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Int J Radiat Oncol Biol Phys. 2008 Mar 15;70(4):1213-8. doi: 10.1016/j.ijrobp.2007.11.041. Epub 2008 Jan 30.

SU11657 enhances radiosensitivity of human meningioma cells.

Author information

1
Department of Radiation Oncology, University of Heidelberg, Heidelberg, Germany. stefanie_milker-zabel@med.uni-heidelberg.de

Abstract

PURPOSE:

To analyze the effect of the multireceptor tyrosine kinase inhibitor SU11657 (primarily vascular endothelial growth factor, platelet-derived growth factor) in combination with irradiation in freshly isolated primary human meningioma cells.

METHODS AND MATERIALS:

Tumor specimens were obtained from meningioma patients undergoing surgery at the Department of Neurosurgery, University of Heidelberg, Germany. For the present study only cells up to passage 6 were used. Benign and atypical meningioma cells and human umbilical vein endothelial cells (HUVEC) were treated with SU11657 alone and in combination with 6-MV photons (0-10 Gy). Clonogenic survival and cell proliferation were determined alone and in coculture assays to determine direct and paracrine effects.

RESULTS:

Radiation and SU11657 alone reduced cell proliferation in atypical and benign meningioma cells as well as in HUVEC in a dose-dependent manner. SU11657 alone also reduced clonogenic survival of benign and atypical meningioma cells. SU11657 increased radiosensitivity of human meningioma cells in clonogenic survival and cell number/proliferation assays. The anticlonogenic and antiproliferative effects alone and the radiosensitization effects of SU11657 were more pronounced in atypical meningioma cells compared with benign meningioma cells.

CONCLUSION:

Small-molecule tyrosine kinase inhibitors like SU11657 are capable of amplifying the growth inhibitory effects of irradiation in meningioma cells. These data provide a rationale for further clinical evaluation of this combination concept, especially in atypical and malignant meningioma patients.

PMID:
18234428
DOI:
10.1016/j.ijrobp.2007.11.041
[Indexed for MEDLINE]

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