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The Effects of 3TSR Fusion Proteins on Epithelial Ovarian Cancer

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Title: The Effects of 3TSR Fusion Proteins on Epithelial Ovarian Cancer
Author: ten Kortenaar, Simone Rebecca
Department: Department of Biomedical Sciences
Program: Biomedical Sciences
Advisor: Petrik, Jim
Abstract: Epithelial ovarian cancer is the most common and most deadly of the gynecological disorders, with late stage detection and inadequate treatment options contributing to its high mortality rate. Angiogenesis is a key mediator of cancer development, and as such represents an attractive therapeutic target for the inhibition of tumour growth. Thrombospondin-1 has been shown to have anti-angiogenic and apoptotic effects on vasculature and ovarian tumour cells. Current issues with thrombospondin-1 mimetic peptides include the short half-life of these compounds, which limits their efficacy. We therefore sought to evaluate the efficacy of a newly developed thrombospondin-1 mimetic fusion protein known as Fc-3TSR. Fc-3TSR is comprised of a linker protein that joins two peptides containing the 3 type I repeats (3TSR) of the TSP-1 gene. We believe Fc-3TSR will have increased anti-tumour and anti-angiogenic effects due to its increased molecular size. Initiating its anti-angiogenic and apoptotic effects through the CD36 receptor on both tumour and endothelial cells, our results presented herein suggest an increased efficacy of this compound when compared to native 3TSR. Results to date demonstrate an increased ability of Fc-3TSR to induce apoptosis and inhibit proliferation in ovarian tumour cells when compared to 3TSR. In addition, Fc-3TSR has been demonstrated to potently reduce the invasiveness of ovarian tumour cells and regulate factors important for angiogenesis and tumor cell survival. We have previously shown that 3TSR can potently induce regression of advanced stage ovarian cancer in a mouse model of disease, and testing of Fc-3TSR in vivo demonstrated that this fusion compound has the ability to induce disease regression even more dramatically than 3TSR. Ultimately, we hope that this work will contribute to the development of more efficacious treatment options for women with advanced stage ovarian cancer.    
Date: 2015-07
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