Oncolytic viral therapy is a promising therapeutic modality for brain tumors. Vasculostatin (Vstat120), is the cleaved and secreted extracellular fragment of BAI1, a brain specific receptor. However, the therapeutic efficacy of Vstat120 delivery into established tumors has not been investigated. Here we tested therapeutic efficacy of combining Vstat120 gene delivery in conjunction with oncolytic viral therapy. We constructed a novel oncolytic virus RAMBO: Rapid Anti-angiogensis Mediated By Oncolytic virus, which expresses Vsta120 under the control of an immediate early viral promotor. Secreted Vstat120 was detectable in infected cells as soon as four hours post infection. Vstat120 produced by RAMBO efficiently inhibited endothelial cell migration and tube formation in vitro (P=0.0005 and P=0.0184 respectively) and inhibited angiogeneisis (P=0.007) in vivo. There was a significant suppression of tumors growth in mice bearing intracranial and subcutaneous gliomas treated with RAMBO compared to the control HSVQ treated mice (P=0.0021, and P<0.05 respectively). Statistically significant reduction in tumor vascular volume fraction and microvessel density was observed in tumors treated with RAMBO. This study is the first report of antitumor effects of Vstat120 in established tumors and supports the further development of RAMBO as a possible treatment for cancer.
A series of 18 primitive neuroectodermal tumors in children (15 cerebral and three spinal) is reported. These are highly malignant neoplasms, both histologically and clinically. They are rapidly growing tumors, with a brief duration of symptoms and a rapidly progressive course. Forty percent of the patients were alive at 6 months, only 10% at 1 year, and all patients had died within 2 years following diagnosis.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.