cells.
Cancer Res 1975 May
PMID:Chemotherapy of the transplantable acute leukemia L5222 in rats. 112 Mar 7

Tyrosine phenol-lyase from Erwinia herbicola was purified with the goal of assessing its effect on growth of malignant melanoma. Ammonium sulfate-sodium citrate fractionation and diethylaminoethyl cellulose-hydroxylapatite chromatography were used. The purified enzyme was shown to reduce plasma tyrosine levels when administered to normal C57BL x DBA/2 F1 mice. The plasma half-life value of the enzyme was found to be 6 to 7 hr. Unlike results reported with glutaminase and asparaginase preparations, the lactate dehydrogenase-elevating virus had no significant influence on plasma clearance of tyrosine phenol-lyase. The enzyme significantly inhibited growth of established B-16 melanoma tumors.
Cancer Res 1976 Jan
PMID:Some biological properties and an in vivo evaluation of tyrosine phenol-lyase on growth of B-16 melanoma. 124 96

Of 55 males, currently above 18 years of age, diagnosed with and treated for different malignancies in childhood between 1960 and 1985 at a single institution, 28 (51%) were azoospermic. The age of the patient, testicular irradiation, four different therapeutic agents (L-asparaginase, cyclophosphamide, doxorubicin, vincristine) and one combination (MOPP, nitrogen mustard, vincristine, procarbazine, prednisone) were each associated with the risk of azoospermia. However, in multivariate analysis vincristine had the statistically most significant independent effect on the risk of azoospermia, the risk being 5-fold (95% confidence limits 1.3-18.8, P = 0.02) that in patients who had not received vincristine. The risk of azoospermia in patients who had received cyclophosphamide was 3.4-fold (0.95-12.3, P = 0.06) and in those who had received testicular irradiation it was 8.2-fold (0.75-90.9, P = 0.09) that of others. Normospermia (22% of patients) was not incompatible with any of the more commonly used modes of therapy. We conclude that vincristine may have a previously unrecognised important role in causing azoospermia, possibly irreversible, when administered in childhood or adolescence.
Eur J Cancer 1992
PMID:Vincristine is associated with the risk of azoospermia in adult male survivors of childhood malignancies. 132 21

Although cellular drug resistance is considered to be an important cause of the poor prognosis of children with relapsed acute lymphoblastic leukaemia (ALL), the knowledge of drug resistance in these patients is very limited. Different aspects of drug resistance were studied in 17 children with relapsed ALL. The in vitro sensitivity profile was determined using the MTT assay. Cells from relapsed children were significantly more resistant to 6-thioguanine, prednisolone, cytosine arabinoside, daunorubicin (DNR), mustine-HCl and mafosfamide but not to L-asparaginase and vincristine (VCR) than cells from 41 children with ALL at initial diagnosis. Some relapsed patients showed a general drug resistance while others were resistant to only 1-3 drugs. The relevance of the multidrug resistance (MDR) model was analysed: In all DNR- and VCR resistant cases a co-resistance to drugs not involved in the MDR model was found. P-glycoprotein was not detected in any of 28 untreated and 14 relapsed samples tested. VCR- and DNR accumulation in the most resistant cells were not lower than in sensitive cells. Resistance modifiers did not potentiate the cytotoxicity of VCR and DNR. We conclude that resistance to anthracyclines and vinca alkaloids in childhood relapsed ALL is not due to P-glycoprotein mediated MDR. Different types of drug resistance varying from a resistance to only one drug to a general chemoresistance, can be detected in children with relapsed ALL. VCR and L-asparaginase seemed to be only infrequently involved in drug resistance. Knowledge of drug resistance might lead to more effective and less toxic therapies for children with relapsed ALL.
Br J Cancer 1992 May
PMID:Different types of non-P-glycoprotein mediated multiple drug resistance in children with relapsed acute lymphoblastic leukaemia. 135 Feb 7

We studied the histamine-releasing activity of several antineoplastic drugs on rat pleural and peritoneal mast cells. The drugs tested included the nitrogen mustards cyclophosphamide and ifosfamide, the nitrosourea carmustine, the triazene dacarbazine, the folic acid analogue methotrexate, the pyrimidine analogue cytarabine and fluorouracil, the vinca alkaloids vinblastine, vincristine and Vinorelbine, the epipodophyllotoxins etoposide and teniposide, and the enzyme L-asparaginase. Methotrexate, carmustine, fluorouracil, vinblastine and vincristine failed to elicit histamine release on rat mast cells. All of the other drugs evoked histamine release in both the presence and the absence of extracellular calcium, but ifosfamide, cytarabine and asparaginase induced a much lower release in the absence of this cation. The response elicited by cytarabine and etoposide was much higher in pleural than in peritoneal mast cells. These results indicate that some antineoplastic drugs may directly activate the release of histamine, which could contribute to some of their secondary effects.
Cancer Chemother Pharmacol 1992
PMID:Non-immunological release of histamine from rat mast cells elicited by antineoplastic agents. 137 74

All cancer chemotherapeutic agents, except altretamine, the nitrosoureas, and dactinomycin, have produced at least an isolated instance of a HSR. Certain drugs, such as L-asparaginase and mitomycin (administered intravesically), cause HSRs of significant degree in approximately 10% of patients. All four types of HSRs are represented in the reactions produced by antitumor drugs, although Type I is the most common. Some of the Type I reactions are IgE-mediated, and others are probably mediated by nonspecific release of vasoactive substances from targets such as mast cells. It is possible to continue therapy with some drugs, despite a prior HSR, if the prophylactic measures outlined in Table 2 are taken. An example of this is provided by taxol in which the lengthening of the infusion time and the administration of preventive medication allowed some patients to continue taxol therapy. The mechanisms of the HSRs have been carefully assessed in only a minority of patients who sustained such toxicity. Such evaluation would increase our understanding of this form of drug toxicity and perhaps lead to means of effectively reducing the risk and severity.
 ...
PMID:Hypersensitivity reactions. 138 49


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