Journal of Neuro-Oncology

, Volume 108, Issue 1, pp 29–35

An experimental xenograft mouse model of diffuse pontine glioma designed for therapeutic testing

  • Yasuyuki Aoki
  • Rintaro Hashizume
  • Tomoko Ozawa
  • Anu Banerjee
  • Michael Prados
  • C. David James
  • Nalin Gupta
Laboratory Investigation

DOI: 10.1007/s11060-011-0796-x

Cite this article as:
Aoki, Y., Hashizume, R., Ozawa, T. et al. J Neurooncol (2012) 108: 29. doi:10.1007/s11060-011-0796-x

Abstract

The prognosis for diffuse infiltrating pontine gliomas (DIPG) remains extremely poor, with the majority of patients surviving less than 2 years. Here, we have adapted standard xenograft techniques to study glioma growth in the mouse brainstem, and have utilized the mouse model for studying a relevant therapeutic for treating DIPGs. bioluminescence imaging monitoring revealed a progressive increase in signal following the injection of either of two tumor cell types into the brainstem. Mice with orthotopic GS2 tumors, and receiving a single 100 mg/kg dose of temozolomide showed a lengthy period of decreased tumor luminescence, with substantially increased survival relative to untreated mice (P < 0.001). A small molecule inhibitor that targets cdk4/6 was used to test AM-38 brainstem xenograft response to treatment. Drug treatment resulted in delayed tumor growth, and significantly extended survival. Our results demonstrate the feasibility of using an orthotopic brainstem tumor model in athymic mice, and for application to testing therapeutic agents in treating DIPG.

Keywords

Brainstem gliomaMouse modelBioluminescence image

Copyright information

© Springer Science+Business Media, LLC. 2012

Authors and Affiliations

  • Yasuyuki Aoki
    • 1
  • Rintaro Hashizume
    • 1
  • Tomoko Ozawa
    • 1
  • Anu Banerjee
    • 2
  • Michael Prados
    • 1
  • C. David James
    • 1
  • Nalin Gupta
    • 1
    • 2
  1. 1.Department of Neurological Surgery and Brain Tumor Research CenterUniversity of California San FranciscoSan FranciscoUSA
  2. 2.Department of PediatricsUniversity of California San FranciscoSan FranciscoUSA