Molecular ablation of tumor blood vessels inhibits therapeutic effects of radiation and bevacizumab.

摘要: Background Glioblastoma (GBM) is an aggressive and highly vascular tumor with median survival below 2 years. Despite advances in surgery, radiotherapy, chemotherapy, has improved modestly. To combat glioma proliferation, anti-angiogenic agents targeting endothelial growth factor (VEGF) were introduced. Preclinically these effective, yet they did not improve overall phase III trials. We tested the hypothesis that ganciclovir (GCV)-mediated killing of proliferating cells expressing herpes simplex virus type 1 thymidine kinase (HSV1-TK) would have direct antitumor effects, whether vessel ablation affect activity anti-VEGF antibodies radiotherapy. Methods Proliferating eliminated using GCV-mediated HSV1-TK (in Tie2-TK-IRES-GFP mice). Syngeneic NRAS/p53 (NP) gliomas implanted into brains mice. Endothelial proliferation activates Tie2 promoter expression. Administration GCV kills slows growth. The effects cell on therapy examined or irradiation. Results administration reduced density, increased apoptosis, prolonged survival. Anti-VEGF irradiation also Surprisingly, combining irradiation, antibodies, their individual therapeutic effects. Conclusion HSV1-TK, all a murine glioma. However, elimination microvascular decreased efficacy therapy. conclude that, our model, integrity vessels necessary for antiglioma radiation