ライフサイエンスコーパス: ara-C

1 ara-C also causes apoptosis in HL-60 cells which can be

2 ara-C caused an increase in membrane-bound PKCbetaII (bu

3 ara-C or TPA-induced translocation of PKCbetaII was inhi

4 type cells and generated 8.5-fold higher [3H]ara-C triphosphate levels after in vitro incubation with

5 te levels after in vitro incubation with [3H]ara-C.

6 B entered complete remission (P =.045) after ara-C and 2-CdA therapy.

7 of deoxynucleotides increased 24 hours after ara-C infusion.

8 d in significantly prolonged survivals after ara-C administration compared with mice implanted with w

9 heir response to the chemotherapeutic agents ara-C, doxorubicin, etoposide and SN-38.

10 xposures that exerted minimal effects alone, ara-C-induced apoptosis and DNA fragmentation were resto

11 Although ara-C is a potent antitumor agent for hematologic malign

12 The nucleoside analogue ara-C is a key agent for treatment of acute myeloid leuk

13 Both IFN-alpha and ara-C induce cytogenetic responses as single-agent thera

14 pharmacodynamic interactions between CdA and ara-C during therapy were investigated.

15 greater extent by administration of CdA and ara-C in combination than by either one alone.

16 The combination of 2-CdA and ara-C seems to be effective therapy for pediatric AML.

17 -deoxyadenosine at 12 mg/m2/d for 5 days and ara-C 1 at g/m2/d for 5 days.

18 by continuous infusion daily for 5 days and ara-C 15mg/m(2) daily in two subcutaneous injections for

19 Administered as prodrugs, dFdC and ara-C are transported across cell membranes and are conv

20 g step in the activation cascade of dFdC and ara-C.

21 Sensitization to DNR and ara-C is mediated in part by activation of the ataxia-te

22 o study the relationship of the CBS gene and ara-C metabolism/sensitivity was developed by transfecti

23 The combination regimen of HHT and ara-C is effective and safe in patients with CML who hav

24 ts were randomized to receive idarubicin and ara-C (IA) versus troxacitabine and ara-C (TA) versus tr

25 gistic effect of sequential methotrexate and ara-C therapy.

26 c-glycero-3-phosphocholine (ET-18-OCH3), and ara-C-induced apoptosis was stimulated by pretreatment o

27 n inhibitor of ribonucleotide reductase, and ara-C for adults with AML.

28 icin and ara-C (IA) versus troxacitabine and ara-C (TA) versus troxacitabine and idarubicin (TI).

29 atment with 1-beta-arabinofuranosylcytosine (ara-C) includes the induction of apoptosis.

30 vitro to 1-beta-D-arabinofuranosylcytosine (ara-C) and generate higher 1-beta-D-arabinofuranosylcyto

31 xicity of 1-beta-D-arabinofuranosylcytosine (ara-C) and modulation of ara-C lethality by protein kina

32 etabolite 1-beta-D-arabinofuranosylcytosine (ara-C) and other genotoxic agents is associated with act

33 sponse to 1-beta-D-arabinofuranosylcytosine (ara-C) and other genotoxic agents.

34 nduced by 1-beta-d-arabinofuranosylcytosine (ara-C) and other genotoxic agents.

35 blasts to 1-beta-D-arabinofuranosylcytosine (ara-C) and the enhanced metabolism of ara-C to ara-C tri

36 ment with 1-beta-D-arabinofuranosylcytosine (ara-C) includes activation of the c-Abl protein tyrosine

37 etabolite 1-beta-D-arabinofuranosylcytosine (ara-C) induces binding of c-Abl and p53.

38 ells with 1-beta-D-arabinofuranosylcytosine (ara-C) is associated with induction of protein kinase ac

39 ells with 1-beta-D-arabinofuranosylcytosine (ara-C) is associated with tyrosine phosphorylation of Cd

40 1-beta-D-Arabinofuranosylcytosine (ara-C) stimulates the formation of both diglyceride and

41 ells with 1-beta-D-arabinofuranosylcytosine (ara-C) was associated with induction of the PKCdelta kin

42 cells to 1-beta-D-arabinofuranosylcytosine (ara-C) were examined.

