ライフサイエンスコーパス: CPT-11

1 dino)-1-piperidino]carbonyloxycamptothec in (CPT-11).

2 I) plus systemic oxaliplatin and irinotecan (CPT-11).

3 terase substrate o-NPA and the bulky prodrug CPT-11.

4 h naive and drug-resistant colon cancer with CPT-11.

5 53 is required for sensitization to TRAIL by CPT-11.

6 week cycle plus escalating doses of systemic CPT-11.

7 ne that plays a direct role in resistance to CPT-11.

8 ase the sensitivity of colon cancer cells to CPT-11.

9 mbination with the topoisomerase 1 inhibitor CPT-11.

10 rected enzyme prodrug therapy approach using CPT-11.

11 ic proteins, for their ability to metabolize CPT-11.

12 metabolite of the topoisomerase I inhibitor, CPT-11.

13 lity of plasma from these mice to metabolize CPT-11.

14 in colorectal tumor cells to treatment with CPT-11.

15 pproved camptothecin analogues topotecan and CPT-11.

16 finity, high-velocity enzyme with respect to CPT-11.

17 vation and conferred sensitivity of cells to CPT-11.

18 combination with the chemotherapeutic agent CPT-11.

19 2, followed by once weekly i.p. injection of CPT-11.

20 er xenografts that was comparable to that of CPT-11.

21 r to that observed with IV administration of CPT-11.

22 ith those of SN-38, the active metabolite of CPT-11.

23 methyl-10,11-methylenedioxycamptothecin, and CPT-11.

24 tander growth suppression in the presence of CPT-11.

25 essing the rabbit CE to the anticancer agent CPT-11.

26 ts and increased the sensitivity of cells to CPT-11.

27 g in an increase in the therapeutic index of CPT-11.

28 the pharmacokinetics and pharmacodynamics of CPT-11.

29 , thereby maximizing the antitumor effect of CPT-11.

30 ensitizes glioma cells to 5-fluorouracil and CPT-11.

31 vided a more stable enzyme for activation of CPT-11.

32 lus and evaluation of its enzyme activity on CPT-11.

33 undetectable following CED of nanoliposomal CPT-11.

34 free CPT-11 and >320 mg/kg for nanoliposomal CPT-11.

35 vivo when combined with cyclophosphamide and CPT-11.

36 CPT-11 100 mg/m(2), paclitaxel 175 mg/m(2), and carbopla

37 or patients in group A was Oxal 100 mg/m(2), CPT-11 150 mg/m(2), and FUDR 0.12 mg/kg x 30 mL divided

38 and, for the 3-weekly schedule, the MTDs are CPT-11 (175 mg/m2), oxaliplatin (85 mg/m2), FU (240 mg/m

39 8 lactone concentration of animals receiving CPT-11 (20-50 mg/kg x 7 days).

40 ated with repeated 4-week courses comprising CPT-11 (60 mg/m(2)) administered on days 1, 8, and 15, a

41 rs alleviates these side effects, which, for CPT-11 {7-ethyl-10-[4-(1-piperidino)-1-piperidino]}, can

42 The MTDs for the weekly schedule are CPT-11 (75 mg/m2), oxaliplatin (50 mg/m2), FU (320 mg/m2

43 The therapeutic efficacy of irinotecan (CPT-11), a DNA topoisomerase inhibitor, is often limited

44 SN38 was far higher than that of irinotecan (CPT-11), a FDA-approved water soluble SN38 prodrug used

45 We describe nanoliposomal CPT-11, a novel nanoparticle/liposome construct containi

46 Moreover, the combination of TRAIL and CPT-11, a water-soluble analogue of camptothecin, greatl

47 However, in contrast to CPT-11, a water-soluble CPT analogue that was recently a

48 at the combined treatment of Apo2L/TRAIL and CPT-11 achieves tumor control in prostate cancer tumors

49 idino)-1-piperidino]carbonyloxycamptothecin (CPT-11) activates NF-kappaB in most colorectal cancer ce

50 oduced extracts that demonstrated proficient CPT-11 activation and conferred sensitivity of cells to

51 hCE-2 likely plays a substantial role in CPT-11 activation in human liver at relevant pharmacolog

52 e prepared PEG conjugates of the irinotecan (CPT-11) active metabolite SN-38 via a phenyl ether that

53 ed 24 h before CPT-11 (sequence II); and (c) CPT-11 administered 24 h before FUra (sequence III).

