ライフサイエンスコーパス: decitabine

1 ): 5-azacitidine and 5-aza-2'-deoxycitidine (decitabine).

2 tic target for hypomethylating agents (e.g., decitabine).

3 , or hypomethylating agents (azacytidine and decitabine).

4 ry tumor cells treated with panobinostat and decitabine.

5 of three cycles (range, one to 25 cycles) of decitabine.

6 40 (35%) with azacitidine and 73 (65%) with decitabine.

7 RRM2B) is a robust transcriptional target of decitabine.

8 loid differentiation agents such as ATRA and decitabine.

9 nts with acute myeloid leukemia treated with decitabine.

10 ation in patients with leukemia treated with decitabine.

11 namic results of different dose schedules of decitabine.

12 19 showed little change in methylation after decitabine.

13 at baseline or after therapy and response to decitabine.

14 does not induce cross-resistance to As2O3 or decitabine.

15 d who also received serial 10-day courses of decitabine.

16 nce after receiving serial 10-day courses of decitabine.

17 fraction of TET1-CD-GFP after treatment with Decitabine.

18 life and exposure than its active metabolite decitabine.

19 following treatment with the DNMT inhibitor, decitabine.

20 nhibitor entinostat or hypomethylating agent decitabine.

21 hematology, with a focus on azacitidine and decitabine.

22 uced by the DNA methyltransferase inhibitor, decitabine.

23 by sensitivity of MPN-derived cell lines to decitabine.

24 relapsed cases were found to be sensitive to decitabine.

25 At the decitabine 0.16 mg/kg dose, plasma concentrations peaked

26 standard treatment with hydroxyurea received decitabine 0.2 mg/kg subcutaneously 1 to 3 times per wee

27 able in patients who had previously received decitabine (1.1 vs 0.9 vs 3.1 months, respectively, P =

28 re seen in two of four patients treated with decitabine 135 mg/m2 and carboplatin AUC 5.

29 4 patients were treated with a fixed dose of decitabine (15 mg/m(2) by IV daily for 10 days) administ

30 g/m(2) intravenously/subcutaneously daily or decitabine 20 mg/m(2) intravenously daily for 3 consecut

31 Induction with decitabine (20 mg/m(2) intravenously on days 1-10) plus

32 asis of these results, additional studies of decitabine (20 mg/m(2)/d for 10 days) alone or with an a

33 4(+) cells but not normal CD34(+) cells with decitabine (5-aza-2'-deoxycytidine [5azaD]), followed by

34 Decitabine (5-aza-2'-deoxycytidine) inhibits DNA methyla

35 f epigenetic therapy, the demethylating drug decitabine (5-aza-2'-deoxycytidine) is increasingly used

36 nt with the DNA methyltransferase inhibitor, decitabine [5-aza-2'-deoxycytidine (5azaD)], followed by

37 a nonsignificant increase in median OS with decitabine (7.7 months; 95% CI, 6.2 to 9.2) versus TC (5

38 mmended dose/schedule for phase II trials is decitabine 90 mg/m2 (day 1) followed by carboplatin AUC

39 t) was seen in two of 10 patients treated at decitabine 90 mg/m2 and carboplatin AUC 6.

40 Furthermore, decitabine 90 mg/m2 induced demethylation of the MAGE1A

41 Treatment of HCT116 cells with Decitabine (a DNMT inhibitor) or trichostatin A (a histo

42 5-Aza-2'-deoxycytidine [5-aza-CdR (decitabine)], a potent inhibitor of DNA methyltransferas

43 Decitabine, a cancer therapeutic that inhibits DNA methy

44 Co-administration of 7a with decitabine, a CDA substrate, boosted the plasma levels o

45 and primary AML xenografts were treated with decitabine, a DNA demethylating agent, and cytarabine, a

46 Epigenetic therapy using decitabine, a DNA hypomethylating agent, is clinically e

47 s, low-dose (20 mg/m(2) per day for 10 days) decitabine, a DNA hypomethylating azanucleoside, produce

48 Treatment with decitabine, a DNA methylation inhibitor, either during L

49 Decitabine, a DNA-targeted hypomethylating agent, is app

50 8 promoter hypermethylation, incubation with decitabine activated SLC5A8 expression.

