ライフサイエンスコーパス: DFMO

1 DFMO also inhibited thrombin-induced SMC proliferation.

2 DFMO and SAM486A caused rapid cell growth inhibition, po

3 DFMO at the highest dose significantly delayed tumor ons

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

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

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

7 DFMO is an irreversible inhibitor of ornithine decarboxy

8 DFMO prevented the overall increase in proximal reabsorp

9 DFMO selectively inhibited a gene reporter construct dep

10 DFMO treatment also inhibited cell growth in all three c

11 DFMO treatment completely depleted putrescine and spermi

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

13 DFMO treatment led to dramatic decreases in ODC activity

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

15 DFMO treatment of neuroblastoma-prone genetically engine

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

17 DFMO treatment-associated hair loss in PKC epsilon trans

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

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

20 DFMO, Rosuvastatin and/or combinations significantly dec

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

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

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

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

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

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

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

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

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

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

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

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

33 BEC and DFMO suppressed arginase activity and restored NOS activ

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

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

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

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

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

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

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

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

42 ls or currently available molecules, such as DFMO.

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

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

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

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

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

48 marked induction in p15 expression caused by DFMO.

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

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

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

52 ersing the decrease in Rb protein induced by DFMO.

53 5-fold in diabetic kidneys and normalized by DFMO, which also attenuated hyperfiltration and hypertro

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

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

56 umber of cells, was substantially reduced by DFMO.

57 al epidermal keratinocytes was unaffected by DFMO treatment.

58 ns that appear to be otherwise unaffected by DFMO.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

88 ase inhibitor alpha-difluoromethylornithine (DFMO).

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

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

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

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

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

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

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

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

97 ase (ODC) inhibitor difluoromethylornithine (DFMO).

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

124 Notably, DFMO treatment prior to ultraviolet irradiation did not

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

126 8059 or U0126 in the presence and absence of DFMO exhibited a marked increase in the expression of p2

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

128 A combination of DFMO and sulindac significantly suppressed production of

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

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

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

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

133 maceuticals devoid of the untoward effect of DFMO.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

150 ncrease in p21 expression in the presence of DFMO.

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

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

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

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

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

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

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

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

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

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

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

162 ptosis were significantly inhibited by prior DFMO treatment.

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

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

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

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

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

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

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

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

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

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

173 The DFMO treatment did not affect the skin tumor multiplicit

174 The DFMO+PTI combination therapy results in sustained intrac

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

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

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

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

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

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

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

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

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

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

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

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

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

188 Whereas DFMO treatment resulted in profound depletion of putresc

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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