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

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Journal of Biomedicine and BiotechnologyVolume 2010 2010, Article ID 350748, 9 pages

Research Article

Department of Neurosurgery, University of Heidelberg, Heidelberg 69120, Germany

German Cancer Research Center, Department of Applied Tumor Virology, Heidelberg 69120, Germany

Department of Gynaecology, University of Tuebingen, Tuebingen 72076, Germany

Department 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.


Purpose. To elucidate the influence of ionizing radiation IR onthe oncolytic activity of Parvovirus H-1 H-1PV in humanhigh-grade glioma cells. Methods. Short term cultures of humanhigh-grade gliomas were irradiated at different doses and infectedwith H-1PV. Cell viability was assessed by determining relativenumbers of surviving cells. Replication of H-1PV was measured byRT-PCR of viral RNA, fluorescence-activated cell sorter FACSanalysis and the synthesis of infectious virus particles. Toidentify a possible mechanism for radiation induced change in theoncolytic activity of H-1PV we performed cell cycle analyses. Results. Previous irradiation rendered glioma cells fullypermissive to H-1PV infection. Irradiation 24 hours prior to H-1PVinfection led to increased cell killing most notably inradioresistant glioma cells. Intracellular levels of NS-1, themain effector of H-1PV induced cytotoxicity, were elevated afterirradiation. S-phase levels were increased one day afterirradiation improving S-phase dependent viral replication andcytotoxicity. Conclusion. This study demonstrates intactsusceptibility of previously irradiated glioma-cells for H-1PVinduced oncolysis. The combination of ionizing radiation followedby H-1PV infection increased viral cytotoxicity, especially inradioresistant gliomas. These findings support the ongoingdevelopment of a clinical trial of H-1PV in patients withrecurrent glioblastomas.

Autor: Karsten Geletneky, Andreas D. Hartkopf, Robert Krempien, Jean Rommelaere, and Joerg R. Schlehofer



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