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)

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

An L-glutaminase-L-asparaginase from Achromobacter has been rendered nonimmunogenic by the covalent attachment of polyethylene glycol (PEG) to nonessential amine groups of the enzyme. PEG-L-glutaminase-L-asparaginase exhibits a greatly enhanced half-life in the bloodstream compared to the unmodified enzyme in normal mice, and is effective in prolonging the survival of BDF1 mice inoculated ip with L5178Y cells. PEG-L-glutaminase-L-asparaginase appears rapidly in the blood following ip injection.
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PMID:Treatment of L5178Y tumor-bearing BDF1 mice with a nonimmunogenic L-glutaminase-L-asparaginase. 46 51

A simple procedure has been developed for the purification of L-asparaginase from Vibrio succinogenes. Only two steps of ion-exchange chromatography are required. A higher yield and higher specific activity are obtained than previously reported.
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PMID:A rapid purification procedure for L-asparaginase from Vibrio succinogenes. 47 39

L-Asparaginase was immobilized in spherical microparticles of polyacrylamide. Particles of three different sizes, mean diameter 0.34, 18 and 36 micron, respectively, were used. The Michaelis constant Km, for L-asparaginase, immobilized in small particles (0.34 micron), is virtually the same as in solution. L-Asparaginase in microparticles was also more stable than free enzyme after storage for 140 days at +4 and +37 degrees C. After an i.v. injection of 200 I.U./kg into rat, the plasma L-asparagine fell to very low values (less than 10 nmol/ml), but was normalized again after 4 to 5 days with both the native and immobilized enzymes. After an i.p. injection of 1000 I.U./kg into rats, the microparticles containing L-asparaginase lowered the plasma L-asparagine level for a substantially longer period of time than L-asparaginase in free solution. Normal L-asparagine level was thus reached on day 14 after the injection with immobilized enzyme. However, L-asparaginase activity was still present in the abdominal lymph nodes after this period of time.
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PMID:Acrylic microspheres in vivo. II. The effect in rat of L-asparaginase given in microparticles of polyacrylamide. 51 28

Morphine and aspartic acid were administered separately and in combination to 80 rats divided into 8 groups. Ten and 20 min following the injections, brain, liver and kidney L-asparaginase activity was determined. Morphine decreased brain and liver L-asparaginase activity and increased that of kidney. Aspartic acid completely antagonized the effect of morphine. Additionally 500 IU/kg L-asparaginase and 5 or 10 mg/kg morphine were i.v. injected into 56 rats divided into 5 groups. L-Asparaginase, which, in turn, increased motor activity, antagonized the morphine-induced hypoactivity and analgesia. These results support our previous findings.
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PMID:The relationship between morphine, aspartic acid and L-asparaginase in rats. 52 70

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

Combination effect of antitumor agents, including doxorubicin and daunorubicin, was evaluated on the concept of pharmacological synergism in ascites sarcoma-180 system. In alternate adminsitration, combinations of doxorubicin plus cyclophosphamide, thio-TEPA, carboquone, actinomycin-D, vinblastine, vincristine, methotrexate, cytarabine, 6-mercaptopurine, or L-asparaginase showed synergism, but in simultaneous one, only three agents, cyclophosphamide, carboquone, and cytarabine, were synergistic. On the other hand, combination of daunorubicin plus one of 8 agents (thio-TEPA, mitomycin-C, bleomycin, actinomycin-D, vinblastine, ancytabine, 6-mercaptopurine, and L-asparaginase) and 6 agents (cyclophosphamide, thio-TEPA, mitomycin-C, bleomycin, actinomycin-D, and vinblastine) provided synergism in alternate and simultaneous administration. Combination effect of agents was affected by the schedule of drug administration for doxorubicin, but weak for daunorubicin. Toxicity of doxorubicin or daunorubicin in combination with other drugs was also affected by the schedule of administration. Combination of a larger number of agents in simultaneous administration provided antagonism compared with an alternate administration.
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PMID:Interaction of antitumor agents including doxorubicin or daunorubicin in sarcoma-180 system. 61 16

A study of four children, two with acute lymphocytic leukemia and two with non-Hodgkin lymphoma, treated for three days with L-asparaginase, suggests that insulin receptors may be involved in the hyperglycemia associated with the use of L-asparaginase. Comparison of insulin receptors of circulating monocytes revealed a marked decrease in their number after treatment. This might also explain the lack of response to insulin treatment in one of the patients with symptomatic hyperglycemia.
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PMID:Hyperglycemia associated with the therapeutic use of L-asparaginase: possible role of insulin receptors. 71 79

Effect of urea on the activity of serum L-asparaginase in outbred guinea pigs (Hartley) was examined for comparison between heat-resistant and heat-sensitive types. The heat-resistant serum L-asparaginase was much more stable to urea-treatment than the heat-sensitive serum enzyme, and the urea-inactivation of the serum enzyme was protected by Na+ or K+. Liver L-asparaginase of the guinea pig, in which the serum enzyme was resistant to heat, was also resistant to heat, and vice versa, although liver enzyme was much more sensitive to heat than serum enzyme. The heat inactivation of liver enzyme was also protected by Na+. Similar results were also demonstrated on purified serum L-asparaginase, although the amino acid compositions between the two purified enzyme preparations were slightly different. When the animal having heat-resistant serum L-asparaginase were crossed with each other, serum enzyme of the resultant progenies was also resistant to heat, and vice versa. The serum enzyme of two inbred strains (JY-1, Hartley/F) was thermostable and the enzyme of the other (Strain 2, Strain 13) was thermolabile.
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PMID:Effect of strain differences on heat-susceptibility of L-asparaginase in the guinea pig. 71 34


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