gms | German Medical Science

55. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e. V. (DGNC)
1. Joint Meeting mit der Ungarischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

25. bis 28.04.2004, Köln

Radio-sensitising effect of thromboxane synthase inhibitors in radiation resistant human glioma cells

Strahlensensibilisierung resistenter menschlicher Gliomzellen durch Thromboxan-Synthetaseinhibitoren

Meeting Abstract

Suche in Medline nach

  • E. Kim - Neurochirurgische Klinik, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Lübeck
  • S. Schlaffer - Neurochirurgische Klinik, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Lübeck
  • E. Pawlak - Neurochirurgische Klinik, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Lübeck
  • corresponding author Alf Giese - Neurochirurgische Klinik, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Lübeck

Deutsche Gesellschaft für Neurochirurgie. Ungarische Gesellschaft für Neurochirurgie. 55. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), 1. Joint Meeting mit der Ungarischen Gesellschaft für Neurochirurgie. Köln, 25.-28.04.2004. Düsseldorf, Köln: German Medical Science; 2004. DocP 05.46

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dgnc2004/04dgnc0329.shtml

Veröffentlicht: 23. April 2004

© 2004 Kim et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Objective

Thromboxane synthase inhibitors are widely used in the treatment of different human pathologies. This class of agents has demonstrated its ability to block the invasive phenotype of glioma cells, and sensitise glioma cells and endothelial cells to drug-induced apoptosis. Recently intracranial infusion of furegrelate in a mouse glioma model has demonstrated significant inhibition of tumor growth in vivo and a synergistic effect with systemic BCNU treatment. In this study we have investigated the effect of thromboxane synthase inhibitor treatment on radiation sensitivity of glioma cells.

Methods

Established glioma cell lines and normal human astrocytes and fibroblasts were treated with increasing concentrations of thromboxane synthase inhibitors and increasing doses of γ- radiation in vitro. The surviving fraction was determined in colony formation assays and the formation of arachidonic acid metabolites was determined by ELISA.

Results

In four glioma cell lines furegrelate treatment resulted in increased radiation sensitivity, specifically at low radiation doses. No such effect was observed in human astrocytes or fibroblasts. The strongest effect was obtained after a 24 hour treatment with 0.5mg/ml/12h furegrelate prior to radiation treatment. When the furegrelate treatment was initiated at the time of radiation or following radiation, no decrease of the surviving fraction of cells was observed. Fractionation of the radiation dose resulted in a significantly increased survival of cells. Pre-treatment with furegrelate reversed the effect of fractionation.

Conclusions

These data suggest that thromboxane synthase inhibitors act as radiation sensitising agents in radiation resistant glioma cells by interference with repair mechanisms of radiation-induced cell damage.