The central goal of this program is to understand the therapeutic utility of novel strategies to induce brain tumor cell killing. The Imaging Core (Core B) will play multiple diverse roles within this program. In summary, our primary roles will be: careful analysis of cellular and molecular processes associated with apoptosis, characterization and quantification of cell types within tumors, examination of protein expression during cell death, examination of cell-cell interactions in vitro, quantitative analysis of the extent and "quality" of angiogenesis and quantification of protein expression by individual cells within tissues. These studies will employ the full array of current light, and potentially, electron microscopic methods including: single and multicolor fluorescence microscopy, laser confocal microscopy live cell imaging, transmission electron microscopy and computer-aided morphometric analyses. The Center for Biologic Imaging, in which this core service will be performed, is equipped to perform a continuum of optical methods including all types of light and electron microscopy essential to this Program Project. Within the scope of this project at the light microscopic level these methods include: histology, immuno-histology, live cell and in situ hybridization methods. At the electron microscopic level we will provide fine structural and immunoelectron microscopic evaluation of specimens as a natural extension of the light microscopic analyses, specifically in the characterization of cellular apoptosis. Furthermore, our considerable experience in computerized image processing and morphometry will allow quantitative analysis of observed phenomena to corroborate qualitative changes in molecular expression, cell number or morphologic appearance. This core will be used by all projects, though the imaging tools used will vary from project to project. Preliminary data have shown the validity of these approaches, and in the last funded grant cycle the core has been used extensively by all projects. We expect this usage to continue at the same level during the coming grant period.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Program Projects (P01)
Project #
5P01NS040923-10
Application #
8377650
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Project Start
Project End
2014-02-28
Budget Start
2012-03-01
Budget End
2013-02-28
Support Year
10
Fiscal Year
2012
Total Cost
$111,742
Indirect Cost
$37,985
Name
University of Pittsburgh
Department
Type
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Jane, Esther P; Premkumar, Daniel R; Cavaleri, Jonathon M et al. (2016) Dinaciclib, a Cyclin-Dependent Kinase Inhibitor Promotes Proteasomal Degradation of Mcl-1 and Enhances ABT-737-Mediated Cell Death in Malignant Human Glioma Cell Lines. J Pharmacol Exp Ther 356:354-65
Pollack, Ian F; Jakacki, Regina I; Butterfield, Lisa H et al. (2016) Antigen-specific immunoreactivity and clinical outcome following vaccination with glioma-associated antigen peptides in children with recurrent high-grade gliomas: results of a pilot study. J Neurooncol :
Pollack, Ian F; Jakacki, Regina I; Butterfield, Lisa H et al. (2016) Immune responses and outcome after vaccination with glioma-associated antigen peptides and poly-ICLC in a pilot study for pediatric recurrent low-grade gliomas. Neuro Oncol 18:1157-68
Premkumar, Daniel R; Jane, Esther P; Pollack, Ian F (2015) Cucurbitacin-I inhibits Aurora kinase A, Aurora kinase B and survivin, induces defects in cell cycle progression and promotes ABT-737-induced cell death in a caspase-independent manner in malignant human glioma cells. Cancer Biol Ther 16:233-43
Mazzacurati, Lucia; Marzulli, Marco; Reinhart, Bonnie et al. (2015) Use of miRNA response sequences to block off-target replication and increase the safety of an unattenuated, glioblastoma-targeted oncolytic HSV. Mol Ther 23:99-107
Ceschin, R; Kurland, B F; Abberbock, S R et al. (2015) Parametric Response Mapping of Apparent Diffusion Coefficient as an Imaging Biomarker to Distinguish Pseudoprogression from True Tumor Progression in Peptide-Based Vaccine Therapy for Pediatric Diffuse Intrinsic Pontine Glioma. AJNR Am J Neuroradiol 36:2170-6
Foster, Kimberly A; Jane, Esther P; Premkumar, Daniel R et al. (2015) NVP-BKM120 potentiates apoptosis in tumor necrosis factor-related apoptosis-inducing ligand-resistant glioma cell lines via upregulation of Noxa and death receptor 5. Int J Oncol 47:506-16
Ohkuri, Takayuki; Ghosh, Arundhati; Kosaka, Akemi et al. (2014) STING contributes to antiglioma immunity via triggering type I IFN signals in the tumor microenvironment. Cancer Immunol Res 2:1199-208
Foster, Kimberly A; Jane, Esther P; Premkumar, Daniel R et al. (2014) Co-administration of ABT-737 and SAHA induces apoptosis, mediated by Noxa upregulation, Bax activation and mitochondrial dysfunction in PTEN-intact malignant human glioma cell lines. J Neurooncol 120:459-72
Pollack, Ian F (2014) Management of low-grade gliomas in childhood. World Neurosurg 81:265-7

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