The Animal Models Core is designed to provide two nnain services. First, the Core will oversee the husbandry, maintenance, and quality control ofthe genetic mouse models of prostate cancer utilized by each Project in the application, including prostate-specific Pten conditional knockout mice (Pterf""""""""'^') and transgenic TRAMP mice. These mouse models are already fully established In the applicants'laboratories, have been properly maintained, and have been used to generate critical preliminary data in support of the various specific aims. As Co-Director of Core B, Dr. Stephen Jones will ensure the maintenance, genotyping, and timely availability of these mouse strains to fulfill the experimental objectives of each Project. The second task of Core B Is to provide state-of-the-art molecular imaging in support of the preclinical evaluation of """"""""network inhibitors"""""""" proposed In the application, which include mitochondria-targeted small molecule Hsp90 inhibitors, Gamitrinibs (Project 1), function-blocking monoclonal antibody (mAb) 6.3G9 to avPe integrin (Project 2), and lentiviral delivery of short hairpin RNA (shRNA) to silence Runx2 in bone metastatic prostate cancer, in vivo (Project 3). For these tasks. Core B will provide quantitative analysis of tumor growth in xenograft studies with genetically engineered prostate cancer cell types, evaluate tumor responses to """"""""network inhibitors"""""""" in localized and metastatic disease models, and map osteoblastic and osteoclastic bone remodeling pathways during intratibial growth of prostate cancer, in vivo. Dr. Alexei Bogdanov, Director of Core B, will lead these efforts by coordinating an extensive portfolio of molecular imaging capabilities, including MRI, (iCT, high resolution X-ray radiography, and bioluminescence. Core B will support equally all three Projects in the application. Overall, these studies will provide a quantitative and unbiased evaluation of prostate cancer responses after treatment with novel molecular therapies, and validate target and pathway specificity, in vivo.

Public Health Relevance

The services provided by Core B are essential to support the preclinical studies of novel molecular therapeutics for advanced prostate cancer as proposed in the application. The synergistic combination of genetic mouse models of prostate cancer, and state-of-the-art molecular imaging will elucidate novel mechanisms of prostate cancer progression, and credential the potential efficacy of network inhibitors as candidate molecular therapies for advanced and metastatic disease In humans.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
1P01CA140043-01A1
Application #
7991940
Study Section
Special Emphasis Panel (ZCA1-RPRB-0 (M1))
Project Start
2010-07-01
Project End
2015-06-30
Budget Start
2010-07-01
Budget End
2011-06-30
Support Year
1
Fiscal Year
2010
Total Cost
$49,801
Indirect Cost
Name
University of Massachusetts Medical School Worcester
Department
Type
DUNS #
603847393
City
Worcester
State
MA
Country
United States
Zip Code
01655
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

Showing the most recent 10 out of 77 publications