© Copyright 2007 by the Society for Neuro-Oncology
Received July 14, 2006
Accepted October 23, 2006
In vivo efficacy of a novel histone deacetylase inhibitor in combination with radiation for the treatment of gliomas
Michal Entin-Meer 1*,
Xiaodong Yang 1,
Scott R. VandenBerg 2,
Kathleen R. Lamborn 3,
Abraham Nudelman 4,
Ada Rephaeli 5,
Daphne Adele Haas-Kogan 6
1 Department of Radiation Oncology, Neurological Surgery, and Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143
2 Department of Pathology and Neurological Surgery, University of California, San Francisco, San Francisco, CA 94143
3 Department of Neurological Surgery and Brain Tumor Research Center, University of California, San Francisco, CA 94143
4 Chemistry Department, Bar Ilan University, Ramat Gan, Israel
5 Felsenstein Medical Research Center, Sackler School of Medicine, Tel Aviv University, Beilinson Campus, Petach Tikva, Israel
6 Department of Radiation Oncology, Neurological Surgery, and Comprehensive Cancer Center, University of California, San Francisco, CA 94143
* To whom correspondence should be addressed. E-mail: memeer{at}cc.ucsf.edu.
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Abstract |
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Histone modification has emerged as a promising approach to cancer therapy. We explored the in vivo efficacy of a butyric acid derivative, pivaloyloxymethyl butyrate (AN-9), for the treatment of gliomas. Relative to control and single-modality treatments, the combination of AN-9 and radiation significantly inhibited tumor growth and prolonged time to failure in mice bearing glioma xenografts. The enhanced response to radiation was accompanied by inhibition of cellular proliferation and by increased phosphorylation of H2AX, implicating DNA double-strand breaks in the antineoplastic effects of AN-9 and radiation. The data suggest that AN-9 in combination with radiation may be an effective therapy for malignant gliomas.
Key Words:
AN-9, 
-H2AX phosphorylation, glioma, histone deacetylase inhibitor, radiation, temozolomide
