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Erica A. Person, Ridhwi Mukerji, Stephanie M. Cohen, Abbas Samadi, Mark S. Cohen; Tumor Size Reduction With Withaferin A In A Murine Model Of Uveal Melanoma. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1458.
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Uveal melanoma most commonly metastasizes to the liver but can spread elsewhere causing significant mortality and presents a substantial therapeutic challenge. One potential chemotherapeutic, Withaferin A, has been shown to decrease cell proliferation, decrease cell viability, and increase apoptosis in vitro using 92.1 cells. A murine model is proposed to study the effectiveness of this agent in vivo.
A murine model of uveal melanoma was established using an injection of 3.5 x 106 92.1 cells to the flank of SCID mice. Mice were monitored regularly until a tumor with minimum size of 3.0mm at largest diameter was measured with a digital caliper. Mice were then randomized into control, 8mg/kg/day, or 12mg/kg/day of Withaferin A daily dosage by intra-peritoneal injection. Mice were monitored for tumor volume with digital caliper, weight, and overall body score three times per week to monitor for improvement and screen for morbidity.
24 mice were treated with daily dosing of Withaferin A. Comparing control vs. the two treatment groups, the treatment groups showed a decrease in tumor size over an initial 14-day treatment period. Average tumor size in the control group increased from 5.4mm to 8.98mm, the 8mg dosage group decreased from 4.18 to 1.5mm and the 12mg dosage group decreased from 4.28mm to 2.11mm.
Control tumors showed a 60% increase in largest diameter over a 14-day treatment period. Treatment groups showed a 64% and 50% decrease in the 8 and 12 mg dosage groups respectively in the same time period. Withaferin A shows a decrease in the average tumor size in a xenograft murine model of uveal melanoma.
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