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

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.
Authors	Yasuyuki Aoki, Rintaro Hashizume, Tomoko Ozawa, Anu Banerjee, Michael Prados, C David James, Nalin Gupta
Journal	Journal of neuro-oncology (J Neurooncol) Vol. 108 Issue 1 Pg. 29-35 (May 2012) ISSN: 1573-7373 [Electronic] United States
PMID	22231932 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Antineoplastic Agents CDKN2A protein, human Cyclin-Dependent Kinase Inhibitor p16 Luminescent Agents Neoplasm Proteins Piperazines Pyridines Retinoblastoma Protein Dacarbazine MIB1 protein, mouse Ubiquitin-Protein Ligases Caspase 3 palbociclib Temozolomide
Topics	Animals Antineoplastic Agents (therapeutic use) Brain Stem Neoplasms (drug therapy, pathology) Caspase 3 (metabolism) Cyclin-Dependent Kinase Inhibitor p16 Dacarbazine (analogs & derivatives, therapeutic use) Disease Models, Animal Female Gene Expression Regulation, Neoplastic (drug effects) Humans Luminescent Agents Mice Mice, Nude Neoplasm Proteins (metabolism) Neoplasm Transplantation (methods) Piperazines (therapeutic use) Pons (pathology) Pyridines (therapeutic use) Retinoblastoma Protein (metabolism) Temozolomide Time Factors Tumor Cells, Cultured Ubiquitin-Protein Ligases (metabolism) Xenograft Model Antitumor Assays

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