ライフサイエンスコーパス: asparaginase

1 mplementary roles in the hepatic response to asparaginase.

2 regimen of vincristine, dexamethasone, and l-asparaginase.

3 se who received intramuscular native E colil-asparaginase.

4 e and mediating GCN2-mTORC1 signaling during asparaginase.

5 required for downregulation of mTORC1 during asparaginase.

6 ent of macrophagelike cells in the uptake of asparaginase.

7 a regimen of prednisone, vincristine, and L-asparaginase.

8 resent in lymphoblasts are able to degrade l-asparaginase.

9 e of asparaginase-associated pancreatitis to asparaginase.

10 was more pronounced in those not allergic to asparaginase.

11 er and pancreas by E. coli but not Wolinella asparaginase.

12 ction and then high-dose methotrexate with l-asparaginase.

13 side, but not to a non-DNA damaging agent, l-asparaginase.

14 ent ER stress during amino acid depletion by asparaginase.

15 was retained in Atf4 (-/-) mice treated with asparaginase.

16 uld be beneficial to replace them with human asparaginases.

17 ment rather than a ping-pong mechanism for l-asparaginases.

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

19 n a randomised comparison of intravenous PEG-asparaginase (15 doses of 2500 IU/m(2) every 2 weeks) or

20 with asparaginase-associated pancreatitis to asparaginase, 18 acute lymphoblastic leukaemia trial gro

21 luded an additional eight doses of pegylated asparaginase, 18 doses of vincristine, and escalated-dos

22 ent inactivation of PEGasparaginase, Erwinia asparaginase (20 000 IU/m(2) 2-3 times weekly) was given

23 nd received a single dose of intravenous PEG-asparaginase (2500 IU/m(2)) over 1 hour during remission

24 P2 evaluated whether substitution of Erwinia asparaginase 25000 IU/m(2) for 6 doses given intramuscul

25 Following allergy to pegaspargase, Erwinia asparaginase 25000 IU/m(2) x 6 intramuscularly M/W/F can

26 ochemically characterized the enzyme human L-asparaginase 3 (hASNase3), which possesses L-asparaginas

27 ld-type and GCN2 null mice were treated with asparaginase (3 IU per g of body weight), rapamycin (2 m

28 ery 2 weeks) or intramuscular native E colil-asparaginase (30 doses of 25 000 IU/m(2) weekly), beginn

29 The antileukemic drug asparaginase, a key component in the treatment of acute

30 Asparaginase, a widely used chemotherapeutic agent, arre

31 Asparaginase activates the integrated stress response (I

32 The anti-leukemic agent asparaginase activates the integrated stress response (I

33 The proportion of patients with plasma asparaginase activity >/= 100 mIU/mL and >/= 400 mIU/mL

34 spargase would provide a 48-hour nadir serum asparaginase activity (NSAA) >/= 0.10 IU/mL.

35 adjusted every 3 weeks based on nadir serum asparaginase activity (NSAA) determinations.

36 00 achieves a significantly longer period of asparaginase activity above defined thresholds and aspar

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

38 ng identified Q59L as a variant that retains asparaginase activity but shows undetectable glutaminase

39 The mean half-life of plasma asparaginase activity for both SC-PEG doses was approxim

40 Serum asparaginase activity more than 0.1 IU/mL was detected i

41 The median nadir serum asparaginase activity was significantly higher in patien

42 endpoints were disease-free survival, serum asparaginase activity, and quality of life during therap

43 Hypoalbuminemia, a biomarker of asparaginase activity, was associated with a lower dexam

44 rameters were estimated by fitting the serum asparaginase activity-time course for all 6 doses given

45 cleavage reaction, all are essential for the asparaginase activity.

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

47 Erwinia asparaginase administered with this schedule achieved th

48 regimen of vincristine, dexamethasone, and L-asparaginase against Ph-like ALL xenografts, offering a

49 The strongest risk factors for asparaginase allergy are variants within genes regulatin

50 is and thromboembolic complications, but not asparaginase allergy, was higher in patients 10 years of

51 Current FDA-approved l-asparaginases also possess significant l-glutaminase act

52 Over the past several decades, L-asparaginase, an important component of therapy for acut

53 94) for patients assigned to intravenous PEG-asparaginase and 89% (85-93) for those assigned to intra

54 Regimens containing l-asparaginase and drugs unaffected by P-glycoprotein are

55 The mutant shows completely preserved asparaginase and glutaminase activities, long-term stora

56 orly understood, in part because of its dual asparaginase and glutaminase activities.

