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)

Crystalline glutaminase-asparaginase which is effective against solid as well as ascites tumors was prepared from soil isolate organism Pseudomonas 7A. This enzyme has a ration of Vmax for L-glutamine and L-asparagine of 2.0. The presence of glutamic acid in the growth medium is essential for optimal enzyme production and glucose inhibits the production of glutaminase-asparaginase. The purification procedure provides an overall yield of 40 to 45% from crude cell extract to homogeneous glutaminase-asparaginase and is adaptable to large scale production of the enzyme. The specific activity of homogeneous enzyme is 160 +/- 15 i.u./mg of protein and the E1% 280 is 9.8. No disulfide or sulfhydryl groups appear to be present on the enzyme. The isoelectric point of glutaminase-asparaginase by isoelectric focusing on ampholine polyacrylamide gel plates is 5.8. The Km values for L-glutamine and L-asparagine are 4.6 and 4.4 X 10(-6) M, respectively. The enzyme catalyzes the hydrolysis of the D isomers of glutamine and asparagine at 87 and 69% the rate of the respective L isomers. L-Glutamic acid gamma-monohydroxamate is hydrolyzed at approximately the same rate as L-glutamine. The enzyme is not inhibited by ethylenediaminetetraacetate (0.1 mM), L-glutamate (30 mM), or L-aspartate (30 mM). Ammonium sulfate (10 mM) inhibits the enzymatic activity. The plasma half-life of Pseudomonas 7A glutaminase-asparaginase if 13 hours in normal mice and 43 hours in mice infected with the lactate dehydrogenase-elevating virus.
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PMID:Purification and properties of a highly potent antitumor glutaminase-asparaginase from Pseudomonas 7Z. 0 41

Spleen antibody-forming cells of mice yield a 3- to 10-fold increase in their response to sheep erythrocyte antigen if they are acutely infected by lactate dehydrogenase-elevating virus. This early stimulation is replaced by a long-term inhibition of the antibody-forming cells as the viremia goes into its persisting chronic stage. These contrasting immunological phenomena are examined as contributing factors responsible for the enhancement by this virus of asparaginase (EC 3.5.1.1; L-asparagine amidolydrolase) therapy against leukemia in mice, and for the alteration of the susceptibility of mice to various neoplastic processes.
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PMID:Antibody-producing cells: virus-induced alteration of response to antigen. 108 81

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.
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PMID:Some biological properties and an in vivo evaluation of tyrosine phenol-lyase on growth of B-16 melanoma. 124 96

Forty-four adult patients with lymphoblastic lymphoma (LBL) were treated according to one of two protocols. Both included (1) induction with cyclophosphamide, doxorubicin, vincristine, prednisone, and L-asparaginase; (2) CNS prophylaxis; and (3) maintenance therapy with methotrexate (MTX) and 6-mercaptopurine. In the second protocol, CNS prophylaxis began earlier than in the first protocol and included cranial irradiation and intrathecal (IT) MTX rather than simultaneous high-dose systemic and IT MTX. The overall response rate was 100% (95% complete). With a 26-month median follow-up, the 1-and 3-year actuarial freedom from relapse (FFR) for the composite patient group was 70% and 56%, respectively. The incidence of CNS relapse was reduced from 31% in the first protocol to 3% in the second protocol (P = .04, Gehan). Patients can be assigned retrospectively to low (n = 19) and high (n = 25) risk prognostic groups, as indicated by a multivariate analysis of pretreatment prognostic factors. High-risk is defined by Ann Arbor stage IV disease with bone marrow or CNS involvement or initial serum lactate dehydrogenase (LDH) concentration of greater than 300 IU/L (normal, less than 200). FFR of low- and high-risk groups at 5 years are 94% and 19%, respectively (P = .0006). Low-risk patients are highly curable using this approach to adult LBL. More intensive treatment for high-risk patients is warranted.
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PMID:Treatment of lymphoblastic lymphoma in adults. 377 16

Sixty-two patients with aggressive non-Hodgkin's lymphoma (diffuse mixed, diffuse large cells, non-cleaved small cells (Burkitt-like), immunoblastic, lymphoblastic and other non-epidermotropic T lymphomas) were treated by intensive sequential chemotherapy combining heavy induction treatment (modified CHOP-Bleo), sequential consolidation treatment (cytosine arabinoside and thioguanine, then high-dose methotrexate and L-asparaginase) and final reinforcement (CVAP-Bleo). Complete remission was achieved in 59 patients (95%); 11 patients (18%) relapsed. Two patients died during the induction phase and one failed to respond. Two patients died of an unrelated disease while in complete remission. Blood toxicity was tolerable and treatment could be conducted without problems in most cases. The median survival cannot be reached with a 14-months follow-up, but the survival rate seems to plateau at 70%. The only two prognostic factors identified were poor general condition and high serum lactate dehydrogenase levels.
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PMID:[Highly malignant non-Hodgkin's lymphoma. Treatment by intensive sequential chemotherapy]. 619 54

