A New L-Asparaginase With Antitumour Activity

Wade, H. E.; Elsworth, R.; Herbert, Deanna; Keppie, J.; Sargeant, K.

doi:10.1016/s0140-6736(68)90977-x

Cited by 93 publications

(33 citation statements)

References 4 publications

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“…Asparaginases from three other bacteria, Serratia Marcescens (104), Erwinia carotovora (117), and Erwinia aroideae (89) also inhibit tumor growth:but that from Bacillus coagulans does not (64). Clinical trials with human patients are now being carried out with asparaginases from~-coli (38,78,79) and f· carotovora (89) .…”

Section: Asparaginase As An Antitumor Agentmentioning

confidence: 99%

L-Asparagine degradation in saccharomyces cerevisiae: Genetic control and biochemical properties of yeast L-asparaginase

Jones¹

1970

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Section: Asparaginase As An Antitumor Agentmentioning

confidence: 99%

L-Asparagine degradation in saccharomyces cerevisiae: Genetic control and biochemical properties of yeast L-asparaginase

Jones¹

1970

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“…In contrast to the normal cell, blasts lack sufficient asparagine synthetase capacity and depend on circulating asparagine (Chabner & Collins, 1990;Capizzi & Holcenberg, 1993;Miller et al, 1969;Ohnuma et al, 1970 (Mashburn & Landin, 1970;Wade et al, 1968).…”

mentioning

confidence: 99%

Dose reduction of asparaginase under pharmacokinetic and pharmacodynamic control during induction therapy in children with acute lymphoblastic leukaemia

et al. 1997

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The enzyme asparaginase is an important element in the therapy of acute lymphoblastic leukaemia (ALL). The usual asparaginase dose as prescribed in the ALL‐BFM‐86/90 treatment protocol for the therapy of ALL is 10 000 IU/m2 at 3 d intervals and had been developed on the basis of the E. coli asparaginase preparation CrasnitinTM from the Bayer company. Using the described schedule the E. coli asparaginase preparation from the Medac company shows significantly higher biological activity than the Bayer preparation. These findings prompted an attempt to reduce the dose of the Asparaginase medacTM under careful pharmacokinetic and pharmacodynamic monitoring. At the first step of dose reduction in ALL treatment protocol I, 11 children received 5000 IU/m2 of Asparaginase medacTM. Another 15 children were given 2500 IU/m2 of the enzyme at the second step of dose reduction. Prior to each asparaginase dose, blood samples were taken to determine amino acids and trough enzyme activity. Concurrent with the asparaginase monitoring, the coagulation parameters were measured. 96% of samples from the first step of dose reduction (5000 IU/m2 every third day) showed complete L‐asparagine depletion (<0.1 μM), the median trough enzyme acitivity was 265 IU/l. At the second step of dose reduction (2500 IU/m2) complete L‐asparagine depletion was seen in 97% of samples, and the median trough enzyme acitivity was 102 IU/l. Cerebrospinal fluid (CSF) depletion was complete in all samples tested (11/11). We concluded that an Asparaginase medacTM dose reduced from the usual 10000 IU/m2 down to 5000 IU/m2 or 2500 IU/m2, applied at 3 d intervals, was sufficient to achieve complete L‐asparagine depletion in serum. Changes of the fibrinogen levels was significantly less pronounced in the group on 2500 IU.

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“…The enzyme may be specific for N4-ethylasparagine, but is probably an asparaginase. Certainly, the asparaginase of Erwinia cartovora will hydrolyse N4-ethylasparagine at 0.4 % of the rate at which it attacks its normal substrate (Howard & Carpenter, 1972 (Ramadan et al, 1964;Wade et al, 1968;Wriston, 1971;Howard & Carpenter, 1972), whereas those transaminating the amide occur mainly in higher plants and animals (Meister et al, 1952;Meister & Fraser, 1954;Guitton, 1963;Cincerova, 1969;Lea & Fowden, 1975 (Soda et al, 1965(Soda et al, , 1966. However, its immediate fate in higher plants is uncertain, though Kito et al (1966Kito et al ( , 1968 have studied the breakdown of N5- ethyl-L-glutamine in Thea sinensis.…”

Section: Discussionmentioning

confidence: 99%

The biochemical pathway for the breakdown of N4-ethyl-L-asparagine in the bacterium Pseudomonas stutzeri

Dineen¹,

Gray²

1978

Biochemical Journal

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N4-Ethyl-L-[u-14C]asparagine and L-[U-14C]aspartate give identical metabolites, mainly intermediates of the tricarboxylic acid cycle and related amino acids, in whole cells of Pseudomonas stutzeri. The labelled asparagine derivative is converted into [14C]-aspartate by cell-free extracts, and this reaction, which has an optimum pH of 8.8 +/- 0.2, is neither inhibited by unlabelled asparagine nor enhanced by unlabelled 2-oxoglutarate. No labelled keto acid corresponding to N4-ethylasparagine was detected in either whole cells or cell-free extracts. Thus N4-ethyl-L-asparagine, like asparagine, must be broken down by hydrolysis, at least in this bacterium.

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A New L-Asparaginase With Antitumour Activity

Cited by 93 publications

References 4 publications

L-Asparagine degradation in saccharomyces cerevisiae: Genetic control and biochemical properties of yeast L-asparaginase

L-Asparagine degradation in saccharomyces cerevisiae: Genetic control and biochemical properties of yeast L-asparaginase

Dose reduction of asparaginase under pharmacokinetic and pharmacodynamic control during induction therapy in children with acute lymphoblastic leukaemia

The biochemical pathway for the breakdown of N4-ethyl-L-asparagine in the bacterium Pseudomonas stutzeri

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