In next 5-year funding period, investigators in Brain Tumor SPORE will continue to utilize the expert services provided by the Animal Core. The majority of projects in the SPORE rely on intracranial (orthotopic) implantation of established, adherent glioma cell lines, which are molecularly well characterized. Improvements in modeling the human disease will be achieved through the use of orthotopic xenografts of human glioma stem cells (GSCs), which are an important component of solid tumors, better replicate the human disease, and may mediate treatment resistance. These patient-derived GSC cell lines (N>50 to date) have been molecularly characterized into proneural, mesenchymal, classical and neural subtypes. In addition, genetically engineered mouse models of glioma (GEMMs) such as the RCAS/Ntv-a system are utilized by SPORE investigators. Specific genes of interest important for tumorigenesis can be evaluated in this model in a cell-type specific manner. Other GEMMs available within the Animal Core include: hGFAP-Cre*;p5S '?'^?'';Pten '?^^ and Nestin-CreERT2 clnk4a/Arf UL cPTEN UL GFAP-tta tet- EGFRviil. Importantly, tumors generated in immunocompetent mice allow for better evaluation of interactions between tumor and the native microenvironment. Finally, we will continue to maintain and provide assistance with the establishment of traditional xenograft models from standard glioma cell lines (e.g. U87, U251, LN229, etc.).
The Specific Aims of the Animal Core are:
Aim 1 : Provide support for animal experiments using patient derived glioma stem cell lines (GSCs) as orthotopic xenografts in immunodeficient mice.
Aim 2 : Provide support for animal experiments using Genetically Engineered Mouse Models (GEMMs).
Aim 3 : Maintain working stocks of cell lines.
Aim 4 : Provide support for xenografts of standard glioma cell lines.
DO NOT EXCEED THE SPACE PROVIDED. Three of the four Brain Turiior SPORE projects are expected to use significant numbers of mice for their experiments. The Brain Tumor Animal Core will provide expert oversight of the animal experiments. Experienced personnel will execute the experimental plans.
|Lu, Sean; Wang, Yugang (2018) Nonmetabolic functions of metabolic enzymes in cancer development. Cancer Commun (Lond) 38:63|
|Qiao, Yang; Gumin, Joy; MacLellan, Christopher J et al. (2018) Magnetic resonance and photoacoustic imaging of brain tumor mediated by mesenchymal stem cell labeled with multifunctional nanoparticle introduced via carotid artery injection. Nanotechnology 29:165101|
|Zinn, Pascal O; Singh, Sanjay K; Kotrotsou, Aikaterini et al. (2018) A Coclinical Radiogenomic Validation Study: Conserved Magnetic Resonance Radiomic Appearance of Periostin-Expressing Glioblastoma in Patients and Xenograft Models. Clin Cancer Res 24:6288-6299|
|Shah, Maitri Y; Ferracin, Manuela; Pileczki, Valentina et al. (2018) Cancer-associated rs6983267 SNP and its accompanying long noncoding RNA CCAT2 induce myeloid malignancies via unique SNP-specific RNA mutations. Genome Res 28:432-447|
|Mostovenko, Ekaterina; Végvári, Ákos; Rezeli, Melinda et al. (2018) Large Scale Identification of Variant Proteins in Glioma Stem Cells. ACS Chem Neurosci 9:73-79|
|Chen, Zhihua; Morales, John E; Guerrero, Paola A et al. (2018) PTPN12/PTP-PEST Regulates Phosphorylation-Dependent Ubiquitination and Stability of Focal Adhesion Substrates in Invasive Glioblastoma Cells. Cancer Res 78:3809-3822|
|Wang, Yugang; Xia, Yan; Lu, Zhimin (2018) Metabolic features of cancer cells. Cancer Commun (Lond) 38:65|
|Noh, Hyangsoon; Zhao, Qingnan; Yan, Jun et al. (2018) Cell surface vimentin-targeted monoclonal antibody 86C increases sensitivity to temozolomide in glioma stem cells. Cancer Lett 433:176-185|
|Lee, Jong-Ho; Liu, Rui; Li, Jing et al. (2018) EGFR-Phosphorylated Platelet Isoform of Phosphofructokinase 1 Promotes PI3K Activation. Mol Cell 70:197-210.e7|
|Lang, Frederick F; Conrad, Charles; Gomez-Manzano, Candelaria et al. (2018) Phase I Study of DNX-2401 (Delta-24-RGD) Oncolytic Adenovirus: Replication and Immunotherapeutic Effects in Recurrent Malignant Glioma. J Clin Oncol 36:1419-1427|
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