Target-specific glioma therapy in an immunocompetent mouse model : meeting abstract

  • Objective: Establishment of an immunocompetent mouse model representing the typical progressive stages observed in malignant human gliomas for the in vivo evaluation of novel target-specific regimens. Methods: Isolated clones from tumours that arose spontaneously in GFAP-v-src transgenic mice were used to develop a transplantable brain tumour model in syngeneic B6C3F1 mice. STAT3 protein was knocked down by infection of tumour cells with replication-defective lentivirus encoding STAT3-siRNA. Apoptosis is designed to be induced by soluble recombinant TRAIL + chemical Bcl-2/Bcl-xL inhibitors. Results: Striatal implantation of 105 mouse tumour cells resulted in the robust development of microscopically (2 – 3 mm) infiltrating malignant gliomas. Immunohistochemically, the gliomas displayed the astroglial marker GFAP and the oncogenic form of STAT3 (Tyr-705-phosphorylated) which is found in many malignancies including gliomas. Phosphorylated STAT3 was particularly prominent in the nucleus but was also found at the plasma membrane of peripherally infiltrating glioma cells. To evaluate the role of STAT3 in tumour progression, we stably expressed siRNA against STAT3 in several murine glioma cell lines. The effect of STAT3 depletion on proliferation, invasion and survival will be first assessed in vitro and subsequently after transplantation in vivo. Upstream and downstream components of the STAT3 signalling pathway as well as possible non-specific side effects of STAT3-siRNA expression after lentiviral infection will be examined, too. Conclusions: Its high rate of engraftment, its similarity to the malignant glioma of origin, and its rapid locally invasive growth should make this murine model useful in testing novel therapies for malignant gliomas.

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Author:Jakob Weissenberger, J. Masri, Daniela Baus, Edith PfitznerORCiDGND, Jörg KreuterGND, Andreas RaabeORCiDGND, Volker Seifert, Donat KögelORCiD
Parent Title (German):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
Publisher:German Medical Science
Place of publication:Düsseldorf ; Köln
Document Type:Conference Proceeding
Year of Completion:2006
Date of first Publication:2006/05/08
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Creating Corporation:Deutsche Gesellschaft für Neurochirurgie
Release Date:2007/06/08
Page Number:4
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.
Source:57th annual meeting of the German Society of Neurosurgery, joint meeting with the Japanese Neurosurgical Society, 11 - 14 May, Essen. - Düsseldorf {[u.a.] : German Medical Science; Doc FR.03.09
Institutes:Biochemie, Chemie und Pharmazie / Pharmazie
Medizin / Medizin
Angeschlossene und kooperierende Institutionen / Georg-Speyer-Haus
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung-Nicht kommerziell-Keine Bearbeitung 3.0