54 administration sequences were evaluated: (a) CPT-11 administered simultaneously with FUra (sequence I

55 single dose of cisplatin (80 mg/m(2)) after CPT-11 administration on day 1.

56 road spectrum antitumor activity superior to CPT-11 against some preclinical xenograft models, includ

57 Treatment with CPT-11 alone significantly decreased the median volume o

58 R tyrosine kinase) as a single agent or with CPT-11 alone were smaller (>50%) than those in control m

59 Control mice were treated with CPT-11 alone, JBT 3002 alone, or saline.

60 idence of metastasis significantly more than CPT-11 alone.

61 characteristics make oral administration of CPT-11 an attractive option for further clinical develop

62 mice was determined to be 80 mg/kg for free CPT-11 and >320 mg/kg for nanoliposomal CPT-11.

63 7 mg/kg i.p. daily on days 1 through 5, and CPT-11 and 5FU were administered at doses of 50 and 100

64 hCE-2 has a 12.5-fold higher affinity for CPT-11 and a 5-fold higher maximal rate of CPT-11 hydrol

65 (36 males and 24 females) were treated with CPT-11 and all were assessable for toxicity, response, a

66 However, cells co-treated with CPT-11 and Apo2L/TRAIL, or pretreated with CPT-11 for up

67 The maximum tolerated doses (MTDs) of CPT-11 and FUra administered as single agents were 100 m

68 odel (Ward colon carcinoma); we administered CPT-11 and FUra by i.v. push once a week for four consec

69 The MTD for combined systemic CPT-11 and HAI FUDR was CPT-11 at 200 mg/m2 every other

70 ypass the need for the in vivo conversion of CPT-11 and increase the therapeutic index, bifunctional

71 the pharmacokinetics and pharmacodynamics of CPT-11 and its active metabolite, SN-38.

72 Plasma concentrations of CPT-11 and its metabolites, SN-38 and SN-38 glucuronide

73 t celecoxib enhances the antitumor effect of CPT-11 and reduces the severity of late diarrhea in a do

74 re toxicity and low plasma concentrations of CPT-11 and SN-38 achieved in this patient population sug

75 d previously that the initial uptake rate of CPT-11 and SN-38 by intestinal cells was significantly d

76 In addition, pharmacokinetic studies of CPT-11 and SN-38 in these animals demonstrated approxima

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

78 control the release of two anticancer drugs (CPT-11 and SN-38).

79 lon tumor model, and compared favorably with CPT-11 and topotecan in the SKNEP anaplastic Wilms' tumo

80 y of MGI-114 in combination with irinotecan (CPT-11) and 5-fluorouracil (5FU).

81 l cancer with the combination of irinotecan (CPT-11) and 5-fluorouracil (FUra) with or without leucov

82 es, such as the anticancer drugs irinotecan (CPT-11) and capecitabine and the pyrethroid insecticides

83 tolerated dose (MTD) of systemic irinotecan (CPT-11) and HAI floxuridine (FUDR) plus dexamethasone (D

84 In the single agent studies, MGI-114, CPT-11, and 5FU all resulted in decreased final tumor we

85 anced activity when MGI-114 is combined with CPT-11, and clinical trials to further evaluate this com

86 luding Demerol, lidocaine, capecitabine, and CPT-11 are hydrolyzed by these enzymes.

87 More than 40% of the variation in CPT-11 area under the curve (AUC) is explained by ABCC2

88 xpressing SW620 cells were more resistant to CPT-11 as compared with tumors established from vector-t

89 g Hct116 cells were 3-fold more sensitive to CPT-11 as compared with vector transfected Hct116 cells.

90 odel, a single CED infusion of nanoliposomal CPT-11 at 1.6 mg resulted in significantly improved medi

91 or combined systemic CPT-11 and HAI FUDR was CPT-11 at 200 mg/m2 every other week and FUDR at 0.12 mg

92 taxel 175 mg/m(2)/3 h, carboplatin AUC 5 and CPT-11 at 40 mg/m(2), all on day 1 every 3 weeks.

