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 tumor inhibitory activity of highly purified asparaginase from guinea pig serum toward the Gardner lymphosarcoma in C3H mice was compared with that of the serum itself. The purified enzyme, homogeneous by ultracentrifugation and immunoelectrophoresis, had activity comparable to that of the serum. The serum was also effective in mice which were made immunologically incompetent by radiation with coba't-60.
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PMID:Antagonism of purified asparaginase from guinea pig serum toward lymphoma. 595 48

Eight patients with overt central nervous system (CNS) leukemia and lymphoma were treated with sequential administration of systemic high-dose cytosine arabinoside (HiDAC) and asparaginase (ASP) with no direct CNS therapy. Complete clearing of the cerebrospinal fluid (CSF) was achieved in six (86%) of seven patients with meningeal disease, generally after the first course of therapy. Two patients presented with evidence of extensive intracerebral disease; both responded with a greater than 50% regression of the tumor infiltrates. Concomitant extraneurologic localizations responded equally well to HiDAC/ASP: responses were seen in four of five patients, including complete remission in three of four patients who presented with marrow involvement. Toxicity was generally moderate and limited to myelosuppression (eight of eight patients), tolerable nausea and vomiting (eight of eight patients), mild hepatotoxicity (two of eight patients), and oral mucositis (one of eight patients). These results indicate that HiDAC/ASP is a tolerable and highly effective treatment modality for CNS leukemia and lymphoma and suggest its potential role for sanctuary chemoprophylaxis.
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PMID:Sequential combination of systemic high-dose ara-C and asparaginase for the treatment of central nervous system leukemia and lymphoma. 636 49

The anti-tumor activity of L-asparaginase (EC. 3.5.1.1.) has been conclusively demonstrated. Its therapeutic application, however, has been hampered by its short clearance time in the circulation and high immunogenicity. In order to solve these problems, polyethylene glycol, a linear synthetic and non-immunogenic polymer, was introduced covalently into the amino groups in the enzyme molecule. Monomethoxypolyethylene glycol with molecular weight of 5000 was activated with cyanuric chloride to obtain activated PEGs [2, 4-bis (O-methoxypolyethyleneglycol)-6-chloro-s-triazine]. L-Asparaginase lost its immunoreactivity against its antibodies after the modification of 52 out of 92 amino groups in the molecule. This modified asparaginase retained 11% of its enzymic activity under the physiological condition. When the modified asparaginase was administered in rodents, it diminished the serum asparagine level and its enzymic activity persisted in the circulation 10 to 20 times longer than that of native enzyme. Furthermore, repeated injections of modified asparaginase did not induce any significant anti-asparaginase antibody production. Modified asparaginase showed a superior anti-tumor activity to the native counterpart irrespective of the presence of anti-asparaginase antibodies, when it was tested with murine Gardner lymphoma. This chemical modification should make it possible for the first time to repeatedly and effectively use L-asparaginase obtained from a bacterium.
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PMID:[Preparation of repeatedly and effectively usable L-asparaginase by a chemical modification]. 654 55

106 EEG investigations were carried out in 17 children with various types of neoplastic disease without cerebral involvement during one or more courses of treatment with cytotoxic agents. EEGs were recorded before and 24 h after administration of the drugs. A transient slowing of the dominant frequency in the alpha-band by about 1 c/s and a decrease in the relative power of alpha-activity by 20-30% was observed in only 4 patients. These children did not receive the same antineoplastic treatment. 1 patient received very high dose methotrexate, 2 patients received vincristine combined with other cytotoxic agents, and the other patient received L-asparaginase. It is suggested that EEG changes in patients receiving intravenous cytotoxic treatment usually occur only where there is a preexisting impairment of the blood-cerebrospinal fluid barrier or the blood-brain barrier.
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PMID:Electroencephalographic findings in children treated with cytotoxic agents. 673 36

Glucose induced insulin release, from collagenase isolated islets of Langerhans obtained from non diabetic male New Zealand White rabbits, was inhibited in vitro by E. coli L-asparatinase. This inhibition was time and dose dependent with maximal inhibition being attained after 1 1/2 hr incubation using a dose of 1000 I.U. L-asparaginase/ml. Tolbutamide potentiated glucose-induced insulin release in the presence of inhibitory doses of the L-asparaginase. This potentiation was decreased at higher dose levels of L-asparaginase. L-leucine, L-arginine and theophylline also potentiated glucose-induced insulin release in the presence of L-asparaginase. This potentiation was intact in the presence of all doses of L-asparaginase tested. Glucose induced insulin release, from collagense isolated islets obtained from male New Zealand White rabbits rendered hypoinsulinemic and diabetic by daily intravenous injections of L-asparaginase in vivo, was similar to that of islets of non diabetic control rabbits when the islets were incubated in vitro in te absence of L-asparaginase. These data suggest that the hypoinsulinemic diabetic syndrome produced by the anti-tumor enzyme, L-asparaginase, is produced at least in part by the suppression of insulin release and that this suppression requires the enzyme to be present.
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PMID:E. coli L-asparaginase and insulin release in vitro. 675 34

