ライフサイエンスコーパス: SN-38

1 or 5 microM 7-ethyl-10-hydroxycamptothecin (SN-38).

2 38 glucuronide (the precursor of enterotoxic SN-38).

3 release of two anticancer drugs (CPT-11 and SN-38).

4 d a variety of human carcinoma cell lines to SN-38.

5 ells treated with the topoisomerase I poison SN-38.

6 ce to camptothecin derivatives topotecan and SN-38.

7 ugate did not produce a high initial Cmax of SN-38.

8 the glucuronidation of the active metabolite SN-38.

9 mitoxantrone, anthracyclines, topotecan, and SN-38.

10 yield the potent topoisomerase I inhibitor, SN-38.

11 an) to the much more potent chemotherapeutic SN-38.

12 nzyme that can efficiently convert CPT-11 to SN-38.

13 fold increase in induction of apoptosis with SN-38.

14 sensitivity of cells to undergo apoptosis by SN-38.

15 yield the potent topoisomerase I inhibitor, SN-38.

16 eptor autophosphorylation were unaffected by SN-38.

17 s to yield the potent topoisomerase I poison SN-38.

18 top1 cleavage complexes than camptothecin or SN-38.

19 ated approximately 5-fold less conversion to SN-38.

20 sults in presystemic conversion of CPT-11 to SN-38.

21 aturation in the conversion of irinotecan to SN-38.

22 ynamics of CPT-11 and its active metabolite, SN-38.

23 s to convert CPT-11 to its active metabolite SN-38.

24 ells when treated with ara-C, doxorubicin or SN-38.

25 tic agents ara-C, doxorubicin, etoposide and SN-38.

26 MMU-132), a Trop-2 ADC, for the targeting of SN-38.

27 tabolism of CPT-11 to its active metabolite, SN-38.

28 ide and teniposide and between merbarone and SN-38.

29 ndex (BI), the estimated biliary exposure of SN-38.

30 effect on the pharmacokinetics of CPT-11 or SN-38.

31 onide is attributed to low hepatic uptake of SN-38.

32 of distinguishing CPT-11 from its metabolite SN-38.

33 d induction of apoptosis in cells exposed to SN-38.

34 was synergistic with oxaliplatin, 5-FU, and SN-38.

35 rogation of the G(2)/M checkpoint induced by SN-38.

36 own to hydrolyze CPT-11 into the active form SN-38.

37 0.53; AUCSN-38 = 5.38 x SN-38(3.5) + 33.61 x SN-38(11.5) - 7.73; and AUCSN-38G = 10.73 x SN-38G9.5 +

38 x CPT-11(11.5) + 1,520.53; AUCSN-38 = 5.38 x SN-38(3.5) + 33.61 x SN-38(11.5) - 7.73; and AUCSN-38G =

39 ing LS.Among 77 patients with IHC testing on SNs, 38 (49%) had loss of staining of 1 or more MMR prot

40 a in this study show metabolism of CPT-11 to SN-38 (7-ethyl-10-hydroxycamptothecin) by a rabbit liver

41 s to yield the potent topoisomerase I poison SN-38 (7-ethyl-10-hydroxycamptothecin).

42 rug of the potent topoisomerase I inhibitor, SN-38 (7-ethyl-10-hydroxycamptothecin).

43 pophilic and clinically attractive analogues SN-38, 9-nitrocamptothecin and DB-67.

44 ) to produce 7-ethyl-10-hydroxycamptothecin (SN-38), a topoisomerase inhibitor used in cancer therapy

45 ydrolyzed by carboxylesterases (CE) to yield SN-38, a potent topoisomerase I poison.

46 est, these cell lines are cross-resistant to SN-38, a putative topo I inhibitor, but cross-resistance

47 This system contains SN-38-a prodrug of the topoisomerase I inhibitor irinote

48 and low plasma concentrations of CPT-11 and SN-38 achieved in this patient population suggest that c

49 led administration of an efficacious dose of SN-38, achieving significant regression of the SW620 tum

50 It is concluded that gefitinib may modulate SN-38 activity at the cellular level to reverse tumor re

51 with treatment with PS-341 alone (20-30%) or SN-38 alone (24-47%; P < 0.002).

