Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

At the present time, a successful regimen for the eradication of occult meningeal leukemia, following induction of a first complete remission in acute lymphoid and undifferentiated childhood leukemia, is the combination of cranial radiotherapy in a dose of 1800 rads in 10 fractions in 12--14 days with six doses of intrathecal methotrexate. This regimen, when given with prednisone and vincristine with or without L-asparaginase for induction and daily oral 6-mercaptopurine and weekly methotrexate for maintenance, can be expected to give a relapse rate for isolated meningeal leukemia of approximately 5% during the first 2 years of follow-up. A modification of this regimen utilizing craniospinal radiation with prior and concurrent intrathecal methotrexate is given for the treatment of overt meningeal leukemia at diagnosis or for an isolated first relapse with meningeal leukemia. Radiation technique and morbidity are discussed.
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PMID:Radiation in the treatment of meningeal leukemia. 39 92

The relative antineoplastic effectiveness of E. coli and Erwinia asparaginases was tested against lymphoid leukemias EARAD-1 and L5178Y/CA55. E. coli and Erwinia asparaginases had similar clearance rates from plasma in mice, and at a dose of 250 IU/kg body weight both enzymes lowered plasma asparagine to undetectable levels. Nevertheless, the dosage of Erwinia asparaginase needed to cause similar prolongation of median survival time in leukemic mice was at least twice that of E. coli asparaginase. The factors which may be responsible for the more potent therapeutic effectiveness of the E. coli asparaginase are discussed.
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PMID:A comparative study of the antitumor effectiveness of E. coli and Erwinia asparaginases. 78 92

L-asparaginase is an enzyme that inhibits protein synthesis by the depletion of sources of L-asparagine, which is necessary for transformed lymphoid cells to proliferate. L-asparaginase is used in the treatment of childhood acute lymphoblastic leukemia. A problem with L-asparaginase therapy is the immunogenicity of the enzyme and the development of anaphylactic reactions. Canine lymphoma is a predominantly B-cell tumor with widespread disease; without treatment, dogs with lymphoma usually survive 1-2 months. Canine lymphoma will respond to L-asparaginase therapy. A randomized double-blind study evaluated a polyethylene glycol (PEG) conjugate L-asparaginase combined with chemotherapy (vincristine, cyclophosphamide, doxorubicin, and prednisone). Thirty-five dogs were randomized to the PEG L-asparaginase group, and 34 dogs were randomized to the native L-asparaginase group. Thirty dogs (85.7%) achieved a complete remission (CR) with a median time to relapse of 217 days, and 32 (94.1%) dogs in the native L-asparaginase group achieved a CR with a median time to relapse of 214 days (P greater than 0.05). The asparaginase was well tolerated in both groups. Two dogs in the native L-asparaginase group had severe allergic reactions, and one dog in the PEG asparaginase group had a generalized urticarial reaction after repeated injections. This study indicates that PEG L-asparaginase has equal therapeutic efficacy to native L-asparaginase.
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PMID:Evaluation of L-asparaginase: polyethylene glycol conjugate versus native L-asparaginase combined with chemotherapy. A randomized double-blind study in canine lymphoma. 152 54

To define the clinical and biologic significance of childhood acute mixed-lineage leukemia diagnosed by stringent criteria, we studied 25 cases of acute lymphoblastic leukemia expressing greater than or equal to 2 myeloid-associated antigens (My+ ALL), and 16 cases of acute myeloid leukemia expressing greater than or equal to 2 lymphoid associated antigens (Ly+ AML). These cases represented 6.1% of 410 newly diagnosed ALLs (two treatment protocols) and 16.8% of 95 AMLs (two protocols). T-lineage--associated antigens were identified in 9 of the My+ ALL cases and in 14 of those classified as Ly+ AML; all but 1 of the 19 cases that could be subclassified had an early thymocyte stage of differentiation. The My+ ALL cases had an increased frequency of French-American-British (FAB) L2 morphology (36%); the Ly+ AML cases were characterized by FAB M1 or M2 morphology, low levels of myeloperoxidase reactivity and combined populations of myeloperoxidase-positive large blasts and small blasts generally of hand-mirror morphology. Karyotypic abnormalities included t(9;22)(q34;q11) in three cases of My+ ALL, 11q23 translocations in two cases of My+ ALL, and 14q32 translocations in three My+ ALL and five Ly+ AML cases. Mixed-lineage expression lacked prognostic significance in either ALL or AML; however, the findings indicate that some patients with Ly+ AML may respond to prednisone, vincristine, and L-asparaginase after failing on protocols for myeloid leukemia. At relapse, two My+ ALLs had converted to AML and two Ly+ AMLs to ALL; one case in each group showed complete replacement of the original karyotype. Acute mixed-lineage leukemia does not adequately describe the heterogeneity of the cases identified in this study and should be replaced by a set of more restrictive terms that indicate the unique biologic features of these leukemias.
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PMID:Characterization of childhood acute leukemia with multiple myeloid and lymphoid markers at diagnosis and at relapse. 158 28

