gms | German Medical Science

57th Annual Meeting of the German Society of Neurosurgery
Joint Meeting with the Japanese Neurosurgical Society

German Society of Neurosurgery (DGNC)

11 - 14 May, Essen

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Target-specific glioma therapy in an immunocompetent mouse model

Targetspezifische Gliomtherapie in einem immunkompetenten Mausmodell

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  • corresponding author J. Weissenberger - Klinik für Neurochirurgie, Johann Wolfgang Goethe-Universität Frankfurt
  • J. Masri - Klinik für Neurochirurgie, Johann Wolfgang Goethe-Universität Frankfurt
  • D. Baus - Georg-Speyer-Haus, Institut für Biomedizinische Forschung, Frankfurt
  • E. Pfitzner - Georg-Speyer-Haus, Institut für Biomedizinische Forschung, Frankfurt
  • J. Kreuter - Institut für Pharmazeutische Technologie, Johann Wolfgang Goethe-Universität Frankfurt
  • A. Raabe - Klinik für Neurochirurgie, Johann Wolfgang Goethe-Universität Frankfurt
  • V. Seifert - Klinik für Neurochirurgie, Johann Wolfgang Goethe-Universität Frankfurt
  • D. Kögel - Klinik für Neurochirurgie, Johann Wolfgang Goethe-Universität Frankfurt

Deutsche Gesellschaft für Neurochirurgie. Japanische Gesellschaft für Neurochirurgie. 57. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie. Essen, 11.-14.05.2006. Düsseldorf, Köln: German Medical Science; 2006. DocFR.03.09

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/dgnc2006/06dgnc017.shtml

Published: May 8, 2006

© 2006 Weissenberger et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

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Objective: Establishment of an immunocompetent mouse model representing the typical progressive stages observed in malignant human gliomas for the in vivo evaluation of novel target-specific regimens.

Methods: Isolated clones from tumours that arose spontaneously in GFAP-v-src transgenic mice were used to develop a transplantable brain tumour model in syngeneic B6C3F1 mice. STAT3 protein was knocked down by infection of tumour cells with replication-defective lentivirus encoding STAT3-siRNA. Apoptosis is designed to be induced by soluble recombinant TRAIL + chemical Bcl-2/Bcl-xL inhibitors.

Results: Striatal implantation of 105 mouse tumour cells resulted in the robust development of microscopically (2 – 3 mm) infiltrating malignant gliomas. Immunohistochemically, the gliomas displayed the astroglial marker GFAP and the oncogenic form of STAT3 (Tyr-705-phosphorylated) which is found in many malignancies including gliomas. Phosphorylated STAT3 was particularly prominent in the nucleus but was also found at the plasma membrane of peripherally infiltrating glioma cells. To evaluate the role of STAT3 in tumour progression, we stably expressed siRNA against STAT3 in several murine glioma cell lines. The effect of STAT3 depletion on proliferation, invasion and survival will be first assessed in vitro and subsequently after transplantation in vivo. Upstream and downstream components of the STAT3 signalling pathway as well as possible non-specific side effects of STAT3-siRNA expression after lentiviral infection will be examined, too.

Conclusions: Its high rate of engraftment, its similarity to the malignant glioma of origin, and its rapid locally invasive growth should make this murine model useful in testing novel therapies for malignant gliomas.