Defining the role of epidural steroid injections in the treatment of radicular pain from degenerative cervical disk disease.

growth was significantly slowed by MBZ treatment, whereas in untreated controls, tumors extended into the ventricles, resembling the human disease. Overall survival was prolonged by 150% in the SHH allograft model and by 100% in the SHH vismodegib-resistant allograft model. In the group 3 xenograft model, median survival was increased by a striking 129% from 21 to 48 days (P , 1 · 1024; Figure). Tumors from MBZ-treated mice lacked the phenotype of hypervascularity and widespread hemorrhage seen at terminal stages in untreated mice. Microvascular density was greatly reduced within treated compared with untreated tumors. Notably, MBZ treatment did not alter the microvascular density within regions with no tumor involvement. Immunohistochemistry of MBZ-treated tumors revealed a marked absence of autophosphorylated VEGFR2 despite the presence of VEGF ligand, suggesting MBZ inhibition of VEGFR2 kinase activity. This inhibition was seen in the autophosphorylation assay with MBZ-treated human umbilical vein endothelial cells and in the cell-free VEGFR2 kinase assay. MBZ prolonged survival in the SHH molecular subtype, a vismodegib-resistant SHH model, and a xenograft model of the group 3 subtype bearing the worst prognosis. This study shows encouraging antiangiogenic effects of MBZ that are limited to the tumor neovasculature and likely mediated through the inhibition of VEGFR2 kinase activity. These data add to the recognition of MBZ as an anticancer agent, including as an antiglioma therapy currently in clinical trials. Achieving adequate intracranial concentrations of other microtubule inhibitory chemotherapy agents such vincristine without neurocognitive sequelae remains challenging. The low-toxicity profile of MBZ, particularly in children, its additional role as an antiangiogenic agent, and the survival outcomes seen in this study further compel the initiation of clinical investigations into the use of this drug for medulloblastoma.