Australian School of Advanced Medicine, Macquarie University, 2 Technology Place, North Ryde, Sydney, NSW 2109, Australia.
Biomed Res Int. 2013;2013:390714. doi: 10.1155/2013/390714. Epub 2013 Nov 6.
Radiosurgery for glioblastoma is limited to the development of resistance, allowing tumor cells to survive and initiate tumor recurrence. Based on our previous work that coadministration of tissue factor and lipopolysaccharide following radiosurgery selectively induced thrombosis in cerebral arteriovenous malformations, achieving thrombosis of 69% of the capillaries and 39% of medium sized vessels, we hypothesized that a rapid and selective shutdown of the capillaries in glioblastoma vasculature would decrease the delivery of oxygen and nutrients, reducing tumor growth, preventing intracranial hypertension, and improving life expectancy. Glioblastoma was formed by implantation of GL261 cells into C57Bl/6 mouse brain. Mice were intravenously injected tissue factor, lipopolysaccharide, a combination of both, or placebo 24 hours after radiosurgery. Control mice received both agents after sham irradiation. Coadministration of tissue factor and lipopolysaccharide led to the formation of thrombi in up to 87 ± 8% of the capillaries and 46 ± 4% of medium sized vessels within glioblastoma. The survival rate of mice in this group was 80% versus no survivor in placebo controls 30 days after irradiation. Animal body weight increased with time in this group (r = 0.88, P = 0.0001). Thus, radiosurgery enhanced treatment with tissue factor, and lipopolysaccharide selectively induces thrombosis in glioblastoma vasculature, improving life expectancy.
放射外科治疗胶质母细胞瘤会导致耐药性的发展，使肿瘤细胞得以存活并引发肿瘤复发。基于我们之前的工作，即在放射外科治疗后同时给予组织因子和脂多糖，可以选择性地诱导脑动静脉畸形中的血栓形成，达到 69%的毛细血管和 39%的中等大小血管的血栓形成，我们假设胶质母细胞瘤血管中的毛细血管迅速而选择性地关闭将减少氧气和营养物质的输送，从而抑制肿瘤生长、预防颅内压升高，并延长预期寿命。胶质母细胞瘤是通过将 GL261 细胞植入 C57Bl/6 小鼠大脑中形成的。在放射外科治疗后 24 小时，小鼠通过静脉注射组织因子、脂多糖、两者的组合或安慰剂。对照组小鼠在假照射后接受这两种药物。组织因子和脂多糖的联合给药导致高达 87±8%的毛细血管和 46±4%的中等大小血管内形成血栓。在该组中，30 天后接受照射的小鼠的存活率为 80%，而安慰剂对照组无一存活。该组的动物体重随时间增加（r=0.88，P=0.0001）。因此，放射外科治疗增强了组织因子和脂多糖的治疗效果，选择性地诱导胶质母细胞瘤血管中的血栓形成，从而延长了预期寿命。
