Core B will provide 3 primary functions to the Program Project. First, Core B will provide research specimens to the investigators and assist with identification, immunostaining and image analysis. Paraffin-embedded sections will be provided from original tumors or tissue microarrays and used to 1) confirm tissue histology using routine H&E;2) analyze apoptosis using ACINUS, proliferation using MIB-1 detection of Ki-67 or BrdU incorporation and androgen receptor using monoclonal antibodies by standard, descriptive immunohistochemistry and quantitative analysis using visual scoring and/or automated image analysis;and 3) identify and quantify steroid receptor co-regulators, androgen metabolism enzymes, androgen-regulated gene products (PSA, Nkx3.1, a-tubulin, translation elongation factor 1a, non-neuronal enolase, tomoregulin, thioredoxin reducatase 1, Mxi-1 and human kallikrein 2), general transcription factors, growth factors and their receptors and stem cell and angiogenesis biomarkers using immunohistochemistry and image analysis. Second, Core B will be responsible for storage, processing and sectioning of clinical (frozen, archival and TMAs) and prostate cancer xenograft (CWR22) research specimens. Core personnel will procure, process and store clinical specimens of castration-recurrent prostate cancer obtained from men with advanced prostate cancer who present with urinary retention due to local recurrence. Research specimens will be used to construct tissue microarrays or laser capture microdissected for biochemical measurements of tissue androgens. Lastly, Core B will provide expert biostatistical (Dr. Wilding) and genitourinary pathological service (Dr. Alexiev) to the Program Project. Drs. Mohler and Smith will co-direct the facility and supervise the activities of individuals who already possess high levels of expertise and currently perform these functions for the Program Project. Drs. Wilding and Alexiev will lead the efforts to integrate biostatistical and pathological expertise into Core B and the 3 projects. The high level of function of Core B is demonstrated best by Core B's publication of 8 methods papers. Core B continues to develop new methods for more accurate measurement of protein expression (4 publications) and remains a leader in the use of TMAs for CaP research (2 publications). Core B has performed services that have resulted in manuscripts published, in press and submitted for Project 1 (20), Project 2 (8) and Project 3 (8). Core B also facilitates interaction among the Projects;12 of 23 publications involved more than 1 Project.

Public Health Relevance

Core B will continue to provide a high level of pathological, technical and biostatistical expertise to the Program Project to assist with management of research specimens, identification of histological sections, immunostaining and quantifying proteins of interest, and data analysis and presentation.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program Projects (P01)
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Special Emphasis Panel (ZCA1-RPRB-O)
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University of North Carolina Chapel Hill
Chapel Hill
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Frasinyuk, Mykhaylo S; Mrug, Galyna P; Bondarenko, Svitlana P et al. (2016) Antineoplastic Isoflavonoids Derived from Intermediate ortho-Quinone Methides Generated from Mannich Bases. ChemMedChem 11:600-11
Montecinos, Viviana P; Morales, Claudio H; Fischer, Thomas H et al. (2015) Selective targeting of bioengineered platelets to prostate cancer vasculature: new paradigm for therapeutic modalities. J Cell Mol Med 19:1530-7
Torres-Estay, Verónica; Carreño, Daniela V; San Francisco, Ignacio F et al. (2015) Androgen receptor in human endothelial cells. J Endocrinol 224:R131-7
Payne Ondracek, Rochelle; Cheng, Jinrong; Gangavarapu, Kalyan J et al. (2015) Impact of devascularization and tissue procurement on cell number and RNA integrity in prostatectomy tissue. Prostate 75:1910-5
Minges, John T; Grossman, Gail; Zhang, Ping et al. (2015) Post-translational Down-regulation of Melanoma Antigen-A11 (MAGE-A11) by Human p14-ARF Tumor Suppressor. J Biol Chem 290:25174-87
Koulikov, Dmitry; Mohler, Maura C; Mehedint, Diana C et al. (2014) Low detectable prostate specific antigen after radical prostatectomy--treat or watch? J Urol 192:1390-6
Wilton, John H; Titus, Mark A; Efstathiou, Eleni et al. (2014) Androgenic biomarker prof|ling in human matrices and cell culture samples using high throughput, electrospray tandem mass spectrometry. Prostate 74:722-31
Heemers, Hannelore V; Mohler, James L (2014) Words of wisdom. Re: Activity of cabazitaxel in castration-resistant prostate cancer progressing after docetaxel and next-generation endocrine agents. Eur Urol 66:597
Kim, Won; Zhang, Li; Wilton, John H et al. (2014) Sequential use of the androgen synthesis inhibitors ketoconazole and abiraterone acetate in castration-resistant prostate cancer and the predictive value of circulating androgens. Clin Cancer Res 20:6269-76
Tan, Jiann-an; Bai, Suxia; Grossman, Gail et al. (2014) Mechanism of androgen receptor corepression by CKβBP2/CRIF1, a multifunctional transcription factor coregulator expressed in prostate cancer. Mol Cell Endocrinol 382:302-13

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