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Journal of Biomedicine and Biotechnology
Volume 2010, Article ID 350748, 9 pages
http://dx.doi.org/10.1155/2010/350748
Research Article

Improved Killing of Human High-Grade Glioma Cells by Combining Ionizing Radiation with Oncolytic Parvovirus H-1 Infection

1Department of Neurosurgery, University of Heidelberg, Heidelberg 69120, Germany
2German Cancer Research Center, Department of Applied Tumor Virology, Heidelberg 69120, Germany
3Department of Gynaecology, University of Tuebingen, Tuebingen 72076, Germany
4Department of Radiation Oncology, HELIOS-Klinikum Berlin, Berlin 13125, Germany

Received 25 March 2009; Revised 6 October 2009; Accepted 19 November 2009

Academic Editor: Daila S. Gridley

Copyright © 2010 Karsten Geletneky 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

Purpose. To elucidate the influence of ionizing radiation (IR) on the oncolytic activity of Parvovirus H-1 (H-1PV) in human high-grade glioma cells. Methods. Short term cultures of human high-grade gliomas were irradiated at different doses and infected with H-1PV. Cell viability was assessed by determining relative numbers of surviving cells. Replication of H-1PV was measured by RT-PCR of viral RNA, fluorescence-activated cell sorter (FACS) analysis and the synthesis of infectious virus particles. To identify a possible mechanism for radiation induced change in the oncolytic activity of H-1PV we performed cell cycle analyses. Results. Previous irradiation rendered glioma cells fully permissive to H-1PV infection. Irradiation 24 hours prior to H-1PV infection led to increased cell killing most notably in radioresistant glioma cells. Intracellular levels of NS-1, the main effector of H-1PV induced cytotoxicity, were elevated after irradiation. S-phase levels were increased one day after irradiation improving S-phase dependent viral replication and cytotoxicity. Conclusion. This study demonstrates intact susceptibility of previously irradiated glioma-cells for H-1PV induced oncolysis. The combination of ionizing radiation followed by H-1PV infection increased viral cytotoxicity, especially in radioresistant gliomas. These findings support the ongoing development of a clinical trial of H-1PV in patients with recurrent glioblastomas.