ライフサイエンスコーパス: DFMO

1 DFMO after completion of immunotherapy was associated wi

2 DFMO also inhibited thrombin-induced SMC proliferation.

3 DFMO and SAM486A caused rapid cell growth inhibition, po

4 DFMO at the highest dose significantly delayed tumor ons

5 DFMO blocked ODC activity in a dose- and time-dependent

6 DFMO combination with immunotherapy or radiotherapy furt

7 DFMO forms a Schiff base with PLP and is covalently atta

8 DFMO had a dose-dependent effect on total tumor burden,

9 DFMO is an irreversible inhibitor of ornithine decarboxy

10 DFMO prevented the overall increase in proximal reabsorp

11 DFMO selectively inhibited a gene reporter construct dep

12 DFMO treatment also inhibited cell growth in all three c

13 DFMO treatment completely depleted putrescine and spermi

14 DFMO treatment for 12 h caused reductions of only 11 and

15 DFMO treatment led to dramatic decreases in ODC activity

16 DFMO treatment of control mice or Gy-CAG/SpmS had no eff

17 DFMO treatment of neuroblastoma-prone genetically engine

18 DFMO treatment of transgenic mice from 28 to 32 weeks of

19 DFMO treatment-associated hair loss in PKC epsilon trans

20 DFMO's effects on both nAChR expression and cellular bio

21 DFMO, as well as the NO donor agents, interfered with ce

22 DFMO, Rosuvastatin and/or combinations significantly dec

23 DFMO-elicited vasodilation was greater in old (O) compar

24 DFMO-induced NF-kappa B activation was accompanied by th

25 Administration of 1.0% DFMO in the drinking water from 4 to 32 weeks of age pre

26 Oral consumption of 1% DFMO (w/v) in the drinking water to TRAMP mice from 8 to

27 d given either deionized water (DFMO-) or 1% DFMO in deionized water (DFMO+).

28 The experimental group was given 0.5% DFMO in their drinking water, while the control group wa

29 At week 5, DFMO treatment greatly decreased (by 48-82%) the levels

30 d not develop carcinoma when infected with a DFMO output strain containing rearranged cagY or the par

31 ptosis in papillomas was unaffected by acute DFMO treatment, tumor cell proliferation was rapidly dec

32 In addition, DFMO inhibited G2-M transition, most likely as a result

33 In addition, DFMO markedly suppressed the expression of the full-leng

34 astic mammary tissue collected 1 month after DFMO treatment demonstrated that DFMO (10 g/kg diet) sig

35 ines had greater sensitivity to single-agent DFMO, and ODC levels were elevated in TNBC patient sampl

36 ells, and co-administration of AMXT 1501 and DFMO leads to potent in vitro activity, and significant

37 compared to low-dose Rosuvastatin (29%) and DFMO (46%), suggesting additive efficacy.

38 BEC and DFMO suppressed arginase activity and restored NOS activ

39 an cancer and found that in vivo, 5AZA-C and DFMO, either alone or in combination, significantly incr

40 nt and post-treatment regimens of DENSPM and DFMO were antagonistic to 5-FU depending on cellular p53

41 In a similar fashion, DFMO and DFMO/SAM486A inhibited the phosphorylation of the G1/S t

42 The tumor-inhibitory effects of DHEA and DFMO on mammary cancer growth appear to occur after the

43 th at concentrations as low as 3 microM, and DFMO elicited effects at concentrations of 100 microM or

44 re the underlying mechanisms by which NO and DFMO activate the MAPK pathway to promote induction of p

45 The cytostatic effect of NO and DFMO was prevented by the MAPK kinase 1/2 inhibitors PD

46 rnithine (DFMO) acts like RS1-Reg(S20E), and DFMO and RS1-Reg(S20E) are not cumulative, we raised the

47 mine the safety and efficacy of sulindac and DFMO (alone or in combination) for preventing a clinical

48 hranilic acid derivatives were identified as DFMO adjunct agents.

49 These findings suggest that agents, such as DFMO, that target the polyamine pathway may show efficac

50 ls or currently available molecules, such as DFMO.

