gms | German Medical Science

62. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
Joint Meeting mit der Polnischen Gesellschaft für Neurochirurgen (PNCH)

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

07. - 11. Mai 2011, Hamburg

Inhibition of glioblastoma growth in an orthotopic xenograft model by using an IGF-1 receptor antibody

Meeting Abstract

  • T. Martens - Klinik für Neurochirurgie, Universitätsklinikum Hamburg-Eppendorf
  • H.S. Günther - Klinik für Neurochirurgie, Universitätsklinikum Hamburg-Eppendorf
  • M. Westphal - Klinik für Neurochirurgie, Universitätsklinikum Hamburg-Eppendorf
  • K. Lamszus - Klinik für Neurochirurgie, Universitätsklinikum Hamburg-Eppendorf

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. DocP 088

DOI: 10.3205/11dgnc309, URN: urn:nbn:de:0183-11dgnc3091

Veröffentlicht: 28. April 2011

© 2011 Martens et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Objective: The Insulin-like growth factor (IGF) is known to play a major role in many human cancers. Overexpression of its receptor IGF-1 stimulates cell migration and proliferation in human gliomas in vitro. Thus the IGF-1 receptor is a potential target for anti-tumor therapies and this has been shown in a subcutaneous model using U87. We used an IGF-1 receptor antibody (IMC-A12) to inhibit glioblastoma growth in an orthotopic mouse model also using U87 in vivo and combined this with intracerebral intraparenchymal drug delivery.

Methods: Orthotopic xenografts were established in nude mice by using U87 glioblastoma cells. After one week osmotic minipumps were implanted in order to administer the IGF-1 receptor antibody directly into the tumor inoculation site over a period of three weeks. Subsequently the mice were sacrificed and tumorsize was analyzed histologically. Vessel density, proliferative activity and fraction of apoptotic tumor cells were determined immunohistochemically.

Results: Tumor growth was inhibited 75% by IMC-A12 in the U87 mouse model compared to controls, which is statistically highly significant (p<0.001). Mean tumor volume after three weeks of treatment was 3,53 mm3 and 14,04 mm3 in the controls respectively.

Conclusions: IMC-A12 administered as local intracerebral treatment can inhibit glioblastoma growth in an orthotopic xenograft model. Efficacious intraparenchymal delivery circumvents problems with blood brain barrier penetration, reduces the amount of drug to be used and minimizes potential systemic side effects. These results are to be confirmed in more invasively growing tumor models.