93 ow-dose combination (MGI-114 at 35 mg/kg and CPT-11 at 50 mg/kg) resulted in final tumor weights simi

94 lfate), liposomes were capable of entrapping CPT-11 at extremely high drug-to-lipid ratios (>800 g CP

95 ancer and liver metastases who received oral CPT-11 at the 80 mg/m2/d dosage achieved a confirmed par

96 riability in SN-38 (the active metabolite of CPT-11) AUC is explained by ABCC1 1684T>C, ABCB1 IVS9 -4

97 e predictions, indicating that activation of CPT-11 by a CE is constrained by size-limited access of

98 We characterized the hydrolysis of CPT-11 by two recently identified human carboxylesterase

99 CPT-11 (Camptosar, irinotecan), a topoisomerase I inhibi

100 induced by the chemotherapeutic irinotecan (CPT-11; Camptosar).

101 e that toxicity associated with high dose of CPT-11 can be eliminated without loss of the antitumor e

102 tor JBT 3002 combined with i.p. injection of CPT-11 can decrease the growth of human pancreatic carci

103 the chemotherapeutic drugs 5-fluorouracil or CPT-11, causing substantial tumor regression or complete

104 -fold and tissue t(1/2) by 22-fold over free CPT-11; CED in intracranial U87 glioma xenografts showed

105 CPT-11/cisplatin is an active combination regimen with m

106 The veliparib and CPT-11 combination can be further explored as a treatmen

107 rmined the therapeutic effect of irinotecan (CPT-11) combined with the immunomodulator JBT 3002, a sy

108 to assess the effects of these mutations on CPT-11 conversion.

109 The combination IFN-beta and irinotecan (CPT-11) cooperatively inhibits cell growth and IRF-5 syn

110 different mechanisms of action, and lack of CPT-11 cross-resistance to previous FUra/LV treatment.

111 the ATP-dependent drug transporter ABCG2 in CPT-11 cytotoxicity is unclear because some ABCG2 mutant

112 ere treated with different concentrations of CPT-11 daily for four consecutive days.

113 , or the combination of cyclophosphamide and CPT-11 does not significantly affect oncolytic virus rep

114 CC2 -24C>T, SLCO1B1*5, HNF1A 79A>C, age, and CPT-11 dose (P < .0001).

115 l modification of CPT-11 doses, resulting in CPT-11 dose attenuations to < or = 40 mg/m(2) in the maj

116 er from severe late diarrhea, which prevents CPT-11 dose intensification and efficacy.

117 Subsequent patients received an intermediate CPT-11 dose of 100 mg/m(2).

118 dification provisions that avoid unnecessary CPT-11 dose reductions to exploit more directly the ther

119 ng severe and lethal mucositis at much lower CPT-11 doses, a result of the proliferative cell loss an

120 y design led to preferential modification of CPT-11 doses, resulting in CPT-11 dose attenuations to <

121 ent of TRAIL-resistant tumors with TRAIL and CPT-11 dramatically slowed tumor growth and induced a tr

122 th a CE-expressing virus in combination with CPT-11 enhances survival of tumor-bearing mice.

123 ndomized studies have shown that irinotecan (CPT-11) extends survival in metastatic colorectal cancer

124 ies and clinical activity of two irinotecan (CPT-11), fluorouracil (FU), leucovorin (LV), and oxalipl

125 With the sequential combination of CPT-11 followed 24 h later by FUra (sequence III), the h

126 trial of the topoisomerase I (Topo I) poison CPT-11 followed by the cyclin-dependent kinase inhibitor

127 n therapy of SN-38 (the active metabolite of CPT-11) followed by flavopiridol, the induction of apopt

128 d subsequent exposure of cells to 1-5 microM CPT-11 for 4 h increased the toxicity of CPT-11 to three

129 use rabbit CE expression in combination with CPT-11 for gene therapy approaches for the treatment of

130 h CPT-11 and Apo2L/TRAIL, or pretreated with CPT-11 for up to 24 h followed by 2 h Apo2L/TRAIL, resul

131 f the peptides are capable of distinguishing CPT-11 from its metabolite SN-38.

132 esulting from the addition of oxaliplatin to CPT-11/FU/LV are significant but manageable.