51 lism in response to chemotherapy, as well as DFMO-induced preferential sensitization of TNBC cells to

52 ity was reduced by approximately 50% by both DFMO and DHEA (P < 0.05).

53 asive carcinoma growth was observed for both DFMO, an inhibitor of ornithine decarboxylase, and DHEA,

54 r incidence was reduced approximately 20% by DFMO (8000 mg/kg) and 30% by DHEA (4000 mg/kg; P < 0.05)

55 NF-kappa B is activated by DFMO through the degradation of the inhibitory protein I

56 trescine to bypass the metabolic blockade by DFMO, restored both enhanced phospholipid flip-flop and

57 marked induction in p15 expression caused by DFMO.

58 trescine content were markedly diminished by DFMO chemoprevention in ear skin, whereas there was a mo

59 We demonstrate inhibition of cell growth by DFMO-associated polyamine depletion is successfully resc

60 PD98059 reversed the G2-M block induced by DFMO (probably as a result of suppression of p21) but no

61 not reverse the cell cycle arrest induced by DFMO because of activation of alternative mechanisms lea

62 ersing the decrease in Rb protein induced by DFMO.

63 5-fold in diabetic kidneys and normalized by DFMO, which also attenuated hyperfiltration and hypertro

64 The data suggest that inhibition of ODC by DFMO induces two opposing pathways in NB: one promoting

65 tudy, we found that the inhibition of ODC by DFMO promotes cell survival by inducing the phosphorylat

66 rate that in vitro treatment of H. pylori by DFMO induces oxidative DNA damage, expression of the DNA

67 umber of cells, was substantially reduced by DFMO.

68 al epidermal keratinocytes was unaffected by DFMO treatment.

69 ns that appear to be otherwise unaffected by DFMO.

70 ng antibody reduced the efficacy of 5AZA-C + DFMO treatment and resulted in fewer M1 macrophages in t

71 Combining DFMO with inhibitors of polyamine uptake have improved t

72 In conclusion, DFMO-induced oxidative stress in H. pylori leads to geno

73 response of Myc, yet in this tumor context, DFMO targets the expression of the p21(Cip1) Cdk inhibit

74 In contrast, DFMO had no effect on a gene reporter construct dependen

75 s observed when mice were treated with DHEA, DFMO, tocopherol acetate, selenomethionine, or 9-cis-ret

76 terone (DHEA), or 2-difluoromethylornithine (DFMO).

77 ynthesis with alpha-difluoromethylornithine (DFMO) also increased MitoROS and ATF4 when ATP13A2 was d

78 DL-alpha-Difluoromethylornithine (DFMO) causes polyamines of the AIDS-associated opportuni

79 ODC inhibitor alpha-difluoromethylornithine (DFMO) depleted polyamine pools and induced G1 cell cycle

80 ynthesis with alpha-difluoromethylornithine (DFMO) has been shown to inhibit proliferation of breast

81 yamines by DL-alpha-difluoromethylornithine (DFMO) induced levels of JunD mRNA and protein, which was

82 Odc inhibitor alpha-difluoromethylornithine (DFMO) inhibited neuroblast proliferation in vitro and su

83 Alpha-difluoromethylornithine (DFMO) inhibits the proto-oncogene ornithine decarboxylas

84 L-Alpha-difluoromethylornithine (DFMO) is a chemopreventive agent for colon cancer in cli

85 ide inhibitor alpha-difluoromethylornithine (DFMO) or Odc heterozygosity markedly impairs lymphoma de

86 ion of ODC by alpha-difluoromethylornithine (DFMO) resulted in a approximately 50% decrease in intrac

87 ts as well as alpha-difluoromethylornithine (DFMO), a known ODC inhibitor, was prevented by addition

88 nic mice with alpha-difluoromethylornithine (DFMO), a specific inhibitor of ODC enzyme activity, caus

89 ce were given alpha-difluoromethylornithine (DFMO), a suicide inactivator of ODC, in the drinking wat

90 in vitro than alpha-difluoromethylornithine (DFMO), a U.S. Food and Drug Administration (FDA) approve

91 ive effect of alpha-difluoromethylornithine (DFMO), an enzyme-activated irreversible inhibitor of ODC

92 inhibited by alpha-difluoromethylornithine (DFMO), an enzyme-activated, irreversible inhibitor of or

93 ls induced by alpha-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase, led to a

94 or absence of alpha-difluoromethylornithine (DFMO), an inhibitor of the polyamine synthetic enzyme or

95 The use of alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ODC enzyme activity,

96 administered alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ODC, to neonatal rat

97 administered alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ODC, to neonatal rat

98 nsport, or by alpha-difluoromethylornithine (DFMO), an ODC inhibitor.

