gms | German Medical Science

55. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e. V. (DGNC)
1. Joint Meeting mit der Ungarischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

25. bis 28.04.2004, Köln

Article

Send article

Glioblastoma multiforme: in vitro and in vivo testing of new platin compounds

In-vitro- und In-vivo-Austestung neuer Platinverbindungen

Meeting Abstract

Search Medline for

  • corresponding author Rezvan Ahmadi - Neurochirurgische Universitätsklinik, Heidelberg
  • K. Becker - Interdisziplinäres Forschungszentrum, Gießen
  • M. Hartmann - Neuroradiologische Universitätsklinik, Heidelberg
  • B. Helmke - Pathologisches Institut der Universität Heidelberg, Heidelberg
  • G. Lowe - Dyson Perrins Laboratory, Oxford University, Oxford /UK
  • A. Unterberg - Neurochirurgische Universitätsklinik, Heidelberg
  • H. H. Steiner - Neurochirurgische Universitätsklinik, Heidelberg
  • C. Herold-Mende - Neurochirurgische Universitätsklinik, Heidelberg

Deutsche Gesellschaft für Neurochirurgie. Ungarische Gesellschaft für Neurochirurgie. 55. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), 1. Joint Meeting mit der Ungarischen Gesellschaft für Neurochirurgie. Köln, 25.-28.04.2004. Düsseldorf, Köln: German Medical Science; 2004. DocMO.12.04

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/dgnc2004/04dgnc0119.shtml

Published: April 23, 2004

© 2004 Ahmadi 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

In spite of aggressive therapy, the prognosis of glioblastoma (GBM) is poor. New therapeutic strategies are needed to treat these highly malignant tumours. Terpyridin-Platin (II)-complexes were shown to bind to double-stranded DNA by intercalation and therefore can be considered as potential cytostatic drugs. 10 different Terpyridin-Platin II-complexes have been tested for the inhibition of the marker enzyme Thioredoxin-Reductase. One of them (I23N) was selected as the most effective agent.

Methods

Antiproliferative effect of I23N was tested on three GBM cell lines by BrdU ELISA using different concentrations and different application schemes. In the C6 glioma model the same compound was systemically applied to Wistar rats in two different doses (25 / 50mg/kg). MRIs were performed to follow-up the tumour growth course. Post mortem tumour tissues as well as normal tissues (kidney, liver, lung, skin, heart, muscle, gut) were collected to assess evidence for intoxication.

Results

In a single dose application scheme I23N inhibited tumour cell proliferation of all three GBM cultures dose dependently with IC50 values from 2.5-10.5 µM. This antiproliferative effect was even improved up to 2.2-6.9 µM when the compound was added 3x to the culture medium in 24h intervals. In vivo, a dose-dependent reduction of tumour growth of 123N-treated animals in comparison to untreated controls was observed as determined by MRI analysis. Histological evaluation of non-tumour tissues did not reveal any pathological alterations.

Conclusions

Our data indicate that I23N might be a good candidate for further preclinical evaluation to improve the observed anti-tumour effects.