57 ive toxicity and efficacy of intravenous PEG-asparaginase and intramuscular native E colil-asparagina

58 However, the asparaginase and intravenous methotrexate used in the au

59 Asparaginase and rapamycin each inhibited mTORC1 signali

60 esident kinase (PERK) in controlling AADR to asparaginase and to compare the effects of asparaginase

61 otherapeutic agents including doxorubicin, l-asparaginase, and dexamethasone.

62 b with vincristine, dexamethasone, pegylated asparaginase, and doxorubicin had acceptable toxicity.

63 Older age, higher exposure to asparaginase, and higher Native American ancestry were i

64 ith dasatinib, sequentially with cytarabine, asparaginase, and methotrexate for 6 months.

65 n of hedgehog signaling proteins, plant-type asparaginases, and pyruvoyl enzymes.

66 e was also more common in patients with anti-asparaginase antibodies (P = .019).

67 igher incidence of hypersensitivity and anti-asparaginase antibodies in patients with HLA-DRB1*07:01

68 The presence of asparaginase antibodies was related to allergies and sil

69 examethasone is higher in patients with anti-asparaginase antibodies.

70 a-tive (10.6 +/- 5.99 L/h per m(2)) for anti-asparaginase antibodies.

71 f plasma clearance of dexamethasone and anti-asparaginase antibody levels on risk of relapse was asse

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

73 Bacterial asparaginases are used in cancer chemotherapy to deplete

74 L-Asparaginases are used to treat acute lymphoblastic leuk

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

76 thotrexate, glucocorticoid, vincristine, and asparaginase, as well as early triple intrathecal therap

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

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

79 L-Asparaginases (ASNases) have been used as first line dru

80 ng periplasmic enzymes glutaminase (Ggt) and asparaginase (AsnB).

81 ed that therapeutic drug monitoring (TDM) of asparaginase (ASP) activity levels in plasma may be an i

82 to asparaginase, including 59 after a severe asparaginase-associated pancreatitis (abdominal pain or

83 as not associated with severity of the first asparaginase-associated pancreatitis and a second aspara

84 ned as acute and persisting complications of asparaginase-associated pancreatitis and risk of re-expo

85 dominal pain after having had two versus one asparaginase-associated pancreatitis did not differ (thr

86 aginase-associated pancreatitis and a second asparaginase-associated pancreatitis did not involve an

87 ations and risk of re-exposing patients with asparaginase-associated pancreatitis to asparaginase, 18

88 exposing patients who suffered an episode of asparaginase-associated pancreatitis to asparaginase.

89 Asparaginase-associated pancreatitis was defined by at l

90 Risk of a second asparaginase-associated pancreatitis was not associated

91 INTERPRETATION: Since the risk of a second asparaginase-associated pancreatitis was not associated

92 44 (46%) patients developed a second asparaginase-associated pancreatitis, 22 (52%) of 43 bei

93 1 year after diagnosis of asparaginase-associated pancreatitis, 31 (11%) of 275 pa

94 Of 465 patients with asparaginase-associated pancreatitis, 33 (8%) of 424 wit

95 sparaginase, hyperlipidaemia, osteonecrosis, asparaginase-associated pancreatitis, arterial hypertens

96 Within 8 years of asparaginase-associated pancreatitis, risk of abdominal

97 n 50 days of asparaginase exposure developed asparaginase-associated pancreatitis.

98 severe toxic effects of treatment, including asparaginase-associated pancreatitis.

99 syndrome in acute promyelocytic leukemia, L-asparaginase-associated thrombosis, leukemic meningitis,

100 hages as a rate-limiting factor in degrading asparaginase both in vitro and in vivo.

