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Updated: Aug 11, 2026

Combination Radiotherapy in an Orthotopic Mouse Brain Tumor Model
Published on: March 6, 2012
A syngeneic mouse glioma model for study of glioblastoma therapy
N E Weiner1, R B Pyles, C L Chalk
1Department of Neurosurgery, University of Cincinnati Medical Center, Ohio, USA.
Abstract:
Animal models of human tumors serve a vital role in the development and testing of new anticancer therapies. Since the immune system is likely to play an essential role in tumor eradication, there is a particular need for modeling human disease in immunocompetent hosts. Few models of glioma have been developed in immunocompetent mice that are commercially available and none of these tumors have histological and antigenic characteristics of human gliomas. We have used a cell line, 4C8, derived from a spontaneous glioma-like tumor that arose in a transgenic mouse to develop a new glioma model. The intracranial injection of 4C8 cells into immunocompetent syngeneic B6D2F1 mice resulted in tumors that were densely cellular, developed a pseudopallisading pattern of necrosis, and expressed GFAP; all important features of human malignant gliomas. The average neurological endpoint was 51 days after intracranial injection. The 4C8 cells also grew rapidly in the flank, retaining histologic features seen in intracranial tumors. Flank tumors reached an average volume of 100 mm3, a volume ideal for therapy testing, by 34 days postinjection. These results suggest that the 4C8 mouse glioma model is an excellent system in which to test new antiglioma therapies for use in humans.
Insights
A new mouse glioma model using 4C8 cells closely mimics human malignant gliomas. This immunocompetent model is ideal for testing novel anticancer therapies against gliomas.
Area of Science:
- Oncology
- Immunology
- Animal Models
Background:
- Developing effective anticancer therapies requires accurate preclinical models.
- Existing mouse glioma models often lack key features of human gliomas, particularly in immunocompetent hosts.
- There is a need for models that replicate human glioma histology and antigenicity in immunocompetent mice.
Purpose of the Study:
- To develop and characterize a novel mouse glioma model using the 4C8 cell line.
- To evaluate the suitability of this model for testing antiglioma therapies.
Main Methods:
- A 4C8 cell line, derived from a spontaneous mouse glioma-like tumor, was used.
- 4C8 cells were injected intracranially and subcutaneously into immunocompetent syngeneic B6D2F1 mice.
- Tumor growth, histology, and expression of glial fibrillary acidic protein (GFAP) were assessed.
Main Results:
- Intracranial tumors exhibited dense cellularity, pseudopallisading necrosis, and GFAP expression, mirroring human malignant gliomas.
- Neurological endpoints for intracranial tumors averaged 51 days.
- Subcutaneous flank tumors grew rapidly, retaining histologic features and reaching a therapeutically relevant volume (100 mm3) in 34 days.
Conclusions:
- The 4C8 mouse glioma model accurately recapitulates key features of human malignant gliomas.
- This model provides a valuable platform for preclinical testing of new antiglioma therapies in an immunocompetent setting.