Immunochemical techniques with enzymes as the antigen have grown in frequency during the last few years. These techniques have allowed evaluation of enzymes in the presence of endogenous inhibitors. Among those enzymes measured by immunochemical techniques and which have found diagnostic application, mention will be made of alkaline phosphatase (with particular reference to the intestinal, placental, and Regan isoenzymes), lactate dehydrogenase (in which renewed interest has developed due to techniques for specifically measuring the LD-1 isoenzyme), aspartate aminotransferase (of which the cytosolic and mitochondrial forms can now be independently measured by immunochemical techniques), acid phosphatase (for which a specific immunochemical assay for the prostatic enzyme has been widely introduced in diagnostic laboratories), and creatine kinase (for which a variety of immunochemical techniques to measure the M- and B-subunits are now part of standard laboratory assays). Other enzymes which will be discussed in this review include phosphohexose isomerase, amylase, ribonuclease, and lysozyme (muramidase). Finally, the use of enzymes, particularly asparaginase, in the chemotherapy of cancer will be outlined.
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PMID:Immunoassay of enzymes--an overview. 634 26

We describe a patient with natural killer (NK)/T cell lymphoma who relapsed after autologous peripheral blood stem cell transplantation (auto-PBSCT) and was successfully treated with Escherichia coli (E. coli) and Erwinia L-asparaginase. A 38-year-old male patient with ulcerated tumor at the left thigh was diagnosed as having nasal type NK/T cell lymphoma on the basis of histopathological and flowcytometric findings of tumor, revealing diffuse infiltration of atypical lymphoid cells into blood vessels and expression of CD7 and CD56 antigens, but not CD3. He had tumor infiltration in the bone marrow and at the right lower lung field. After five cycles of CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) therapy, the patient achieved complete remission and received high-dose chemotherapy with auto-PBSCT, although the tumor recurred in the right leg 10 months later. Despite salvage chemotherapy, followed by local irradiation and surgical amputation, a tumor recurred at the left upper gingiva 10 days after. Using E. coli L-asparaginase (6000 U/m2/day), the tumor regressed, fever was alleviated and the serum lactate dehydrogenase decreased to normal range after several days. The asparagine synthetase expression in tumor cells was immunohistochemically negative on paraffin-embedded tissues. Because of the anaphylactoid reaction developing after E. coli L-asparaginase, alternative Erwinia L-asparaginase (6000 U/m2/day) was administered, resulting in regression of tumor and fever lysis. L-asparaginase is a promising agent for the treatment of NK/T cell lymphoma.
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PMID:Successful treatment with Erwinia L-asparaginase for recurrent natural killer/T cell lymphoma. 1280 30

We analysed the long-term outcome of the L86 protocol using L-asparaginase (L-asp), vincristine (VCR) and prednisolone (PSL), collectively known as LVP or L97 protocol using LVP along with pirarubicin hydrochloride (THP-ADR) for 97 patients with acute lymphoblastic leukemia (ALL) diagnosed between 1986 and 2002. No significant differences were seen in the two protocols regarding the complete remission (CR) rate or survival. Seventy-five of the 97 patients (77%) achieved a CR. The overall survival (OS) and disease-free survival (DFS) rates were 32.1% and 30.4% at 10 years, respectively. By univariate analysis, we identified seven adverse factors for DFS which included the L2 subtype by French-American-British classification, hepatosplenomegaly, a white blood cell count of more than 30 x 10(9)/L, a blast cell count of more than 10 x 10(9)/L in the peripheral blood, hemoglobin concentration greater than 10 g/dL, a serum lactate dehydrogenase value greater than twice the upper limit of normal and the presence of the Philadelphia chromosome (Ph). According to multivariate analysis, only the presence of Ph was a significant unfavourable factor for DFS and OS. In the 30 patients under 35 years of age without Ph, the OS in the 20 patients treated with L86 and in the 10 patients treated with L97 were 48 and 86%, respectively (P = 0.011). These results indicate that intensified chemotherapy, such as the L97 protocol that includes an anthracycline, might be beneficial for younger patients who are Ph-negative.
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PMID:Long-term outcome of L86 and L97 protocols for adult acute lymphoblastic leukemia. 1902 Oct 56