101 not only suffer from diminished exposure to asparaginase but also, by maintaining high clearance of

102 In wild-type mice, asparaginase but not rapamycin increased p-eIF2, p-ERK1/

103 or liver toxicity by the anti-leukemic agent asparaginase, but the mechanism is unknown.

104 Rapamycin modifies the hepatic AADR to asparaginase by preventing CHOP induction while maximizi

105 ylene glycol conjugate of Escherichia coli L-asparaginase, by intravenous infusion in children with A

106 of rapamycin (mTOR) and show that the enzyme asparaginase can be used to target this dependence.

107 Asparaginases catalyze the hydrolysis of the amino acid

108 Asparaginases catalyze the hydrolysis of the amino acid

109 MSCs protected ALL cells from asparaginase cytotoxicity in coculture experiments.

110 n current treatment of ALL using different l-asparaginase delivery and encapsulation methods as well

111 r treatment with the glutaminolytic enzyme l-asparaginase depleted the cell contents of Gln, glutamat

112 Asparaginase depletes circulating asparagine and glutami

113 structural and functional integrity of the L-asparaginase domain and provide a direct comparison of s

114 Cumulative asparaginase dose >/=120,000 IU/m(2) was associated with

115 a novel dosing method of Escherichia coli L-asparaginase (EC-Asnase) in children and adolescents wit

116 levels may also be inversely correlated with asparaginase efficacy in certain solid tumors as well.

117 , possibly affecting the interaction between asparaginase epitopes and the HLA-DRB1 protein.

118 alleles that confer high-affinity binding to asparaginase epitopes lead to a higher frequency of reac

119 the binding affinity of HLA-DRB1 alleles for asparaginase epitopes, and patients whose HLA genetics p

120 bed structures of the Erwinia chrysanthemi l-asparaginase (ErA) to inform the design of mutants with

121 the tetrameric enzyme Erwinia chrysanthemil-asparaginase (ErA), in which case electrophoresis-compat

122 erapy intensification (including 30 weeks of asparaginase exposure and dexamethasone/vincristine puls

123 1996, and Jan 1, 2016, who within 50 days of asparaginase exposure developed asparaginase-associated

124 echanisms of liver protection during chronic asparaginase exposure in mice.

125 aginase, suggesting mTORC1 inhibition during asparaginase exposure is not driven via eIF2-ATF4-Sestri

126 ic risk factors identifying patients in whom asparaginase exposure should be restricted is needed.

127 amples, increased expression of ASNS after l-asparaginase exposure was not associated with in vitro r

128 sensitivity reactions can lead to suboptimal asparaginase exposure.

129 of mTORC1 and maintenance of ApoB100 during asparaginase exposure.

130 n, obesity promotes a maladaptive ISR during asparaginase exposure.

131 ot increased in the pancreas or by Wolinella asparaginase, expression of the amino acid stress respon

132 an evolutionary conserved motif among this L-asparaginase family.

133 etermined mainly by the anticipated need for asparaginase for antileukaemic efficacy.

134 sponses to this drug, mice were administered asparaginase from either Escherichia coli (clinically us

135 AnsA is the cytoplasmic asparaginase from Escherichia coli involved in intracell

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

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

138 nt-proxy in the intramuscular native E colil-asparaginase group than in the intravenous PEG-asparagin

139 ions (47 [20%] of 232 in the intravenous PEG-asparaginase group vs 51 [22%] of 231 patients in the in

140 [28%] of 232 patients in the intravenous PEG-asparaginase group vs 59 [26%] of 231 patients in the in

141 of 231 patients in the intramuscular E colil-asparaginase group) and asparaginase-related allergic re

142 patients in the intramuscular native E colil-asparaginase group, p=0.60), or in the individual freque

143 paraginase group than in the intravenous PEG-asparaginase group.

144 Pegylated Escherichia coli asparaginase (PEG-asparaginase) has a longer half-life and is potentially

145 ur long-term goal is the design of a human l-asparaginase (hASNase3) variant, suitable for use in can

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

147 Similar to nonmammalian plant-type asparaginases, hASRGL1 is shown to be an Ntn hydrolase f

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

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

150 14 acute toxic effects (hypersensitivity to asparaginase, hyperlipidaemia, osteonecrosis, asparagina

151 de approach to identify loci associated with asparaginase hypersensitivity in children with ALL enrol

152 spondingly, pharmacologic profiling showed L-asparaginase hypersensitivity in the siTop1 cells.

