Date of Award

2013

Document Type

Thesis

Department

Biology

First Advisor

Dr. Lori Hensley

Second Advisor

Dr. Sara Hubbard

Third Advisor

Dr. David Caddell

Abstract

Ewing's Sarcoma is a pediatric bone cancer with a five-year survival rate of only 30%. New treatment options for this highly aggressive disease are desperately needed. Ajulemic acid (AJA), a synthetic cannabinoid, has been the focus of our research, and has demonstratedd the ability to decrease tumor cell viability and inhibit endothelial cell migration and angiogenesis. Based on these results, AJA is a potential therapeutic agent for Ewing's Sarcoma and other solid pediatric cancers. In order to create a realistic environment in vitro in which to study these tumors, we created 3-dimensional spheroids with three cell types, each of which fluoresces a different color. These include: fibroblasts, which give the spheroids a connective tissue component, endothelial cells, which line and form blood vessels in the body, and cancer cells. These spheroids were then treated with different concentrations of AJA and compared to control groups in an effort to understand cellular proteins and pathways being modulated by the drug. Also, in order to test AJA in a more realistic model of human cancer, we developed a novel bioluminescent mouse model of Ewing's Sarcoma. We compared luminescent to physical measurements and assessed the ability of AJA to decrease tumor growth in vivo. Our findings show support for AJA as a potential new cancer treatment option.

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