43 Taxol, 1-beta-D-arabinofuranosylcytosine (ara-C), and etoposide induce apoptosis in HL-60 cells th

44 iation of 1-beta-D-arabinofuranosylcytosine (ara-C)-induced apoptosis in human myelomonocytic leukemi

45 xic agent 1-beta-d-arabinofuranosylcytosine (ara-C).

46 ontaining 1-beta-D-arabinofuranosylcytosine (ara-C).

47 Cytarabine arabinoside (ara-C) is an antimetabolite used to treat hematologic ma

48 y of DS myeloblasts to cytosine arabinoside (ara-C) and daunorubicin and the greater generation of ar

49 Cytosine arabinoside (ara-C) and gemcitabine (dFdC) are two standard chemother

50 atives of cytidine and cytosine arabinoside (ara-C) have been prepared via phosphite addition or a Le

51 Cytosine arabinoside (ara-C) is a cytidine analog that incorporates into repli

52 AML, linked to greater cytosine arabinoside (ara-C) sensitivity and higher transcript levels of the c

53 rivatives of cytidine, cytosine arabinoside (ara-C), and uridine have been prepared via the correspon

54 leukemic resistance to cytosine arabinoside (ara-C), daunorubicin, and etoposide.

55 up to 1.7-fold reduced cytosine arabinoside (ara-C)-induced apoptosis, compared with mock-transfected

56 e active metabolite of cytosine arabinoside (ara-C, cytarabine), ara-CTP, has been investigated and v

57 cleoside analogs such as arabinosylcytosine (ara-C) and fludarabine occurs after their incorporation

58 The effectiveness of arabinosylcytosine (ara-C) for the treatment of acute myelogenous leukemia (

59 Therapeutic nucleoside analogues such as ara-C, gemcitabine, and fludarabine exert their cytotoxi

60 ertain conventional cytotoxic agents such as ara-C, overexpression of Bcl-2 or Bcl-x(L) are largely i

61 Because ara-C incorporation is known to alter base stacking and

62 The expression of c-Abl (K-R) blocked ara-C-induced apoptosis by a mechanism that is at least

63 conjugated a synthetic phospholipid to both ara-C and dFdC and investigated their chemotherapeutic p

64 d ceramide generation and SAPK activation by ara-C, whereas the induction of apoptosis was unaffected

65 nstrate that the stimulation of apoptosis by ara-C is self-limiting and can be enhanced by inhibition

66 However, down-regulation of Cdk2 by ara-C was found in cells expressing wild type c-Abl and

67 of the Fas receptor but not that induced by ara-C.

68 tive c-Abl (K-R) are resistant to killing by ara-C.

69 (days 2 through 6) followed 4 hours later by ara-C at 1 g/m(2) per day as a 2-hour intravenous infusi

70 e that ara-C-induced apoptosis is limited by ara-C-stimulated PKCbetaII through effects on Bcl-2.

71 anipulations prevented activation of MAPK by ara-C.

72 Down-regulation of SHPTP1 by ara-C was blocked by the PKCdelta inhibitor rottlerin bu

73 therapy: daunorubicin (DNR) and cytarabine (ara-C).

74 eated with IFNalpha and low-dose cytarabine (ara-C) between 1990 and 1994 was later used to confirm t

75 harringtonine (HHT) and low-dose cytarabine (ara-C) in patients with Philadelphia chromosome (Ph)-pos

76 e trials that included high-dose cytarabine (ara-C) in the chemotherapy schedule were the ones in whi

77 ifosfamide, etoposide, high-dose cytarabine (ara-C), and IT MTX (IVAC).

78 on was alternated with high-dose cytarabine (ara-C), etoposide, and ifosfamide (IVAC) for a total of

79 continuous infusion of high-dose cytarabine (ara-C).

80 The separation of cytarabine (ara-C) from the endogenous compounds in mouse plasma by

81 ase the antileukemic activity of cytarabine (ara-C).

