ライフサイエンスコーパス: vorinostat

1 mbination with various HDACi (MS/SNDX-275 or vorinostat).

2 nalidomide, and 92 received azacitidine plus vorinostat.

3 ths of maintenance therapy with single-agent vorinostat.

4 reated with the FDA-approved HDAC inhibitor, vorinostat.

5 ctivity of the histone deacetylase inhibitor vorinostat.

6 pair the DSBs despite continued culture with vorinostat.

7 nd hyponatremia also were more frequent with vorinostat.

8 predicting the response of CTCL patients to vorinostat.

9 rall survival and safety and tolerability of vorinostat.

10 ing exposure to the latency-reversing agent, vorinostat.

11 xposure to the histone deacetylase inhibitor vorinostat.

12 AC6 with tubacin recapitulated the effect of vorinostat.

13 milarly treated patients who did not receive vorinostat.

14 cetylase (HDAC) inhibitors valproic acid and vorinostat.

15 n, entinostat, panobinostat, belinostat, and vorinostat.

16 inhibitors (HDACis) valproic acid (VPA) and vorinostat.

17 Vorinostat (0.35 microM) and VPA (0.25 mM) in combinatio

18 to evaluate the safety and activity of oral vorinostat 100 to 300 mg twice or thrice daily for 14 da

19 Vorinostat (100 mg twice daily) was started on day -10 a

20 ade 4 platelet toxicity was more common with vorinostat (18% v 3%; P < .05).

21 hypertriglyceridemia, resulting in a MTD of vorinostat 180 mg/m(2)/d 4 times per week and 13cRA 80 m

22 or, have been merged with the HDAC inhibitor vorinostat (2), leading to new molecules that are bispec

23 at analysis (n = 62), overall pCR was 27.4% (vorinostat, 25.8%; placebo, 29.0%).

24 Patients received oral vorinostat 300 mg (or matching placebo) twice daily on d

25 days with 4 days rest, and group 3 received vorinostat 300 mg twice daily for 14 days with 7 days re

26 ed vorinostat 400 mg daily, group 2 received vorinostat 300 mg twice daily for 3 days with 4 days res

27 mg/day on days 1 to 21); or azacitidine plus vorinostat (300 mg twice daily on days 3 to 9).

28 Group 1 received vorinostat 400 mg daily, group 2 received vorinostat 300

29 d paclitaxel (200 mg/m(2) day 3) with either vorinostat (400 mg by mouth daily) or placebo.

30 and nab-paclitaxel (100 mg/m(2) weekly) with vorinostat (400 mg orally daily, days 1-3 of every 7-d p

31 Induction therapy was vorinostat 500 mg orally three times a day (days 1 to 3)

32 inhibitor, suberoylanilide hydroxamic acid (vorinostat), a new anticancer drug.

33 We performed a phase II study of oral vorinostat, a histone and protein deacetylase inhibitor,

34 ith either drug alone or in combination with vorinostat, a histone deacetylase inhibitor (HDACi), usi

35 PURPOSE Vorinostat, a histone deacetylase inhibitor, exerts anti

36 Vorinostat, a histone deacetylase inhibitor, represents

37 he present study, we describe the effects of vorinostat, a small-molecule inhibitor of histone deacet

38 tment of colon cancer cells with sorafenib + vorinostat activates CD95 via de novo ceramide synthesis

39 We demonstrate that vorinostat acts following viral fusion and enhances the

40 ng toxicities (DLT), and pharmacokinetics of vorinostat administered as a single agent and in combina

41 acetylase (HDAC) inhibitors Panobinostat and Vorinostat also enhanced AhR ligand-mediated induction a

42 Furthermore, vorinostat also interacted with a selective inhibitor of

43 ical HDACi such as the hydroxamic acid-based vorinostat (also known as SAHA and Zolinza) inhibits cla

44 as the histone deacetylase (HDAC) inhibitor vorinostat, also has been reported to trigger HIV-1 reac

45 ibitor, and suberoylanilide hydroxamic acid (vorinostat), an inhibitor of class I, II, and IV HDACs,

46 h 93% of samples treated with venetoclax and vorinostat and 73% of samples treated with venetoclax an

47 d by an increased acetylation in response to vorinostat and a reduced Ser315 phosphorylation in respo

