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)

The effects of E. coli L-asparaginase on cultured human pancreatic carcinoma (MIA PaCa-2) have been studied. The enzyme (1 U/ml) inhibited growth and protein synthesis in both MIA PaCa-2 and PANC-1, another pancreatic carcinoma cell line, but had little or no effect on human breast carcinoma or melanoma cells. The inhibition of protein synthesis by E. coli L-asparaginase was largely reversed by L-glutamine but not by L-asparagine. The growth of both MIA PaCa-2 and PANC-1 showed absolute dependence on L-glutamine. These results indicate that the effect of E. coli L-asparaginase on cultured pancreatic carcinoma cells is exerted at least in part through its L-glutaminase activity. Although the addition of L-glutamine to the culture appeared to prevent cell death caused by L-asparaginase, it did not restore the ability of the cells to proliferate. Asparaginase derived from vibrio succinogenes, which is virtually free of L-glutaminase activity, was equally inhibitory to MIA PaCa-2 cell growth but did not affect protein synthesis. It is concluded that the inhibition of growth of cultured pancreatic carcinoma cells by E. coli asparaginase is a combined function of both its L-asparaginase and L-glutaminase activity.
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PMID:Mechanism of sensitivity of cultured pancreatic carcinoma to asparaginase. 36 26

The effect of L-glutamine and L-asparagine depletion by Acinetobacter L-glutaminase-L-asparaginase on the toxicity and antitumor activity of L-(alphaS,5S)-alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid (NSC-163501) was tested in mice. The LD50 of six daily doses of NSC-163501 in BDF1 female mice decreased from 7.5 to 0.3 mg/kg/day by combination treatment with the enzyme. Enzyme therapy also decreased the dose of NSC-163501 needed for maximal prolongation of survival in these mice inoculated with L1210 leukemia. Nevertheless, the combination did not prolong survival in L1210-bearing mice beyond that of higher doses of NSC-163501 alone. In contrast, the combination of enzyme plus NSC-163501 inhibited the growth of established sc implanted Ehrlich ascites carcinoma in ICRf male mice much more than either agent alone. Treatment with Acinetobacter L-glutaminase-L-asparaginase decreased the L-asparagine and L-glutamine levels in acid extracts of the Ehrlich tumor. NSC-163501 did not affect the amide levels or alter the decrease produced by enzyme therapy.
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PMID:Enhanced effect of an L-glutamine antagonist, L-(alphaS,5S)-alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid, by Acinetobacter L-glutaminase-L-asparaginase. 46 50

An undifferentiated human pancreatic carcinoma has been established in continuous culture and is grown in Dulbecco's modified. Eagle's medium fortified with 10% fetal calf serum and 2.5% horse serum. The established cell line (MIA PaCa-2) has a doubling time of 40 h. The cells are large with abundant cytoplasm, exhibit a high degree of aneuploidy and have a tendency to grow on top of other cells. MIA PaCa-2 grows in soft agar with a colony-forming efficiency of 19%. Both MIA PaCa-2 cells and a cell line from another pancreatic carcinoma obtained from National Cancer Institute (NCI) are sensitive to asparaginase, a property not shared by several other human tumor cell lines tested.
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PMID:Human pancreatic carcinoma (MIA PaCa-2) in continuous culture: sensitivity to asparaginase. 83 18

Human cell lines resistant to L-asparaginase or albizziin were isolated by multistep selection of HT1080 fibrosarcoma and MIA PaCa-2 pancreatic carcinoma cells. Mutants were cross-resistant to both drugs, but more resistant to the drug used for selection. The drug-resistant cell lines expressed elevated levels of asparagine synthetase activity and protein, up to 17-fold over that of the parental cells. Enzyme overproduction was due to gene amplification in the albizziin-resistant cells, whereas increased expression without amplification was observed in L-asparaginase-resistant cells.
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PMID:Molecular and genetic characterization of human cell lines resistant to L-asparaginase and albizziin. 196 81

Among the neurological side-effects, peripheral neuropathy is a result of therapy with vindesine and above all vincristine. Although in most cases it is responsible only for paresthesias, it may cause extensive paralysis and requires that the drug be discontinued. These drugs may also affect the neurovegetative system. Ototoxicity may be seen with cis-platinum and vigilance disturbances with L-asparaginase. Genetic consequences are mainly due to alkylating agents. These agents almost constantly impair male and female fertility but recovery is possible. Libido is also affected with the attendant psychological consequences. The offspring of patients previously treated by chemotherapeutic agents are normal. Development of secondary carcinoma or leukemia is currently a major concern. Secondary malignant disease may develop after the treatment of any cancer, especially if radiotherapy was associated with alkylating agents. Leukemias are of the acute myeloid type and usually follow a preleukemic phase. A table summarizes the main toxicities of the most usual drugs.
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PMID:[Complications of antitumor and antileukemia chemotherapy. 3 (conclusion)]. 629 11