99 e addition of alpha-difluoromethylornithine (DFMO), an ornithine decarboxylase inhibitor, may further

100 e (DENSPM) or alpha-difluoromethylornithine (DFMO), have synergistic effects in killing HCT116 colon

101 is, including alpha-difluoromethylornithine (DFMO), inhibit tumor growth, but compensatory uptake of

102 NO, like alpha-difluoromethylornithine (DFMO), interferes with cell proliferation by inhibiting

103 y used drugs, alpha-difluoromethylornithine (DFMO), is a suicide inhibitor of ODC.

104 ventive agent alpha-difluoromethylornithine (DFMO), known to inhibit the enzyme ornithine decarboxyla

105 he transgene, alpha-difluoromethylornithine (DFMO), reversibly blocked the appearance of squamous pap

106 bitor of ODC, alpha-difluoromethylornithine (DFMO), was used.

107 ase inhibitor alpha-difluoromethylornithine (DFMO).

108 ibitor of ODC alpha-difluoromethylornithine (DFMO, 0.5% w/v) in the drinking water during TPA promoti

109 nine (nor-NOHA) and difluoromethylornithine (DFMO).

110 pecific ODC blocker difluoromethylornithine (DFMO), and ODC activity, intracellular polyamine concent

111 t ODC inhibition by difluoromethylornithine (DFMO) increased efficacy of SPA.

112 rsibly inhibited by difluoromethylornithine (DFMO).

113 Two compounds, difluoromethylornithine (DFMO) and 5-fluorouracil (5-FU) were investigated.

114 control rats given difluoromethylornithine (DFMO; Marion Merrell Dow, Cincinnati, Ohio, USA) to inhi

115 e the ODC inhibitor difluoromethylornithine (DFMO) acts like RS1-Reg(S20E), and DFMO and RS1-Reg(S20E

116 h the ODC inhibitor difluoromethylornithine (DFMO) sensitized TNBC cells to chemotherapy, but this wa

117 the ODC1 inhibitor difluoromethylornithine (DFMO) was measured in the absence and presence of glucos

118 ase (ODC) inhibitor difluoromethylornithine (DFMO), beginning at the time they were weaned and contin

119 synthesis inhibitor difluoromethylornithine (DFMO), provides a method to target cancers with high pol

120 ase (ODC) inhibitor difluoromethylornithine (DFMO).

121 boxylase inhibitor, difluoromethylornithine (DFMO), and induced to undergo apoptosis by ultraviolet i

122 the ODC inhibitor, difluoromethylornithine (DFMO).

123 r polyamine levels: difluoromethylornithine (DFMO; also called eflornithine), which is a suicide inhi

124 the combination of difluoromethylornithine (DFMO) and sulindac on biomarkers and investigated factor

125 reventive effect of difluoromethylornithine (DFMO) on the development of mammary cancer were investig

126 Administration of difluoromethylornithine (DFMO), a clinically approved inhibitor of polyamine gene

127 In combination with difluoromethylornithine (DFMO), P-S reduced tumor multiplicity in Apc/Min mice by

128 itor, eflornithine (difluoromethylornithine; DFMO).

129 ing Rosuvastatin and difluromethylornithine (DFMO) individually and in combination for 40 weeks.

130 At week 12 after NMBA dosing, DFMO reduced the incidence of esophageal tumors from 80

131 a predictable consequence of these effects, DFMO caused a G1-S block.

132 rboxylase (ODC) using low-dose eflornithine (DFMO, CPP-1X), combined with maximal PA export using low

133 we present new analyses to further evaluate DFMO as HRNB postimmunotherapy maintenance.