48 the histone deacetylase inhibitors (HDACis) vorinostat and AR-42 reduced the viability of a canine m

49 Combination pretreatment with vorinostat and decitabine resulted in even greater cytot

50 Weaning NOD mice received low doses of vorinostat and givinostat in their drinking water until

51 ate that the clinically well-tolerated KDACi vorinostat and givinostat revert diabetes in the nonobes

52 ant for the anticancer effects of HDACi, and vorinostat and IFN-gamma acted in concert to enhance the

53 authors evaluated the effects of the HDACIs vorinostat and m-carboxycinnamic acid bis-hydroxamide on

54 r refractory lymphoma attained a response to vorinostat and niacinamide, and 57% experienced disease

55 histone deacetylase inhibitors, for example, vorinostat and panobinostat (LBH589; Novartis Pharmaceut

56 r the robust anticancer effects of the HDACi vorinostat and panobinostat against a colon adenocarcino

57 ractions between resveratrol and pan-HDACIs (vorinostat and panobinostat) were examined in human acut

58 Specifically, vorinostat and romidepsin have been approved by the US F

59 ts following the FDA approval of two HDACis, vorinostat and romidepsin.

60 hat ROS plays an important role in action of vorinostat and that combination with a redox-modulating

61 In vivo results demonstrate that combining vorinostat and the IKK inhibitor Bay 117085 significantl

62 imes unlike the hydroxamate-containing HDACi vorinostat and trichostatin-A.

63 molar inhibition of HDAC4 and HDAC5, whereas vorinostat and TSA inhibit HDAC4 and HDAC5 in the higher

64 acetylase (HDAC) inhibitors, including SAHA (vorinostat) and LBH589, which are currently being tested

65 one deacetylase inhibitors (e.g. romidepsin, vorinostat, and balinostat), purine analogs and agents t

66 After a 24-h culture of cells with vorinostat, and reculture without the HDACi, gammaH2AX w

67 T cells, were implicated as effectors of the vorinostat antitumor immune response.

68 HDAC inhibitors, particularly vorinostat, are currently being investigated clinically

69 ne deacetylase (HDAC) inhibitors, especially vorinostat, are currently under investigation as potenti

70 l (13.0 months v 9.7 months; P = .17) in the vorinostat arm.

71 Chemosensitivity testing identified vorinostat as a potential therapeutic agent.

72 by Makki and Haqqi that proposes the use of vorinostat as a therapeutic agent for the management of

73 nsights into the effects of panobinostat and vorinostat as LRAs for latent HIV-1.

74 The combination of idarubicin with vorinostat at 0.075 microM or VPA at 0.25 mM resulted in

75 The finding that vorinostat augments the effectiveness of doxorubicin pro

76 ry of suberoylanilide hydroxamic acid (SAHA, vorinostat) began over three decades ago with our studie

77 Low doses of sorafenib and vorinostat, but not the individual drugs, rapidly increa

78 The effect of vorinostat co-treatment on the development of resistance

79 we further demonstrated that decitabine and vorinostat cooperate to suppress colon carcinoma metasta

80 ed that epigenetic inhibitors decitabine and vorinostat cooperate to upregulate Fas expression in met

81 The median number of vorinostat cycles received was nine.

82 B-IVA MF/SS were treated with 400 mg of oral vorinostat daily until disease progression or intolerabl

83 pregulates BNIP3 and Bik expression, whereas vorinostat decreased Bcl-x(L) expression.

84 Vorinostat demonstrated activity in heavily pretreated p

85 Wide interpatient variability was noted in vorinostat disposition, with area under the concentratio

86 Vorinostat does not enhance viral fusion with cells but

87 The daily vorinostat dose was escalated within each hepatic dysfun

88 The recommended vorinostat doses in mild, moderate, and severe hepatic d

89 Finally, subeffective vorinostat doses markedly increased CFZ-mediated tumor g

90 One week later, daily vorinostat dosing was begun and continued until toxicity

91 Vorinostat downregulated baseline NF-kappaB activity and

92 Coadministration of vorinostat dramatically increased MK-0457 lethality in K

93 However, CFZ/vorinostat dramatically induced resistant cell apoptosis

94 n, implicating HIF-2alpha as a biomarker for Vorinostat efficacy in STS.