133 Response results document that CPT-11, given with a standard starting dose and treatmen

134 We conclude that CED of nanoliposomal CPT-11 greatly prolonged tissue residence while also sub

135 rrent HAI and systemic Oxal plus irinotecan (CPT-11; group A) or Oxal, fluorouracil (FU), and leucovo

136 e treated with the combination of AEE788 and CPT-11 had significantly smaller tumors (P < 0.01) and c

137 r CPT-11 and a 5-fold higher maximal rate of CPT-11 hydrolysis when compared with hCE-1.

138 rs undergo apoptosis in response to TRAIL or CPT-11, implying that these proteins have nonoverlapping

139 1 was shown to be as active as camptothecin (CPT)-11 in the HCT-8 colon tumor model, and compared fav

140 ly superior efficacy when compared with free CPT-11 in human breast (BT474) and colon (HT29) cancer x

141 esters are also 20-40-fold less potent than CPT-11 in inhibiting human acetylcholinesterase.

142 on in SN-38 production after incubation with CPT-11 in vitro.

143 At equivalent CED doses, nanoliposomal CPT-11 increased area under the time-concentration curve

144 a transient upregulation of DR5 mRNA, while CPT-11 increased both death and decoy receptor expressio

145 ested (0.06-1.6 mg/rat), whereas CED of free CPT-11 induced severe CNS toxicity at 0.4 mg/rat.

146 e and sustained selective protection against CPT-11-induced delayed diarrhea and lethality.

147 ed cellular toxicity, we postulated that the CPT-11-induced diarrhea was preventable by influencing t

148 gt1(DeltaGI) mice were highly susceptible to CPT-11-induced diarrhea, developing severe and lethal mu

149 ementation as a preventive mechanism against CPT-11-induced diarrhea.

150 this group was found to protect mice against CPT-11-induced diarrhea.

151 IL-15 to provide significant protection from CPT-11-induced intestinal toxicity with maintenance of a

152 involvement of COX-2 in the pathogenesis of CPT-11-induced late diarrhea using a rat model.

153 chemotherapeutic CPT-11 treatment prevented CPT-11-induced serious diarrhea while maintaining the an

154 stration of an inhibitor protected mice from CPT-11-induced toxicity.

155 3, 8, and 11 doses, i.p.) to protect against CPT-11-induced toxicity.

156 rase (AcChE), in vitro assays confirmed that CPT-11 inhibited both human and electric eel AcChE with

157 AEE788 alone or in combination with CPT-11 inhibited pEGFR, pVEGFR, and phosphorylated Akt e

158 Est55 was shown to hydrolyze CPT-11 into the active form SN-38.

159 e prodrugs, cyclophosphamide and irinotecan (CPT-11), into their active metabolites, respectively.

160 Camptothecin (CPT)-11 (irinotecan) has been used widely for cancer tre

161 For the anticancer drug CPT-11 (irinotecan) and the nonsteroidal anti-inflammato

162 , which converts the camptothecin derivative CPT-11 (irinotecan) to the much more potent chemotherape

163 l nanoparticle/liposome construct containing CPT-11 (irinotecan) with unprecedented drug loading effi

164 combined with the topoisomerase I inhibitor CPT-11 (irinotecan), Apo2L/TRAIL exhibits enhanced apopt

165 sensitivity of a solid tumor to the prodrug CPT-11 (irinotecan), we constructed an adenovirus vector

166 idino)-1-piperidino]carbonyloxycamptothecin [CPT-11 (irinotecan)] is a water-soluble camptothecin-der

167 The camptothecin prodrug CPT-11 (irinotecan, 7-ethyl-10-[4-(1-piperidino)-1-piper

168 described adenovirus/rabbit carboxylesterase/CPT-11 (irinotecan, 7-ethyl-10[4-(1-piperidino)-1-piperi

169 MTD and recommended phase II dosage for oral CPT-11 is 66 mg/m2/d in patients younger than 65 years o

170 CPT-11 is a clinically used cancer drug, and it is a pro

171 CPT-11 is a prodrug that is activated by esterases to yi

172 CPT-11 is a prodrug that is converted in vivo to the top

173 CPT-11 is a prodrug that is hydrolyzed by hepatic and in

174 Because CPT-11 is activated by carboxylesterases (CEs), we asses

175 CPT-11 is an antitumor prodrug that is hydrolyzed by car

176 One of the major side effects observed with CPT-11 is gastrointestinal toxicity, and we supposed tha

177 er drug administration, a very high level of CPT-11 is present in the bile; this is deposited into th