134 In a similar fashion, DFMO and DFMO/SAM486A inhibited the phosphorylation of t

135 These findings support a role for DFMO as a chemopreventive agent.

136 trials and reveals potential new targets for DFMO-based combination therapies for NB treatment.

137 The median follow-up time for DFMO/treated patients was 6.1 years (IQR, 5.2-7.2) versu

138 gion of the cagY gene of output strains from DFMO-treated animals, which were associated with alterat

139 Furthermore, DFMO treatment resulted in the marked reduction in the p

140 However, DFMO treatment led to marked hair loss in PKC epsilon tr

141 yses revealed increased DNA fragmentation in DFMO regressed tumors compared with similarly sized spon

142 hibiting the uptake of spermidine (1 muM) in DFMO-treated L3.6pl human pancreatic cancer cells.

143 Cdk-2 activity was drastically reduced in DFMO-treated breast cancer cells which exhibited a reduc

144 nd beta-catenin, was found to be restored in DFMO-fed animals as compared with the non-DFMO-fed mice.

145 ility to inhibit the import of spermidine in DFMO-treated Chinese hamster ovary (CHO) and L3.6pl huma

146 The decreased vasculature in DFMO regressed tumors was not attributable to altered ex

147 nce of the polyamine biosynthesis inhibitors DFMO (alpha-dimethyl-fluoroornitithine) and MGBG [methyl

148 Interestingly, DFMO-treated cells often escape polyamine depletion via

149 Intriguingly, DFMO also induced the phosphorylation of p27Kip1 at resi

150 These observations suggested that NO, like DFMO, may directly inhibit ODC.

151 Neither DFMO nor PD98059, either alone or in combination, reduce

152 pared EFS and OS for overall groups, 3:1 (NO-DFMO:DFMO) propensity score-matched cohorts balanced on

153 -7.2) versus 5.0 years (IQR, 3.5-7.0) for NO-DFMO/control patients.

154 er immunotherapy, but did not enroll (the NO-DFMO/control group).

155 Non-DFMO-fed animals, on the other hand, displayed extensive

156 in DFMO-fed animals as compared with the non-DFMO-fed mice.

157 Notably, DFMO treatment prior to ultraviolet irradiation did not

158 th ( approximately 6 weeks), and only 25% of DFMO-treated mice developed tumors by 15 weeks of age.

159 d the potential capsule-crippling ability of DFMO and the possible synergistic effects of the polyami

160 Deletion of mutS2 abrogated the ability of DFMO to induce cagY rearrangements directly.

161 8059 or U0126 in the presence and absence of DFMO exhibited a marked increase in the expression of p2

162 fore, we analysed the mechanism of action of DFMO and/or SAM486A in two established MYCN-amplified hu

163 he elucidation of the mechanism of action of DFMO derivatives paves the way for the rational design o

164 A combination of DFMO and sulindac significantly suppressed production of

165 we studied the effect of oral consumption of DFMO on development of prostate carcinogenesis and surro

166 gressed tumors within the first four days of DFMO treatment.

167 Mice were exposed to four different doses of DFMO in the diet (3.5, 4.9, 7.0 and 10 g/kg diet).

168 However, the effect of DFMO on human neuroblastoma (NB) cells and the exact mec

169 maceuticals devoid of the untoward effect of DFMO.

170 line biomarker levels modified the effect of DFMO/sulindac for CRA prevention.

171 (MAPK) pathway on the cell cycle effects of DFMO because this compound has been shown to activate MA

172 pathway accounts for some of the effects of DFMO on cell cycle events of breast cancer cells.

173 address this issue, we tested the effects of DFMO on cell cycle variables of MDA-MB-435 human breast

174 Inhibitory effects of DFMO on cell growth and survival were lost as the cells

175 n conclusion, the chemopreventive effects of DFMO on mammary cancer progression were mediated by chan

176 The selective anticancer effects of DFMO on mouse and human MYCN-amplified neuroblastoma als

177 The mechanism for the ototoxic effects of DFMO remains uncertain.

178 These chemopreventive effects of DFMO were further confirmed by immunohistochemical analy

179 These effects of DFMO were reversible with exogenous putrescine, thus ind

180 herefore, we further examined the effects of DFMO, alone and in combination with phosphatidylinositol

181 In addition, short-term effects of DFMO, RS1-Reg mutants, the ODC1 product putrescine, and/

182 on that may explain the moderate efficacy of DFMO monotherapy in clinical trials and reveals potentia

183 nterface and the delta-carbon amino group of DFMO is positioned between Asp361 of one subunit and Asp

184 d AMXT 1501, and also measured the impact of DFMO on amino acid decarboxylase activities.