82 rimental regimen idarubicin plus cytarabine (ara-C) plus cyclosporine for treatment of patients with

83 ctivation of Chk1 in response to cytarabine (ara-C) induced an S-phase checkpoint characterized by th

84 ngle agent or when combined with cytarabine (ara-C) or with idarubicin.

85 s (DLTs) of its combination with cytarabine (ara-C), idarubicin, or topotecan.

86 dFdC) and cytosine arabinoside (cytarabine, ara-C) represent a class of nucleoside analogs used in c

87 beta-d-arabinofuranosylcytosine (cytarabine; ara-C), gemcitabine, and troxacitabine, which inhibited

88 uced by 1-[beta-d-arabinofuranosyl]cytosine (ara-C) and other genotoxic agents.

89 tion of 1-[beta-D-arabinofuranosyl]cytosine (ara-C)-induced apoptosis in human myeloid leukemia cells

90 of CHR was higher with IFN-alpha plus daily ara-C compared with IFN-alpha plus intermittent ara-C an

91 on induction chemotherapy with daunorubicin, ara-C, and etoposide (DAV).

92 lls was associated with a 100-fold decreased ara-C sensitivity and 40-fold decreased ara-CTP generati

93 with induction regimens containing high-dose ara-C (HiDAC) at M.D. Anderson Cancer Center refractory

94 the other a continuous infusion of high-dose ara-C and L-asparaginase.

95 combination of IFN-alpha plus daily low-dose ara-C seems to be promising for the treatment of CML.

96 NA damaging chemotherapy agents doxorubicin, ara-C and VP16, but not microtubule active agents paclit

97 inhibited PKCbetaII activation and enhanced ara-C-induced apoptosis.

98 yostatin 1 and UCN-01 both markedly enhanced ara-C-induced mitochondrial injury (e.g., cytochrome c a

99 incubation media and converted extracellular ara-C completely to 1-beta-D-arabinofuranosyluracil with

100 ning topotecan + ara-C (TA) or fludarabine + ara-C (FA) +/- idarubicin are superior to regimens conta

101 AEB-t, 62 patients) to receive fludarabine + ara-C + idarubicin (FAI) alone, FAI + ATRA, FAI + G-CSF,

102 survival advantage to the bacteria following ara-C treatment.

103 esponse rate was 71% for DepoCyt and 15% for ara-C on an intent-to-treat basis (P =.006).

104 top1 poisoning is a potential mechanism for ara-C cytotoxicity.

105 However, the signaling role for ara-C-induced diacylglycerol (DAG) is not defined.

106 fsky score relative to that produced by free ara-C injected twice a week.

107 ive DepoCyt 50 mg once every 2 weeks or free ara-C 50 mg twice a week for 1 month.

108 ite, which dramatically protected cells from ara-C lethality, delayed but did not prevent flavopirido

109 ed Bcl-2 mutant protein protected cells from ara-C/UCN-01- but not ara-C/bryostatin 1-mediated lethal

110 eration of ara-C triphosphate (ara-CTP) from ara-C compared with myeloblasts from non-DS patients.

111 ',3'-bis TBS protected aldehyde derived from ara-C gave only the 5'R adduct.

112 historic newly diagnosed APL patients given ara-C with either doxorubicin, amsacrine (AMSA), or daun

113 MK cells were accompanied by 10-fold greater ara-C sensitivity and 2.4-fold higher levels of ara-CTP

114 in vitro incubations with 5 micromol/L (3)H-ara-C (P =.0003).

115 ) assay (P =.003) and the generation of (3)H-ara-C triphosphate (ara-CTP) after in vitro incubations

116 superior to regimens containing idarubicin + ara-C (IA) without either fludarabine or topotecan for t

117 gest that the association of Lyn and Cdk2 in ara-C-treated cells may contribute to regulation of Cdk2

118 olin block resulted in a further increase in ara-C-mediated apoptosis, suggesting enhanced drug sensi

119 ession of genes encoding enzymes involved in ara-C metabolism between DS and non-DS myeloblasts may l

120 d enhanced the decrease in Bcl-2 observed in ara-C-treated cells.