51 gn, 33 patients received escalating doses of decitabine administered as a 6-hour infusion on day 1 fo

52 e clinical and biologic activity of low-dose decitabine administered before carboplatin in platinum-r

53 e in vivo mechanisms of responses seen after decitabine administration.

54 -expression end point), 14 patients received decitabine alone for 10 days.

55 Clinical responses appeared similar for decitabine alone or with VA.

56 c trioxide (As2O3) or 5-aza-2-deoxycytidine (decitabine) alone and in combination with imatinib.

57 In parallel with these responses, decitabine also upregulated the proapoptotic BCL-2 famil

58 Decitabine also upregulates BNIP3 and Bik expression, wh

59 results of this study suggest that low-dose decitabine altered DNA methylation of genes and cancer p

60 Treating neonatal rats with decitabine, an inhibitor of DNA methylation, during inte

61 Decitabine, an old drug, has now made a comeback as a ta

62 The DNA methylation inhibitors decitabine and azacitidine are efficacious for hematolog

63 Low-dose decitabine and azacitidine may have broad applicability

64 : 20 and 13 months for patients treated with decitabine and azacitidine, respectively (P = .1).

65 and 49% (P = .03) for patients treated with decitabine and azacitidine, respectively.

66 Sequential treatment with decitabine and cytarabine was found to be more effective

67 AEs were similar for decitabine and cytarabine, although patients received a

68 ) is a novel hypomethylating dinucleotide of decitabine and deoxyguanosine resistant to degradation b

69 nhibitors of DNA methyltransferases (DNMTs), decitabine and FdCyd, block mutant huntingtin (Htt)-indu

70 ombination of two clinically approved drugs, decitabine and gemcitabine, reduced HIV infectivity by 7

71 del of KRAS-mutant ovarian cancer, combining decitabine and navitoclax heightened antitumor activity

72 Ldb1 was more than double that observed with decitabine and pomalidomide; butyrate had an intermediat

73 Given the clinical efficacy of decitabine and the uncertainties about its mode of actio

74 Treatment with epigenetic compounds decitabine and trichostatin A rescued the BPA effects as

75 is mouse model, we further demonstrated that decitabine and vorinostat cooperate to suppress colon ca

76 , we demonstrated that epigenetic inhibitors decitabine and vorinostat cooperate to upregulate Fas ex

77 h their function in apoptosis sensitization, decitabine and vorinostat significantly increased the ef

78 mice, suggesting a critical role for FasL in decitabine and vorinostat-mediated tumor suppression in

79 infiltrating CD8(+) T cells are FasL(+), and decitabine and vorinostat-mediated tumor-suppression eff

80 f the combination of 5-aza-2'-deoxycytidine (decitabine) and the histone deacetylase inhibitor valpro

81 patient blasts using 5-aza-2'-deoxycytidine (decitabine) and trichostatin A increased H3K4me3 and mai

82 on is reversible, drugs like 5'-azacytidine, decitabine, and histone deacetylase inhibitors are being

83 US regulatory approval of azacitidine, decitabine, and lenalidomide between 2004 and 2006 seeme

84 Lenalidomide, azacitidine, and decitabine are all FDA-approved agents to treat MDS; how

85 cent clinical and translational studies with decitabine are reviewed.

86 Hypomethylating agents, including decitabine are used to treat elderly AML patients with r

87 gues azacytidine and 5-aza-2'-deoxycytidine (decitabine) are commonly used to treat myelodysplastic s

88 igenetic drugs: 5-aza-2'-deoxycytidine (DAC; decitabine), arsenic trioxide (ATO), and MS-275 [entinos

89 determine an optimal biologic dose (OBD) of decitabine as a single agent and then the maximum-tolera

90 here is now a revived interest in the use of Decitabine as a therapeutic agent for cancers in which e

91 cy and toxicity of the hypomethylating agent decitabine as initial therapy in older patients with AML

92 uding the inhibitor of DNA methyltransferase decitabine as well as the inhibitors of histone deacetyl

93 azacytidine and 2'-deoxy-5-azacytidine (DAC, decitabine) as demethylating agents.