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

154 ly to the periplasm and acts together with l-asparaginase I to provide S Typhimurium the ability to c

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

156 py with a glucocorticoid, vincristine, and L-asparaginase if the patient responds poorly.

157 Escherichia coli L-asparaginase II (EcAII), the only nonhuman enzyme approv

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

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

160 L-Asparaginase II is necessary and sufficient to suppress

161 Furthermore, we report that l-asparaginase II localizes primarily to the periplasm and

162 agine deprivation such as that mediated by l-asparaginase II of S Typhimurium causes suppression of a

163 We previously showed that l-asparaginase II produced by Salmonella enterica serovar

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

165 omogeneity determined that the periplasmic l-asparaginase II, AnsB (EC 3.5.1.1), co-purified with Aph

166 rium inhibit T cell responses by producing L-Asparaginase II, which catalyzes the hydrolysis of L-asp

167 L-Asparaginase-II from Escherichia coli (EcA) is a central

168 stingly, rapamycin blocked CHOP induction by asparaginase in both wild-type and GCN2 null livers.

169 sparaginase and intramuscular native E colil-asparaginase in children with newly diagnosed acute lymp

170 not always completely depleted with Erwinia asparaginase in contrast to PEGasparaginase.

171 Use of native E coli asparaginase in induction leads to high hypersensitivity

172 ntensification after receiving native E coli asparaginase in induction.

173 t GCN2 is required for activation of AADR to asparaginase in liver.

174 ution studies showed a rapid accumulation of asparaginase in macrophage-rich tissues such as the live

175 iew collates research on the use of enzymes, asparaginase in particular, to mitigate acrylamide forma

176 i asparaginase (PEGasparaginase) and Erwinia asparaginase in pediatric acute lymphoblastic leukemia (

177 ls markedly prolonged the serum half-life of asparaginase in vivo and decreased drug uptake in these

178 yme a suitable replacement for the bacterial asparaginases in cancer therapy.

179 96 patients were re-exposed to asparaginase, including 59 after a severe asparaginase-a

180 In experiment 1, asparaginase increased hepatic p-eIF2 in wild-type mice

181 not associated with in vitro resistance to l-asparaginase, indicating that ASNS-independent mechanism

182 ut not in normal lymphocytes, ABT-737 plus L-asparaginase induced greater mitochondrial depolarizatio

183 e is a genetic component to the mechanism of asparaginase-induced immune responses, we imputed human

184 sm is unknown, and genetic predisposition to asparaginase-induced pancreatitis has not been previousl

185 To determine clinical risk factors for asparaginase-induced pancreatitis, we studied a cohort o

186 e CPA2 gene had a markedly increased risk of asparaginase-induced pancreatitis.

187 After vincristine, prednisone, and asparaginase induction, 650 of 653 eligible patients att

188 ASNS inhibitor amino sulfoximine 5 (AS5) or asparaginase inhibited mouse and human sarcoma growth in

189 pancreatitis is one of the common causes of asparaginase intolerance.

190 L-asparaginase is a chemotherapy drug used to treat acute

191 Asparaginase is a critical agent used to treat acute lym

192 l-Asparaginase is a key therapeutic agent for treatment of

193 Consequently, asparaginase is a major component of ALL therapy, but th

194 Asparaginase is a powerful tool for the food industry an

195 Asparaginase is a therapeutic enzyme used to treat leuke

196 l-asparaginase is a universal component of treatment for c

197 This asparaginase is an N-terminal nucleophile (Ntn) family m

198 mic protein macromolecule Escherichia coli L-asparaginase is degraded by leukemic lysosomal cysteine

199 L-asparaginase is important in the induction regimen for t

200 regimens, but the optimal implementation of asparaginase is not well studied, considering its potent

201 We showed that asparaginase is rapidly cleared from the serum by liver-

202 nstrate that the nutrient stress response to asparaginase is tissue-specific and exacerbated by gluta

203 clude that intravenous administration of PEG-asparaginase is tolerable in children with ALL, and pote

204 Asparaginase is used to treat acute lymphoblastic leukem

205 main prerequisite for clinical efficacy of L-asparaginases is micromolar KM for asparagine to allow f

206 e depletion of blood asparagine by bacterial asparaginases is their low micromolar KM value.

