Validation of an imageable surgical resection animal model of Glioblastoma (GBM).
BACKGROUND: Glioblastoma (GBM) is the most common and malignant primary brain tumour having a median survival of just 12-18 months following standard therapy protocols. Local recurrence, post-resection and adjuvant therapy occurs in most cases.
NEW METHOD: U87MG-luc2-bearing GBM xenografts underwent 4.5mm craniectomy and tumour resection using microsurgical techniques. The cranial defect was repaired using a novel modified cranial window technique consisting of a circular microscope coverslip held in place with glue.
RESULTS: Immediate post-operative bioluminescence imaging (BLI) revealed a gross total resection rate of 75%. At censor point 4 weeks post-resection, Kaplan-Meier survival analysis revealed 100% survival in the surgical group compared to 0% in the non-surgical cohort (p=0.01). No neurological defects or infections in the surgical group were observed. GBM recurrence was reliably imaged using facile non-invasive optical bioluminescence (BLI) imaging with recurrence observed at week 4.
COMPARISON WITH EXISTING METHOD(S): For the first time, we have used a novel cranial defect repair method to extend and improve intracranial surgical resection methods for application in translational GBM rodent disease models. Combining BLI and the cranial window technique described herein facilitates non-invasive serial imaging follow-up.
CONCLUSION: Within the current context we have developed a robust methodology for establishing a clinically relevant imageable GBM surgical resection model that appropriately mimics GBM recurrence post resection in patients.
This research was supported by a grant from Science Foundation Ireland (08/IN1/B1949) and by the National Biophotonics and Imaging Platform Ireland (PRTLI Cycle 4) funded through the Irish Higher Education Authority to JHMP. AB is supported by the European Union's Seventh Framework Programme for research, technological development and demonstration under grant agreements no. 278981 ‘AngioPredict’ and no. 251528 ‘AngioTox’
CommentsThis article is also available at http://ac.els-cdn.com/S0165027014001605/1-s2.0-S0165027014001605-main.pdf?_tid=ba0c0aac-2980-11e6-beff-00000aacb35d&acdnat=1464954533_34b8dae0e7242ba1a3d022a5ad859eea
Published CitationSweeney KJ, Jarzabek MA, Dicker P, O'Brien DF, Callanan JJ, Byrne AT, Prehn JH. Validation of an imageable surgical resection animal model of Glioblastoma (GBM). Journal of Neuroscience Methods. 2014;233:99-104
- Beaumont Hospital
- Centre for Systems Medicine
- Physiology and Medical Physics
- Public Health and Epidemiology