gms | German Medical Science

59th Annual Meeting of the German Society of Neurosurgery (DGNC)
3rd Joint Meeting with the Italian Neurosurgical Society (SINch)

German Society of Neurosurgery (DGNC)

1 - 4 June 2008, Würzburg

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Anti-angiogenic therapy using SU11248 improves microvascular delivery of chemotherapy in surviving glioma vasculature

Antiangiogene Therapie mittels SU 11248 verbessert die mikrovaskuläre Anflutung von Chemotherapie in den überlebenden Gliomgefäßen

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  • corresponding author M. Czabanka - Department of Neurosurgery, Charité-Universitätsmedizin Berlin
  • R. Erber - Department of Neurosurgery, Charité-Universitätsmedizin Berlin
  • T. Blaeske - Department of Neurosurgery, Charité-Universitätsmedizin Berlin
  • A. Ullrich - Max-Planck Institute for Biochemistry, Martinsried
  • P. Vajkoczy - Department of Neurosurgery, Charité-Universitätsmedizin Berlin

Deutsche Gesellschaft für Neurochirurgie. Società Italiana di Neurochirurgia. 59. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), 3. Joint Meeting mit der Italienischen Gesellschaft für Neurochirurgie (SINch). Würzburg, 01.-04.06.2008. Düsseldorf: German Medical Science GMS Publishing House; 2008. DocP 002

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/dgnc2008/08dgnc270.shtml

Published: May 30, 2008

© 2008 Czabanka 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: SU11248 represents a promising anti-angiogenic therapy option for the treatment of malignant glioma. The aim of the study was to characterize the effects of Sutent on glioma microcirculation and microvascular delivery of chemotherapy.

Methods: For intravital microscopic analysis glioma cells were implanted into dorsal skinfold chambers (n=8 per group). Treatment was initiated 7 days after implantation. Analysis included total (TVD) and functional (FVD) vessel densities, perfusion index (PI), microvascular diameter (D) and blood flow rate (Q). Delivery of doxorubicin was investigated by analysing microvascular delivery of doxorubicin to interstitium (MD) and microvascular delivery index (MDI) of surviving tumor vasculature. Effects on tumor growth were characterized by sc implantation.

Results: SU11248 significantly reduced tumor growth due to anti-angiogenic and anti-vascular properties (TVD 110±62cm/cm2 vs. 298±12cm/cm2; FVD 211±46cm/cm2 vs 90±45cm/cm2). Therapy surviving vessels displayed significantly improved microhemodynamic characteristics (PI: 63%±7 vs. 78%±10, D: 10±3µm vs. 16±6µm; Q: 35±26nl/sec vs. 368±253nl/sec). These alterations resulted in a significantly increased MDI (0.59±0.19 vs. 0.20±0.07) of surviving vasculature. Therefore, MD was maintained despite reduced FVD.

Conclusions: SU11248 treatment improves the delivery process of chemotherapy in surviving tumor vessels by altering microvascular hemodynamics and significantly inhibits glioma growth by anti-angiogenic and anti-vascular properties. These effects might be exploited for future combined therapy procedures in clinical glioma treatment.