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)

A 10-year-old boy with leukaemia-associated hypercalcaemia was treated with aminohydroxypropylidene biphosphonate (AHPrBP previously APD) in a total dosage of 60 mg over 5 days, when the condition failed to respond to rehydration and frusemide and no sustained effect was produced by haemodialysis with a calcium (Ca)-free dialysate. Bone films showed no lytic lesions, and AHPrBP, which is a potent inhibitor of osteoclast-mediated bone resorption was well tolerated and induced a rapid and sustained fall in plasma Ca (from 3.42 to 2.07 mM in 5 days). Plasma magnesium and alkaline phosphatase remained normal. The results could have been affected by other drugs [vincristine, cyclophosphamide, zorubicin (Rubidazone) L-asparaginase and prednisone] which were simultaneously administered. However, the observation that: (1) the response curve of plasma Ca was similar to that reported when AHPrBP was used alone, (2) there was complete inhibition of urinary Ca excretion and (3) hypocalcaemia occurred suggests that AHPrBP was the major cause of the reduction in plasma Ca. AHPrBP should be considered a potential therapy for hypercalcaemia in childhood malignancy.
Pediatr Nephrol 1990 Sep
PMID:Leukaemia-associated hypercalcaemia in a 10-year-old boy: effectiveness of aminohydroxypropylidene biphosphonate. 224 18

A 46-year-old woman was admitted to our hospital because of leukocytosis. A diagnosis of acute lymphoblastic leukemia (FAB: L2 type) was made by reviewing peripheral blood smear and bone marrow aspirate. Chromosome analysis showed the presence of Philadelphia chromosome. A combination chemotherapy with L-asparaginase, doxorubicin, vincristine, and prednisolone was started, but complete remission was not achieved. During a neutropenic period after combination chemotherapy with doxorubicin, vincristine, vinblastine, and VP-16, high fever and tender swelling of the right cheek were noticed. A diagnosis of maxillary sinusitis was made with tomography and CT scan of the maxillary sinus. Since culture of the aspirate from the maxillary sinus grew aspergillus, a diagnosis of aspergillosis of the maxillary sinus was made. Immediately after the intravenous administration of amphotericin B and the lavage of the sinus with amphotericin B was started, high fever subsided and clinical improvement was observed. Several regimens of chemotherapy failed to obtain hematological remission, she died of sepsis of Enterobactor cloacae without evidence or relapse of dissemination of aspergillosis after initial successful treatment. While a few cases with aspergillus maxillary sinusitis were reported in leukemic patients, the possible occurrence of this complication must be kept in mind in a severe neutropenic period after intensive chemotherapy. The combination of intravenous administration and local lavage of amphotericin B appeared to be an effective treatment in the Aspergillus maxillary sinusitis.
Rinsho Ketsueki 1990 Sep
PMID:[Aspergillosis of the maxillary sinus in a patient with Ph1 positive acute lymphoblastic leukemia: a case report]. 224 25

We have isolated a full-length cDNA (HPAsn.6) for human placenta glycosylasparaginase using a 221-bp PCR amplified fragment containing rat liver asparaginase gene sequences. The deduced amino acid sequence from the human clone showed sequence identity to both the alpha and beta subunits of the rat enzyme. The human enzyme is encoded as a 34.6 kDa polypeptide that is post-translationally processed to generate two subunits of approx. 19.5 (alpha) and 15 (beta) kDa. A charge enriched region is present at the predicted site where cleavage occurs. Using polyclonal antibodies against the alpha and beta subunits of rat liver asparaginase, we have shown that the human enzyme is similar in structure to the rat enzyme.
FEBS Lett 1990 Sep 03
PMID:Cloning and sequence analysis of a cDNA for human glycosylasparaginase. A single gene encodes the subunits of this lysosomal amidase. 240 70