185 astoma (NB) cells and the exact mechanism of DFMO-induced cell death are largely unknown.

186 Here, we show that the ototoxicity of DFMO may be mediated by alteration of the inward rectifi

187 ncrease in p21 expression in the presence of DFMO.

188 cal analysis of the dorsolateral prostate of DFMO-fed animals displayed marginal epithelial stratific

189 of a phase IIb/III chemoprevention trial of DFMO/sulindac.

190 s observed in PKC epsilon transgenic mice on DFMO during skin tumor promotion has not been reported b

191 pregnant dams treated with piroxicam and/or DFMO were reduced in number and their ratio to Apc+/+ pr

192 revealed that treatment of RASMC with NO or DFMO leads to activation of p42/p44 MAPK and induction o

193 st influenced the cytostatic effect of NO or DFMO or their ability to activate these signal transduct

194 ct was due to the inhibition of ODC by NO or DFMO.

195 alpha-Difluoromethyl-ornithine (DFMO) is an irreversible inhibitor of the polyamine bios

196 tions of d,l-alpha-difluoromethyl-ornithine (DFMO), which decreases polyamine levels by a different m

197 ontaining a difluoromethyl-1,3,4-oxadiazole (DFMO) moiety are potent and single-digit nanomolar inhib

198 mbined treatment of mice with piroxicam plus DFMO was much more effective than either agent alone and

199 Low-dose Rosuvastatin plus DFMO suppressed colon adenocarcinoma multiplicity by 76%

200 rategy using clinically relevant statin plus DFMO doses which shows a significant suppression of colo

201 nts with HRNB treated with postimmunotherapy DFMO.

202 ptosis were significantly inhibited by prior DFMO treatment.

203 enopus laevis, injected hRS1-Reg(S20E), QEP, DFMO, and/or alpha-methyl-d-glucopyranoside (AMG), and m

204 In the group that received DFMO/sulindac, spermidine-to-spermine ratio (Spd:Spm) in

205 and were reduced by 50% in animals receiving DFMO (P = 0.0001).

206 f ATP13A2 was required for lowering rotenone/DFMO-induced MitoROS, whereas exogenous spermine quenche

207 ion by molecular replacement using the TbODC DFMO-bound structure as the search model.

208 Biochemical data confirm that DFMO 6 is a tight-binding HDAC6i capable of inhibiting H

209 month after DFMO treatment demonstrated that DFMO (10 g/kg diet) significantly increased the ratio of

210 2, and mutations in cagY, demonstrating that DFMO directly affects genomic stability.

211 alidated target, combined with the fact that DFMO is currently the only ODC inhibitor in clinical use

212 We found that DFMO caused a p53-independent increase in p21 and its as

213 graphy, and mass spectrometry, we found that DFMO derivatives are slow-binding substrate analogs of H

214 Here, we report that DFMO treatment, but not Odc heterozygosity, impairs MYCN

215 Importantly, we show that DFMO augments antitumor efficacy of conventional cytotox

216 Our findings show that DFMO inhibited pneumococcal polyamine and capsule biosyn

217 Our data showed that DFMO effectively inhibited the increased esophageal cell

218 Recent evidence shows that DFMO can also target arginine decarboxylation.

219 on of the hearing threshold, suggesting that DFMO may affect a common trait along the cochlear spiral

220 We show for the first time that DFMO and SAM486A induce G1 cell cycle arrest in NB cells

221 The DFMO treatment did not affect the skin tumor multiplicit

222 The DFMO+PTI combination therapy results in sustained intrac

223 The DFMO-induced NF-kappa B complexes contain the p65 and p5

224 atment consistent with (n = 5) ANBL0032 (the DFMO/treated group) and 852 patients from ANBL0032 who c

225 PK pathway with PD98059 or U0126 blocked the DFMO-induced induction of p21 and the reduction of cdk-2

226 to adenylyl cyclase showed a deficit in the DFMO group, as evaluated with the response to fluoride;

227 ed 145 degrees toward the active site in the DFMO-bound structure.