52 SN-38 alone induced a senescence-like sustained G2 arres

53 to SN-38 in combination with MSC compared to SN-38 alone.

54 bition of clonogenicity over that induced by SN-38 alone.

55 er exposure to SN-38 with MSC, compared with SN-38 alone.

56 reated with the combination as compared with SN-38 alone.

57 of the human colon cancer cells Hct116 with SN-38 (an active metabolite of CPT-11) resulted in G2 ce

58 t induced by 7-ethyl-10-hydroxycamptothecin (SN-38), an active metabolite of irinotecan, in p53-null

59 I inhibitor 7-ethyl-10-hydroxycamptothecin (SN-38), an inducer of premature senescence in tumor cell

60 In this study, we chose SN-38, an active metabolite of irinotecan, to characteri

61 The combination of SN-38 and 17AAG was shown to be synergistic in p53-null

62 significant correlation was observed between SN-38 and bilirubin glucuronidation (r = 0.89; P = 0.001

63 egulation of ATR or Chk1 sensitized cells to SN-38 and camptothecin.

64 reverse the ABCG2-mediated resistance toward SN-38 and inhibit the ATPase activity.

65 IF7 conjugated to the potent anticancer drug SN-38 and injected intravenously into nude mice carrying

66 was tested with the chemotherapeutic agents SN-38 and mitoxantrone (MX).

67 es for epirubicin and to a lesser extent for SN-38 and mitoxantrone.

68 between merbarone and etoposide and between SN-38 and other topo I inhibitors.

69 78 and 350 times over single treatment with SN-38 and phototherapy alone, respectively.

70 inhibited activation of NF-kappaB induced by SN-38 and resulted in a significantly higher level of gr

71 s ABCG2-mediated resistance to topotecan and SN-38 and significantly increases accumulation of topote

72 okinetics of irinotecan and its metabolites, SN-38 and SN-38 glucuronide (SN-38G), were analyzed.

73 oncentrations of CPT-11 and its metabolites, SN-38 and SN-38 glucuronide (SN-38G), were determined in

74 SN-38 and SN-38G had low plasma availabilities (3% and 1

75 okinetics of irinotecan and its metabolites, SN-38 and SN-38G, by possibly reducing biliary excretion

76 dly up-regulated during cell cycle arrest by SN-38 and suppressed during apoptosis by SN-38 followed

77 f the UGT responsible for glucuronidation of SN-38 and the anthraquinone NU/ICRF 505 was achieved by

78 seen between pharmacokinetics of irinotecan/SN-38 and the clinical parameters of response, survival,

79 oxicity assays, ABCG2-mediated resistance to SN-38 and topotecan was abrogated in ABCG2-transfected H

80 ross-resistance to CPT derivatives including SN-38 and topotecan, but are not cross-resistant to the

81 eems to confer relatively less resistance to SN-38 and topotecan.

82 3 increased the steady-state accumulation of SN-38 and TPT by 9.4 +/- 1.9- and 1.8 +/- 0.2-fold, resp

83 1033 enhanced the uptake and cytotoxicity of SN-38 and TPT in cells transfected with BCRP but not emp

84 Conversely, concurrent treatment with SN-38 and UCN-01 resulted in S-phase checkpoint override

85 activity of the sympathetic nervous system (SNS) (-38%), and plasma leptin (-44%), insulin (-54%), a

86 po) I inhibitor (camptothecin, topotecan, or SN-38) and tumor necrosis factor-related apoptosis-induc

87 , etoposide, 7-ethyl-10-hydroxycamptothecin (SN-38), and doxorubicin in MCF-7 breast cancer cells.

