ライフサイエンスコーパス: L-asparaginase

1 xpectedly high rate of allergic reactions to L-asparaginase.

2 a continuous infusion of high-dose ara-C and L-asparaginase.

3 n regimen of vincristine, dexamethasone, and l-asparaginase.

4 th a regimen of prednisone, vincristine, and L-asparaginase.

5 present in lymphoblasts are able to degrade l-asparaginase.

6 duction and then high-dose methotrexate with l-asparaginase.

7 ase (ASNS) was not predictive of response to l-asparaginase.

8 poside, but not to a non-DNA damaging agent, l-asparaginase.

9 n pattern was associated with sensitivity to l-asparaginase.

10 almost identical to that observed for other L-asparaginases.

11 ent regions found in other type-II bacterial L-asparaginases.

12 th the structures of other type-II bacterial L-asparaginases.

13 cement rather than a ping-pong mechanism for l-asparaginases.

14 Because gpASNase1 and human L-asparaginase 1 (hASNase1) share 70% amino-acid identi

15 biochemically characterized the enzyme human L-asparaginase 3 (hASNase3), which possesses L-asparagin

16 After exposure to l-asparaginase, 5 cell lines and 10 clinical samples exh

17 L-asparaginase 3 (hASNase3), which possesses L-asparaginase activity and belongs to the N-terminal nu

18 ty than WoA-P121, yet both showed comparable L-asparaginase activity.

19 e regimen of vincristine, dexamethasone, and L-asparaginase against Ph-like ALL xenografts, offering

20 Current FDA-approved l-asparaginases also possess significant l-glutaminase a

21 Over the past several decades, L-asparaginase, an important component of therapy for ac

22 Regimens containing l-asparaginase and drugs unaffected by P-glycoprotein ar

23 n the amino acid sequence of W. succinogenes L-asparaginase and that of related enzymes are discussed

24 emotherapeutic agents including doxorubicin, l-asparaginase, and dexamethasone.

25 Since currently approved L-asparaginases are of bacterial origin, immunogenicity

26 L-Asparaginases are used to treat acute lymphoblastic le

27 Coupled with the success of L-asparaginase as a therapy for childhood leukemia, the

28 illing factor was shown to be an enzyme with L-asparaginase (ASNase) activity.

29 l-asparaginase (ASNase) is a first-line therapy for ALL

30 L-Asparaginases (ASNases) have been used as first line d

31 ic syndrome in acute promyelocytic leukemia, L-asparaginase-associated thrombosis, leukemic meningiti

32 thylene glycol conjugate of Escherichia coli L-asparaginase, by intravenous infusion in children with

33 sted of five drugs (vincristine, prednisone, l-asparaginase, daunorubicin, and cyclophosphamide).

34 ion current treatment of ALL using different l-asparaginase delivery and encapsulation methods as wel

35 or treatment with the glutaminolytic enzyme l-asparaginase depleted the cell contents of Gln, glutam

36 e structural and functional integrity of the L-asparaginase domain and provide a direct comparison of

37 nd a novel dosing method of Escherichia coli L-asparaginase (EC-Asnase) in children and adolescents w

38 Bacterial L-asparaginases, enzymes that catalyze the hydrolysis of

39 ribed structures of the Erwinia chrysanthemi l-asparaginase (ErA) to inform the design of mutants wit

40 res of the complexes of Erwinia chrysanthemi L-asparaginase (ErA) with the products of such reactions

41 s for the clinical agents 5-fluorouracil and L-asparaginase exemplify how variations in the transcrip

42 samples, increased expression of ASNS after l-asparaginase exposure was not associated with in vitro

43 f an evolutionary conserved motif among this L-asparaginase family.

44 We are exploring the guinea pig L-asparaginase (gpASNase1) as a potential replacement of

45 We recently identified the low KM guinea pig L-asparaginase (gpASNase1).

46 Our long-term goal is the design of a human l-asparaginase (hASNase3) variant, suitable for use in c

47 ic use, we determined the structure of human l-asparaginase (hASNase3).

48 Many side effects of current FDA-approved L-asparaginases have been related to their secondary L-g

49 However, all human L-asparaginases have millimolar KM for asparagine.

50 respondingly, pharmacologic profiling showed L-asparaginase hypersensitivity in the siTop1 cells.

51 del of infection, S Typhimurium lacking both l-asparaginase I and II genes competes poorly with wild-

52 rily to the periplasm and acts together with l-asparaginase I to provide S Typhimurium the ability to

53 L-asparaginase structural homology isozymes L-asparaginases I (AnsA) and II (AnsB), which are shown

54 rapy with a glucocorticoid, vincristine, and L-asparaginase if the patient responds poorly.

55 Escherichia coli L-asparaginase II (EcAII), the only nonhuman enzyme appr

56 , we have studied the catalytic mechanism of L-asparaginase II computationally.

