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

Microhemodynamic consequences of tumor angiogenesis targeting using the tyrosine kinase inhibitor SU11248

Mikrohämodynamische Veränderungen der Tumormikrozirkulation bei antioangiogener Tumortherapie mittels SU 11248

Meeting Abstract

  • corresponding author M. Czabanka - Neurochirurgische Klinik, Klinikum Mannheim, Medizinische Fakultät Mannheim der Universität Heidelberg
  • R. Erber - Neurochirurgische Klinik, Klinikum Mannheim, Medizinische Fakultät Mannheim der Universität Heidelberg
  • M. Vinci - Neurochirurgische Klinik, Klinikum Mannheim, Medizinische Fakultät Mannheim der Universität Heidelberg
  • A. Ullrich - Max Planck Institut für Biochemie, Martinsried
  • P. Vajkoczy - Neurochirurgische Klinik, Klinikum Mannheim, Medizinische Fakultät Mannheim der Universität Heidelberg

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. DocP 089

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dgnc2007/07dgnc344.shtml

Veröffentlicht: 11. April 2007

© 2007 Czabanka 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: SU11248 represents a multi-targeted receptor tyrosine kinase inhibitor directed against VEGFR, PDGFR, KIT and FLT3 with potent anti-angiogenic and anti-tumor activity. The aim of the study was to characterize the effects of SU11248-treatment on tumor growth, tumor microcirculation and microhemodynamics in an in vivo glioma model.

Methods: SF126 glioma cells were implanted s.c. into nude mice (n=6 per group). Treatment with SU11248 or vehicle (i.p.) was initiated when tumors reached a size of 500mm3. Furthermore, glioma cells were implanted into dorsal skinfold chambers (1,5*106 cells; n=4 per group) followed by intravital microscopy. SU11248 or vehicle treatment was started 7 days after implantation. Quantitative analysis included total and functional vessel densities, perfusion index, vessel diameter, microvascular red blood cell velocity and microvascular blood flow rate. Histological analysis included murine Ki67 (EC proliferation), Pecam-Desmin (Pericate coverage) and Phospho-Histone (Tumor proliferation) staining.

Results: SU11248 significantly reduced tumor growth as well as total (SU: 110±62cmcm2; NaCl: 298±12cm/cm2) and functional vessel density (SU: 84±67cmcm2; NaCl: 176±38cm/cm2). In parallel, treatment with SU11248 resulted in a significant increase of the perfusion index (SU: 74%±17, NaCl: 58%±10), the microvascular red blood cell velocity and microvascular blood flow (SU: 176±154nl/sec; NaCl: 32±14nl/sec) within tumor vasculature that survived the anti-angiogenic intervention. Vessel diameters were not affected by SU11248. Hisological analysis revealed significantly reduced tumor cell and endothelial cell proliferation in treated tumors. Pericyate coverage was also significantly diminished

Conclusions: We conclude that SU11248 represents a potent anti-angiogenic and anti-tumor drug. SU 11248 treatment decreases tumor proliferation, endothelial cell proliferation and leads to desintegration of vascular pericytes. In addition, we observed increased microvascular perfusion of the remainaing tumorvasculature, suggesting that SU 11248 may improve vascular delivery to the remnant tumor. This beneficial effect may be exploited for future combination therapies aiming at tumor erradication.