Efficacy assessment of sustained intraperitoneal paclitaxel therapy in a murine model of ovarian cancer using bioluminescent imaging.

Efficacy assessment of sustained intraperitoneal paclitaxel therapy in a murine model of ovarian cancer using bioluminescent imaging.
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DOI:
10.1038/sj.bjc.6604803
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发表时间:
2008-12-16
影响因子:
8.8
通讯作者:
Piquette-Miller, M.
Piquette-Miller, M.
中科院分区:
医学1区
文献类型:
--
作者:
Vassileva, V.;Moriyama, E. H.;De Souza, R.;Grant, J.;Allen, C. J.;Wilson, B. C.;Piquette-Miller, M.

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我们评估了一种新的腹膜内(i. p.)使用生物发光成像(BLI)的紫杉醇缓释制剂(PTXePC)治疗卵巢癌。将稳定表达萤火虫荧光素酶基因(SKOV 3Luc)的人卵巢癌细胞腹膜内注射到SCID小鼠中。在用紫杉醇(PTX)腹膜内持续或间歇治疗过程中评价肿瘤生长。体外生物发光与细胞存活和细胞毒性密切相关。生物发光成像检测肿瘤之前,他们的宏观外观和强烈相关的肿瘤重量和生存。与Taxol®间歇治疗相比,持续PTXePC治疗可显著降低肿瘤增殖、重量和BLI信号强度,增强细胞凋亡并延长生存时间。我们的研究结果表明,BLI是一个有用的工具,在临床前评估卵巢癌的治疗干预措施。此外,这些结果提供了持续PTXePC植入系统增强治疗效果的证据,这可能转化为成功的临床结局。
We evaluated the pre-clinical efficacy of a novel intraperitoneal (i.p.) sustained-release paclitaxel formulation (PTXePC) using bioluminescent imaging (BLI) in the treatment of ovarian cancer. Human ovarian carcinoma cells stably expressing the firefly luciferase gene (SKOV3Luc) were injected i.p. into SCID mice. Tumour growth was evaluated during sustained or intermittent courses of i.p. treatment with paclitaxel (PTX). In vitro bioluminescence strongly correlated with cell survival and cytotoxicity. Bioluminescent imaging detected tumours before their macroscopic appearance and strongly correlated with tumour weight and survival. As compared with intermittent therapy with Taxol®, sustained PTXePC therapy resulted in significant reduction of tumour proliferation, weight and BLI signal intensity, enhanced apoptosis and increased survival times. Our results demonstrate that BLI is a useful tool in the pre-clinical evaluation of therapeutic interventions for ovarian cancer. Moreover, these results provide evidence of enhanced therapeutic efficacy with the sustained PTXePC implant system, which could potentially translate into successful clinical outcomes.
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