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BioMed Research International
Volume 2013 (2013), Article ID 390714, 11 pages
http://dx.doi.org/10.1155/2013/390714
Research Article

A Combination of Radiosurgery and Soluble Tissue Factor Enhances Vascular Targeting for Experimental Glioblastoma

1Australian School of Advanced Medicine, Macquarie University, 2 Technology Place, North Ryde, Sydney, NSW 2109, Australia
2Department of Neurosurgery, The 9th Medical Clinical College of Beijing University, Beijing 100850, China
3Department of Electromagnetic and Laser Biology, Beijing Institute of Radiation Medicine, Beijing 100038, China

Received 28 April 2013; Accepted 25 September 2013

Academic Editor: Pasquale F. Innominato

Copyright © 2013 Jian Tu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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 ( , ). Thus, radiosurgery enhanced treatment with tissue factor, and lipopolysaccharide selectively induces thrombosis in glioblastoma vasculature, improving life expectancy.