gms | German Medical Science

58. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e. V. (DGNC)

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

26. bis 29.04.2007, Leipzig

Thromboxane synthetase inhibitor treatment of glioblastoma in a mouse modell

Behandlung von Glioblastomen mit einem Thromboxansynthetaseinhibitor in einem Mausmodell

Meeting Abstract

  • corresponding author J. Leppert - Klinik für Neurochirurgie, Universitätsklinikum Schleswig-Holstein, Campus Lübeck
  • A. Schauff - Klinik für Neurochirurgie, Universitätsklinikum Schleswig-Holstein, Campus Lübeck
  • N. Petkus - Klinik für Neurochirurgie, Georg-August-Universität Göttingen
  • R. Wüstenberg - Klinik für Neurochirurgie, Universitätsklinikum Schleswig-Holstein, Campus Lübeck
  • S. Kantelhardt - Klinik für Neurochirurgie, Georg-August-Universität Göttingen
  • A. Giese - Klinik für Neurochirurgie, Georg-August-Universität Göttingen
  • V. Tronnier - Klinik für Neurochirurgie, Universitätsklinikum Schleswig-Holstein, Campus Lübeck

Deutsche Gesellschaft für Neurochirurgie. 58. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC). Leipzig, 26.-29.04.2007. Düsseldorf: German Medical Science GMS Publishing House; 2007. DocDO.02.06

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dgnc2007/07dgnc016.shtml

Veröffentlicht: 11. April 2007

© 2007 Leppert 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: Malignant gliomas are the most common tumor entity with origin in the brain parenchyma. The highly invasive phenotypes of glial tumor compromises surgical eradication of the disease. Furthermore recurrent glioblastomas are highly resistant to irradiation and chemotherapy. We have shown that overexpression of the thromboxane synthetase gene and elevated enzymatic activity are associated with a increased migration in glioma cells in vitro and that inhibition of this enzyme by furegrelate blocks cell migration and influences drug induced apoptosis or apoptosis induced by irradiation.

Methods: To study the effect of the thromboxane sythetase inhibitor furegrelate we have used an intracraniell mouse modell. NU-/NU--mices were stereotactically injected with a cell suspension of the glioblastoma cell line U87. After 1 week incubation an osmotic pump was implanted subcutanously and a catheter was placed at the intracranial implantation site. A continuous injection of 2mg/kg per day of furegrelate was delivered intratumorally over a period of 3 weeks. A radiation group of mice was irradiated in 5 fractions of 1 gy. After 3 weeks all animals were terminated and the tumor volume was determined by conventional histology.

Results: Thromboxane synthase inhibitor treatment resulted in a signifcant reduction of tumor volumes in mice treated with irradiation (p=0.0103). The control group(n=10) treated with PBS showed a median tumorvolume of 55.81 mm3. The group treated with furegrelate (n=10) reached 43.45 mm3, the irradiation group (n=10) 24.02 mm3 and the combination of furegrelate and irradiation (n=10) 13.23 mm3.

Conclusions: Our results demonstrate that inhibitors of the invasion gene thromboxane synthase sensitize U87 intracranial xenografts to irradiation in vivo. This may offer a novel strategy for therapy of malignant gliomas.