美國俄亥俄州立大學(xué)的研究人員開發(fā)出一種全新的腫瘤攻擊病毒(tumor-attacking virus),，不但能夠殺死大腦內(nèi)的腫瘤細胞，還能夠阻斷腫瘤內(nèi)血管的生長,。該研究表明,，這種能夠殺死腫瘤的溶瘤病毒(oncolytic viruses)如果攜帶能夠抑制血管生長的蛋白——vasculostatin，那么或許能夠更有效的治療侵潤性腦部腫瘤,。這項研究發(fā)表在Molecular Therapy雜志網(wǎng)絡(luò)版上,。
Vasculostatin蛋白通常產(chǎn)生于大腦中,。研究人員發(fā)現(xiàn)，攜帶該蛋白的溶瘤細胞可以清除動物大腦中的人類膠質(zhì)母細胞瘤,，并且明顯降低腫瘤的復(fù)發(fā)率,。膠質(zhì)母細胞瘤，是一種致命性的人類大腦癌癥,，該腫瘤中含有大量的血管,，被診斷出患有這種癌癥的患者通常存活時間不超過15個月。
這項研究表明,，將溶瘤病毒和自然血管生長抑制因子如vasculostatin相結(jié)合或許是一種全新的腫瘤治療方法,。但目前還是需要進一步研究這種方法與化療或放療相結(jié)合治療癌癥的安全性和有效性。（生物谷Bioon.com）
生物谷推薦原始出處：
Molecular Therapy (2009); doi:10.1038/mt.2009.232
Enhanced Antitumor Efficacy of Vasculostatin (Vstat120) Expressing Oncolytic HSV-1
Jayson Hardcastle1,2, Kazuhiko Kurozumi1,, Nina Dmitrieva1, Martin P Sayers1,3, Sarwat Ahmad4, Peter Waterman5,6, Ralph Weissleder5,6, E Antonio Chiocca1 and Balveen Kaur1
1Dardinger Laboratory for Neuro-oncology and Neurosciences, Department of Neurological Surgery, James Comprehensive Cancer Center and The Ohio State University Medical Center, Columbus, Ohio, USA
2Integrated Biomedical Sciences Graduate Program, The Ohio State University Medical Center, Columbus, Ohio, USA
3Undergraduate Major in Biomedical Science, The Ohio State University Medical Center, Columbus, Ohio, USA
4College of Medicine, The Ohio State University Medical Center, Columbus, Ohio, USA
5Center for Molecular Imaging Research, Massachusetts General Hospital, Charlestown, Massachusetts, USA
6Center for Systems Biology, Massachusetts General Hospital, Boston, Massachusetts, USA
Oncolytic viral (OV) therapy is a promising therapeutic modality for brain tumors. Vasculostatin (Vstat120) is the cleaved and secreted extracellular fragment of brain-specific angiogenesis inhibitor 1 (BAI1), a brain-specific receptor. To date, the therapeutic efficacy of Vstat120 delivery into established tumors has not been investigated. Here we tested the therapeutic efficacy of combining Vstat120 gene delivery in conjunction with OV therapy. We constructed RAMBO (Rapid Antiangiogenesis Mediated By Oncolytic virus), which expresses Vstat120 under the control of the herpes simplex virus (HSV) IE4/5 promoter. Secreted Vstat120 was detected as soon as 4 hours postinfection in vitro and was retained for up to 13 days after OV therapy in subcutaneous tumors. RAMBO-produced Vstat120 efficiently inhibited endothelial cell migration and tube formation in vitro (P = 0.0005 and P = 0.0184, respectively) and inhibited angiogenesis (P = 0.007) in vivo. There was a significant suppression of intracranial and subcutaneous glioma growth in mice treated with RAMBO compared to the control virus, HSVQ (P = 0.0021 and P < 0.05, respectively). Statistically significant reduction in tumor vascular volume fraction (VVF) and microvessel density (MVD) was observed in tumors treated with RAMBO. This is the first study to report the antitumor effects of Vstat120 delivery into established tumors and supports the further development of RAMBO as a possible cancer therapy.
