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Open Access Research

Effects of ionizing radiation in combination with Erufosine on T98G glioblastoma xenograft tumours: a study in NMRI nu/nu mice

Guido Henke1, Verena Meier1, Lars H Lindner2, Hansjörg Eibl3, Michael Bamberg1, Claus Belka4, Wilfried Budach5 and Verena Jendrossek16*

Author Affiliations

1 Department of Radiooncology, University Hospital Tübingen, Hoppe-Seyler-Str. 3, Tübingen, 72076, Germany

2 Department of Medicine III, University Hospital Grosshadern, Ludwig-Maximilians-University, Marchionistr.15, München, 81377, Germany

3 Max-Planck-Institute for Biophysical Chemistry, Am Fassberg 11, Göttingen, 37077, Germany

4 Department of Radiooncology, University Hospital Grosshadern, Ludwig-Maximilians-University, Marchionistr.15, München, 81377, Germany

5 Department of Radiooncology, University Hospital Düsseldorf, Moorenstrasse 5, Düsseldorf, 40225, Germany

6 Department of Molecular Cell Biology, Institute of Cell Biology (Cancer Research), University Hospital Essen, Virchowstrasse 173, Essen, 45122, Germany

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Radiation Oncology 2012, 7:172  doi:10.1186/1748-717X-7-172

Published: 18 October 2012

Abstract

Background

Erufosine is a promising anticancer drug that increases the efficacy of radiotherapy in glioblastoma cell lines in vitro. Moreover, treatment of nude mice with repeated intraperitoneal or subcutaneous injections of Erufosine is well tolerated and yields drug concentrations in the brain tissue that are higher than the concentrations required for cytotoxic drug effects on glioblastoma cell lines in vitro.

Methods

In the present study we aimed to evaluate the effects of a combined treatment with radiotherapy and Erufosine on growth and local control of T98G subcutaneous glioblastoma xenograft-tumours in NMRI nu/nu mice.

Results

We show that repeated intraperitoneal injections of Erufosine resulted in a significant drug accumulation in T98G xenograft tumours on NMRI nu/nu mice. Moreover, short-term treatment with 5 intraperitoneal Erufosine injections caused a transient decrease in the growth of T98G tumours without radiotherapy. Furthermore, an increased radiation-induced growth delay of T98G xenograft tumours was observed when fractionated irradiation was combined with short-term Erufosine-treatment. However, no beneficial drug effects on fractionated radiotherapy in terms of local tumour control were observed.

Conclusions

We conclude that short-term treatment with Erufosine is not sufficient to significantly improve local control in combination with radiotherapy in T98G glioblastoma xenograft tumours. Further studies are needed to evaluate efficacy of extended drug treatment schedules.

Keywords:
Erufosine; Radiotherapy; Combination therapy; T98G glioblastoma; Xenograft tumours; Mouse model; Local control