121 The present studies in ara-C-treated U-937 cells extend these findings by demon

122 phate (CdAMP) at its 3'-end by incorporating ara-C monophosphate (ara-CMP).

123 s effectively, HL-60-DOX cells and increased ara-C cytotoxicity in both cell lines.

124 pressing cells that contributes to increased ara-C phosphorylation and drug activity.

125 he results further show that STI571 inhibits ara-C-induced loss of mitochondrial transmembrane potent

126 -C compared with IFN-alpha plus intermittent ara-C and IFN-alpha alone (no ara-C) (92% v 84% v 80%, P

127 iving IFN-alpha with or without intermittent ara-C (7 days/mo).

128 The rate-limiting step in intracellular ara-C activation is phosphorylation of the prodrug by de

129 eloblasts after incubation with 5 micromol/L ara-C (621.4 v 228.4 pmol/mg protein).

130 v 41.7 pmol/mg protein at 1 and 5 micromol/L ara-C, respectively).

131 Lastly, ara-C-mediated increases in mitogen-activated protein ki

132 PKC-dependent MAPK activity seemed to limit ara-C action in that the toxicity of ara-C was enhanced

133 myelosuppression (70% of cases); the median ara-C dose was 7.5 mg daily.

134 After a 6-h exposure to 1 microM ara-C, cells stably transfected with a p21WAF1/CIP1 anti

135 lt in elevated CBS activity, which modulates ara-C metabolism by altering reduced folate pools, deoxy

136 s intermittent ara-C and IFN-alpha alone (no ara-C) (92% v 84% v 80%, P = .01), as were the incidence

137 cl-2 against Taxol-induced apoptosis but not ara-C- or etoposide-induced apoptosis.

138 n protected cells from ara-C/UCN-01- but not ara-C/bryostatin 1-mediated lethality.

139 hat do (fludarabine, gemcitabine) or do not (ara-C) affect ribonucleotide reductase are incorporated

140 d parental DNA strands, approximately 60% of ara-C nucleotide in DNA was incorporated by repair synth

141 accompanied by restoration of the ability of ara-C to induce CPP32 cleavage and activation, poly(ADP-

142 ffered from the S phase-arresting actions of ara-C and gemcitabine, other deoxycytidine analogs that

143 The addition of ara-C did not improve the response rates but may have im

144 er exposure to an equimolar concentration of ara-C (10 microM for 6 hr), HL-60/Bcl-2 cells were signi

145 like tyrosine kinase Lyn as a consequence of ara-C-treatment.

146 The cytotoxicity of ara-C also was substantially increased by pharmacologica

147 ty and sharply increased the cytotoxicity of ara-C, suggesting the direct involvement of MAPK as a do

148 ty in additions to an aldehyde derivative of ara-C.

149 tely 2.5 min/sample for the determination of ara-C at nanograms per milliliter in mouse plasma was pa

150 Identical doses of ara-C were administered on days 3, 4, 5, and 6.

151 sensitizes cells to the cytotoxic effects of ara-C and other anticancer agents.

152 ioma cells lines to the cytotoxic effects of ara-C in vitro.

153 KC) activation, we determined the effects of ara-C on PKC isozymes.

154 Since the effects of ara-C-induced DAG could be due to protein kinase C (PKC)

155 er induction of apoptosis and enhancement of ara-C cytotoxicity in 11 of 19 primary AML samples.

156 ate (dCTP) pools, slightly greater extent of ara-C incorporation into DNA, and increased relative num

157 -2 expression was manifested by a failure of ara-C to induce activation/cleavage of the Yama protease

158 d daunorubicin and the greater generation of ara-C triphosphate (ara-CTP) from ara-C compared with my

159 ide pools and increased the incorporation of ara-C into DNA by replicative synthesis.

160 is was maintained until the next infusion of ara-C.

161 The mouse plasma levels of ara-C obtained by the pSFC-MS/MS method were found to be

162 protocol stipulated an infusion of 1 g/m2 of ara-C over 2 hours on day 1.

