The Pathology Core is designed to provide three services to support the experimental aims of this Program Project application. First, the Core will ensure timely and reliable availability of tumor tissues collected from the preclinical studies with genetic models of prostate cancer used in each Project. This will involve schedule-dependent animal harvesting, necropsy, tissue dissection, and tissue processing, including bone lesions. The second objective of Core C is to provide histopathological evaluation of signaling pathways in localized and metastatic prostate cancer, as well as bone-tumor interplay after treatment with the various """"""""network inhibitors"""""""" tested in Projects 1, 2, and 3. To accomplish these tasks. Core C will support quantitative and standardized immunohistochemical evaluation of tumor markers, determine parameters of apoptosis and cell proliferation, provide volumetric quantification of lung metastasis by stereologic microscopy, and examine a potential modulation of ancillary pathways of tumor growth, i.e. angiogenesis. Third, Core C will identify, characterize and test molecular biomarkers of pathway and target validation for the proposed preclinical studies, in vivo. This will involve analysis of markers of mitochondrial dysfunction and oxidative damage for Project 1, dynamic changes in integrin signaling for Project 2, and evaluation of a Runx2 """"""""gene signature"""""""" for modulation of bone-tumor responses in Project 3. The tasks provided by Core C will support equally each Project, and will be accomplished under the supervision of two senior pathologists. Drs. Irwin Leav, Director of Core C, and Zhong Jiang, Co-Director of Core C, have extensive experience in histopathology of prostate cancer, disease models in rodents, and evaluation of molecular biomarkers of tumor responses. The centralization of the morphologic studies in Core C will facilitate collaborative research among the investigators on this application, while obviating the need for each Project to individually develop key techniques.

Public Health Relevance

The services provided by Core C are pivotal to accomplish the specific aims contained in each Project, and to obtain a comprehensive evaluation of tumor responses after treatment with new molecular therapeutics, i.e. nebwork inhibitors. The combination of high-resolution molecular imaging (Core B) with quantitative and standardized histopathology (Core C) will enhance the synergistic integration of each Project, and strengthen the feasibility of their mechanistic and preclinical goals.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
7P01CA140043-02
Application #
8280366
Study Section
Special Emphasis Panel (ZCA1)
Project Start
Project End
Budget Start
2011-07-01
Budget End
2012-06-30
Support Year
2
Fiscal Year
2010
Total Cost
$51,294
Indirect Cost
Name
Wistar Institute
Department
Type
DUNS #
075524595
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Patel, Sima; Fu, Shuyu; Mastio, Jerome et al. (2018) Unique pattern of neutrophil migration and function during tumor progression. Nat Immunol 19:1236-1247
Wang, Tao; Huang, Jiayi; Vue, Mai et al. (2018) ?v?3 Integrin Mediates Radioresistance of Prostate Cancer Cells Through Regulation of Survivin. Mol Cancer Res :
Seo, Jae Ho; Agarwal, Ekta; Bryant, Kelly G et al. (2018) Syntaphilin Ubiquitination Regulates Mitochondrial Dynamics and Tumor Cell Movements. Cancer Res 78:4215-4228
Lu, Huimin; Bowler, Nicholas; Harshyne, Larry A et al. (2018) Exosomal ?v?6 integrin is required for monocyte M2 polarization in prostate cancer. Matrix Biol 70:20-35
Reyes-Uribe, Patricia; Adrianzen-Ruesta, Maria Paz; Deng, Zhong et al. (2018) Exploiting TERT dependency as a therapeutic strategy for NRAS-mutant melanoma. Oncogene 37:4058-4072
Caino, M Cecilia; Seo, Jae Ho; Wang, Yuan et al. (2017) Syntaphilin controls a mitochondrial rheostat for proliferation-motility decisions in cancer. J Clin Invest 127:3755-3769
Altieri, Dario C (2017) Mitochondria on the move: emerging paradigms of organelle trafficking in tumour plasticity and metastasis. Br J Cancer 117:301-305
Kumar, Vinit; Donthireddy, Laxminarasimha; Marvel, Douglas et al. (2017) Cancer-Associated Fibroblasts Neutralize the Anti-tumor Effect of CSF1 Receptor Blockade by Inducing PMN-MDSC Infiltration of Tumors. Cancer Cell 32:654-668.e5
Bryant, Kelly G; Chae, Young Chan; Martinez, Rogelio L et al. (2017) A Mitochondrial-targeted purine-based HSP90 antagonist for leukemia therapy. Oncotarget 8:112184-112198
Zingiryan, Areg; Farina, Nicholas H; Finstad, Kristiaan H et al. (2017) Dissection of Individual Prostate Lobes in Mouse Models of Prostate Cancer to Obtain High Quality RNA. J Cell Physiol 232:14-8

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