Enhanced Antitumor Efficacy of an Oncolytic Herpes Simplex Virus Expressing an Endostatin–Angiostatin Fusion Gene in Human Glioblastoma Stem Cell Xenografts

作者: Guobin Zhang , Guishan Jin , Xiutao Nie , Ruifang Mi , Guidong Zhu

DOI: 10.1371/JOURNAL.PONE.0095872

关键词:

摘要: Viruses have demonstrated strong potential for the therapeutic targeting of glioblastoma stem cells (GSCs). In this study, use a herpes simplex virus carrying endostatin–angiostatin (VAE) as novel strategy glioblastoma-derived cancer was investigated. We isolated six stable GSC-enriched cultures from 36 human specimens and selected one GSCs lines establishing GSC-carrying orthotopic nude mouse models. The following results were obtained: (a) VAE rapidly proliferated in expressed endo–angio vitro vivo 48 h 10 d after infection, respectively; (b) compared with control gliomas treated rHSV or Endostar, subcutaneous derived showed significant reduction microvessel density treatment; (c) control, improvement observed length survival mice intracranial VAE; (d) MRI analysis that tumor volumes generated by remarkably decreased treatment controls. conclusion, oncolytic efficacy animal models an fusion gene, which enhanced antitumor most likely restricting microvasculature development.

参考文章(43)
Thomas Boehm, Judah Folkman, Timothy Browder, Michael S. O'Reilly, Antiangiogenic therapy of experimental cancer does not induce acquired drug resistance Nature. ,vol. 390, pp. 404- 407 ,(1997) , 10.1038/37126
Fernando A. Angarita, Sergio A. Acuna, Kathryn Ottolino-Perry, Siham Zerhouni, J. Andrea McCart, Mounting a strategic offense: fighting tumor vasculature with oncolytic viruses Trends in Molecular Medicine. ,vol. 19, pp. 378- 392 ,(2013) , 10.1016/J.MOLMED.2013.02.008
Roberto Manservigi, HSV Recombinant Vectors for Gene Therapy The Open Virology Journal. ,vol. 4, pp. 123- 156 ,(2010) , 10.2174/1874357901004010123
Álvaro Pinto, Andrés Redondo, Pilar Zamora, Beatriz Castelo, Enrique Espinosa, Angiogenesis as a therapeutic target in urothelial carcinoma Anti-Cancer Drugs. ,vol. 21, pp. 890- 896 ,(2010) , 10.1097/CAD.0B013E32833E83B2
Roberto Manservigi, Rafaela Argnani, Peggy Marconi, HSV Recombinant Vectors for Gene Therapy~!2009-12-17~!2010-13-31~!2010-06-17~! The Open Virology Journal. ,vol. 4, pp. 123- 156 ,(2010) , 10.2174/1874357901004030123
Linheng Li, William B. Neaves, Normal Stem Cells and Cancer Stem Cells: The Niche Matters: Figure 1. Cancer Research. ,vol. 66, pp. 4553- 4557 ,(2006) , 10.1158/0008-5472.CAN-05-3986
Dagmar Beier, Peter Hau, Martin Proescholdt, Annette Lohmeier, Jörg Wischhusen, Peter J. Oefner, Ludwig Aigner, Alexander Brawanski, Ulrich Bogdahn, Christoph P. Beier, CD133(+) and CD133(-) glioblastoma-derived cancer stem cells show differential growth characteristics and molecular profiles. Cancer Research. ,vol. 67, pp. 4010- 4015 ,(2007) , 10.1158/0008-5472.CAN-06-4180
David T. Scadden, The stem-cell niche as an entity of action Nature. ,vol. 441, pp. 1075- 1079 ,(2006) , 10.1038/NATURE04957
Jian-Min Liu, Bo-Yong Mao, Sun Hong, Yan-Hui Liu, Xiu-Jie Wang, The postoperative brain tumour stem cell (BTSC) niche and cancer recurrence Advances in Therapy. ,vol. 25, pp. 389- 398 ,(2008) , 10.1007/S12325-008-0050-X
Guidong Zhu, Wei Su, Guishan Jin, Fujian Xu, Shuyu Hao, Fangxia Guan, William Jia, Fusheng Liu, Glioma stem cells targeted by oncolytic virus carrying endostatin-angiostatin fusion gene and the expression of its exogenous gene in vitro. Brain Research. ,vol. 1390, pp. 59- 69 ,(2011) , 10.1016/J.BRAINRES.2011.03.050