gms | German Medical Science

60th Annual Meeting of the German Society of Neurosurgery (DGNC)
Joint Meeting with the Benelux countries and Bulgaria

German Society of Neurosurgery (DGNC)

24 - 27 May 2009, Münster

Attenuation of tumor growth and antiangiogenic effects of the nitric oxide donor JS-K in U87 gliomas in vivo

Meeting Abstract

  • A. Weyerbrock - Abteilung Allgemeine Neurochirurgie, Universitätsklinikum Freiburg
  • N. Psarras - Abteilung Allgemeine Neurochirurgie, Universitätsklinikum Freiburg
  • B. Baumer - Abteilung Allgemeine Neurochirurgie, Universitätsklinikum Freiburg
  • E. Kogias - Abteilung Allgemeine Neurochirurgie, Universitätsklinikum Freiburg
  • A. Papazoglou - Abteilung Stereotaktische Neurochirurgie, Universitätsklinikum Freiburg

Deutsche Gesellschaft für Neurochirurgie. 60. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit den Benelux-Ländern und Bulgarien. Münster, 24.-27.05.2009. Düsseldorf: German Medical Science GMS Publishing House; 2009. DocP14-08

DOI: 10.3205/09dgnc406, URN: urn:nbn:de:0183-09dgnc4065

Published: May 20, 2009

© 2009 Weyerbrock 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: The diazeniumdiolate JS-K generates nitric oxide (NO) after enzymatic activation by GST and has potent growth-inhibitory effects in U87 glioma cells and induced chemosensitization to imatinib (Glivec®) in vitro. The objective was to evaluate this approach in vivo.

Methods: Nude rats were inoculated with 106 U87 cells into both flanks. Treatment with JS-K (O2-(2,4-dinitrophenyl)1-[(4-ethoxycarbonyl)piperazine-1-yl]diazene-1-ium-1,2-diolate; 6mg/kg/d s.c.), imatinib (50mg/kg/d i.p.) or a combination was administered daily over 7 days when tumors reached a volume of 800-900 mm3. Tumor size was measured three times per week using calipers over a study period of up to 42 days, and tumor volume (formula: l x w2/2), tumor volume quadrupling time and survival/reaching of endpoint criteria (tumor volume=50.000mm3) were analyzed using ANOVA and survival analysis. Tumor specimens were analyzed histologically und immunohistochemically.

Results: Treatment with s.c. JS-K was safe and induced a significant attenuation of tumor growth (p=0.009). Tumor volume quadrupling time was doubled from 8 to 16 days in the JS-K group. Although survival in the JS-K group was longer, it did not reach statistical significance. No chemosensitizing effect was observed as the combination of JS-K + imatinib and imatinib alone were not effective. Histological workup revealed tumor necrosis and a reduction in tumor vasculature suggesting an antiangiogenic effect of JS-K.

Conclusions: This is the first report that the NO donor JS-K has antiproliferative and antiangiogenic effects in a U87 flank tumor model in vivo. Current projects study the efficacy in an intracranial model and the effects on tumor vasculature.