178 of the common colon cancer chemotherapeutic CPT-11 is severe diarrhea caused by symbiotic bacterial

179 Irinotecan (CPT-11) is a chemotherapeutic agent that is active in th

180 idino] carbonyloxy-camptothecin (irinotecan; CPT-11) is a prodrug activated by carboxylesterase enzym

181 Irinotecan (CPT-11) is a promising antitumor agent, recently approve

182 idino)-1-piperidino]carbonyloxycamptothecin (CPT-11) is activated by carboxylesterases (CE) to yield

183 ridino]carbonyloxy-camptothecin (irinotecan; CPT-11) is delayed diarrhea.

184 idino)-1-piperidino]carbonyloxycamptothecin (CPT-11)] is metabolized by esterases to yield the potent

185 protracted tumor drug exposure compared with CPT-11, leading to long-term "cures" in NB models of int

186 These results suggest that gut toxicity from CPT-11 may be due in part to direct drug conversion by C

187 an CE gene and concomitant administration of CPT-11 may have potential as a strategy for local contro

188 xtended benefits of combining celecoxib with CPT-11 may significantly improve the outcome of cancer p

189 esterase is responsible for the majority of CPT-11 metabolism in mice.

190 The most significant change in CPT-11 metabolism was observed with the L424R variant rC

191 ues in rCE, L252 and L424, were important in CPT-11 metabolism.

192 oxylesterase (CE) that was very efficient at CPT-11 metabolism; however, a human homolog that was mor

193 extremely high drug-to-lipid ratios (>800 g CPT-11/mol phospholipid) and retaining encapsulated drug

194 This enzyme activates the prodrug CPT-11 more efficiently than do human enzymes.

195 ghly stable nanoparticle/liposome containing CPT-11 (nanoliposomal CPT-11) would provide a dual drug

196 lines and results in marked sensitization to CPT-11 of all of the transduced cells.

197 Additionally, we investigated the effect of CPT-11 on oxaliplatin pharmacokinetics.

198 were comparable with those in mice receiving CPT-11 only.

199 T-11, or 5FU, or MGI-114 in combination with CPT-11 or 5FU.

200 g topoisomerase I inhibitor camptothecin-11 (CPT-11) or SN38 (7-ethyl-10-hydroxycamptothecin) under h

201 re treated with either single agent MGI-114, CPT-11, or 5FU, or MGI-114 in combination with CPT-11 or

202 Importantly, cyclophosphamide, CPT-11, or the combination of cyclophosphamide and CPT-1

203 y-two cohort 2 patients received intravenous CPT-11/oxaliplatin (infusion, day 1) and FU/LV (90-minut

204 y for enhanced cumulative neurotoxicity with CPT-11/oxaliplatin combinations.

205 notherapy with the same doses of MGI-114 and CPT-11 (P< or =0.001).

206 were genotyped in 12 candidate genes of the CPT-11 pathway using several methodologies.

207 CPT-11 pharmacokinetic parameters were comparable to tho

208 t can explain the variability in irinotecan (CPT-11) pharmacokinetics and neutropenia in cancer patie

209 al toxicity, was significantly higher on the CPT-11 plus FU plus LV arm.

210 ated the efficacy and safety of weekly bolus CPT-11 plus FU plus LV in the treatment of patients with

211 kly bolus FU plus LV regimen or weekly bolus CPT-11 plus FU plus LV.

212 The combination therapy of CPT-11 plus JBT 3002 decreased tumor volume and incidenc

213 ly sequence dependent and that a sequence of CPT-11 preceding FUra is superior with a significant inc

214 Caspase 8 inhibition protects both CPT-11 pretreated wild-type and Bax-/- HCT116 cells from

215 Dose escalation of CPT-11 proceeded to 80 mg/m(2) then 125 mg/m(2) before d

216 Moreover, the combination of MGI-114 and CPT-11 produced partial responses in nearly all of the a

217 received a median of two courses of BVZ plus CPT-11 (range, 1 to 19).

