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Neuro-Oncology 2003 5(1):1-7; doi:10.1093/neuonc/5.1.1
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© 2003 by the Society forNeuro-Oncology

Anti-vascular endothelial growth factor antibody and nimustine ascombined therapy: Effects on tumor growth and angiogenesis in humanglioblastoma xenografts

Shingo Takano2, Koji Tsuboi, Akira Matsumura and Tadao Nose

Department of Neurosurgery, Institute of Clinical Medicine,University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan

2 Address correspondence and reprint requests to Shingo Takano, M.D., Ph.D.,Department of Neurosurgery, Institute of Clinical Medicine, University ofTsukuba, 1-1-1 Tennoudai, Ibaraki 305-8575, Japan.


  Abstract

We evaluated the effectiveness of vascular endothelial growth factor (VEGF)blockade alone and in combination with1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea(ACNU, nimustine), a cytotoxic agent commonly used in the treatment ofmalignant gliomas, to eradicate tumors of human glioblastoma cell linesimplanted in SCID (severe combined immunodeficiency) mice. ACNU, but notcisplatin and etoposide, elevated VEGF expression in a glioma cell line invitro. VEGF antibody alone inhibited glioma growth in vivo as a result ofangiogenesis inhibition. The combination with ACNU resulted in an additiveeffect for inhibition of glioma growth. ACNU also induced VEGF up-regulationin glioma tissues, which was decreased with VEGF antibody treatment. One ofthe mechanisms of the additive effect of the VEGF antibody and ACNUcombination is the blockade of VEGF up-regulation induced by ACNU. As such,the combination of antiangiogenic therapy with conventional therapy ispromising for glioma treatment in the future.

Received January 29, 2002; Accepted June 27, 2002


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