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)

Of 4 lines of myelogenous rat leukemias induced by N-nitrosobutylurea (NBU), DBLA-6 was selected as a screening model for antileukemic agents because of the following characteristics: a) High transplantability either by intravenous (i.v.) or intraperitoneal (i.p.) inoculation; b) linear relationship between inoculum size and survival time; c) marked increase of leucocyte counts in the peripheral blood as the tumor progresses after intravenous inoculation. To investigate reliability in its predicting clinical efficacy, its sensitivity to known antileukemics was studied. To determine the effects, a change of leucocyte counts in the peripheral blood together with the prolongation of life span was checked in the following systems; i.v.-i.v. (i.v.-inoculation, i.v.-injection), i.v.-i.p., i.p.-i.p., i.p.-i.v. Fifty percent cure was obtained with Vincristine, Vinblastine, Daunorubicin, 6-Mercaptopurine, and alkylating agent 838D or 864T. The success of treatment was measured by decrease of leucocytes. Methotrexate, cytosine arabinoside (Ara-C), and cyclophosphamide showed only poor effects, and Mitomycin C, L-asparaginase, and Bleomycin were ineffective. In addition, the chemotherapeutic effects of Vincristine and 864 on this leukemia were quite dependend both on the route of drug injection and on the site of tumor inoculation. Subsequently, our studies are being extended to cover the correlation between drug distribution and tumor localization or dissemination.
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PMID:Sensitivity of DBLA-6 leukemia of rats to known antitumor agents in relation to their clinical effects. 116 99

Ninety-seven patients with aggressive malignant lymphoma (ML) were treated with an intensive and sequential chemotherapy (protocol LNH-80). There were 42 patients with intermediate grade ML, 53 patients with high-grade ML, and two patients with true histiocytic ML. Most of the patients were in advanced stage: 21 stage III and 61 stage IV. The LNH-80 protocol schedule comprised three phases: (1) induction with three courses of an intensified CHOP-Bleo (cyclophosphamide, doxorubicin, vindesine, methylprednisolone, and bleomycin); (2) consolidation with cytarabine, followed by high-dose methotrexate and folinic acid rescue, then asparaginase; and (3) final intensification with two courses of CVAP-Bleo (cyclophosphamide, teniposide, cytarabine, methylprednisolone, and bleomycin). CNS prophylaxis included one injection of methotrexate during each induction course and the drugs of the consolidation phase. In cases of initial CNS localization, cranial radiotherapy was added. Eighty-four patients (87%) went into complete remission (CR), 18 (21%) of whom relapsed, usually during the phase of treatment or within 6 months of completing chemotherapy. Sixty-three patients are alive with an overall median follow-up of 24 months. The median survival time and the median disease-free survival have not been reached, and the survival curve seems to have plateaued at above 60%. There was no statistical difference between intermediate-grade ML (CR 90%, relapse 18%) and high-grade ML (CR 84%, relapse 24%). The toxicity of this treatment is mainly encountered during the induction phase: almost all patients had short-term neutropenia, less than 0.500 g/L in 57, with a documented infection in 25. Overall treatment-related mortality was 6%, with four patients dying during the induction phase.
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PMID:Intensive and sequential combination chemotherapy for aggressive malignant lymphomas (protocol LNH-80). 241 66

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

Hypersensitivity reactions from cytotoxic agents have not been accorded much attention. Certain drugs (L-asparaginase, cisplatin, intravenous melphalan, topical mechlorethamine, zinostatin, and teniposide) produce reactions often enough to be a clinical problem. Others (cyclophosphamide, doxorubicin, daunorubicin, methotrexate, and procarbazine) do so only occasionally. Bleomycin uniquely produces an occasional hyperpyrexic reaction with clinical findings similar to anaphylaxis. Some cytotoxic agents have never been known to produce hypersensitivity reactions. This paper reviews the frequency and clinical information about such reactions, factors augmenting or decreasing the frequency, and, where possible, the etiologic mechanisms.
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PMID:Hypersensitivity reactions to cancer chemotherapeutic agents. 700 2

Bleomycin and asparaginase are widely used antineoplastic agents which may induce allergic or inflammatory side-effects. Mast cells are implicated as effector cells in allergic and inflammatory responses. The aim of this study was to establish whether bleomycin or asparaginase modulate leukotriene production in vitro and in vivo. Leukotriene C4 (LTC4) production by murine bone marrow-derived mast cells (BMMC) was determined by radioimmunoassay (RIA). Leukotriene production in patients was assessed by determining leukotriene E4 and N-acetyl-leukotriene E4 in urine by means of combined HPLC and RIA. Bleomycin induced an up to 2.1-fold increase in LTC4 production both in unstimulated and in calcium ionophore-stimulated mast cells. In 3 of 7 patients treated with bleomycin, a greater than 2-fold increase in endogenous leukotriene production was observed. This effect was associated with febrile responses and was most pronounced in a patient who developed an Adult Respiratory Distress Syndrome (ARDS). Asparaginase increased leukotriene production up to 10-fold in stimulated but not in unstimulated BMMC. In a patient who developed an anaphylactic reaction after treatment with asparaginase, a pronounced increase in urinary leukotriene concentration was observed. In contrast to bleomycin or asparaginase, a number of other cytostatic agents did not significantly change leukotriene production by BMMC. Our data indicate that some of the inflammatory and allergic side-effects of bleomycin and asparaginase could be mediated by leukotrienes, a possible source of which may be mast cells.
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PMID:Induction of leukotriene production by bleomycin and asparaginase in mast cells in vitro and in patients in vivo. 951 79