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A. Neekhra, S. Wang, S. R. Darjatmoko, C. M. Sorenson, D. M. Albert, N. Sheibani; Suppression of Uveal Melanoma Tumor Growth byThrombospondin-1. Invest. Ophthalmol. Vis. Sci. 2009;50(13):39.
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To determine the potential anti-tumor activity of thrombospondin-1 (TSP1) in uveal melanoma tumors in the Tyr-tag mice model.
Three-week-old Tyr-tag transgenic mice received TSP1-antiangiogenic peptide or control peptide for five weeks at 100 mg/Kg/day, five days a week. The histopathological evaluations were performed with eyes obtained from three and eight-week-old Tyr-Tag transgenic mice receiving TSP1-anti-angiogenic peptide or control peptide. Additionally, tumor vasculature, growth, and apoptosis in Tyr-Tag mice were evaluated using immunohistochemical methods.
We have observed a significant decrease in the expression of TSP1 with tumor growth. In addition, tumor growth was significantly attenuated in transgenic mice that over express TSP1 in their eye. Our preliminary evaluations indicate that TSP1 anti-angiogenic peptides are effective in attenuation of tumor growth in Tyr-tag mice.
TSP1 expression decreases with uveal melanoma tumor growth. This is consistent with the angiogenic switch and increased vascularization observed during tumor progression. Our in vivo studies indicate that increased levels of TSP1 in the eye and/or administration of TSP1-antiangiogenic peptides are effective in inhibition of tumor angiogenesis and growth. Thus, TSP1 and/or its antiangiogenic peptides may be effective for the treatment of uveal melanoma.
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