Two hundred and nine children (20 years and below) diagnosed as acute lymphoblastic leukemia between January 1980 and December 1983 were retrospectively analysed to evaluate the clinical features, prognostic factors and the results of therapy. One hundred and eighty one evaluable patients were treated with three different chemotherapy regimens consisting of vincristine and prednisolone (Group-A), vincristine, prednisolone and L-asparaginase (Group B-60 patients), and vincristine, prednisolone and adriamycin (Group C-81 patients). Complete remission was achieved in 152 (84%) patients, remission induction being 75 percent, 85 percent and 88 percent in Group A, B and C respectively. At a median follow-up of 36 months the disease free survival for complete responders was 35.5 patient. The disease-free survival for Group A, B and C was 20 percent, 47 percent 34 percent respectively indicating the superiority of a three drug regimen over the conventional two drug regimen. Patients at standard risk in each group had significantly better survival when compared to those at high risk. A 3-drug treatment regimen was superior to the 2-drug regimen and a low initial leucocyte count was an important favourable prognostic factor.
Indian J Cancer 1989 Sep
PMID:Acute lymphoblastic leukemia in childhood: treatment, results and prognostic factors. 263 Apr 28

Hemostatic changes were evaluated in ten patients with acute lymphoblastic leukemia and lymphoma who received chemotherapy with L-asparaginase, vincristine, and prednisolone for 1 week. Following treatment, prothrombin time and activated partial thromboplastin time were significantly prolonged, while a marked decrease in fibrinogen levels was observed. The values for cross-linked fibrin degradation products, however, remained within normal limits during treatment, which excluded the possibility of disseminated intravascular coagulation. The concentrations of coagulation inhibitors (antithrombin III, protein C, and protein S), plasminogen, and alpha 2 antiplasmin also significantly decreased; however, levels of both tissue-type plasminogen activator and plasminogen activator inhibitor, which are synthesized in endothelial cells, increased during the treatment. Although a decrease was observed in concentrations of many coagulation factors, including subunits A and B of factor XIII, the activity and antigenicity of factor VII significantly increased following the treatment. From this study, we concluded that these hemostatic abnormalities caused by the administration of L-asparaginase produced a labile condition that easily inclines to bleeding or thrombosis.
Am J Hematol 1989 Sep
PMID:Changes in hemostatic and fibrinolytic proteins in patients receiving L-asparaginase therapy. 275

A simple rapid and reproducible procedure for transferring monoclonal antibodies into mammalian cells by electroporation is described. Two functionally different monoclonal antibodies (Mab 3F3 and Mab 2B4) specific for asparagine synthetase (EC 6.3.1.1) were used for electroporation into HeLa, HT-5, and L5178Y D10/R (L-asparaginase-resistant) cells. The conditions were optimized so that the viability of the electroporated cells was very high (80-90%), and 90% of the viable cells had antibody incorporated. Electropermeabilized cells were structurally intact, and the high voltage electric pulse had no inhibitory effect on overall cellular DNA and protein synthesis. Incorporated immunoglobulins showed unaltered structural integrity and were functionally active. L5178Y D10/R cells incorporated with an antibody (Mab 3F3) known to be a potent inhibitor of tumor asparagine synthetase showed increased dependence on an exogenous source of asparagine in the culture medium, while the growth of cells incorporated with a control (noninhibitory) antibody (Mab 2B4) remained unaffected. These studies demonstrate that electroporation can be employed successfully for large scale transfer of antibodies into cultured mammalian cells for the study of cellular metabolism.
J Biol Chem 1989 Sep 15
PMID:Transfer of monoclonal antibodies into mammalian cells by electroporation. 276 74

Tetranectin is a tetrameric protein that binds to kringle 4 of plasminogen. Increase of electrophoretic mobility of the otherwise slowly migrating tetranectin in the presence of ethylenediaminetetraacetate was used to develop a reproducible electroimmunoassay to quantify plasma levels. Plasma levels in normals were found within narrow limits of 100 +/- 16 (SD)%, (100% = 0.15 mumol/l). There was no difference between males and females, smokers and non-smokers, and there were no significant changes with age from 20 to 49 years. Patients with severe liver cirrhosis showed a large variation in plasma tetranectin levels but no systematic or average reduction, in contrast to strong reductions in plasma levels of other proteins. Patients treated with L-asparaginase showed a gradual reduction in time in plasma levels of various proteins, though tetranectin showed no significant reduction. It is concluded that tetranectin can be assayed reproducibly in plasma and has a well regulated plasma level. This level is not sensitive to conditions with reductions in synthesis of many proteins, such as during cirrhosis of the liver and during L-asparaginase therapy. The reductions in plasma levels during the use of oral contraceptives and pregnancy indicate involvement of sex steroids in the metabolism of tetranectin.
Thromb Haemost 1989 Sep 29
PMID:Quantitation of plasma levels of tetranectin--effects of oral contraceptives, pregnancy, treatment with L-asparaginase and liver cirrhosis. 281 26

