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

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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.

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Acknowledgment

This work was supported by the Pediatric Brain Tumor Foundation Institute Award to the Brain Tumor Research Center at UCSF.

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Authors and Affiliations

  1. Department of Neurological Surgery and Brain Tumor Research Center, University of California San Francisco, 505 Parnassus Ave., Rm M779, San Francisco, CA, 94143-0112, USA

    Yasuyuki Aoki, Rintaro Hashizume, Tomoko Ozawa, Michael Prados, C. David James & Nalin Gupta

  2. Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA

    Anu Banerjee & Nalin Gupta

Authors
  1. Yasuyuki Aoki
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  2. Rintaro Hashizume
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  3. Tomoko Ozawa
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  4. Anu Banerjee
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  5. Michael Prados
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  6. C. David James
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  7. Nalin Gupta
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Corresponding author

Correspondence to Nalin Gupta.

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Aoki, Y., Hashizume, R., Ozawa, T. et al. An experimental xenograft mouse model of diffuse pontine glioma designed for therapeutic testing. J Neurooncol 108, 29–35 (2012). https://doi.org/10.1007/s11060-011-0796-x

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  • DOI: https://doi.org/10.1007/s11060-011-0796-x

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