88 its clinical derivatives, topotecan, CPT-11, SN-38, and 9-aminocamptothecin differed in their potency

89 cking and hydrophobicity interaction between SN-38, and a unique class of photonic nanoporphyrin mice

90 to convert CPT-11 to its active metabolite, SN-38, and effectively suppressed resistant cell growth

91 CPT-11, SN-38, and SN-38G area under the plasma concentration-ti

92 LSMs for CPT-11, SN-38, and SN-38G AUCs displayed excellent fit to the tr

93 Total plasma concentrations of CPT-11, SN-38, and SN-38G from 1.0 to 11.5 hours from the start

94 Total CPT-11, SN-38, and SN-38G were quantitated in plasma and urine s

95 asma concentration-time curve of irinotecan, SN-38, and SN-38G, respectively.

96 effect on the plasma availability of CPT-11, SN-38, and SN-38G.

97 The -3156 genotype and the SN-38 area under the concentration versus time curve wer

98 er with cefixime than without cefixime (mean SN-38 area under the curve: 19.5 ng x h/mL; standard dev

99 with the 7/7 genotype tended to have higher SN-38 area under the plasma time-concentration curve (AU

100 type, dosing by genotype resulted in similar SN-38 areas under the curve (AUCs; r(2) = 0.0003; P = .9

101 In particular, SN-38 arrested cells in S phase, enhanced the accumulati

102 o better than the active form of irinotecan, SN-38 at 1 microM, FL118 effectively inhibited cancer ce

103 Systemic exposure to SN-38 at the MTD was significantly higher with cefixime

104 ntration curve (AUC) values and lower SN-38G/SN-38 AUC ratios.

105 -11), SN-38 glucuronide (SN-38G), and SN-38G/SN-38 AUCs, respectively.

106 vity toward daunorubicin (P-gp and MRP1) and SN-38 (BCRP) in A2780/ADR (P-gp), H69AR (MRP1), and MDCK

107 an achieved similar intratumoral exposure of SN-38 but with superior antitumor activity.

108 verse measure of exposure) of irinotecan and SN-38 by 37% and 38%, respectively (P < .0001).

109 in (SN-38) or direct conversion of CPT-11 to SN-38 by carboxylesterases (CE) in the small intestine.

110 verted in vivo to the topoisomerase I poison SN-38 by carboxylesterases (CEs).

111 g that is converted to the active metabolite SN-38 by carboxylesterases.

112 y that the initial uptake rate of CPT-11 and SN-38 by intestinal cells was significantly different be

113 gest that the enhanced cellular lethality of SN-38 by MSC was not associated with cell cycle regulati

114 Because the decreased initial uptake of SN-38 carboxylate resulted in a reduced cellular toxicit

115 prodrug irinotecan and its active metabolite SN-38 compared with free irinotecan.

116 entify a linker, dose and dosing regimen for SN-38 conjugated to polyoxazoline-modified dendrimer tha

117 An assessment of individual differences in SN-38 conjugation remains to be established.

118 Conjugates of hMN-14 and SN-38 derivatives 16 and 17 were found promising for fur

119 lonal antibody, hMN-14, prepared using these SN-38 derivatives were evaluated in vitro for stability

120 Cells treated with SN-38 displayed morphological characteristics of senesce

121 in the metabolic conversion of irinotecan to SN-38 due to pretreatment.

122 Tumors in which higher SN-38 duration was achieved displayed more robust growth

123 h inhibition compared with tumors with lower SN-38 duration, confirming the importance of this factor

124 tivity predicted a concave increase in tumor SN-38 duration, which was confirmed experimentally in 13

125 pically very difficult to produce sub-100nm, SN-38-encapsulated nanoparticles without modification of

126 light irradiation, combination therapy with SN-38-encapsulated nanoporphyrin micelles (SN-NPM) enhan

127 ort on the successful production of 20-30nm, SN-38-encapsulated photonic micelles for effectively tri

128 Therefore, these sub-100nm, SN-38-encapsulated photonic micelles show great promise

129 release half-life of 21h achieved sustained SN-38 exposure in blood, above the target concentration.

130 by SN-38 and suppressed during apoptosis by SN-38 followed by flavopiridol in Hct116 cells is Drg1.