A 17-year-old male with bilineal hybrid acute leukemia is described. Two-color flow cytometric analysis of blast surface phenotype revealed that there were two groups of blasts which showed either CD 10+ CD 19+ CD 13- CD 33- or CD 10- CD 19- CD 13+ CD 33+, but not both. He developed a complete remission by treatment with vincristine, prednisolone, adriamycin, and L-asparaginase. After 8 months, however, leukemia relapsed and lymphoid blasts were dominant. Cytogenetic analysis at presentation showed 46,XY,t(3;9)(p21;p22), and at relapse it showed 46,XY,t(1;3;9)(1pter----1q32::3p25----3pter;3 qter----3p21::9p22----9pter; 9qter----9p22::3p21----3p25::1q32----1q ter),t(2;19)(p21;q13). Analysis of the heavy chain joining region at diagnosis showed three hybridizing bands, all rearranged, but at relapse only one rearranged band. Analysis of the constant region for the beta T-cell receptor gene (TCR beta) both at diagnosis and at relapse showed one rearranged and one germline band, suggesting that rearrangement of one allele of TCR beta of not only lymphoid but also myeloid blasts occurred. It is considered that the target cell of lymphoid leukemia cells and that of myeloid leukemia cells at diagnosis were the same, which differentiated to two lineages, and the clone which evolved from lymphoid lineage proliferated at relapse.
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PMID:Transformation of bilineal hybrid acute leukemia to acute lymphoid leukemia: a case report with serial analyses of cytogenetics and gene rearrangement. 216 90

Ten patients with lymphoid-type blast crisis of chronic myeloid leukemia were treated with combination chemotherapy comprising doxorubicin, vincristine, L-asparaginase, and prednisone. Once remission was achieved in 9 (90%), consolidation with doxorubicin, vincristine and cyclophosphamide was given, and then maintenance chemotherapy with 6-mercaptopurine and methotrexate. Median remission duration was 12 months (range 2-18) and survival 17 (range 3-29). Drug-related toxicity was manageable, leading to a major schedule alteration in 3 cases. These data suggest that combination chemotherapy including doxorubicin improves the prognosis of lymphoid blast crisis in chronic myeloid leukemia.
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PMID:Treatment of the lymphoid blast crisis of chronic myeloid leukemia. 347 57

The immunosuppression first introduced in the 1950s acted indiscriminately, blocking or damaging all the cells that happened to be in mytosis. The toxic side effects were usually so severe that the overall results were not considered satisfactory. The major drawback to the commonly used combination of steroids and cytotoxic drugs is the high risk of overwhelming infections. The next step was the development of lymphocytotoxic drugs or procedures which were restricted to the elimination of the immunocompetent cells. This was achieved by the use of total lymphoid irradiation, thoracic duct cannulation, antilymphocyte globulin, L-asparaginase and steroids. Steroids not only intervene at many points of the immune response, but they also possess a remarkable anti-inflammatory potency. The current or third stage is that of immunopharmacology, which is characterized by selective immunoregulation using compounds or methods that specifically modulate defined subpopulations of immunocompetent cells. Ciclosporin is the first drug that fulfilled these requirements to some extent and that has proved of permanent clinical value. The new technology of monoclonals has allowed the production of highly specific antibodies directed toward lymphocyte subsets. The modulation of lymphokines is another potential approach for both immunosuppression and immunostimulation. The final phase of immunosuppression will be the induction of antigen-specific depression of allograft reactivity. Classical transplantation tolerance has been induced in a developing immune system, but it is virtually impossible to achieve in a fully developed immune system.
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PMID:The mode of action of immunosuppressive drugs. 350 52

Treatment of mice with L-asparaginase from Escherichia coli resulted in a marked suppression of the immune response, as assessed both cellularly and humorally. Suppression occurred only when the enzyme was injected together with the sheep erythrocytes used as antigen. There was little or no effect when the enzyme was injected before the antigen. Simultaneous injection of asparagine prevented suppression, an indication that the effect of the enzyme was due to depletion of an amino acid probably essential for normal lymphoid cell function during antibody production.
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PMID:L-asparaginase-induced immunosuppression: effects on antibody-forming cells and serum titers. 490 50

The cell-killing activity of asparaginase on three classes of Chinese hamster ovary cell mutants was examined: a mutant which overproduces asparagine synthetase (AH5); mutants defective in asparagine synthetase (N3 and N4); and mutants conditionally defective in asparagyl-transfer RNA synthetase (Asn 3, Asn 7, and Asn 9). The overproducer was more resistant to the cell-killing activity of asparaginase than wild-type Chinese hamster ovary cells, while mutants defective in asparagine synthetase were more sensitive. Surprisingly, the asparagyl-transfer RNA synthetase mutants were even more sensitive to asparaginase than the asparagine synthetase mutants. In a preliminary survey of four human lymphoid cell lines (RPMI 8402, RPMI 8392, B46M, and Molt-4F) which showed dramatically different asparaginase sensitivity, however, sensitivity to the cell-killing activity of asparaginase was correlated with reduced levels of asparagine synthetase and not with reduced levels of asparagyl-transfer RNA synthetase.
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PMID:Role of asparaginase synthetase and asparagyl-transfer RNA synthetase in the cell-killing activity of asparaginase in Chinese hamster ovary cell mutants. 611 89

The blast cells of a 14-year-old patient in the blastic phase of chronic myelogenous leukemia (CML) were studied. Cellular morphology, presence of the enzyme terminal deoxynucleotidyl transferase (TdT), and reactivity to the common acute lymphoblastic leukemia antiserum (CALLA) substantiated a lymphoid blast cell line. Immunologic surface markers were nonreactive for E-rosette (T) cells and immunoglobulin-bearing (B) cells. Cytogenetic, studies revealed persistance of the Philadelphia chromosome and a near-haploid cell line, i.e., 28,XY,t(9;22), +14, +15, +21, +22(GTG). The patient responded to chemotherapy with vincristine, prednisone, and L-asparaginase, first line drugs used for remission-induction of acute lymphoblastic leukemia in childhood. We suggest that severe hypodiploidy or near-haploidy, along with TdT and CALLA, may provide more accurate prognostic information in patients with CML and the lymphoid blastic crisis.
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PMID:Near-haploid cell line in the blastic crisis of chronic myelogenous leukemia: a possible marker for lymphoid malignancy. 660 58


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