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)

An intracellular L-asparaginase with antitumour activity was purified from a strain of Citrobacter. The optimum conditions for enzyme production by fermentation on scales up to 2700 l were investigated. Highest enzyme yield was obtained in corn-steep liquor medium (9-2%, W/V) at 37 degrees C. Oxygen limitation was not necessary for high enzyme yield. A total recovery of 4-3% from nucleic-acid-free extract and a 180-fold increase in specific activity were obtained after purificaiton. The specific activity of the purified preparation was 45 i.u./mg protein. The enzyme hydrolysed D-asparagine and L-glutamine at 7 and 5%, respectively, of its activity toward L-asparagine, but L-glutaminase activity could be demonstrated only at substrate concentrations above 5 mM. The Km values for L-asparagine and D-asparagine were 2-6 X 10(-5) and 1-4 X 10(-4) respectively. The anti-lymphoma activity of the enzyme was demonstrated with Gardner lymphosarcoma and was found only slightly less potent that Crasnitin, the most active asparaginase so far tested in this system.
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PMID:The properties and large-scale production of L-asparaginase from citrobacter. 0 Apr 65

A group of 20 children, including 14 with acute lymphoblastic leukemia and 6 with lymphosarcoma, was studied. 24 cures of l-asparaginase therapy were carried out. The increase of serum immunoglobulin (IgG, IgA, IgM) levels was found in children treated with smaller (from 300 to 500 I.U./kg b. w.) doses of asparaginase. In the group treated with higher doses (from 501 to 760 I.U./kg b. w.) the maximal increase of immunoglobulins was observed in the second half of the cure with l-asparaginase, followed by a decrease of the immunoglobulins levels at the end of treatment. The presence of anti-asparaginase antibodies in two children with anaphylactic shocks after l-asparaginase has been shown. In these two children and 6 others the lymphocyte count significantly dropped down on the day of shock before l-asparaginase injection.
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PMID:[Immunological aspects in the L-asparaginase treatment of children with lymphoproliferative diseases]. 5 15

In 42 children being in the advanced stage of an acute lymphoblastic leukaemia as well in 7 children with lymphosarcoma a total of 83 series of treatment with L-asparaginase were carried out. During the first blastic crisis of acute leukaemia 74% of complete or partial remissions could be obtained by two treatments and 52% by the following ones. The best results were obtained by organ manifestations of acute leukaemia (80% of complete or partial remissions). Less satisfactory results were achieved in treating lymphosarcoma. All remissions were only of a short duration.
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PMID:[Repeated, 2-10 fold asparaginase treatments in children with lymphoproliferative diseases]. 6 4

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

Forty-two patients with chronic lymphocytic leukemia (CLL) were studied for morphology of lymphocytes by light and electron microscopy (EM), in vitro responses of lymphocytes to a battery of physical and chemical agents, overall clinical status, immunologic status, course, and response to therapy. CLL lymphocytes could be classified by EM into four groups on the basis of cell size and nuclear contour and by light microscopy into two groups, small cells and large cells (lymphosarcoma cells). Patient survival did not vary with cell size or morphology as determined by light or electron microscopy. In vitro testing of CLL lymphocytes following exposure to X-ray, PHA, DMSO 2 hr at 43 degrees C, prednisolone, glutaminase, and asparaginase permitted a separation of patients into categories of normal and abnormal in vitro responses. A normal in vitro response predicted a good response to therapy but an abnormal in vitro response did not preclude a good response to therapy. Following therapy, normalization of abnormal EM morphology and in vitro response was seen in some patients. Most patients tested had decreased serum immunoglobulins and abnormal PHA responses. There was a high incidence of infections and second neoplasms. Immunologic deficits could not be correlated with variations in lymphocyte morphology or in vitro response.
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PMID:Chronic lymphocytic leukemia: correlation of clinical course and therapeutic response with in vitro testing and morphology of lymphocytes. 86 70