207 l-asparaginase (l-ase) is an anticancer agent also harbori

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

209 Type II bacterial L-asparaginases (L-ASP) have played an important therapeut

210 Switching to Erwinia asparaginase leads to effective asparaginase levels in m

211 g to Erwinia asparaginase leads to effective asparaginase levels in most patients.

212 cus and identify the p.G178R mutation in the asparaginase like-1 gene (ASRGL1), segregating with the

213 and enzymatic characterization of the human asparaginase-like protein 1 (hASRGL1).

214 we also show that these highly human-like L-asparaginases maintain their in vitro ALL killing potent

215 Patients allergic to asparaginase may be doubly disadvantaged: they not only

216 ypothesized that higher systemic exposure to asparaginase may cause increased exposure to dexamethaso

217 donors, the authors support the notion that asparaginase may offer a therapeutic benefit in AML-not

218 we successfully predicted the more active L-asparaginase mutants N24T and N24A.

219 gned to receive intramuscular native E colil-asparaginase (n=231) or intravenous PEG-asparaginase (n=

220 olil-asparaginase (n=231) or intravenous PEG-asparaginase (n=232).

221 layed intensification consisted of pegylated asparaginase on day 4; vincristine, dexamethasone (alter

222 After one dose of pegylated asparaginase on induction day 4, plasma asparagine was u

223 o asparaginase and to compare the effects of asparaginase on mTORC1 to that of rapamycin.

224 l-asparaginase, one of the primary drugs used in treatment

225 Gcn2 (-/-), and Atf4 (-/-) mice treated with asparaginase or excipient and further explored selected

226 rved in all 7 cell lines with ABT-737 plus L-asparaginase or vincristine, and in 5 of 7 cell lines wi

227 verse effects included allergic reactions to asparaginase, osteonecrosis, thrombosis, and disseminate

228 lutaminase activity of these highly active l-asparaginases, our engineered ErA variants hold promise

229 ge (P < .001), and higher cumulative dose of asparaginase (P < .001).

230 ose assigned to intramuscular native E colil-asparaginase (p=0.58).

231 Pegylated Escherichia coli asparaginase (PEG-asparaginase) has a longer half-life a

232 longed courses of pegylated Escherichia coli asparaginase (PEGasparaginase) and Erwinia asparaginase

233 ellular and molecular components controlling asparaginase pharmacokinetics.

234 Bacterial L-asparaginases play an important role in the treatment of

235 ginase, supporting its use as the front-line asparaginase preparation in children with newly diagnose

236 ively by normal and leukemic cells, degraded asparaginase produced by Escherichia coli (ASNase) and E

237 dyl succinate (SS) linker, is the first-line asparaginase product used in Children's Oncology Group (

238 biochemical analysis of livers revealed that asparaginase provoked hepatic steatosis that coincided w

239 involve an increased risk of complications, asparaginase re-exposure should be determined mainly by

240 the key regions that govern cleavage and the asparaginase reaction, which may inform the design of va

241 ) for the enzyme-activating autocleavage and asparaginase reactions, we prepared the T168S, T186V and

242 E. coli asparaginase reduced protein synthesis in liver and sple

243 ntramuscular E colil-asparaginase group) and asparaginase-related allergic reactions (14 [6%] vs 6 [3

244 treatment group than in the standard group (asparaginase-related hypersensitivity in 18 [6.7%] in th

245 roup vs two [0.8%] in the standard group and asparaginase-related pancreatitis in eight [3.0%] vs one

246 er significantly in the overall frequency of asparaginase-related toxicities (65 [28%] of 232 patient

247 ised comparison was the overall frequency of asparaginase-related toxicities (defined as allergy, pan

248 The most common grade 3/4 asparaginase-related toxicities were lengthy hyperbiliru

249 Asparaginase-related toxicities were monitored after 173

250 There was no difference in asparaginase-related toxicity by EC-Asnase dosing method

251 = .04), but did not reduce the frequency of asparaginase-related toxicity.