163 t our hypothesis that enhanced metabolism of ara-C in DS cells may be a contributing factor to the su

164 ay be a factor in the enhanced metabolism of ara-C in DS cells.

165 osine (ara-C) and the enhanced metabolism of ara-C to ara-C triphosphate.

166 Sensitivity and metabolism of ara-C was examined in myeloblasts from DS and non-DS pat

167 ofuranosylcytosine (ara-C) and modulation of ara-C lethality by protein kinase C PKC inhibition/down-

168 drug's cytotoxicity; and (3) potentiation of ara-C action by bryostatin 1 or safingol was not associa

169 than increased SAPK, in the potentiation of ara-C cytotoxicity by interference with PKC-dependent si

170 actor (TNF) alpha; moreover, potentiation of ara-C lethality by bryostatin 1 (but not by UCN-01) was

171 these findings suggest that potentiation of ara-C lethality in human myeloid leukemia cells by bryos

172 negative caspase-8 abrogated potentiation of ara-C-mediated apoptosis by bryostatin 1 but not by UCN-

173 o limit ara-C action in that the toxicity of ara-C was enhanced by pharmacological reductions of PKC,

174 fore, we evaluated a pilot clinical trial of ara-C in combination with UCN-01 in patients with relaps

175 f its active metabolite, the triphosphate of ara-C (ara-CTP).

176 es, molecular actions of the triphosphate of ara-C and CdA on DNA extension by human DNA polymerase a

177 f ATRA should assess the utility of omitting ara-C from treatment of newly diagnosed APL, thus allowi

178 rexpression also had no detectable effect on ara-C-induced cleavage of PKC delta.

179 XIAP had no detectable effect on ara-C-induced release of mitochondrial cytochrome c and

180 not increase their susceptibility to DNR or ara-C.

181 Exposure to etoposide (50 microM) or ara-C (100 microM) for 4 h induced apoptosis in HL-60/ne

182 perturbations, nor did ara-CTP formation or (ara-C)DNA incorporation differ significantly between the

183 ed folate and S-adenosylmethionine pathways; ara-C metabolism and folate pools are linked by the know

184 redictive for response to the IFN-alpha plus ara-C combination.

185 h the standard regimen of anthracycline plus ara-C.

186 ducted a phase 1-2 study of clofarabine plus ara-C in 32 patients with relapsed acute leukemia (25 ac

187 Response rates were identical with HHT plus ara-C versus HHT alone, but the survival was significant

188 oot syndrome (HFS) on the troxacitabine plus ara-C combination.

189 the mechanism by which bryostatin 1 promotes ara-C-induced mitochondrial injury, caspase activation,

190 They were randomly assigned to receive ara-C as either a 2-hour daily infusion (arm A) or a con

191 4)-mediated hydrophosphonylation of the same ara-C aldehyde favored the 5'S stereoisomer by a 2:1 rat

192 In the present studies, Taxol-, ara-C-, or etoposide-induced apoptosis was examined in H

193 The results also demonstrate that ara-C induces cleavage of procaspase-3 by a caspase-8-de

194 We also demonstrate that ara-C treatment of established intradermal and intracere

195 This study also demonstrates that ara-C treatment and DNA incorporation trap top1 cleavage

196 These findings indicate that ara-C and other DNA-damaging agents activate a CrmA-inse

197 These data indicate that ara-C-induced apoptosis is limited by ara-C-stimulated P

198 The results further show that ara-C induces activation of the CPP32 protease by a CrmA

199 In addition, we show that ara-C induces the association of XIAP with the cleaved f

200 The present studies show that ara-C treatment of U-937 cells is associated with induct

201 The ara-C-induced protease activity was sensitive to overexp

202 ves favoring the 5'S stereochemistry and the ara-C derivative favoring the 5'R isomer.

203 the observed inhibition of religation at the ara-C site suggests the importance of the alignment of t

204 n and mitochondrial targeting of SAPK in the ara-C response.

