gms | German Medical Science

62nd Annual Meeting of the German Society of Neurosurgery (DGNC)
Joint Meeting with the Polish Society of Neurosurgeons (PNCH)

German Society of Neurosurgery (DGNC)

7 - 11 May 2011, Hamburg

Combination therapy using antiangiogenesis and temozolomide for experimental glioma treatment

Meeting Abstract

  • M. Czabanka - Neurochirurgische Klinik, Charité - Universitätsmedizin, Berlin
  • J. Bruenner - Neurochirurgische Klinik, Charité - Universitätsmedizin, Berlin
  • M. Topalovic - Neurochirurgische Klinik, Charité - Universitätsmedizin, Berlin
  • F. Heppner - Institut für Neuropathologie, Charité - Universitätsmedizin, Berlin
  • A. Koch - Institut für Neuropathologie, Charité - Universitätsmedizin, Berlin
  • P. Vajkoczy - Neurochirurgische Klinik, Charité - Universitätsmedizin, Berlin

Deutsche Gesellschaft für Neurochirurgie. Polnische Gesellschaft für Neurochirurgen. 62. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Polnischen Gesellschaft für Neurochirurgen (PNCH). Hamburg, 07.-11.05.2011. Düsseldorf: German Medical Science GMS Publishing House; 2011. DocMO.05.02

DOI: 10.3205/11dgnc021, URN: urn:nbn:de:0183-11dgnc0210

Published: April 28, 2011

© 2011 Czabanka et al.
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Outline

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Objective: Treatment of malignant glioma remains a major clinical challenge. It was the aim of our study to investigate the anti-tumor effects of combined antiangiogenic and temozolomide treatment for malignant glioma.

Methods: SF126 and U87 glioma cells were implanted subcutaneously in nude mice (N = 6 per group) and tumor growth was assessed. Control group received NaCl, TMZ-group received temozolomide (200 mg/kg BW), SU-group received Sunitinib (40 mg/kg BW) and TMZ/SU-group (200mg + 40mg/kg BW) received the combination of both agents. Histological analysis included tumor cell proliferation, endothelial cell proliferation, apoptosis, vessel density and vascular pericyte coverage.

Results: Tumor growth was significantly reduced between treated groups and control group in both cell lines. TMZ/SU resulted in significantly reduced tumor growth compared to either mono treatment (NaCl: 174 ± 38 mm3; TMZ: 106 ± 13 mm3; SU: 114 ± 53 mm3; TMZ/SU: 34 ± 7 mm3). Combination treatment induced significantly increased apoptosis (NaCl: 5 ± 3; TMZ: 58 ± 10; SU: 60 ± 3; TMZ/SU: 80 ± 10) and reduced endothelial cell proliferation (NaCl: 27 ± 7 n/ROI; TMZ: 17 ± 1n/ROI; SU: 13 ± 1 n/ROI; TMZ/SU: 8 ± 2 n/ROI) as compared to either monotherapy. Combined therapy induced a significantly stronger antiangiogenic response as mono antiangiogenic treatment (vessel density SU: 110 ± 15 n/ROI; TMZ/SU: 80 ± 12 n/ROI). Pericyte coverage was significantly increased in tumor vessels in response to combination therapy (NaCl: 90 ± 7%, TMZ: 90 ± 8%, SU: 68 ± 9%, TMZ/SU: 80 ± 9%).

Conclusions: Combined antiangiogenic and temozolomide treatment induces a beneficial anti-glioma response due to additive antiangiogenic and proapoptotic effects. However, combined treatment may aggravate vascular resistance mechanisms.