The guinea-pig, Cavia porcellus, is unusual in possessing plasma L-asparaginase, an enzyme with anti-tumor activity, 21 additional species have been examined as to the presence of this enzyme: the results confirm and extend its remarkably limited species distribution.
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PMID:On the distribution of plasma L-asparaginase. 683 16

The antitumor effect of immobilized L-asparaginase was tested against lymphoid leukemia in mice with concomitant scanning of the L-asparagine level in serum. L-Asparaginase was immobilized in microspheres of polyacrylamide or polyacryldextran. These particles were used in C3H mice bearing the L-asparagine-dependent lymphoma (6C3HED). The tumor was maintained as an ascites tumor, 1 X 10(6) cells were injected intraperitoneally and on day 4 after inoculation, L-asparaginase was injected intramuscularly or intraperitoneally in microparticles. After injection of 5.0 IU ip of L-asparaginase in microparticles, partial remission was induced, generally, however, the cancer relapsed and killed the mice within 2-3 weeks. To obtain complete regression, it was necessary to inject 20 IU of L-asparaginase in microparticles intraperitoneally. The best therapeutic effect was obtained when the particles were administered intramuscularly. After injection of 5 IU the survival time was prolonged, but complete regression was not achieved. The best effect was obtained when the particles were given intramuscularly in two small doses (2.5 IU) at a 3-day interval. Such treatment induced complete regression; 10 out of 12 treated mice were completely cured and lived for several months. It is concluded that the L-asparagine level in serum has to be depressed to less than 20% of the normal level for at least 6-7 days to obtain complete regression of the tumor.
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PMID:Acrylic microspheres in vivo VI: antitumor effect of microparticles with immobilized L-asparaginase against 6C3HED lymphoma. 687 26

One hundred and six EEG investigations were carried out in 17 children with various types of neoplastic disease without cerebral involvement during one or more courses of treatment with cytotoxic agents EEGs were recorded before and 24 hr after administration of the drugs. The EEGs were evaluated visually and by spectral analysis. A transient slowing of the dominant frequency in the alpha band by about 1 Hz and a decrease in the relative power of alpha activity by 20-30% was observed in only 4 patients. These children did not show any clinical or biochemical signs of neurotoxicity. The children did not receive the same antineoplastic treatment. One patient received very high dose methotrexate, 2 patients received vincristine combined with other cytotoxic agents and the other patient received L-asparaginase. It is suggested that EEG changes in patients receiving intravenous cytotoxic treatment usually occur only where there is pre-existing impairment of the blood--cerebrospinal fluid barrier or blood-brain barrier. No clinical signs of epilepsy, new epileptiform waves in the EEG or long-term changes in the background activity of the EEG were observed in this pilot study.
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PMID:Conventional and spectral EEG analysis in children treated with cytotoxic agents. 689 29

Therapy of the 6C3HED lymphoma in syngeneic C3H/HeN mice was studied using tumor-specific antiserum in combination with adriamycin, cyclophosphamide, or L-asparaginase. Antiserum therapy is only effective in the control of small numbers of tumor cells, and cell cures were only obtained when this number did not exceed 5 x 10(5). Complete suppression of larger numbers of tumor cells (10(6) to 5 x 10(7)) could be achieved with the inclusion of chemotherapy at levels that reduced the tumor cell number to less than 10(5) in the case of L-asparaginase and less than 10(4) with cyclophosphamide and adriamycin. The differences in drug cooperative effectiveness are likely to be due to drug-induced impairment of macrophage mobilization to the tumor site.
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PMID:Therapy of a murine lymphoma with tumor-specific antiserum in combination with adriamycin, cyclophosphamide, or L-asparaginase. 689 81

Cytological examination of spleens of mice with growing Gardner lymphosarcoma contaminated with LDH virus indicates the augmentation of erythropoiesis and granulopoiesis, as well as the decrease of lymphopoiesis. Similar changes were observed after infection with LDH-virus. The counts from the bone marrow smear showed more pronounced changes only in tumorous mice, in which repeatedly increased granulopoiesis was found. When the mice bearing Gardner lymphosarcoma were treated with L-asparaginase, then the cytological findings in the spleens and marrows of femors were almost normal. The examination of spleen and bone marrow smears revealed no tumor cells. Histologically examined spleens of mice with 12-day-growing Gardner lymphosarcoma demonstrated infiltration of the follicles with tumor cells. In the marrow of sternum no infiltration of tumor cells could be established.
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PMID:Changes in hemopoiesis of mice of the C3H strain following transplantation of Gardner lymphosarcoma and infection with LDH-virus. II. Spleen and bone marrow. 689 5


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