95 Vorinostat (either 100 mg or 200 mg, twice a day) was in

96 CONCLUSION Vorinostat enhances the efficacy of carboplatin and pacl

97 ), erlotinib, lapatinib, and combinations of vorinostat/erlotinib and vorinostat/lapatinib.

98 ed the safety and efficacy of pazopanib plus vorinostat, everolimus, lapatinib or trastuzumab, and ME

99 ase CD95 plasma membrane levels; sorafenib + vorinostat exposure killed HCT116 cells via an intrinsic

100 Vorinostat for GVHD prevention is an effective strategy

101 ll patients received a single 400-mg dose of vorinostat for pharmacokinetic studies.

102 e studies are needed to assess the effect of vorinostat for prevention of GVHD in broader settings of

103 d by the US Food and Drug Administration for vorinostat for treatment of cutaneous T-cell lymphoma.

104 ed this phase 3 trial to investigate whether vorinostat given as a second-line or third-line therapy

105 In this randomised trial, vorinostat given as a second-line or third-line therapy

106 fatigue or malaise (51 [16%] patients in the vorinostat group vs 25 [8%] in the placebo group]) and d

107 In clinical trials, vorinostat has activity against hematologic and solid ca

108 ly, the histone deacetylase (HDAC) inhibitor vorinostat has been demonstrated to induce HIV transcrip

109 Vorinostat has demonstrated significant anticancer activ

110 Further evaluation of vorinostat in AML/MDS is warranted.

111 ngs can explain, in part, the selectivity of vorinostat in causing cancer cell death at concentration

112 Additional testing of vorinostat in combination regimens is warranted.

113 o-controlled study evaluated the efficacy of vorinostat in combination with carboplatin and paclitaxe

114 uture clinical studies looking at the use of vorinostat in combination with conventional chemotherapy

115 Administration of vorinostat in combination with standard GVHD prophylaxis

116 The IL-8/CXCL8 expression induced by vorinostat in EOC cells is dependent on IkappaB kinase (

117 , significantly enhanced the cytotoxicity of vorinostat in leukemia cell lines and primary leukemia c

118 ion analysis performed in a phase 1 trial of vorinostat in leukemia indicated that overexpression of

119 TAT3, and STAT5 correlate with resistance to vorinostat in lymphoma cell lines.

120 ximum-tolerated dose and pharmacokinetics of vorinostat in patients with hepatic dysfunction.

121 uding depsipeptide and MGCD0103, differ from vorinostat in structure and isoenzyme specificity, and h

122 s and RNA expression profiling indicate that vorinostat in this dose and schedule affects target path

123 doxorubicin and the pan-HDAC inhibitor SAHA (vorinostat) in transformed cells (LNCaP, MCF-7), an effe

124 We aimed to study the safety and activity of vorinostat, in combination with standard immunoprophylax

125 s observed with the combination of 13cRA and vorinostat included thrombocytopenia, neutropenia, anore

126 In SW480 cells, sorafenib + vorinostat increased CD95 plasma membrane levels and pro

127 Vorinostat increased p53 expression and activated caspas

128 the small molecule HDAC inhibitors, ISOX and vorinostat, increased MBNL1 expression in DM1 patient-de

129 We demonstrate here that vorinostat increases the susceptibility of uninfected CD

130 HDACIs, such as vorinostat, induce caspase-dependent apoptosis in Rb cel

131 his study, we report that the HDAC inhibitor vorinostat induced p21 expression and decreased Bcl-xL l

132 CFZ/vorinostat induced pronounced lethality in 3 primary DLB

133 Vorinostat induced reactive oxygen species (ROS) through

134 Vorinostat induced the accumulation of acetylated histon

135 and -3, whereas caspase inhibition abrogated vorinostat-induced apoptosis.

