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Rheal A Towner
Oklahoma Medical Research Foundation, USA
Posters & Accepted Abstracts: Pediat Therapeut
Pediatric glioblastomas (pGBM) are one of the leading causes of cancer-related deaths in children, with tumors essentially refractory to existing treatments. OKN-007 is a novel nitrone-based compound that has anti-cancer activity in both adult and pediatric GBM. Magnetic resonance imaging (MRI) techniques were used to assess the efficacy of OKN-007 in an orthotopic xenograft pGBM mouse (IC-3752GBM) model. OKN-007 was found to significantly decrease tumor volumes (p<0.05) and increase animal survival (p<0.05) in all OKN-007-treated mice compared to untreated animals, as well as increase diffusion (p<0.01) and perfusion rates (p<0.05). OKN-007 also significantly reduced lipid tumor metabolism [(Lip1.3 and Lip0.9)-to-creatine ratio (p<0.05)], as well as significantly decreased tumor cell proliferation (p<0.05) and microvessel density (p<0.05). Immunohistochemistry support data was also obtained for cell proliferation and tumor growth signaling. Furthermore, in relationship to the PDGFRÃ?Â± (platelet-derived growth factor receptor-Ã?Â±) pathway, OKN-007 was able to significantly decrease PDGFR-Ã?Â± (p<0.05) and SULF2 (p<0.05) immunoexpression, and significantly increase decorin expression (p<0.05). This study indicates that OKN-007 may be an effective anti-cancer agent for pediatric patients with pGBMs by inhibiting cell proliferation and angiogenesis, possibly via the PDGFRÃ?Â± pathway, and could be considered as an additional therapy for pediatric brain tumor patients.
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