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

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

254 at ASNS-independent mechanisms of in vitro l-asparaginase resistance are common in ALL.

255 believe to be a new basis for understanding asparaginase resistance in ALL and indicate that MSC nic

256 bitors may have clinical utility in treating asparaginase-resistant forms of childhood ALL.

257 hemotherapy (dexamethasone, vincristine, PEG-asparaginase) resulted in significantly improved surviva

258 characterization of water dynamics on the L-asparaginase structural homology isozymes L-asparaginase

259 the first N-terminal nucleophile plant-type asparaginase structure in the covalent intermediate stat

260 y-nine patients were included in the Erwinia asparaginase study; 2 (3%) developed an allergy and none

261 trin2, an ATF4 gene target, was increased by asparaginase, suggesting mTORC1 inhibition during aspara

262 y compared with intramuscular native E colil-asparaginase, supporting its use as the front-line aspar

263 d on the characterization of another human L-asparaginase, termed hASNase1.

264 ration (P < .001) and to a lower exposure to asparaginase than in the standard/high-risk arm.

265 her in patients who received intravenous PEG-asparaginase than in those who received intramuscular na

266 cooperative regulation of the intracellular asparaginase that is required for proper functioning wit

267 nderstanding of the catalytic mechanism of L-asparaginases that is in agreement with the available ex

268 ty of giving polyethylene glycosylated (PEG)-asparaginase, the polyethylene glycol conjugate of Esche

269 However, unlike the bacterial asparaginases, the human enzymes have a millimolar K(m)

270 munized mice and ALL patients who were given asparaginase therapy for several weeks recognized the K2

271 expression is associated with resistance to asparaginase therapy in childhood acute lymphoblastic le

272 f these variants could significantly advance asparaginase therapy of leukemia in the future.

273 dded to our ALL-11 protocol to individualize asparaginase therapy.

274 The use of asparaginase to convert asparagine to aspartic acid may

275 idotransferases that couple an amidase or an asparaginase to liberate ammonia with a tRNA-dependent k

276 The addition of dexamethasone and/or L-asparaginase to reduced-intensity dasatinib therapy impr

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

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

279 p (age and leukocyte count at diagnosis) and asparaginase treatment group, but not TEL/AML1 status, w

280 Asparaginase treatment is standard in all pediatric acut

281 However, the potential adverse effects of asparaginase treatment on sensory properties of cooked f

282 Extensive asparaginase use preceded reinduction in the 101 childre

283 the in vivo biodistribution of radiolabeled asparaginase, using a combination of imaging and biochem

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

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

286 Intravenous PEG-asparaginase was not more toxic than, was similarly effi

287 lization of (111)In-labeled Escherichia coli asparaginase was performed in C57BL/6 mice by both small

288 N24A and N24A R195S mutations to the drug L-asparaginase, we are a step closer to individualized dru

289 two groups, but fewer allergic reactions to asparaginase were observed in the rituximab group.

290 In GCN2 null livers, all responses to asparaginase were precluded except CHOP mRNA expression,

291 ult of this observation, several bacterial L-asparaginases were developed and are currently approved

292 tion genes (ureF, rocF [arginase], and ansB [asparaginase]), were found in cells grown at pH 2.5 with

293 e capacity of MSCs to protect ALL cells from asparaginase, whereas enforced ASNS expression conferred

294 otable examples of a therapeutic enzyme is L-asparaginase, which has been established as an antileuke

295 istent with enzymes designated as plant-type asparaginases, which had thus far been found in only pla

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

297 ur engineered ErA variants hold promise as l-asparaginases with fewer side effects.

298 Therefore, l-asparaginases with reduced l-glutaminase activity are pr

299 vorin rescue or escalating dose MTX with PEG asparaginase without leucovorin rescue.

300 therapy with dexamethasone, vincristine, and asparaginase, without anthracyclines.

301 The Wolinella succinogenes L-asparaginase (WoA) has been reported to be L-glutaminase

302 Gcn2 intensified hepatic PERK activation to asparaginase, yet surprisingly, mRNA levels of key ISR g