An experimental xenograft mouse model of diffuse pontine glioma designed for therapeutic testing.
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.
Department of Neurological Surgery and Brain Tumor Research Center, University of California San Francisco, San Francisco, CA 94143-0112, USA.
Yasuyuki
Y
Aoki
Rintaro
R
Hashizume
Tomoko
T
Ozawa
Anu
A
Banerjee
Michael
M
Prados
C David
CD
James
Nalin
N
Gupta
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D020295:Brain Stem Neoplasms / Q000188:drug therapy* / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D049408:Luminescent Agents; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000378:metabolism; D009368:Neoplasm Transplantation / Q000379:methods; D010879:Piperazines / Q000627:therapeutic use; D011149:Pons / Q000473:pathology*; D011725:Pyridines / Q000627:therapeutic use; D016160:Retinoblastoma Protein / Q000378:metabolism; D000077204:Temozolomide; D013997:Time Factors; D014407:Tumor Cells, Cultured; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D049408:Luminescent Agents; D009363:Neoplasm Proteins; D010879:Piperazines; D011725:Pyridines; D016160:Retinoblastoma Protein; D003606:Dacarbazine; C470629:MIB1 protein, mouse; D044767:Ubiquitin-Protein Ligases; D053148:Caspase 3; C500026:palbociclib; D000077204:Temozolomide