A majority of aging men develop benign and/or malignant prostatic growth. One out of six American men is diagnosed with prostate cancer in his lifetime, and 1/2 develops benign prostatic hyperplasia (BPH). The Prostate Cancer Prevention Trial recently demonstrated a 25% incidence of prostate cancer in U.S. men >55 years of age over a 7 year period. Currently used screening tests (serum prostate-specific antigen (PSA) and digital rectal exam) have shown only modest predictive value, and serum PSA isoforms have added little specificity. Body fluids such as urine may contain molecular information regarding the presence of prostate cancer. I propose to study several recently-identified molecular changes commonly associated with prostate neoplasia as biomarkers for prostate cancer in urine, in the hopes of improving the specificity of noninvasive detection efforts. Three urinary analyses will form the cornerstones of this study: methylation of DNA at CpG islands of the pi-class glutathione-s transferase (GSTP1) promoter, a noncoding RNA """"""""differential display 3"""""""" (DD3), and the protein alpha methylacyl CoA racemase (AMACR). My main aim is to learn how to evaluate and study new cancer biomarkers. As a urologic surgeon with a background in molecular biology, this will require formal training in biostatistics, study design, biomarker applications, and data analysis. My institution and department are supporting my efforts to formally study biomarkers and also develop a clinical expertise in prostate disease. My department has created many leaders in prostate disease research due to its productive, translational, and open research environment. The sponsorship of two world leaders in prostate cancer and BPH, and regular didactic interactions with them and a prostate cancer biostatistician, will allow my career training goal to be met. Over a 5-year period of study, I will have learned how to critically evaluate biomarkers, collect biomarker data, and interpret it properly. Hopefully, useful biomarker information for prostate cancer will also result from my period of study.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Mentored Patient-Oriented Research Career Development Award (K23)
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Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
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Rankin, Tracy L
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Johns Hopkins University
Schools of Medicine
United States
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Fujita, Kazutoshi; Ewing, Charles M; Isaacs, William B et al. (2011) Immunomodulatory IL-18 binding protein is produced by prostate cancer cells and its levels in urine and serum correlate with tumor status. Int J Cancer 129:424-32
Hyndman, Matthew Eric; Mullins, Jeffrey K; Pavlovich, Christian P (2010) Pelvic node dissection in prostate cancer: extended, limited, or not at all? Curr Opin Urol 20:211-7
Fujita, Kazutoshi; Ewing, Charles M; Getzenberg, Robert H et al. (2010) Monocyte chemotactic protein-1 (MCP-1/CCL2) is associated with prostatic growth dysregulation and benign prostatic hyperplasia. Prostate 70:473-81
Fujita, Kazutoshi; Pavlovich, Christian P; Netto, George J et al. (2009) Specific detection of prostate cancer cells in urine by multiplex immunofluorescence cytology. Hum Pathol 40:924-33
Fujita, Kazutoshi; Ewing, Charles M; Chan, David Y S et al. (2009) Endoglin (CD105) as a urinary and serum marker of prostate cancer. Int J Cancer 124:664-9
Fujita, Kazutoshi; Ewing, Charles M; Sokoll, Lori J et al. (2008) Cytokine profiling of prostatic fluid from cancerous prostate glands identifies cytokines associated with extent of tumor and inflammation. Prostate 68:872-82