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)

The synthesis of L-asparaginase in Escherichia coli W and E. coli K-12 was almost completely supressed if glucose was added at a concentration of 0.5 per cent to a growth medium. The level of L-asparaginase synthesis decreased by ca. 75 per cent as a result of cyamutations when the bacteria could not produce cyclo-3',5'-AMP (cAMP). Apparently, a decrease in the intracellular content of cAMP caused by glucose could not be the only factor inhibiting L-asparaginase synthesis. Lactate was found to stimulate L-asparaginase synthesis. Glucose caused the catabolite repression and catabolite inhibition of the components of a system involved in lactate transport. The inhibition of L-asparaginase synthesis by glucose seems to be due, at least partly, to the fact that it prevents the assimilation of lactate by the cells, as well as the utilization of some other compounds which stimulate synthesis of this enzyme.
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PMID:[Mechanism of action of glucose on L-asparaginase synthesis by Escherichia coli bacteria]. 19 80

Despite prolonged therapy (18 months), children with advanced non-lymphoblastic, non-Hodgkin's lymphoma (NHL) treated on previous Children's Cancer Group (CCG) trials achieved less than a 60% 5-year event-free survival (EFS). In this study we piloted a shorter but more intensive protocol ('Orange') to determine the feasibility, safety, and efficacy of this alternative treatment approach. Thirty-nine children received a CHOP-based induction, etoposide/ifosfamide consolidation, DECAL (dexamethasone, etoposide, cisplatin, cytosine arabinoside (Ara-C) and L-asparaginase) intensification, and either one or two similar but less intense maintenance courses. Patients were stratified to standard-risk (5 months) vs high-risk (7 months) treatment. High risk was defined as either bone marrow disease, CNS disease, mediastinal mass > or = one-third thoracic diameter at T5 and/or LDH > or =2 times institutional upper limits of normal. All other patients were considered to be standard risk. Results were compared with the previous CCG NHL study (CCG-503). Sixteen and 23 patients were considered standard- vs. high-risk, respectively. The 5-year EFS and overall survival (OS) were 77 +/- 7% and 80 +/- 7%, respectively. The 5-year EFS and OS were significantly better in the standard- vs. high-risk subgroups (100% vs. 61 +/- 11%) (P < 0.003) and (100% vs. 65 +/- 11%) (P < 0.01), respectively. Lactate dehydrogenase (LDH) > or =2 x normal (NL) was associated with significantly poorer outcomes (LDH > or =2 x NL vs. <2 x NL) (5-year EFS: 55 +/- 12% vs. 100%) (P < 0.0004). This CCG hybrid regimen, 'Orange', of short and more intensive therapy resulted in a significant improvement in outcomes compared with the previous CCG trial of more prolonged but less intense therapy. This regimen that deletes high-dose methotrexate, if confirmed in a larger trial, could be considered as an alternative treatment approach in children without high tumor burdens (LDH <2 x NL) and Murphy stage III disease.
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PMID:Long-term follow-up of short intensive multiagent chemotherapy without high-dose methotrexate ('Orange') in children with advanced non-lymphoblastic non-Hodgkin's lymphoma: a children's cancer group report. 1196 Mar 38