136 Suppression or neutralization of vorinostat-induced IL-8/CXCL8 potentiates the vorinostat

137 Previously, we found that vorinostat induces DNA breaks in normal and transformed

138 Thus, the HDACi, vorinostat, induces DNA damage which normal but not canc

139 Furthermore, vorinostat inhibited STAT6 phosphorylation and decreased

140 orinostat-induced IL-8/CXCL8 potentiates the vorinostat inhibitory effect on cell viability and proli

141 Vorinostat inhibits STS tumour growth, an effect amelior

142 The targeted therapeutics sorafenib and vorinostat interact in a synergistic fashion to kill car

143 Vorinostat is a histone deacetylase inhibitor that chang

144 Vorinostat is a histone deacetylase inhibitor that induc

145 duction of cytosolic Ca(2+) by sorafenib and vorinostat is a primary event that elevates dihydroceram

146 Oral vorinostat is a promising agent in FL and MZL, with an a

147 Vorinostat is an inhibitor of histone deacetylases and w

148 Vorinostat is the first US Food and Drug Administration-

149 In children with recurrent solid tumors, vorinostat is well-tolerated at 230 mg/m(2)/d, with a mo

150 e oral histone deacetylase (HDAC) inhibitor (vorinostat) is safe and results in low incidence of acut

151 clinical trials, and one drug of this class, vorinostat, is US Food and Drug Administration approved

152 and combinations of vorinostat/erlotinib and vorinostat/lapatinib.

153 L-60/LR) cells that are resistant to LAQ824, vorinostat, LBH589, and sodium butyrate.

154 Thus, the HDACi vorinostat leads to both transcriptional and posttranscr

155 rbonyl)-aminomethyl]-benzamide (MS-275), and vorinostat led to differential increases in H3K4 methyla

156 ells, knockdown of CD95 enhanced sorafenib + vorinostat lethality, which correlated with less drug-in

157 JNK inhibition significantly diminished CFZ/vorinostat lethality.

158 -dependent manner (belinostat < givinostat < vorinostat < panobinostat < romidepsin) via degradation

159 ore DNA content, whereas coadministration of vorinostat markedly enhanced aurora kinase inhibition by

160 Finally, vorinostat markedly induced Bim expression, while blocka

161 We found that vorinostat markedly inhibited proliferation and induced

162 Pharmacokinetic analysis showed lower vorinostat maximum concentration and area under the curv

163 Our results suggest that vorinostat may have therapeutic potential for the treatm

164 ion with HIV, raising clinical concerns that vorinostat may reseed the viral reservoirs it is meant t

165 including the histone deacetylase inhibitor vorinostat, may sensitize tumors to chemotherapy and enh

166 is via cathepsin D accumulation and enhances vorinostat-mediated cell death in breast cancer models.

167 g a critical role for FasL in decitabine and vorinostat-mediated tumor suppression in vivo.

168 8(+) T cells are FasL(+), and decitabine and vorinostat-mediated tumor-suppression efficacy was signi

169 sion profiling and qRT-PCR demonstrated that vorinostat modulated the mRNA levels of genes important

170 CONCLUSION:Vorinostat monotherapy is well tolerated in patients wit

171 lled and randomly assigned to receive either vorinostat (n=329) or placebo (n=332) and included in th

172 trate that the histone deacetylase inhibitor vorinostat not only reprograms the aberrant gene express

173 cally approved histone deacetylase inhibitor vorinostat not only restored spatial memory, but also ex

174 enzamide) showed similar effects compared to vorinostat on inhibition of cellular HDACs in a pan-HDAC

175 t, givinostat, panobinostat, romidepsin, and vorinostat) on the productive infection of macrophages.

176 that suberoylanilide hydroxamic acid (SAHA; vorinostat), one of the histone deacetylase inhibitors d

177 Exposure to the pan-HDACIs vorinostat or LBH-589 induced phosphorylation of IKKalph

178 oparticle albumin-bound paclitaxel (CP) with vorinostat or placebo in women with stage II/III, human

179 Preoperative CP with vorinostat or placebo is associated with similar pCR rat

180 Vorinostat or placebo was given on days 1 through 14 of

181 block size of four to either treatment with vorinostat or placebo.

182 with a histone deacetylase (HDAC) inhibitor, vorinostat or romidepsin.

183 ally achievable concentrations of the HDACIs vorinostat or sodium valproate.

184 selectivity profile of 19i in comparison to vorinostat or trichostatin A (TSA).

185 Vorinostat or trichostatin A decreased MYC mRNA and prot

186 ithdrawn mice incubated with the HDACi SAHA (vorinostat) or trichostatin A (TSA) for 2 h, the hyposen

187 v azacitidine), and 27% for azacitidine plus vorinostat ( P = .16 v azacitidine).

188 in PBMC was observed after administration of vorinostat, particularly at higher doses.