Acute lymphoblastic leukemia (ALL) 5-year survival rates are approaching 90% in children and 50% in adults who are receiving contemporary risk-directed treatment protocols. Current efforts focus not only on further improving cure rate but also on patient quality of life. Hence, all protocols decrease or limit the use of cranial irradiation as central nervous system (CNS)-directed therapy, even in patients with high-risk presenting features, such as the presence of leukemia cells in the cerebrospinal fluid (even resulting from traumatic lumbar puncture), adverse genetic features, T-cell immunophenotype, and a large leukemia cell burden. Current strategies for CNS-directed therapy involve effective systemic chemotherapy (eg, dexamethasone, high-dose methotrexate, intensive asparaginase) and early intensification and optimization of intrathecal therapy. Options under investigation for the treatment of relapsed or refractory CNS leukemia in ALL patients include thiotepa and intrathecal liposomal cytarabine. CNS involvement in non-Hodgkin lymphoma (NHL) is associated with young age, advanced stage, number of extranodal sites, elevated lactate dehydrogenase, and International Prognostic Index score. Refractory CNS lymphoma in patients with NHL carries a poor prognosis, with a median survival of 2 to 6 months; the most promising treatment, autologous stem cell transplant, can extend median survival from 10 to 26 months. CNS prophylaxis is required during the initial treatment of NHL subtypes that carry a high risk of CNS relapse, such as B-cell ALL, Burkitt lymphoma, and lymphoblastic lymphoma. The use of CNS prophylaxis in the treatment of diffuse large B-cell lymphoma is controversial because of the low risk of CNS relapse ( approximately 5%) in this population. In this article, we review current and past practice of intrathecal therapy in ALL and NHL and the risk models that aim to identify predictors of CNS relapse in NHL.
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PMID:Central nervous system disease in hematologic malignancies: historical perspective and practical applications. 1966 Jun 80

We reviewed 173 patients with an initial diagnosis of peripheral T-cell non-Hodgkin lymphoma (PTCL) and compared the patients with bone marrow involvement (BMI) to those without to have a better understanding of the clinical characteristics, treatments, survival and prognosis of PTCLs with BMI. We found that 40% (70/173) of the patients had BMI, and its frequency was 64% in angioimmunoblastic T-cell lymphoma (TCL), 46% in PTCL unspecified, 29% in anaplastic large T-cell lymphoma, 23% in extranodal NK/T-cell lymphoma and 13% in enteropathy-type TCL. In the BMI group, 36% of patients had lymphoma-associated hemophagocytic syndrome (LAHS), compared with 8% of the patients without BMI (8/103, P < 0.001). The estimated 1-year overall survival (OS) rates of patients with LAHS in the BMI and non-BMI groups were 5 and 49%, respectively. The increased levels of lactate dehydrogenase, fasting triglycerides and beta(2)-microglobulin between the BMI and non-BMI groups were not significantly different, but ferritin increased significantly and liver dysfunction-related diseases were seen more in the BMI group. As much as 51% of patients of the BMI group had anemia, compared with 27% of the patients without BMI (P = 0.001). The estimated 2-year OS rates in the two groups were 10 and 34%. The estimated 2-year OS rate of the 67 patients with BMI, who did not lose to follow-up, was 22%, compared with 38% in the non-BMI group. The median survival times of the 2 groups were 120 and 356 days. The estimated 2-year OS rate of patients treated by CHOP regimen was 9%, compared with 51% of those with intensive chemotherapy, with a significant difference (log rank P = 0.0008). The median survival time of the 14 patients subjected to chemotherapy combined with L: -asparaginase was 365 days and that of the 7 patients undergoing hemopoietic stem cell transplantation (HSCT) was 575 days. A total of 3 patients in a critical condition underwent plasmapheresis as initial therapy and achieved stable condition. We conclude that patients with PTCLs with BMI on initial diagnosis usually have hemaphagocytic syndrome and poor prognosis. BMI without lymphadenopathy is a patent clinical feature in most PTCLs. Patients with anemia on initial diagnosis in the BMI group usually have poor prognosis than those without. Intense chemotherapy, addition of L: -asparaginase in chemotherapy and HSCT are comparatively efficient treatments of PTCLs. For patients in critical conditions, plasmapheresis before chemotherapy would lower the risk and improve the tolerance to chemotherapy.
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PMID:Clinicopathological study on peripheral T-cell non-Hodgkin lymphoma with bone marrow involvement: a retrospective analysis from China. 1972 28


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