94 Subjects received low-dose decitabine at 20 mg/m(2) i.v. over 1 h on days 1 to 10.

95 Patient cohorts received decitabine at 5, 10, 15, or 20 mg/m2 intravenously over

96 we show dose-dependent hypomethylation after decitabine at low doses.

97 To determine the MTD, 11 patients received decitabine (at OBD, days 1 through 10) plus dose-escalat

98 ly demonstrated that 5-aza-2'-deoxycytidine (decitabine) augments fetal hemoglobin (HbF) levels in pa

99 ve chemotherapy (n = 557) or azacitidine- or decitabine-based therapy (n = 114).

100 Thirty-two percent of patients treated with decitabine became transfusion independent compared with

101 biologic activity of epigenetic priming with decitabine before standard induction chemotherapy in pat

102 Decitabine, but not 5-azacytidine, also produced a G(2)/

103 This suggests that decitabine can be administered in an outpatient setting

104 irates from patients with leukemia receiving decitabine can be assessed genome-wide using commerciall

105 Decitabine can be combined safely with carboplatin at a

106 mine the feasibility of delivering a dose of decitabine, combined with carboplatin, that would be cap

107 n of 2.5 to 5 micromol/L (similar to that of decitabine), complete degradation of DNMT1 protein was a

108 We examined if subcutaneous decitabine could increase HbF levels and improve SSD pat

109 levels by 5-aza-2'-deoxycytidine (5-aza-CdR, decitabine) could serve as an alternate mode of treatmen

110 Decitabine (DAC) and 5-azacitidine have recently been ap

111 t clinical studies on combination therapy of decitabine (DAC) and arsenic trioxide (ATO) have demonst

112 At low doses, the cytosine analogue decitabine (DAC) can be used to deplete DNA methyl-trans

113 The deoxycytidine analog decitabine (DAC) can deplete DNA methyl-transferase 1 (D

114 a comparative study of azacitidine (AZA) and decitabine (DAC) in combination with allogeneic NK cells

115 patients who were responsive or resistant to decitabine (DAC) in order to develop a molecular means o

116 In vitro treatment of AML blasts with decitabine (DAC) or 5-azacytidine, 2 hypomethylating age

117 The DNA hypomethylating drug decitabine (DAC) reactivates silenced gene expression in

118 treated with hypomethylating agents, such as decitabine (DAC), although the mechanisms by which it in

119 hat the FDA-approved hypomethylating agents, decitabine (Dec) and azacitidine (AzaC), induce FOXP3 ex

120 d before treatment with azacitidine (AZA) or decitabine (DEC).

121 Here, we demonstrated that resistance to decitabine (decitabine(R)) or PKC412 (PKC412(R)) eventua

122 Pretreatment with decitabine decreased the cytotoxic activity of MEK inhib

123 clinical and DNA-hypomethylating activity of decitabine delivered at 20 mg/m(2) by either a 1-hour in

124 The mechanism of p53R2 gene induction by decitabine does not seem to be promoter DNA hypomethylat

125 odysplastic syndrome (n=25) received reduced decitabine dosages (0.1-0.2 mg/kg/day compared with the

126 Oral decitabine doses, administered after oral THU 10 mg/kg,

127 designed to determine the effect of repeated decitabine dosing on HbF levels and hematologic toxicity

128 Lenalidomide, azacitidine, and decitabine, each recently approved by the US Food and Dr

129 Treating rats with decitabine either during LT-IH or during recovery from L

130 Together, 5-azacytidine and decitabine exert growth-inhibitory and proapoptotic effe

131 The USFDA approved "epigenetic drug", Decitabine, exerts its effect by hypomethylating DNA, de

132 lanoma, and breast cancer cells treated with decitabine, finding that RAS/MEK/ERK pathway activation