205 the DepoCyt arm but only 53% of those on the ara-C arm were able to complete the planned 1-month indu

206 kinase declined on addition of UCN-01 to the ara-C infusion, an action accompanied by an activation o

207 greater cytotoxic activity compared with the ara-C conjugate and demonstrated notable cytotoxicity ag

208 Thus, ara-C action was (1) partially attenuated by diradylglyc

209 Thus, ara-C stimulates the synthesis of two second messengers

210 a-C) and the enhanced metabolism of ara-C to ara-C triphosphate.

211 Exposure of cells to ara-C and bryostatin 1 (but not UCN-01) resulted in sust

212 isms of increased sensitivity of DS cells to ara-C related to the CBS gene may lead to the applicatio

213 ceptibility of antisense-expressing cells to ara-C was accompanied by a corresponding reduction in cl

214 contrast, exposure of Lyn-deficient cells to ara-C, ionizing radiation, or cisplatin had no effect on

215 ce of Bcl-2-overexpressing leukemic cells to ara-C-induced apoptosis and activation of the protease c

216 The increased sensitivity of these cells to ara-C-mediated lethality could not be attributed to cyto

217 sceptibility of U937 human leukemia cells to ara-C-related lethality, and this phenomenon occurs as a

218 ith no detectable top1 are crossresistant to ara-C, which suggests that top1 poisoning is a potential

219 late chronic phase; 43% had been exposed to ara-C and 11% had been exposed to HHT.

220 myelogenous leukemia (AML) blasts exposed to ara-C and UCN-01 demonstrated a selective loss in clonin

221 Exposure to ara-C (10 microM) for 6 hr promoted extensive apoptotic

222 th non-DS myeloblasts, following exposure to ara-C for 72 hours.

223 After exposure to ara-C, p21 antisense-expressing cells displayed a greate

224 lls lacking the c-abl gene also responded to ara-C and MMS with increases in p53 levels and induction

225 tion of PKCdelta in the cellular response to ara-C and other DNA-damaging agents.

226 ributes in part to the apoptotic response to ara-C treatment and that SHPTP1 attenuates this response

227 he mitochondria in the apoptotic response to ara-C.

228 were approximately 10-fold more sensitive to ara-C (measured by the 3-[4,5-dimethyl-thiazol-2-yl]-2,5

229 ing 51% of the variability in sensitivity to ara-C among the CEU and 5 SNPs explaining 58% of the var

230 SNPs) for association with susceptibility to ara-C and narrowed our focus by concentrating on SNPs th

231 netic factors important in susceptibility to ara-C cytotoxicity may allow for individualization of tr

232 a median 15-fold more sensitive in vitro to ara-C compared with wild-type cells and generated 8.5-fo

233 lear whether regimens containing topotecan + ara-C (TA) or fludarabine + ara-C (FA) +/- idarubicin ar

234 All regimens used ara-C doses of 1 to 2 gm/m(2)/d, given by continuous inf

235 correlation of SOD transcripts with in vitro ara-C and daunorubicin sensitivities.

236 nscript levels correlated with both in vitro ara-C sensitivity measured by the 3-[4,5-dimethyl-thiazo

237 S transcript levels correlated with in vitro ara-C sensitivity.

238 enhancement of top1 cleavage complexes when ara-C was incorporated at the +1 position (immediately 3

239 infusion over 30 minutes on days 1 to 5 with ara-C 1.0 mg/m(2)/d IV over 2 hours on days 1 to 5, idar

240 l after 8-h incubation of the biosensor with ara-C.

241 treatment of human U-937 leukemia cells with ara-C is associated with translocation of SAPK to mitoch

242 The combination of clofarabine with ara-C is safe and active.

243 Thus, use of UCN-01 in combination with ara-C decreases Chk1 phosphorylation, inhibits the Akt s

244 DA transcripts significantly correlated with ara-C sensitivities and ara-CTP generation.

245 ra-CTP is increased when 2-CdA is given with ara-C, but no schedule-dependent differences in this eff

246 ls than pCI-neo-K562 cells when treated with ara-C, doxorubicin or SN-38.

247 n of the dCK gene followed by treatment with ara-C represents a new chemosensitization strategy for c

248 rferon-alpha2b (IFN-alpha2b) with or without ara-C.