We prospectively assigned 289 consecutive children with acute lymphoblastic leukemia to receive one of two treatment programs on the basis of the presence or absence of certain risk factors at the time of diagnosis. Patients at high risk (62 percent of the total) had one or more of the following risk factors: age below two or above nine years, a white-cell count of 20,000 per cubic millimeter or more, the presence of T-cell immunologic markers, radiologic evidence of a mediastinal mass, and involvement of the central nervous system. Patients in both the standard-risk and high-risk groups were treated for two years, receiving intensive remission-induction therapy, central nervous system prophylaxis, weekly administration of high-dose asparaginase, and multiple-drug continuation therapy (which in the high-risk group included doxorubicin and a larger dose of prednisone). At a median follow-up of 35 months, the mean (+/- SE) event-free survival rates at four years among the patients in the standard-risk and high-risk groups were 86 +/- 4 percent and 71 +/- 4 percent, respectively (P = 0.003), for a total event-free survival of 77 +/- 3 percent. Within the high-risk group, the white-cell count at diagnosis and the sex of the patient were not significant prognostic indicators, but age below 12 months at diagnosis was associated with a very poor outcome. As compared with previous methods, this treatment program using four-drug induction and intensive asparaginase therapy has resulted in improved event-free survival in children with acute lymphoblastic leukemia.
N Engl J Med 1986 Sep 11
PMID:Four-agent induction and intensive asparaginase therapy for treatment of childhood acute lymphoblastic leukemia. 294 92

The clinical, laboratory, and ultrasonographic findings in children receiving L-asparaginase therapy were retrospectively reviewed and correlated to determine the diagnostic reliability and clinical usefulness of serial pancreatic sonograms in detecting L-asparaginase-induced pancreatitis. A total of 217 sonograms were obtained in 92 patients. Six of the 92 (6.5%) had L-asparaginase-induced pancreatitis. The diagnosis of pancreatitis was based solely on clinical symptoms in three patients, on clinical and laboratory findings in two, and on sonographic and laboratory findings in one. No confirmed cases of pancreatitis were detected solely by ultrasonography before clinical or laboratory evidence was obtained. Sonograms were useful only in confirming clinical and/or laboratory evidence of pancreatitis, but were of no value in making the early or preclinical diagnosis of drug-induced pancreatitis. We have discontinued the practice of obtaining routine serial pancreatic sonograms in children receiving L-asparaginase at our institution.
South Med J 1987 Sep
PMID:Serial sonograms to detect pancreatitis in children receiving L-asparaginase. 330 44

A new salvage treatment protocol consisting of VP-16, cytosine arabinoside (Ara-C), methotrexate (MTX) and L-asparaginase, known as VAMA, was administered to twelve patients with relapsed or resistant non-Hodgkin's lymphoma. All twelve patients were in advanced stage with aggressive histologic type. Four of eight patients whose tumor cells had been immunologically determined, had T-cell phenotype. Three complete and five partial responses were obtained, for an overall response rate of 67%. It is of particular interest that all four patients with T-cell phenotype responded(CR; 3 cases, PR; 1 case), and a CR duration over 31 months has been achieved in a case of T-lymphoblastic lymphoma. Severe myelosuppression was the major toxic effect, but it was generally well-tolerated with supportive therapy. These results indicate that VAMA salvage regimen can play an important role in the treatment of relapsed or resistant non-Hodgkin's lymphoma.
Gan To Kagaku Ryoho 1988 Sep
PMID:[VAMA salvage regimen (VP-16, ARA-C, MTX and L-asparaginase) in relapsed or resistant non-Hodgkin's lymphoma]. 341 72


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