131 Sequential treatment with SN-38 followed by UCN-01 resulted in enhancement of cyto

132 The exposure of HT-29 cells to SN-38 for a limited period of time (<2 h) was sufficient

133 Gunn rats and CN-I patients lacked SN-38 glucuronidating activity, indicating the role of U

134 or relationship between para-nitrophenol and SN-38 glucuronidation (r = 0.08; P = 0.703).

135 Intact SN-38 glucuronidation was observed only in HK293 cells t

136 e that UGT1A1 is the isoform responsible for SN-38 glucuronidation.

137 vity, indicating the role of UGT1 isoform in SN-38 glucuronidation.

138 SN-38, the extent of which is determined by SN-38 glucuronidation.

139 tify the specific isoform of UGT involved in SN-38 glucuronidation.

140 efficacy of acetaminophen (AAP) to phenotype SN-38 glucuronidation.

141 AAP was a poor predictor of SN-38 glucuronidation.

142 e variation in APC (a metabolite of CPT-11), SN-38 glucuronide (SN-38G), and SN-38G/SN-38 AUCs, respe

143 of irinotecan and its metabolites, SN-38 and SN-38 glucuronide (SN-38G), were analyzed.

144 ons of CPT-11 and its metabolites, SN-38 and SN-38 glucuronide (SN-38G), were determined in a subset

145 AUC) and the relative area ratio of SN-38 to SN-38 glucuronide (SN-38G).

146 for extended periods, and forms very little SN-38 glucuronide (the precursor of enterotoxic SN-38).

147 A wide intersubject variability in in vitro SN-38 glucuronide formation rates was found in humans.

148 The low SN-38 glucuronide is attributed to low hepatic uptake of

149 t kinase 1, thereby sensitizing cells in the SN-38 --> gemcitabine sequence.

150 metabolite, 7-ethyl-10-hydroxy-camptothecin (SN-38), have a labile alpha-hydroxy-lactone ring that un

151 Cell cycle arrest induced by SN-38, however, was not abrogated or potentiated by MSC.

152 isms of cytotoxicity and cross-resistance of SN-38 in CEM/M70-B cells might be similar to those of me

153 ctivity was observed in the cells exposed to SN-38 in combination with MSC compared to SN-38 alone.

154 e encapsulated the topoisomerase-I inhibitor SN-38 in polymeric nanoparticles (NPs) surface-decorated

155 ition, pharmacokinetic studies of CPT-11 and SN-38 in these animals demonstrated approximately 5-fold

156 ical factors in achieving longer duration of SN-38 in tumors.

157 esistance to 7-ethyl-10-hydroxycamptothecin (SN-38) in colon cancer cells in vitro, and attenuates PX

158 delivery of 7-ethyl-10-hydroxycamptothecin (SN-38), in an expanded phase II trial of patients with r

159 Low-dose metformin or SN-38 increases FOXO3 nuclear localization as well as th

160 potentiates 7-ethyl-10-hydroxycamptothecin (SN-38)-induced cell lethality in vitro in the p53-defect

161 s increased the resistance of these cells to SN-38-induced apoptosis by 2-5-fold.

162 ) sensitized both p53+/+ and p53-/- cells to SN-38-induced apoptosis with increase of gamma H2AX, a m

163 ficient for initiation and/or maintenance of SN-38-induced arrest/senescence.

164 osure of cells to an IC(50) concentration of SN-38 induces biphasic DNA double-strand break (DSBs): a

165 In contrast to menadione, the SN-38 induction of the PRC program occurred over an exte

166 Here we show that low-dose metformin or SN-38 inhibits cell growth or survival in ovarian and br

167 monstrate the correlation between the CPT-11/SN-38 initial uptake rate and the induced toxicity, cell

168 SN-38 is a very important and highly potent drug for sev

169 Specifically, the chemotherapeutic agent SN-38 is incorporated into a central 'core' layer, betwe

170 likely that direct conversion of the drug to SN-38 is partially responsible for the diarrhea associat

171 Its active metabolite, SN-38, is glucuronidated by hepatic uridine diphosphate

172 due to the ultra-flat aromatic structure of SN-38, it is typically very difficult to produce sub-100

173 showed that a weekly dosing schedule of 4mg SN-38/kg was the most efficacious regimen.

