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

5 the protein layer to release antibody-bound SN-38.

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

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

8 ce to camptothecin derivatives topotecan and SN-38.

9 the glucuronidation of the active metabolite SN-38.

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

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

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

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

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

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

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

17 eptor autophosphorylation were unaffected by SN-38.

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

19 top1 cleavage complexes than camptothecin or SN-38.

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

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

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

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

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

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

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

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

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

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

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

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

32 I (TOP1) inhibitors topotecan and irinotecan/SN-38.

33 cacious as an anti-tumor agent than systemic SN-38.

34 by linkers that slowly cleave to release the SN-38.

35 ing prodrug of the topoisomerase 1 inhibitor SN-38.

36 antibody conjugated to the cytotoxic payload SN-38.

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

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

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

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

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

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

43 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 +

44 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 =

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

46 K-1) selectively potentiated cytotoxicity of SN-38, 5-fluorouracil (5-FU) and mitoxantrone, but not t

47 K-1) selectively potentiated cytotoxicity of SN-38, 5-fluorouracil and mitoxantrone, but not that of

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

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

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

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

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

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

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

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

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

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

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

59 using AZD6738 did not enhance temozolomide + SN-38 activity in ALT neuroblastoma cells.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

75 selective approach to measure free and total SN-38 and its glucuronidation metabolite (SN-38G) using

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

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

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

79 78 and 350 times over single treatment with SN-38 and phototherapy alone, respectively.

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

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

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

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

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

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

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

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

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

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

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

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

92 3 increased the steady-state accumulation of SN-38 and TPT by 9.4 +/- 1.9- and 1.8 +/- 0.2-fold, resp

93 1033 enhanced the uptake and cytotoxicity of SN-38 and TPT in cells transfected with BCRP but not emp

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

113 ximally accelerated cell death combined with SN-38 at 17 nM.

114 All four lines exhibited sensitivity to SN-38 at sub-nanomolar concentrations, with a direct cor

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

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

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

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

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

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

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

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

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

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

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

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

127 vatable conversion of Irinotecan (CPT-11) to SN-38, carboxylesterase 2 (CES2) is a significant predic

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

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

130 at 100 degrees C) was established to release SN-38, conjugated to the antibody by carbonate linkage.

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

132 rged as an attractive alternative to develop SN-38 delivery systems, combining several strategies in

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

165 , controlled and tumor-responsive release of SN-38 have demonstrated to enhance its antitumoral effec

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

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

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

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

170 e presence of trace level of SN-38G and free SN-38 in plasma, which suggests an improved therapeutic

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

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

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

174 ovo resistance to temozolomide + irinotecan [SN-38 in vitro, P < 0.05; in vivo mouse event-free survi

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

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

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

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

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

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

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

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

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

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

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

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

187 Here, long-acting IT MS ~ SN-38 is delivered with concurrent systemic PARP inhibit

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

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

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

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

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

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

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

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

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

197 58 prevented S-phase checkpoint induction by SN-38, leading to increased DNA damage and apoptosis in

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

199 High SN-38 levels from high CES2 activity lead to harmful eff

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

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

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

203 ound 19, concentration-dependently increased SN-38-mediated cancer cell death at 11 nM (EC(50)), time

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

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

206 of a 15 nm 4-arm 40 kDa PEG tethered to four SN-38 moieties by linkers that slowly cleave to release

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

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

209 ugated with active metabolite of irinotecan (SN-38), on Trop-2 positive cervical cancer cell lines an

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

211 SN-38 or 7-ethyl-10-hydroxycamptothecin is the active me

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

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

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

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

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

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

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

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

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

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

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

223 rst-in-class antibody-drug conjugate with an SN-38 payload targeting trophoblast cell-surface antigen

224 P-2-directed antibody-drug conjugate with an SN-38 payload that has shown preliminary activity in mUC

225 p-2-directed antibody-drug conjugate with an SN-38 payload, approved for patients with locally advanc

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

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

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

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

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

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

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

233 Compound 2k actively inhibited ARC-111- and SN-38-resistant HCT-116 cells and showed in vivo activit

234 overexpressing cells toward daunorubicin and SN-38, respectively, in concentration ranges that qualif

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

236 SN-38's antitumoral effect is 100 to 1000 times more pot

237 , with a direct correlation observed between SN-38 sensitivity and expression levels of topoisomerase

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

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

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

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

242 The assay involves the extraction of free SN-38, SN-38G by protein precipitation, and subsequent a

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

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

245 xygen-species (ROS)-responsive ADC (VL-DAB31-SN-38) that is highly selective and cytotoxic to B-cell

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

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

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

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

250 1, as oxaliplatin, 5-fluorouracil (5-FU), or SN-38 (the active metabolite of irinotecan) induced Notc

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

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

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

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

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

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

257 L decreased rifampicin-induced resistance to SN-38, the active metabolite of irinotecan, in LS174T ce

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

259 antibody-drug conjugate containing cytotoxic SN-38, the active metabolite of irinotecan.

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

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

262 8, a variant that reduces the elimination of SN-38, the active metabolite of irinotecan.

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

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

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

266 linically relevant topoisomerase I inhibitor SN-38, thereby inhibiting the ATR/Chk1 signaling pathway

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

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

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

270 y enables delivery of high concentrations of SN-38 to tumors.

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

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

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

274 at 11 nM (EC(50)), time-dependently doubled SN-38 toxicity in a period of 7 days at 10 nM, and half-

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

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

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

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

279 In post-surgical tissue, the median total SN-38 was 249.8 ng/g for BCBM and 104.5 ng/g for rGBM, t

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

281 higher (P < 0.001) with BBB disruption, but SN-38 was only detected in <50% of the samples and only

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

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

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

285 IT MS ~ SN-38 was ~ tenfold more efficacious as an anti-tumor ag

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

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

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

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

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

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

292 oblast cell-surface antigen 2 (Trop-2), with SN-38, which is conjugated to the antibody by a cleavabl

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

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

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

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

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

298 conjugated with the TOP1 inhibitor molecule SN-38, with a trastuzumab antigen binding fragment (HER2

299 2 phosphorylation at threonine-68 induced by SN-38, with no significant effect on chk1 phosphorylatio

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