228 Importantly, in none of the DFMO-fed TRAMP mice were any distant metastases to lymph

229 e T. brucei ODC (TbODC) mutant K69A bound to DFMO has been determined by X-ray crystallography to 2.0

230 vivo analysis of splenic NK cells exposed to DFMO, Rosuvastatin or combination resulted in an increas

231 be lost from P. carinii even when exposed to DFMO.

232 Exposure to DFMO (0.5 or 1.0% in water) caused a dose-dependent decr

233 Within 2-3 days of exposure to DFMO in the drinking water, the Gy mice suffered a catas

234 s in pneumococcal metabolites in response to DFMO and AMXT 1501, and also measured the impact of DFMO

235 regulated in DIPG, leading to sensitivity to DFMO.

236 ork will identify small molecules similar to DFMO/AMXT 1501, which act in a serotype-independent mann

237 toma and that, in this malignancy, transient DFMO treatment is sufficient to confer protection.

238 water (DFMO-) or 1% DFMO in deionized water (DFMO+).

239 zinc) diet and given either deionized water (DFMO-) or 1% DFMO in deionized water (DFMO+).

240 Whereas DFMO treatment resulted in profound depletion of putresc

241 reased apoptosis in the mechanism(s) whereby DFMO brings about the inhibition of cell proliferation a

242 In the present study, we questioned whether DFMO might directly affect H. pylori pathogenicity.

243 However, the precise mechanism by which DFMO provokes these changes in NB cells remained unknown

244 the wild-type cagY was replaced by cagY with DFMO-induced rearrangements.

245 fety and efficacy of BAT in combination with DFMO for patients with metastatic castration-resistant p

246 shown that the use of 31 in combination with DFMO led to a cytostatic growth inhibition of a variety

247 mine depletion when used in combination with DFMO, a well-studied polyamine biosynthesis inhibitor.

248 In nontransgenic littermates fed with DFMO, no significant alterations in the above parameters

249 trast, simultaneous combination of 5-FU with DFMO, an inhibitor of the polyamine biosynthetic enzyme

250 re, treatment of papilloma-bearing mice with DFMO caused rapid tumor regression, also in a reversible

251 Treatment of tumor-bearing mice with DFMO reduced both tumor size and tumor number within sev

252 midine uptake yet works synergistically with DFMO to limit cell growth in the presence of exogenous s

253 ferase enzymatic activity, and together with DFMO it reduces polyamine levels in vitro and in vivo.

254 t strains isolated from gerbils treated with DFMO exhibit reduced ability to translocate CagA in gast

255 The loss of balance in Gy mice treated with DFMO was due to inhibition of polyamine synthesis becaus

256 rom ODC/Ras transgenic mice not treated with DFMO.

257 Treatment with DFMO in combination with SAM486A, an S-adenosylmethionin

258 cer and supports chemoprevention trials with DFMO, particularly in individuals homozygous for the T a

259 fter MNU and was continued for 29 weeks with DFMO.

260 ere divided into four groups: Zn+/DFMO-, Zn+/DFMO+, Zn-/DFMO-, and Zn-/DFMO+.

261 ling rats were divided into four groups: Zn+/DFMO-, Zn+/DFMO+, Zn-/DFMO-, and Zn-/DFMO+.

262 ps: Zn+/DFMO-, Zn+/DFMO+, Zn-/DFMO-, and Zn-/DFMO+.

263 into four groups: Zn+/DFMO-, Zn+/DFMO+, Zn-/DFMO-, and Zn-/DFMO+.

264 proliferative, zinc-deficient esophagus (Zn-/DFMO-).

265 , was markedly stronger in esophagi from Zn-/DFMO+ animals that showed increased apoptosis, whereas i