174 The median SN-38 lactone area under the plasma concentration versus

175 as well as a 20% reduction of the intestinal SN-38 lactone concentration of animals receiving CPT-11

176 SN-38 lactone exposures were similar to those reported w

177 tration-time curve (AUC) for both CPT-11 and SN-38 lactone, implying no saturation in the conversion

178 Analysis of intracellular SN-38 levels by high-performance liquid chromatography a

179 Plasma carboxylesterase activity and SN-38 levels in mice receiving both rCE-expressing HB1.F

180 uperhydrophobicity, in vitro cytotoxicity of SN-38 loaded meshes, and compatibility provide key desig

181 e results suggest that low-dose metformin or SN-38 may reprogram these cancer cells into non-cancerou

182 und that DNA-protein complexes stabilized by SN-38 might be different from those stabilized by topo I

183 rent mechanisms, whereas cross-resistance to SN-38 might be through a merbarone-related mechanism.

184 , a rabbit liver CE (rCE) converts CPT-11 to SN-38 most efficiently.

185 In addition to topotecan and SN-38, MXR-overexpressing cells are highly resistant to

186 ro gefitinib potently reversed resistance to SN-38 only in a cell line that overexpressed functional

187 nd Chk2 had minimal effect of sensitivity to SN-38 or camptothecin.

188 d not affect complex formation stabilized by SN-38 or camptothecin.

189 ragments were observed in cells treated with SN-38 or MSC alone.

190 covalent topo I-DNA complexes stabilized by SN-38 or the related agent topotecan (TPT).

191 C-3 or NSCLC-5) cells with the topo I poison SN-38 or the topo II poison etoposide (VP-16) leads to a

192 utant IkappaBalpha (mIkappaBalpha) inhibited SN-38 or VP-16 induced transcription and DNA binding act

193 atment with MG-132, exposure to MG-132 after SN-38 or VP-16 treatment of neo or mIkappaBalpha cells d

194 in neo and mIkappaBalpha cells treated with SN-38 or VP-16.

195 and apoptosis but not DNA damage induced by SN-38 or VP-16.

196 e metabolite 7-ethyl-10-hydroxycamptothecin (SN-38) or direct conversion of CPT-11 to SN-38 by carbox

197 No alteration in irinotecan, SN-38, or SN-38G pharmacokinetics resulted from the admi

198 ied the duration for which concentrations of SN-38 persisted above a critical intratumoral threshold

199 , we show that clinically relevant levels of SN-38 potently induce cell cycle arrest and temporary se

200 xicity and interpatient variability than the SN-38 prodrugs thus far studied.

201 the rat indicate that, in contrast to other SN-38 prodrugs, the slowly released SN-38 shows a very l

202 and this resulted in a 200-fold reduction in SN-38 production after incubation with CPT-11 in vitro.

203 The systemic exposure to SN-38 relative to irinotecan was greater than anticipate

204 and the ability to reverse the BCRP-mediated SN-38 resistance.

205 pancreatic cancer cells with gemcitabine and SN-38 resulted in antagonistic effects.

206 We found that Drg1 had profound effects on SN-38 sensitivity.

207 ntributing to synergy of the gemcitabine --> SN-38 sequence.

208 The addition of a model bioactive agent (SN-38) showed a release rate with a striking dependence

209 to other SN-38 prodrugs, the slowly released SN-38 shows a very low C(max), is kept above target conc

210 Etoposide and SN-38 stabilized fewer DNA-topoisomerase complexes in CE

211 irinotecan, 7-ethyl-10-hydroxycamptothecin (SN-38), than their parental cell lines.

