In:
Journal of Biomedicine and Biotechnology, Hindawi Limited, Vol. 2010 ( 2010), p. 1-9
Kurzfassung:
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.
Materialart:
Online-Ressource
ISSN:
1110-7243
,
1110-7251
Sprache:
Englisch
Verlag:
Hindawi Limited
Publikationsdatum:
2010
ZDB Id:
2698540-8
ZDB Id:
2512507-2
SSG:
12