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

Vassileva V, Moriyama EH, De Souza R, Grant J, Allen CJ, Wilson BC, Piquette-Miller M - Br. J. Cancer (2008)

Bottom Line: Bioluminescent imaging detected tumours before their macroscopic appearance and strongly correlated with tumour weight and survival.As compared with intermittent therapy with Taxol, sustained PTX(ePC) therapy resulted in significant reduction of tumour proliferation, weight and BLI signal intensity, enhanced apoptosis and increased survival times.Moreover, these results provide evidence of enhanced therapeutic efficacy with the sustained PTX(ePC) implant system, which could potentially translate into successful clinical outcomes.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College Street, Rm. 1003, Toronto, Ontario, Canada M5S 3M2.

ABSTRACT
We evaluated the pre-clinical efficacy of a novel intraperitoneal (i.p.) sustained-release paclitaxel formulation (PTX(ePC)) using bioluminescent imaging (BLI) in the treatment of ovarian cancer. Human ovarian carcinoma cells stably expressing the firefly luciferase gene (SKOV3(Luc)) 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 PTX(ePC) 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 PTX(ePC) implant system, which could potentially translate into successful clinical outcomes.

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Correlation between bioluminescence and the MTT cell viability assay in SKOV3Luc cells in response to various PTX concentrations and exposure times. There was a significant correlation between both assays (r=0.93, P<0.05). Experiments were conducted in triplicates. Data presented as mean±s.e.
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fig1: Correlation between bioluminescence and the MTT cell viability assay in SKOV3Luc cells in response to various PTX concentrations and exposure times. There was a significant correlation between both assays (r=0.93, P<0.05). Experiments were conducted in triplicates. Data presented as mean±s.e.

Mentions: PTX inhibited SKOV3Luc cell survival in a concentration and time-dependent manner as evaluated by BLI and MTT. As duration of exposure was increased, cell survival decreased and the IC50 values were 683±72, 137±29 and 27±12 nM PTX at 24, 48 and 72 h, respectively. The bioluminescent signal (% control) significantly correlated with the MTT assessment of cell viability (Figure 1). Furthermore, SKOV3Luc sensitivity to PTX was similar to the parental SKOV3 cell line (data not shown).


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

Vassileva V, Moriyama EH, De Souza R, Grant J, Allen CJ, Wilson BC, Piquette-Miller M - Br. J. Cancer (2008)

Correlation between bioluminescence and the MTT cell viability assay in SKOV3Luc cells in response to various PTX concentrations and exposure times. There was a significant correlation between both assays (r=0.93, P<0.05). Experiments were conducted in triplicates. Data presented as mean±s.e.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2607231&req=5

fig1: Correlation between bioluminescence and the MTT cell viability assay in SKOV3Luc cells in response to various PTX concentrations and exposure times. There was a significant correlation between both assays (r=0.93, P<0.05). Experiments were conducted in triplicates. Data presented as mean±s.e.
Mentions: PTX inhibited SKOV3Luc cell survival in a concentration and time-dependent manner as evaluated by BLI and MTT. As duration of exposure was increased, cell survival decreased and the IC50 values were 683±72, 137±29 and 27±12 nM PTX at 24, 48 and 72 h, respectively. The bioluminescent signal (% control) significantly correlated with the MTT assessment of cell viability (Figure 1). Furthermore, SKOV3Luc sensitivity to PTX was similar to the parental SKOV3 cell line (data not shown).

Bottom Line: Bioluminescent imaging detected tumours before their macroscopic appearance and strongly correlated with tumour weight and survival.As compared with intermittent therapy with Taxol, sustained PTX(ePC) therapy resulted in significant reduction of tumour proliferation, weight and BLI signal intensity, enhanced apoptosis and increased survival times.Moreover, these results provide evidence of enhanced therapeutic efficacy with the sustained PTX(ePC) implant system, which could potentially translate into successful clinical outcomes.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College Street, Rm. 1003, Toronto, Ontario, Canada M5S 3M2.

ABSTRACT
We evaluated the pre-clinical efficacy of a novel intraperitoneal (i.p.) sustained-release paclitaxel formulation (PTX(ePC)) using bioluminescent imaging (BLI) in the treatment of ovarian cancer. Human ovarian carcinoma cells stably expressing the firefly luciferase gene (SKOV3(Luc)) 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 PTX(ePC) 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 PTX(ePC) implant system, which could potentially translate into successful clinical outcomes.

Show MeSH
Related in: MedlinePlus