57 S. Typhimurium lacking the L-Asparaginase II gene (STM3106) are unable to inhibit T

58 L-Asparaginase II is necessary and sufficient to suppres

59 Furthermore, we report that l-asparaginase II localizes primarily to the periplasm a

60 aragine deprivation such as that mediated by l-asparaginase II of S Typhimurium causes suppression of

61 We previously showed that l-asparaginase II produced by Salmonella enterica serova

62 (dsbA) of Escherichia coli, is required for l-asparaginase II stability and function.

63 homogeneity determined that the periplasmic l-asparaginase II, AnsB (EC 3.5.1.1), co-purified with A

64 murium inhibit T cell responses by producing L-Asparaginase II, which catalyzes the hydrolysis of L-a

65 L-Asparaginase-II from Escherichia coli (EcA) is a centr

66 h at baseline and after in vitro exposure to l-asparaginase in cell lines and pediatric ALL samples.

67 s not associated with in vitro resistance to l-asparaginase, indicating that ASNS-independent mechani

68 but not in normal lymphocytes, ABT-737 plus L-asparaginase induced greater mitochondrial depolarizat

69 orated cyclophosphamide and the early use of L-asparaginase into the backbone of daunorubicin, vincri

70 L-asparaginase is a chemotherapy drug used to treat acut

71 l-Asparaginase is a key therapeutic agent for treatment

72 l-asparaginase is a universal component of treatment for

73 of the two Bacillus subtilis genes encoding L-asparaginase is controlled by independent regulatory f

74 kemic protein macromolecule Escherichia coli L-asparaginase is degraded by leukemic lysosomal cystein

75 L-asparaginase is important in the induction regimen for

76 e main prerequisite for clinical efficacy of L-asparaginases is micromolar KM for asparagine to allow

77 l-asparaginase (l-ase) is an anticancer agent also harbo

78 L-Asparaginase (L-ASP) is a key component of therapy for

79 Allergies to Escherichia coli L-asparaginase (L-ASP) occurred in 35% of patients.

80 Type II bacterial L-asparaginases (L-ASP) have played an important therape

81 y, we also show that these highly human-like L-asparaginases maintain their in vitro ALL killing pote

82 s, we successfully predicted the more active L-asparaginase mutants N24T and N24A.

83 To investigate the effect of l-asparaginase on acute lymphoblastic leukemia (ALL), we

84 l-asparaginase, one of the primary drugs used in treatme

85 served in all 7 cell lines with ABT-737 plus L-asparaginase or vincristine, and in 5 of 7 cell lines

86 -glutaminase activity of these highly active l-asparaginases, our engineered ErA variants hold promis

87 Bacterial L-asparaginases play an important role in the treatment

88 The mechanisms of therapeutic failure with l-asparaginase remain speculative.

89 This bacterial-type cytoplasmic L-asparaginase resides in the N-terminal subdomain of an

90 that ASNS-independent mechanisms of in vitro l-asparaginase resistance are common in ALL.

91 LL cells may provide a novel way to overcome l-asparaginase resistance.

92 seline gene expression pattern distinguished l-asparaginase sensitivity from resistance.

93 ructure of ErA with those of other bacterial L-asparaginases shows that the presence of two active-si

94 he characterization of water dynamics on the L-asparaginase structural homology isozymes L-asparagina

95 sed on the characterization of another human L-asparaginase, termed hASNase1.

96 understanding of the catalytic mechanism of L-asparaginases that is in agreement with the available

97 y mutational analysis to encode a functional L-asparaginase, the expression of which is activated dur

98 The addition of dexamethasone and/or L-asparaginase to reduced-intensity dasatinib therapy im

99 he present study, we successfully engineered L-asparaginase to resist proteolytic cleavage and at the

100 The exact mechanism used by L-asparaginases to catalyze the hydrolysis of asparagine

101 ination with vincristine, dexamethasone, and L-asparaginase (VXL) in 7 ALL cell lines.

102 e the MTD in combination with cytarabine and l-asparaginase was 2 mg/m(2).

103 n of the ansA gene, which encodes the second L-asparaginase, was found to be induced by asparagine.

104 he N24A and N24A R195S mutations to the drug L-asparaginase, we are a step closer to individualized d

105 tertiary structure of Wolinella succinogenes L-asparaginase were determined, and were compared with t

106 esult of this observation, several bacterial L-asparaginases were developed and are currently approve

107 notable examples of a therapeutic enzyme is L-asparaginase, which has been established as an antileu

108 S-PEG), a pegylated form of Escherichia coli L-asparaginase with a succinimidyl succinate (SS) linker

109 our engineered ErA variants hold promise as l-asparaginases with fewer side effects.

110 Therefore, l-asparaginases with reduced l-glutaminase activity are

111 The Wolinella succinogenes L-asparaginase (WoA) has been reported to be L-glutamina