We tested the effectiveness of dihydroxyanthracenedione (DHAD) on cell growth of two human pancreatic carcinoma cell lines MIA PaCa-2 and PANC-1. At the level of ID50, the drug was almost equally effective against both cell lines. When the time exposure of MIA PaCa-2 cells to the drug was increased from 1 h to continuous exposure for 5 days, the ID50 was decreased about three-fold only (1.4 X 10(-8)M and 4 X 10(-9)M respectively). At the level of ID50 also the difference between 6 h exposure and continuous exposure for 5 days was minimal. In equimolar concentrations and with 1 h exposure, DHAD was more effective against MIA PaCa-2 cells than other chemotherapeutic agents including adriamycin, mitomycin-C, 5-FU, vincristine, vindesine, vinblastine, VP-16-213, bleomycin, cis-platinum, asparaginase and acivicin. In concentrations of 5 X 10(-7)M, DHAD caused about 40% inhibition of 14C-thymidine incorporation of MIA PaCa-2 cells. Treatment of MIA PaCa-2 cells with the ID50 of DHAD for 1 h caused retardation of cellular traverse, with the major effect appearing to be in G2 + M phase of the cycle. From these data DHAD appears to be a potent drug against human pancreatic carcinoma in vitro.
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PMID:Sensitivity of cultured human pancreatic carcinoma cells to dihydroxyanthracenedione. 669 38

The histidine ammonia-lyase from bacterial strain CAMR 5315 was partially purified to assess its effect on the growth of murine tumours. This strain was selected as the source after an extensive screening programme for histidine ammonia-lyases. The enzyme was partially purified by ammonium sulphate fractionation, chromatography on DEAE-cellulose and Sephadex G-150. The enzyme reduced circulating L-histidine levels in Wistar rats and in mice persisted with a half-life of 6-7 h. Neither LDH virus nor chemical modification with ethylacetimidate increased the half-life as observed with L-asparaginase and L-glutaminase. The enzyme was tested in mice against Ehrlich carcinoma, L5178Y lymphoblastic leukaemia, Mc/S sarcoma, B16 melanoma, P8157 mastocytoma, P1798 lymphosarcoma and the Gardner 6C3HED lymphosarcoma. The only tumours to show sensitivity to the enzyme were the Mc/S sarcoma against which a 65% increase in life span was observed at the highest enzyme dose, 1000 U/kg on alternate days over 14 days and the Ehrlich ascites carcinoma where cures were obtained at 250 U/kg on alternate days over 14 days, but only at inocula levels of 10(5) and 10(3) cells/animal respectively.
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PMID:The effect of histidine ammonia-lyase on some murine tumours. 688 63

Cultured human pancreatic carcinoma cells (MIA PaCa-2) have been shown previously to be very sensitive to E. coli L-asparaginase (EC II). The present studies have demonstrated that another enzyme, Acinetobacter glutaminase-asparaginase (AGA) is much more effective in inhibiting cell growth. At the concentration of 0.0025 U/ml of AGA activity the enzyme totally inhibited cell growth, whereas the EC II with the same concentration did not show any effect. The inhibition of cell growth correlated well with inhibition of protein and glycoprotein synthesis. The addition of L-glutamine at the concentration of 1 mM completely reversed the inhibition of protein synthesis. Similarly, the addition of L-glutamine at the concentration of 3 mM daily on 3 successive days after adding AGA resulted in significant reversal of growth inhibition. The results of this study indicate that the action of AGA on MIA PaCa-2 is, to a great extent, exerted through its L-glutaminase activity.
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PMID:Sensitivity of cultured pancreatic carcinoma cells to Acinetobacter glutaminase-asparaginase. 717 49

L-Asparaginase was given to ten patients with advanced nonresectable pancreatic carcinoma because of the demonstration of in vitro sensitivity of the tumor to the drug. No therapeutic value was demonstrated for L-asparaginase. Toxicity was significant, mainly as evidenced by increasing mental confusion and early signs of a coagulopathy. On the basis of this limited study, L-asparaginase seems to have no value in advanced pancreatic carcinoma. The usefulness of L-asparaginase as primary therapy in patients with less advanced disease remains to be determined.
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PMID:Phase II study of L-asparaginase in the treatment of pancreatic carcinoma. 747 Nov 24

Ten percent (214/2,059) of all dogs with cancer at North Carolina State University Veterinary Teaching Hospital had thrombocytopenia. The thrombocytopenia was associated with infectious/inflammatory etiologies in 4%, miscellaneous disorders (therapy, bone marrow failure, disseminated intravascular coagulation) in 35%, and neoplasia without identifiable secondary factors in 61% of cancer-bearing dogs. Classifying these dogs by tumor groups revealed the following proportionate ratios: lymphoid, 29%; carcinoma, 28%; sarcoma, 20%; hemic neoplasia, 7%; multiple, 5%; unclassified, 3%; benign, 3%; brain, 3%; and endocrine, 3%. Dogs with hemangiosarcoma, lymphoma, and melanoma were at increased risk of developing thrombocytopenia. Cytotoxic therapy was the major factor increasing the risk of thrombocytopenia in dogs with melanoma. Golden Retrievers were the only breed recognized with a predisposition to develop thrombocytopenia. If thrombocytopenia is identified in a dog with cancer, we recommend thorough evaluation of the coagulation system before surgery or therapy, and careful consideration of the risks and potential benefits of myelosuppressive or L-asparaginase therapy.
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PMID:Thrombocytopenia associated with neoplasia in dogs. 788 25


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