218 Patients treated with high doses of CPT-11 rapidly develop a cholinergic syndrome that can b

219 as a strategy for local control of acquired CPT-11 resistance of solid tumors.

220 , but chemotherapeutics including Camptosar (CPT-11) restore TRAIL sensitivity.

221 rtantly, prolonged exposure to nanoliposomal CPT-11 resulted in no measurable central nervous system

222 In contrast, CED of free CPT-11 resulted in rapid drug clearance (tissue t(1/2) =

223 s Hct116 with SN-38 (an active metabolite of CPT-11) resulted in G2 cell cycle arrest without inducti

224 NFalpha and of the chemotherapeutic compound CPT-11, resulting in tumor regression.

225 ntestinal tissues after treatment with LD of CPT-11 revealed dramatic protection of duodenal and colo

226 quence I); (b) FUra administered 24 h before CPT-11 (sequence II); and (c) CPT-11 administered 24 h b

227 Nanoliposomal CPT-11 showed markedly superior efficacy when compared w

228 When MGI-114 at 3.5 mg/kg was combined with CPT-11, significant decrements in final tumor weights oc

229 Combining veliparib with CPT-11 significantly enhanced DNA damage and apoptosis u

230 However, combined with irinotecan (CPT-11), significantly greater than additive activity wa

231 27% of the variation in APC (a metabolite of CPT-11), SN-38 glucuronide (SN-38G), and SN-38G/SN-38 AU

232 CPT-11, SN-38, and SN-38G area under the plasma concentr

233 ther demonstrate the correlation between the CPT-11/SN-38 initial uptake rate and the induced toxicit

234 CPT-11/SN38 treatment had only marginal effects on tumor

235 CPT-11 solution for intravenous (IV) use was mixed with

236 curve (AUC) 6 over 30 minutes on day 1, and CPT-11 starting at 40 mg/m(2) over 90 minutes, days 1 an

237 rCE-expressing HB1.F3.C1 cells and 15 mg/kg CPT-11 survived for 1 year without detectable tumors.

238 ated mice and 30% of mice that received only CPT-11 survived long term.

239 ng this mutant were 3-fold less sensitive to CPT-11 than COS-7 cells expressing the wild-type protein

240 424R variant rCE that converted 10-fold less CPT-11 than the wild-type protein.

241 .C1 cells and schedules of administration of CPT-11 that produced levels of active drug (SN-38) toler

242 is associated with resistance to irinotecan (CPT-11) therapy in preclinical colorectal cancer models

243 cutaneous A549 tumors in nude mice receiving CPT-11, there was 35% reduction in tumor size at day 27

244 ant A549-based tumors in nude mice receiving CPT-11, there was a 1.8-fold reduction in tumor size at

245 ies, and extracts of these tissues converted CPT-11 to 7-ethyl-10-hydroxycamptothecin in vitro.

246 e antitumor efficacy by reducing the dose of CPT-11 to at least 50% of its MTD, whereas the dose of F

247 ases from colorectal cancer, adding systemic CPT-11 to HAI therapy in an adjuvant regimen is feasible

248 f lysates from the infected cells to convert CPT-11 to its active metabolite SN-38.

249 Data in this study show metabolism of CPT-11 to SN-38 (7-ethyl-10-hydroxycamptothecin) by a ra

250 camptothecin (SN-38) or direct conversion of CPT-11 to SN-38 by carboxylesterases (CE) in the small i

251 d thus far, a rabbit liver CE (rCE) converts CPT-11 to SN-38 most efficiently.

252 ine butyryl-cholinesterase (BuChE) converted CPT-11 to SN-38 with K(m)s of 42.4 and 44.2 microM for t

253 ated that are efficient in the conversion of CPT-11 to SN-38, yet both demonstrate little homology to

254 ctive CE enzyme that can efficiently convert CPT-11 to SN-38.

255 dosing results in presystemic conversion of CPT-11 to SN-38.