133 that sequential treatment of AML blasts with decitabine followed by selinexor (XPO1 inhibitor) enhanc

134 Sequential treatment of decitabine followed by selinexor in an MV4-11 xenograft

135 linical results, a phase 1 clinical trial of decitabine followed by selinexor in elderly patients wit

136 Following exposure to 2.5 microM decitabine, GDM decreased to approximately 50% of the ba

137 p53R2 as a novel hypomethylation-independent decitabine gene target associated with clinical response

138 Decitabine given in a low-dose, 5-day regimen has activi

139 Decitabine given on a 5-day schedule provided meaningful

140 za) and its congener 5-aza-2'-deoxycytidine (decitabine) has provided an alternate approach to cancer

141 The hypomethylating drugs azacitidine and decitabine have shown efficacy in myelodysplastic syndro

142 stem cells, and two of them (azacytidine and decitabine) have been approved for treatment of myelodys

143 The cytosine analog 5-aza-2'-deoxycytidine (decitabine) hypomethylates DNA by inhibiting DNA methylt

144 In older patients with AML, decitabine improved response rates compared with standar

145 se (MTD) of valproic acid (VA) combined with decitabine in acute myeloid leukemia (AML).

146 tment schedule is suitable for evaluation of decitabine in combination with agents whose activity may

147 Treatment with the DNA-hypomethylating agent decitabine in cultured melanoma cells induced transcript

148 included 32 additional patients who received decitabine in different protocols.

149 gions, suggesting a differential activity of decitabine in distinct chromosome regions.

150 2; conversely, KIT depletion synergized with decitabine in eliminating decitabine(R).

151 ng clinical activity for a 10-day regimen of decitabine in older AML patients; high miR-29b expressio

152 f two low-dose regimens of subcutaneous (SC) decitabine in patients with low- or intermediate-1-risk

153 dy, low-dose prolonged exposure schedules of decitabine in relapsed/refractory leukemias.

154 CDA substrate, boosted the plasma levels of decitabine in rhesus monkeys.

155 a continuous 1-week intravenous infusion of decitabine in solid tumor patients.

156 ve reported substantial clinical activity of decitabine in the myelodysplastic syndrome and in chroni

157 were used to study the effects of HDACIs and decitabine in this system.

158 ide) and DNA methyltransferases (DNMT; i.e., decitabine) in RUNX1/MTG8-positive Kasumi-1 cells.

159 Decitabine induced DNA hypomethylation at all dose level

160 Decitabine induced dose-dependent, reversible demethylat

161 Neither 5-azacytidine nor decitabine induced substantial apoptosis or growth arres

162 ctivator, rifampicin, significantly reversed decitabine-induced ABCC3 and SLCO2A1 expression.

163 as initially applied for characterization of decitabine-induced GDM changes in in-vitro-treated leuke

164 This method was applied to characterize decitabine-induced promoter DNA methylation changes of t

165 Decitabine induces hypomethylation and has clinical acti

166 ransferase inhibitor 5-aza-2'-deoxycytidine (decitabine) induces DNA demethylation and re-expression

167 lude hypomethylating agents (azacitidine and decitabine), intensive chemotherapy (ICT), and allogenei

168 Decitabine is a cytosine analogue synthesized in the 196

169 We conclude that decitabine is effective in myeloid malignancies, and low

170 the initial RR-mediated 5-azaC conversion to decitabine is terminated through its own inhibition.

171 eutic activity of the deoxycytidine analogue decitabine is thought to reflect its ability to reactiva

172 Demethylation induced by decitabine is traditionally thought to be active in tumo

173 rating that inhibition of DNA methylation by decitabine is transient.

174 A 168-hour continuous infusion of decitabine is well tolerated and results in the inhibiti

175 de analog 5-aza-2'-deoxycytidine (5-aza-CdR, decitabine) is a potent inhibitor of DNA methylation in

176 5-Aza-2'-deoxycytidine (decitabine) is postulated to have clinical activity in m

177 inantly noncytotoxic mechanism of action for decitabine, leading to altered biology of the neoplastic

178 ation of the DNA methyltransferase inhibitor decitabine led to reexpression of genes shown to be pref

179 t, supporting a functional role for p53R2 in decitabine-mediated cellular responses.

