Pediatric
glioblastomas (pGBM), although rare, are one of the leading causes of
cancer-related deaths in children, with
tumors essentially refractory to existing treatments. Here, we describe the use of conventional and advanced in vivo magnetic resonance imaging (MRI) techniques to assess a novel orthotopic xenograft pGBM mouse (IC-3752GBM patient-derived culture) model, and to monitor the effects of the anti-
cancer agent
OKN-007 as an inhibitor of pGBM
tumor growth. Immunohistochemistry support data is also presented for cell proliferation and
tumor growth signaling.
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. In a responsive cohort of treated animals,
OKN-007 was able to significantly decrease
tumor volumes (p<0.0001), increase survival (p<0.001), and increase diffusion (p<0.01) and perfusion rates (p<0.05).
OKN-007 also significantly reduced
lipid tumor metabolism in responsive animals [(Lip1.3 and Lip0.9)-to-
creatine ratio (p<0.05)], as well as significantly decrease
tumor cell proliferation (p<0.05) and microvessel density (p<0.05). Furthermore, in relationship to the PDGFRα pathway,
OKN-007 was able to significantly decrease SULF2 (p<0.05) and PDGFR-α (
platelet-derived growth factor receptor-α) (p<0.05) immunoexpression, and significantly increase
decorin expression (p<0.05) in responsive mice. This study indicates that
OKN-007 may be an effective anti-
cancer agent for some patients with pGBMs by inhibiting cell proliferation and angiogenesis, possibly via the PDGFRα pathway, and could be considered as an additional
therapy for pediatric
brain tumor patients.