212 Almost 30% of the variability in SN-38 (the active metabolite of CPT-11) AUC is explained

213 With the combination therapy of SN-38 (the active metabolite of CPT-11) followed by flav

214 Moreover, a synergistic activity of 5c with SN-38 (the active metabolite of irinotecan) and 5-fluoro

215 On day 1, the median systemic exposure to SN-38 (the active metabolite of irinotecan) at the MTD w

216 1, as oxaliplatin, 5-fluorouracil (5-FU), or SN-38 (the active metabolite of irinotecan) induced Notc

217 dy-state plasma concentration (Css) of total SN-38 (the active metabolite of irinotecan) was 6.42 +/-

218 2), a transporter that confers resistance to SN-38 (the active metabolite of irinotecan), was readily

219 po) I poison 7-ethyl-10-hydroxycamptothecin (SN-38), the active metabolite of irinotecan, in a number

220 tothecin and 7-ethyl-10-hydroxycamptothecin (SN-38), the active metabolite of irinotecan.

221 tecan, and at least comparable with those of SN-38, the active metabolite of CPT-11.

222 lular exposure to cytotoxic concentration of SN-38, the active metabolite of irinotecan (0.1 microM)

223 hicle for improving the therapeutic index of SN-38, the active metabolite of irinotecan.

224 targets Trop-2 for the selective delivery of SN-38, the active metabolite of irinotecan.

225 q21, correlates in vitro with sensitivity to SN-38, the active metabolite of irinotecan.

226 8, a variant that reduces the elimination of SN-38, the active metabolite of irinotecan.

227 logue PS-341 (1 microM) prior to exposure to SN-38, the active metabolite of the topoisomerase I inhi

228 to be secondary to the biliary excretion of SN-38, the extent of which is determined by SN-38 glucur

229 ytidine) and 7-ethyl-10-hydroxycamptothecin (SN-38; the active metabolite of irinotecan), two S-phase

230 area under the concentration curve (AUC) of SN-38 to irinotecan of 0.24 +/- 0.08.

231 e curve (AUC) and the relative area ratio of SN-38 to SN-38 glucuronide (SN-38G).

232 By conjugating SN-38 to the dendrimer via different linker technologies

233 CPT-11 that produced levels of active drug (SN-38) tolerated by patients.

234 more potent topoisomerase I inhibition than SN-38, topotecan, and camptothecin in preclinical studie

235 The mean metabolic ratio ([AUC(SN-38 total) + AUC(SN-38G total)]/AUC(CPT-11 total)) was

236 However, subsequent treatment of SN-38-treated Hct116 cells with flavopiridol induced apo

237 the resistant cells could be observed after SN-38 treatment but not after camptothecin treatment.

238 d the 30-300 kb DNA fragmentation induced by SN-38 treatment.

239 of the irinotecan (CPT-11) active metabolite SN-38 via a phenyl ether that release the drug with pred

240 An average of 72% of SN-38 was maintained in the lactone form during the firs

241 In vitro glucuronidation of SN-38 was screened in hepatic microsomes from normal rat

242 owed that the extent of tumor penetration by SN-38 was significantly higher in mice receiving the tar

243 in micelles (NPM), the extremely hydrophobic SN-38 was successfully encapsulated into NPM with signif

244 erapeutic index, bifunctional derivatives of SN-38 were prepared for use in antibody-based targeted t

245 ts of simultaneous treatment with CI1033 and SN-38 were synergistic in T98G glioblastoma cells and HC

246 cs for irinotecan and its active metabolite, SN-38, were determined in 18 patients.

247 ins is critical toward the detoxification of SN-38, whereas induction of the UGT1A1 gene may serve to

248 ces high initial and local concentrations of SN-38, which are associated with gastrointestinal toxici

249 atic and intestinal carboxylesterase to form SN-38, which in turn is detoxified primarily through UDP

250 xylate form and from metabolic conversion to SN-38 while circulating.

251 l-cholinesterase (BuChE) converted CPT-11 to SN-38 with K(m)s of 42.4 and 44.2 microM for the human a

252 ins cdc6, MCM2, and cdc25A after exposure to SN-38 with MSC further indicates a relationship between

253 Exposure to SN-38 with MSC resulted in a significant increase of pol

254 pairs of DNA fragmentation after exposure to SN-38 with MSC, compared with SN-38 alone.

255 2 phosphorylation at threonine-68 induced by SN-38, with no significant effect on chk1 phosphorylatio

256 are efficient in the conversion of CPT-11 to SN-38, yet both demonstrate little homology to the rabbi