180 Decitabine-mediated hypomethylation of HCT116 displays h

181 the DNA methyltransferase inhibitor (DNMTi) decitabine, MLL-r (but not MLL wild-type cell lines) sho

182 However, in this study of 10-day courses of decitabine, neither of these risk factors was associated

183 of 2 demethylating agents, 5-azacytidine and decitabine on growth and survival of neoplastic MCs and

184 that a low-dose, dose-intensity schedule of decitabine optimizes epigenetic modulation and clinical

185 istant NPM-ALK(+) KARPAS-299-CR06 cells with decitabine or ectopic miR-150 expression reduced viabili

186 lls are sensitive to 5-aza-2'-deoxycytidine (decitabine) or midostaurin (PKC412), because decitabine

187 Decitabine, or 5-aza-2'-deoxycytidine (5-aza-CdR), is a

188 ibility and preliminary clinical activity of decitabine plus bortezomib in AML and identifies FLT3 as

189 In patients treated with decitabine plus VA, dose-limiting encephalopathy occurre

190 re gastro-intestinal toxicity with 7 days of decitabine priming.

191 he DNA methyltransferase 1 (DNMT1) inhibitor decitabine produce p53-independent cell-cycle exits by r

192 All explored HDACIs in combination with decitabine produced a synergistic effect in growth inhib

193 Weekly subcutaneous decitabine produces cumulative increases in HbF and tota

194 Indeed, both decitabine(R) and PKC412(R) displayed the up-regulation

195 Importantly, when engrafted into nude mice, decitabine(R) and PKC412(R) had faster proliferation wit

196 Interestingly, decitabine(R) and PKC412(R) had higher capability of col

197 ivation of KIT or DNMT1 reciprocally blocked decitabine(R) or PKC412(R) cell proliferation.

198 demonstrated that resistance to decitabine (decitabine(R)) or PKC412 (PKC412(R)) eventually results

199 on synergized with decitabine in eliminating decitabine(R).

200 pomethylation was related to the activity of decitabine rather than to a mere decrease in leukemia bu

201 Myeloid Leukemia, we demonstrate that while Decitabine reduces the global levels of 5-methylcytosine

202 Decitabine regimens can be redesigned to minimize cytoto

203 Decitabine-related methylation changes were concordant w

204 nt with the DNA methyltransferase inhibitor, decitabine, restored expression of some hypermethylated

205 decitabine) or midostaurin (PKC412), because decitabine restores the expression of methylation-silenc

206 Combination pretreatment with vorinostat and decitabine resulted in even greater cytotoxicity compare

207 ice with the DNA methyltransferase inhibitor decitabine resulted in failure to form GCs after immune

208 nes with the DNA methyltransferase inhibitor decitabine resulted in reversal of aberrant hypermethyla

209 , and treatment with 5-aza-2'-deoxycytidine (decitabine) resulted in up-regulated expression of sever

210 at demethylation of the survivin promoter by decitabine results in p53-dependent survivin repression

211 Decitabine's mechanism of action in chronic myelomonocyt

212 ic leukemia (CMML) were randomized to 1 of 3 decitabine schedules: (1) 20 mg/m2 intravenously daily f

213 we showed that KRAS genomic status predicted decitabine sensitivity in low-grade and high-grade serou

214 hat otherwise rapidly deaminates/inactivates decitabine, severely limiting its half-life, tissue dist

215 Results of a randomized survival study of decitabine should be available in 2008.

216 In this phase II study, low-dose decitabine showed promising results in patients with low

217 Decitabine significantly reduced global methylation comp

218 ed that post-MPN AML cells were sensitive to decitabine, the JAK1/2 inhibitor ruxolitinib, or the hea

219 ecular determinants of clinical responses to decitabine therapy in patients with acute myeloid leukem

220 enous leukemia (MDS/AML) patients undergoing decitabine therapy.

