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

Combined inhibition of VEGF- and PDGF-signalling: effects on orthotopic glioma angiogenesis, microcirculation and growth

Kombinierte Hemmung der VEGF- und PDGF-Signalwege: Einfluss auf orthotope Gliomangiogenese, Mikrozirkulation und Tumorwachstum

Meeting Abstract

  • corresponding author Mohammad Reza Farhadi - Department of Neurosurgery, University Hospital, Mannheim
  • H. H. Capelle - Department of Neurosurgery, University Hospital, Mannheim
  • R. Erber - Department of Neurosurgery, University Hospital, Mannheim
  • A. Ullrich - Department of Molecular Biology, Max-Planck-Institute for Biochemistry, Martinsried
  • P. Vajkoczy - Department of Neurosurgery, University Hospital, Mannheim

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. DocMO.04.06

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dgnc2004/04dgnc0049.shtml

Veröffentlicht: 23. April 2004

© 2004 Farhadi 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

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Objective

Inhibition of angiogenic signalling pathways represents a promising therapy for malignant glioma. Here we determined the effects of SU6668, a selective receptor tyrosine kinase inhibitor against VEGFR-2 and PDGFR-β, on tumour angiogenesis and tumour growth in an orthotopic (i.e. intracranial) glioma model.

Methods

Fluorescently-labeled C6 glioma cells were implanted into the chronic cranial window of nude mice. Animals were treated with SU 6668 (75 mg/kg/d, i.p.) immediately (n=5) or 7 days (n=5) following tumour implantation. Controls received vehicle (50 μl DMSO, i.p.) (n=5 and n=4). Tumour growth, angiogenesis, and microcirculation were assessed by intravital fluorescence videomicroscopy over a 14-day observation period. In order to assess the effects of SU6668 on overall survival, C6 glioma cells were implantated stereotactically into the brains of seperate animals (n=24) and treatment was initiated on 7 day after implantation.

Results

In both the immediate and delayed experimental setting, SU6668 treatment resulted in a significant reduction of total and functional tumour vessel density (both p<0.05), reflecting a suppression of angiogenesis and impairment of tumour perfusion. As a consequence, tumour growth was significantly inhibited (p<0.05). Histology demonstrated reduced solid and infiltrative tumour growth into the adjacent brain of treated animals. The survival experiments confirmed the significance of our results in that survival was significantly prolonged following SU6668 therapy (p<0.05).

Conclusions

Targeting of VEGFR-2 and PDGFR-β by selective tyrosine kinase inhibitors represents a promising strategy to interfere with vascularization and growth of angiogenesis-dependent tumours. This also applies to malignant brain tumours despite the uniqueness of the cerebral microenvironment and the unique pathobiology of this tumour entity.