gms | German Medical Science

57th Annual Meeting of the German Society of Neurosurgery
Joint Meeting with the Japanese Neurosurgical Society

German Society of Neurosurgery (DGNC)

11 - 14 May, Essen

Imatinib mesylate in combination with irradiation of glioblastoma cells in vitro

Imatinib-Mesylat in Kombination mit Bestrahlung von Glioblastomzellen in vitro

Meeting Abstract

  • T. Körschgen - Klinik für Strahlentherapie und Radioonkologie, Universitätsklinikum Mannheim, Fakultät für klinische Medizin Mannheim der Universität Heidelberg
  • F. Lohr - Klinik für Strahlentherapie und Radioonkologie, Universitätsklinikum Mannheim, Fakultät für klinische Medizin Mannheim der Universität Heidelberg
  • A. Hochhaus - III. Medizinische Klinik, Universitätsklinikum Mannheim, Fakultät für klinische Medizin Mannheim der Universität Heidelberg
  • P. Vajkoczy - Neurochirurgische Klinik, Universitätsklinikum Mannheim, Fakultät für klinische Medizin Mannheim der Universität Heidelberg
  • F. Wenz - Klinik für Strahlentherapie und Radioonkologie, Universitätsklinikum Mannheim, Fakultät für klinische Medizin Mannheim der Universität Heidelberg
  • corresponding author C. Herskind - Klinik für Strahlentherapie und Radioonkologie, Universitätsklinikum Mannheim, Fakultät für klinische Medizin Mannheim der Universität Heidelberg

Deutsche Gesellschaft für Neurochirurgie. Japanische Gesellschaft für Neurochirurgie. 57. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie. Essen, 11.-14.05.2006. Düsseldorf, Köln: German Medical Science; 2006. DocP 08.101

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/dgnc2006/06dgnc318.shtml

Published: May 8, 2006

© 2006 Körschgen 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

Text

Objective: The tyrosine kinase inhibitor imatinib mesylate at low concentration selectively prevents phosphorylation of certain protein TKs including activated Bcr-Abl, c-kit, and the PDGF receptor, as well as their substrates. In a current clinical study, imatinib mesylate is given alternately with radiotherapy in inoperable glioblastoma patients. Parallel with this, a translational study is conducted on the effect of imatinib and radiation on glioblastoma cells in vitro. The purpose of the present work was to study the effect of simultaneous and sequential therapy with imatinib and radiotherapy treatment of the two agents.

Methods: Clonogenic survival of U343MG glioblastoma cells was used to test the cytostatic effect of imatinib alone and its effect on radiosensitivity using the colony formation assay. The surviving fraction as function of dose was fitted by the linear-quadratic model using SigmaPlot. Statistical analysis was performed with the JMP software package (SAS Institute Inc.).

Results: Low concentrations of imatinib (1-10 µM) showed a weak to moderate cytostatic effect on clonogenic proliferation. The cytostatic effect depended on the culture conditions since higher concentrations were needed to inhibit growth in mass culture conditions. Irradiation in dilute culture conditions showed a concentration-dependent synergistic effect on clonogenic cell survival. The sensitizing effect was not significantly different when cells were grown with PPP as supplement instead of FBS. Addition of the inhibitor after irradiation was as efficient as addition prior to irradiation whereas no effect was observed when the inhibitor was present only at the time of irradiation.

Conclusions: Imatinib showed a synergistic effect in combination with radiation. However, the inhibitor did not act as a radiosensitizer in the classical sense. We suggest that the synergistic effect is associated with an inhibitory effect on cell proliferation.