189 There were no significant differences in vorinostat pharmacokinetic parameters among the normal o

190 quire appropriate dose reduction even though vorinostat pharmacokinetics are unaltered.

191 obtained from CTCL patients enrolled in the vorinostat phase IIb trial showed that nuclear accumulat

192 Vorinostat plasma concentrations were quantitated by a v

193 lanilidehydroxamic acid (SAHA, also known as vorinostat) potently reactivates KSHV lytic replication

194 dine-based combinations with lenalidomide or vorinostat produce superior overall response rates (ORRs

195 rafenib and vorinostat together (sorafenib + vorinostat) promoted colocalization of CD95 with caspase

196 ity toward androgens and the anticancer drug vorinostat (R > 0.9, P < .001).

197 Addition of vorinostat reactivated proapoptotic genes and enhanced l

198 cell function, all the LRAs except the HDACi Vorinostat reduced, but did not abolish, one or more mea

199 Notably, the MK-0457/vorinostat regimen was highly active against primary CD3

200 No excess vorinostat-related toxicity was observed.

201 eregulation of STAT activity plays a role in vorinostat resistance in CTCL, and strategies that block

202 ses sensitivity to HDACIs and also overcomes vorinostat resistance.

203 Antioxidant gene expression may confer vorinostat resistance.

204 udy was to identify biomarkers predictive of vorinostat response in CTCL using preclinical model syst

205 rategies that block this pathway may improve vorinostat response.

206 h the histone deacetylase inhibitor (HDAC-I) vorinostat restored physiological levels of histone H3 a

207 Concentrations above 0.675 microM of vorinostat resulted in at least 80% loss of cell viabili

208 a) and broad-spectrum HDAC inhibitors (e.g., Vorinostat, Romidepsin).

209 Vorinostat, romidepsin, belinostat, and panobinostat are

210 cells increases their sensitivity to HDACi (vorinostat, romidepsin, or entinostat) induced cell deat

211 limited response to the broad-spectrum HDACi Vorinostat (SAHA) in A549 cells, we find that combinatio

212 iferative activity with greater potency than vorinostat (SAHA), erlotinib, lapatinib, and combination

213 stone deacetylase (HDAC) inhibitors, such as vorinostat (SAHA), have shown promise as therapeutic age

214 suppression by histone deacetylase inhibitor vorinostat (SAHA).

215 latency disrupting compounds such as JQ1 or vorinostat/SAHA, the CARM1 inhibitor achieved synergisti

216 ga-position of the polyethylene chain of the vorinostat scaffold, allowed the selection of a new clas

217 bitor suberoylanilide hydroxamic acid (SAHA; vorinostat) show increases in unspliced cellular HIV-1 R

218 n in apoptosis sensitization, decitabine and vorinostat significantly increased the efficacy of CTL a

219 Here, we demonstrate that vorinostat significantly increases the susceptibility of

220 In addition, vorinostat significantly inhibited JAK2V617F-expressing

221 marginally lethal concentrations of HDACIs (vorinostat, SNDX-275, or SBHA) synergistically increased

222 The clinically approved HDAC inhibitor Vorinostat specifically increases HIF-2alpha, but not HI

223 Together, these findings indicate that vorinostat strikingly increases MK-0457 activity against

224 se cells were treated with trichostatin A or vorinostat (suberoylanilide hydroxamic acid [SAHA]) to e

225 ent histone deacetylase inhibitors (HDACIs): vorinostat (suberoylanilide hydroxamic acid) and valproi

226 safety of the histone deacetylase inhibitor vorinostat (suberoylanilide hydroxamic acid) in persiste

227 Hydroxamic acid-based HDACIs such as vorinostat (suberoylanilide hydroxamic acid) induce the

228 Vorinostat (suberoylanilide hydroxamic acid, SAHA) is a

229 safety of the histone deacetylase inhibitor vorinostat (suberoylanilide hydroxamic acid, SAHA) were

230 ive HDAC inhibitors trichostatin A (TSA) and vorinostat (suberoylanilide hydroxamic acid, SAHA), alth

231 Here, we show that the HDACi, vorinostat (Suberoylanilide hydroxamic acid, SAHA), indu

232 samples showed changes in genes regulated by vorinostat, such as upregulation of E-cadherin (P = .02)

233 Further, we found that vorinostat suppressed DNA DSB repair proteins, e.g., RAD

234 nd to characterize the pharmacokinetics of a vorinostat suspension in children.

