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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
2P50CA127001-06
Application #
8588580
Study Section
Special Emphasis Panel (ZCA1-RPRB-7 (M1))
Project Start
2007-04-01
Project End
2018-08-31
Budget Start
2013-09-17
Budget End
2014-08-31
Support Year
6
Fiscal Year
2013
Total Cost
$242,680
Indirect Cost
$91,005
Name
University of Texas MD Anderson Cancer Center
Department
Type
DUNS #
800772139
City
Houston
State
TX
Country
United States
Zip Code
77030
Figueroa, Javier; Phillips, Lynette M; Shahar, Tal et al. (2017) Exosomes from Glioma-Associated Mesenchymal Stem Cells Increase the Tumorigenicity of Glioma Stem-like Cells via Transfer of miR-1587. Cancer Res 77:5808-5819
Narang, Shivali; Kim, Donnie; Aithala, Sathvik et al. (2017) Tumor image-derived texture features are associated with CD3 T-cell infiltration status in glioblastoma. Oncotarget 8:101244-101254
Carstens, Julienne L; Correa de Sampaio, Pedro; Yang, Dalu et al. (2017) Spatial computation of intratumoral T cells correlates with survival of patients with pancreatic cancer. Nat Commun 8:15095
Hu, Jingzhe; Salzillo, Travis C; Sailasuta, Napapon et al. (2017) Interrogating IDH Mutation in Brain Tumor: Magnetic Resonance and Hyperpolarization. Top Magn Reson Imaging 26:27-32
Lehrer, Michael; Bhadra, Anindya; Ravikumar, Visweswaran et al. (2017) Multiple-response regression analysis links magnetic resonance imaging features to de-regulated protein expression and pathway activity in lower grade glioma. Oncoscience 4:57-66
Koul, Dimpy; Wang, Shuzhen; Wu, Shaofang et al. (2017) Preclinical therapeutic efficacy of a novel blood-brain barrier-penetrant dual PI3K/mTOR inhibitor with preferential response in PI3K/PTEN mutant glioma. Oncotarget 8:21741-21753
Qian, Xu; Li, Xinjian; Cai, Qingsong et al. (2017) Phosphoglycerate Kinase 1 Phosphorylates Beclin1 to Induce Autophagy. Mol Cell 65:917-931.e6
Van Roosbroeck, Katrien; Fanini, Francesca; Setoyama, Tetsuro et al. (2017) Combining Anti-Mir-155 with Chemotherapy for the Treatment of Lung Cancers. Clin Cancer Res 23:2891-2904
Gressot, Loyola V; Doucette, Tiffany; Yang, Yuhui et al. (2017) Analysis of the inhibitors of apoptosis identifies BIRC3 as a facilitator of malignant progression in glioma. Oncotarget 8:12695-12704
Jiang, Hong; Rivera-Molina, Yisel; Gomez-Manzano, Candelaria et al. (2017) Oncolytic Adenovirus and Tumor-Targeting Immune Modulatory Therapy Improve Autologous Cancer Vaccination. Cancer Res 77:3894-3907

Showing the most recent 10 out of 208 publications