A method potentially capable of enhancing the effectiveness of therapeutic enzymes such as L-asparaginase was investigated. The method was suggested by the following properties that have been observed for lectins injected into tissues: (1) six lectins with differing specificities were retained near the site of injection in the feet of mice 10 to 100 times longer than several non-lectin proteins. Prolonged retention of 125I-labelled concanavalin A was also observed in other normal and malignant mouse tissues. (2) The retention of 125I-labelled concanavalin A was not affected by prior immunization against concanavalin A. (3) Electrophoresis of tissue extracts on sodium dodecyl sulfate-poly-acrylamide gels followed by radioautography indicated that the 125I-labelled concanavalin A retained in the tissue remained as intact in form as prior to injection. Since the therapeutic efficacy of many enzymes may be enhanced by localization at the intended site of action, in principle it should be possible to enhance the effectiveness of therapeutic enzymes by combining the tissue-localizing properties of a lectin with therapeutic effectiveness of the enzyme. A conjugate of E. coli L-asparaginase and concanavalin A has been prepared by covalent cross-linking with glutaraldehyde and has been shown to be retained in mouse tissue 90 times longer than the free enzyme. However, it is completely ineffective in the treatment of the L-asparaginase-sensitive lymphosarcoma 6C3HED in C3H/HeJ mice. The ineffectiveness of the conjugated enzyme may be associated with the interiorization of the conjugate by the cells of the tumor.
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PMID:Effect of localization of L-asparaginase as the concanavalin A conjugate on anti-tumor activity. 103 89

14 children with acute lymphoblastic leukemia and 6 with lymphosarcoma were treated in 13 cures with 300-500 IU/kg bodyweight/day of L-asparaginase and in 11 cures with 501-760 IU/kg/day. An increase of all fractions of immunoglobulins with maximal values at the end of the cures was observed in the group treated with low doses. In the children receiving the high doses of this drug, an increase was observed only in the first 3 or 4 days of therapy and a decrease occurred at the end of the cure. Decreased IgM levels at the end of therapy were noted in children with acute leukemia. Anti-asparaginase antibodies occurred only in 3 children with anaphylactic shock.
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PMID:Immunological aspects of L-asparaginase treatment in children with lymphoproliferative disease. 106 Jun 5

For the purpose of clinical application to the therapy of human leukemia and lymphosarcoma, L-asparaginase from Escherichia coli was modified with 2,4-bis(O-methoxypolyethylene glycol)-6-chloro-s-triazine (activated PEG2) by an improved method, which involves a purification step of activated PEG2 by gel filtration. The PEG2-modified asparaginase retained approximately 30% (73 IU/mg of protein) of the enzymic activity of the native enzyme, while it had almost wholly lost the immunoreactivity towards anti-asparaginase antibodies. The modified enzyme retained the characteristics of the native enzyme in terms of the pH- and temperature-dependencies of activity and stability, and the Km value for L-asparagine. Administration of the modified enzyme to a dog with spontaneous lymphosarcoma induced complete remission without any toxic side effects. Seven children with multiple relapses of acute leukemia were treated with a regimen of cycles of methotrexate and native asparaginase. Three of these children developed anaphylactic shock. In contrast to the native enzyme, the successive administration of PEG2-modified asparaginase to those three patients was therapeutically effective without causing any allergic reaction.
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PMID:Characterization of polyethylene glycol-modified L-asparaginase from Escherichia coli and its application to therapy of leukemia. 310 31

The general principles of chemotherapy in oncology and the various types of antineoplastic drugs are discussed. Particular attention was paid to the results of chemotherapy in dogs and cats as reported in the literature. Chemotherapy is indicated in neoplastic disease characterised by early metastasis and/or local invasive growth. The results of chemotherapy in dogs and cats are so far moderate. Chemotherapy studies in the Netherlands are discussed: predictive in vitro, PEG-asparaginase studies in canine lymphosarcoma and regional perfusion in canine osteosarcoma.
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PMID:[Chemotherapy of tumors in dogs]. 328 98

L-asparaginase was used to treat a 4-year-old Holstein cow with lymphosarcoma that involved the spinal cord, subiliac lymph nodes, and retrobulbar space. The cow received 60,000 IU of L-asparaginase IV for a total of 4 treatments. After each treatment, the cow's condition improved, characterized by decreased weakness, decreased ataxia, a reduction in size of the left subiliac lymph node, and decreased exophthalmos. Side effects were not observed. The cow was kept alive for 57 days. This treatment offers a way of salvaging the genetic potential of valuable cows and bulls.
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PMID:Treatment of bovine lymphosarcoma with L-asparaginase. 339 57


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