256 roM CPT-11 for 4 h increased the toxicity of CPT-11 to three neuroblastoma cell lines (SJNB-1, NB-169

257 The addition of CPT-11 to weekly bolus FU plus LV did not result in impr

258 ion trial of orally administered irinotecan (CPT-11) to characterize the maximum-tolerated dose (MTD)

259 SN22 vs. SN38 (the active form of irinotecan/CPT-11) to overcome efflux pump-driven drug resistance w

260 re shown to activate the prodrug irinotecan (CPT-11) to produce 7-ethyl-10-hydroxycamptothecin (SN-38

261 ([AUC(SN-38 total) + AUC(SN-38G total)]/AUC(CPT-11 total)) was 0.7 to 0.8, which suggests that oral

262 ve contribution of each protein in mediating CPT-11 toxicity by both drug accumulation and cell growt

263 the expression of ABCG2 protects cells from CPT-11 toxicity, even in the presence of high levels of

264 CPT-11-treated Ugt1(DeltaHep) mice showed a similar leth

265 mice showed a similar lethality rate to the CPT-11-treated Ugt1(F/F) mice.

266 avage of p21 protein in the Apo2L/TRAIL plus CPT-11 treatment contributes to the positive cooperation

267 ection from apoptosis induced in response to CPT-11 treatment is effectively inhibited by the transie

268 TRAIL plus CPT-11 treatment of both 3- and 10-day established TRAIL

269 uinoline (42) combined with chemotherapeutic CPT-11 treatment prevented CPT-11-induced serious diarrh

270 CPT-11 treatment resulted in accumulation of cells at G(

271 or control at 42 days after Apo2L/TRAIL plus CPT-11 treatment.

272 r the usage of this measure as an adjunct to CPT-11 treatment.

273 ity and improve the efficacy associated with CPT-11 treatment.

274 y shows that intraliposomal stabilization of CPT-11 using a polymeric or highly charged, nonpolymeric

275 gnificantly enhanced tumoricidal response to CPT-11 via increased induction of apoptosis.

276 CPT-11 was also protected from hydrolysis to the inactiv

277 The therapeutic efficacy of PEG-[SN22](4) to CPT-11 was compared in: (i) spontaneous neuroblastomas (

278 that the ability of each enzyme to activate CPT-11 was dependent on the size of the entrance to the

279 CPT-11 was given as a 90-minute intravenous (i.v.) infus

280 at brains, tissue retention of nanoliposomal CPT-11 was greatly prolonged, with >20% injected dose re

281 most clinically significant toxicity of oral CPT-11 was neutropenia.

282 Although CPT-11 was not a substrate for acetylcholinesterase (AcC

283 Upregulation of decoy receptors by CPT-11 was partially inhibited by co-administration of A

284 ) could be maintained, even when the dose of CPT-11 was reduced to 12.5% of the MTD as long as the do

285 BVZ plus CPT-11 was well-tolerated but had minimal efficacy in ch

286 study of bevacizumab (BVZ) plus irinotecan (CPT-11) was conducted in children with recurrent maligna

287 ing HB1.F3.C1 cells (HB1.F3.C1/AdCMVrCE) and CPT-11 were comparable with those in mice receiving CPT-

288 Both HB1.F3.C1 cells and CPT-11 were given i.v.

289 rectal tumor xenografts in mice treated with CPT-11, whereas either agent alone was less effective.

290 han the currently used camptothecin analogue CPT-11, which requires metabolic activation and is toxic

291 6 cells) to evaluate the effect of combining CPT-11 with celecoxib on tumor growth.

292 control mice, and these extracts metabolized CPT-11 with equal efficiency.

293 antitumor activity and toxicity of combining CPT-11 with FUra is highly sequence dependent and that a

294 ll survival was observed after incubation of CPT-11 with hCE-1.

295 cytotoxicity assays, incubation of 1 microM CPT-11 with hCE-2 (3.6 microg/ml) resulted in a 60% redu

296 s of this protein, hCE1 and hiCE, metabolize CPT-11 with significantly lower efficiencies.

297 e of binding the anticancer drug irinotecan (CPT-11) with micromolar affinity.

298 hat this might be due to local activation of CPT-11 within the gut.

299 Modeling of CPT-11 within the predicted active site of AcChE and BuC

300 ated by the active site gorge were such that CPT-11 would be unlikely to be activated by AcChE.

301 le/liposome containing CPT-11 (nanoliposomal CPT-11) would provide a dual drug delivery strategy for