Brain Tumor Angiogenesis

Glioblastoma multiforme (GBM) is an incurable malignant brain tumor, usually fatal within one year of diagnosis. Using a syngeneic rat 9L gliosarcoma model, we have developed a novel drug delivery method in which naked plasmid DNA is selectively targeted to brain tumors via intra-arterial injection. Using a plasmid encoding the anti-angiogenic endostatin, transgene expression can be detected in tumor cells in vivo, and therapeutic efficacy is observed. Administration of a plasmid encoding an angiostatic peptide, endostatin, resulted in an 80% tumor volume reduction one week after treatment and enhanced survival time by up to 47%. Treated tumors exhibited a 40% decrease in tumor vessel density accompanied by alterations in tumor vessel ultrastructure (narrowed or collapsed lumens). We conclude that intra-arterial injection of plasmids can selectively target therapeutic genes to CNS neoplasms. This method of gene therapy holds promise for the treatment of these highly malignant brain tumors.

Relevant Publications:

Dorrell, M., Aguilar, E., Schepke, L., Barnett, F., and M. Friedlander. (2007). Combination angiostatic therapy completely inhibits ocular and tumor angiogenesis. Proc. Natl. Acad. Sci. 104(3):967-72.

Barnett, F.H., Scharer-Schusz Wood, M.M., Yu, X., Wagner, T.E. and Friedlander, M. (2004). Intra-arterial delivery of endostatin gene to brain tumors prolongs survival and alters tumor vessel ultrastructure. Gene Therapy, 11:1283-1289.