235 Sorafenib and vorinostat synergized (sorafenib + vorinostat) to kill H

236 ecursor of the histone deacetylase inhibitor vorinostat that was efficiently uncaged by heterogeneous

237 The administration of LRAs (panobinostat or vorinostat) to HIV-1-infected individuals on antiretrovi

238 fenib and vorinostat synergized (sorafenib + vorinostat) to kill HCT116 and SW480 cells.

239 bitor pacritnib with the pan-HDAC inhibitor, vorinostat, to create bispecific single molecules with b

240 agged proteins, treatment with sorafenib and vorinostat together (sorafenib + vorinostat) promoted co

241 patient-matched to SW480 cells, sorafenib + vorinostat toxicity was significantly lower, which corre

242 e resultant doxorubicin-resistant (DoxR) and vorinostat-treated doxorubicin resistant (DoxR-v) cells

243 = .041; ST2, P = .002) at day 30 post-HCT in vorinostat-treated subjects compared with similarly trea

244 on of JAK2, Stat5, Stat3, Akt, and Erk1/2 in vorinostat-treated, JAK2V617F-expressing human erythrole

245 Sorafenib + vorinostat treatment activated the c-Jun NH(2)-terminal

246 ore potent against established lymphoma than vorinostat treatment alone.

247 Vorinostat treatment also decreased the mutant allele bu

248 and ART intensification are warranted during vorinostat treatment and indicate that HDAC inhibitors t

249 In HCT116 cells, sorafenib + vorinostat treatment caused DISC formation without reduc

250 Vorinostat treatment increased the frequency of function

251 More importantly, we observed that vorinostat treatment normalized the peripheral blood cou

252 Sorafenib and vorinostat treatment radiosensitized liver and pancreati

253 alysis performed in paired baseline and post-vorinostat treatment samples in a separate surgical subg

254 Further, sorafenib and vorinostat treatment suppressed the growth of pancreatic

255 ssion of SOCS1 and SOCS3 was up-regulated by vorinostat treatment.

256 drug application has been approved for SAHA (vorinostat) treatment of cutaneous T-cell lymphoma.

257 The confirmed response rate was 34% with vorinostat versus 12.5% with placebo (P = .02).

258 The histone deacetylase (HDAC) inhibitor vorinostat (VOR) can increase HIV RNA expression in vivo

259 the HDACi suberoylanilide hydroxamic acid or vorinostat (VOR) resulted in increases in HIV gag RNA an

260 le dose of the histone deacetylase inhibitor vorinostat (VOR) up-regulates HIV RNA expression within

261 beroylanilide hydroxamic acid (also known as vorinostat, VOR) can disrupt HIV-1 latency in vitro, the

262 Median overall survival for vorinostat was 30.7 weeks (95% CI 26.7-36.1) versus 27.1

263 Vorinostat was administered at a dose of 200 mg orally t

264 Oral vorinostat was administered at a dose of 200 mg twice da

265 Vorinostat was administered orally daily starting at 180

266 Oral vorinostat was effective in treatment refractory MF/SS w

267 The effect of vorinostat was recapitulated using the cytoplasmic histo

268 Vorinostat was safe and tolerable.

269 l mesothelioma treated in a phase 1 study of vorinostat, we designed this phase 3 trial to investigat

270 K-0457 and the histone deacetylase inhibitor vorinostat were examined in Bcr/Abl(+) leukemia cells, i

271 rse adverse events for patients treated with vorinostat were fatigue or malaise (51 [16%] patients in

272 levels increased with continued culture with vorinostat, whereas in normal cells, this marker decreas

273 While vorinostat will be given in the context of antiretrovira

274 dose reduction being required when combining vorinostat with 13cRA.

275 combining the histone deacetylase inhibitor vorinostat with a PI3K inhibitor led to enhanced FOXO-de

276 Furthermore, we show that a combination of vorinostat with alpha-galactosylceramide (alpha-GalCer),

277 The combination of vorinostat with idarubicin and cytarabine is safe and ac

278 cover suberoylanilide hydroxamic acid (SAHA; vorinostat (Zolinza)), which is a histone deacetylase in