221 ial (NCT01685515) combined 2 small molecules-decitabine to deplete DNMT1 and tetrahydrouridine (THU)

222 AML or MDS in a single-institution trial of decitabine to identify somatic mutations and their relat

223 Administration of oral THU-decitabine to patients with SCD was safe in this study a

224 of 5-azacytidine and 5-aza-2'-deoxycytidine (Decitabine) to demonstrate the correlation between loss

225 dynamics of neoplastic cell clearance during decitabine treatment (100 mg/m(2) per course every 4 wee

226 s those enriched in demethylated genes after decitabine treatment included pathways involved in cance

227 ated CpG islands of AIM1 in DERL2 cells, and decitabine treatment induced a significant increase in A

228 In cancer cells, decitabine treatment induces p53R2 mRNA expression, prot

229 es the extent of cell cycle arrest following decitabine treatment, supporting a functional role for p

230 t cancer-derived cell lines before and after decitabine treatment, we established that reelin express

231 for stratification of older AML patients to decitabine treatment.

232 omoter is methylated was increased following decitabine treatment.

233 epsipeptide or stabilized on the promoter by decitabine treatment.

234 xcess blasts after failure of azacitidine or decitabine treatment.

235 hylation and synthesis through conversion to decitabine triphosphate and subsequent DNA incorporation

236 Patients continued to receive decitabine until disease progression or an unacceptable

237 The CR rate plus CRp was 17.8% with decitabine versus 7.8% with TC (odds ratio, 2.5; 95% CI,

238 pite standard-of-care, randomized 3:2 to THU-decitabine versus placebo in 5 cohorts of 5 patients tre

239 patients received a median of four cycles of decitabine versus two cycles of TC.

240 ificant upregulation of CDKN1A and FOXO3A in decitabine- versus control-treated cells.

241 AEs) were not significantly different in THU-decitabine-versus placebo-treated patients.

242 compared the safety and efficacy of low-dose decitabine vs low-dose azacitidine in this group of pati

243 The OBD of decitabine was 20 mg/m(2)/d intravenously, with limited

244 Decitabine was administered at 15 mg/m2 intravenously ov

245 Decitabine was administered at 2 mg/kg/d via continuous

246 Decitabine was administered at a dose of 20 mg per squar

247 Decitabine was administered by intravenous infusion at a

248 Decitabine was associated with improved median overall s

249 A phase II clinical trial with single-agent decitabine was conducted in older patients (>or=60 years

250 ethylation in CD34(+) bone marrow cells when decitabine was delivered by a short pulse (Arm A).

251 Thus, a phase 1 trial of bortezomib and decitabine was developed.

252 In these neurons and in cortical slices, decitabine was found to rescue the effect of BPA on Kcc2

253 In conclusion, this schedule of decitabine was highly active and well tolerated in this

254 e of intensive chemotherapy, azacitidine, or decitabine was more favorable in patients who had previo

255 Low-dose decitabine was safe and showed encouraging clinical and

256 Similar results were seen when decitabine was used in combination with another ribonucl

257 Given the DNA hypomethylating effect of decitabine, we examined the relationship of clinical res

258 did not correlate with clinical response to decitabine, we observed a significant correlation betwee

259 To assess the genome-wide activity of decitabine, we profiled pretreatment and post treatment

260 5-Azacitidine and decitabine were approved in the United States based on c

261 histone deacetylase inhibitors (HDACIs) and decitabine were investigated in models of diffuse large

262 The most common drug-related AEs with decitabine were thrombocytopenia (27%) and neutropenia (

263 tered by the combination of panobinostat and decitabine were VHL, TCEB1, WT1, and DIRAS3.

264 e the hypomethylating agents azacitidine and decitabine, which should be administered for a minimum o

265 anned survival analysis showed a benefit for decitabine, which was not observed at the time of the pr

266 There is considerable interest in combining decitabine with histone deacetylase inhibitors and in us

267 II trial compared the efficacy and safety of decitabine with treatment choice (TC) in older patients