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Efficacy assessment of sustained intraperitoneal paclitaxel therapy in a murine model of ovarian cancer using bioluminescent imaging
Authors:V Vassileva   E H Moriyama   R De Souza   J Grant   C J Allen   B C Wilson     M Piquette-Miller
Affiliation:1Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College Street, Rm. 1003, Toronto, Ontario, Canada, M5S 3M2;2Division of Biophysics and Bioimaging, Ontario Cancer Institute, Princess Margaret Hospital, University of Toronto, 610 University Avenue, Suite 7-420, Toronto, Ontario, Canada, M5G 2M9
Abstract: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.
Keywords:bioluminescent imaging   paclitaxel   intraperitoneal therapy   sustained chemotherapy   tumour proliferation   ovarian cancer
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