Biological & Environmental Mediators of Vitamin D and Aggressive Prostate Cancer

生物

• 批准号: 8794426
• 负责人: Adam Bryant Murphy
• 金额: --
• 依托单位: JESSE BROWN VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8794426
• 关键词: 25-hydroxyvitamin D; Affect; African American; Analysis of Covariance; Animal Model; Antineoplastic Agents; Apoptosis; Apoptotic; Appointment; Area; Award; Basal Cell; Basic Science; Benign; Biological; Biological Assay; Biological Markers; Cell Culture Techniques; Cell Proliferation; Chicago; Clinic; Clinical; Clinical Trials; Collaborations; Communities; Confidence Intervals; Consultations; DNA Nucleotidylexotransferase; Data; Data Analyses; Databases; Department of Defense; Dihydroxycholecalciferols; Disease; Dissection; Education; Environment; Epidemiologic Studies; Epithelial; Epithelial Cells; Epithelium; Equation; Formalin; Freezing; Gene Expression; Gene Expression Profile; Gene Expression Profiling; Genes; Genetic; Genetic Polymorphism; Genotype; Gleason Grade for Prostate Cancer; Grant; Health Care Costs; Human; Illinois; Immunohistochemistry; In Vitro; Incidence; Institution; Intervention; Knowledge; Label; Lasers; Lead; Link; Malignant - descriptor; Malignant Epithelial Cell; Malignant Neoplasms; Malignant neoplasm of prostate; Measures; Mediator of activation protein; Medical center; Mentors; Mentorship; Metabolic Pathway; Metabolism; Methods; Mixed Function Oxygenases; Modeling; Newly Diagnosed; Normal Range; Outcome; PSA Velocity; Paraffin Embedding; Pathway interactions; Patients; Pattern; Phase; Physicians; Population; Property; Prostate; Prostate carcinoma; Prostatectomy; Prostatic; Prostatic Neoplasms; Protocols documentation; Proxy; RNA; Race; Radical Prostatectomy; Relative (related person); Research; Research Personnel; Research Training; Residencies; Reverse Transcription; Risk; Role; Sample Size; Scientist; Serum; Slide; Specimen; Specimen Handling; Staging; Staining method; Stains; Testing; Therapeutic; Therapeutic Uses; Time; Tissue Banking; Tissue Banks; Tissues; Training; Transferase; Universities; Urologist; Urology; Veterans; Visit; Vitamin D; Vitamin D Analog; Vitamin D Deficiency; Vitamin D3 Receptor; Vitamins; Width; abstracting; androgen independent prostate cancer; base; cancer cell; cancer education; career development; epidemiologic data; gene discovery; genetic epidemiology; health administration; high risk; in vitro testing; in vivo; insight; laser capture microdissection; meetings; men; mortality; outcome forecast; prevent; prostate cancer cell line; public health relevance; skills; tumor; tumor progression

DESCRIPTION (provided by applicant): Murphy, Adam B. Biological and Environmental Mediators of Vitamin D and Aggressive Prostate Cancer! Candidate: Dr. Adam Murphy is an academic urologist who completed residency two years ago. Adam aims to deepen his basic science skills to be a well-rounded translational scientist. He is in his final year of a mentored Department of Defense Physician Research Training Award focused on the role of vitamin D and related genetic polymorphisms in prostate cancer heath disparities. Dr. Kittles is the primary mentor on his DOD grant prepared Adam to lead related protocols and community-based projects. The career development provided by the proposed protocol would deepen his knowledge of immunohistochemistry, specimen processing, laser capture micro-dissection, tissue banking, genotyping and gene expression analysis. The current translational project focuses on validating serum and prostatic vitamin D as an anti-cancer agent with therapeutic potential in human prostate cancer tumors. The training plan includes Genetic Epidemiology and Clinical Trials will spur him to be an independent translational researcher. Environment: Adam has dual appointments at Jesse Brown VA Medical Center and Northwestern University in the Department of Urology. Also, Adam now has visiting researcher status at University of Illinois at Chicago. Dr. Andre K. Balla and Adam met over a year ago and have planned this protocol jointly with consultation from Dr. Kittles. Dr. Murphy has developed appropriate collaborations across 3 Chicago area institutions with the right researchers and a study coordinator. Dr. Murphy also developed a weekly Prostate Cancer Education Clinic for all men with newly diagnosed prostate cancer at Jesse Brown VA to provide education, to streamline the pathway to treatment and to facilitate research recruitment within the Jesse Brown Urology clinics. Research: Dr. Murphy's research protocols have been focused on database analysis, basic genetic data analysis and community based participatory projects. In order to be translational, Dr. Murphy will deepen his basic science skill set by training and mentorship provided by this project. Abstract: Vitamin D has anti-cancer properties in vitro in normal prostate epithelial cells, in prostate cancer cell lines, and in animal models. Activated vitamin D, 1,25 dihydroxyvitamin D, is known to reduce proliferation and promote apoptosis in prostate cancer cell lines. In several epidemiologic studies, vitamin D deficiency is associated with increased risk of prostate cancer and in some studies, aggressive disease. However serum vitamin D levels may not accurately reflect the vitamin D levels in the prostate as the normal prostate has the hydroxylases to activate and metabolize vitamin D. Prostate cancer cell lines have been shown to commonly lose 1-alpha hydroxylase activity with tumor progression. Therefore we seek to 1) validate serum vitamin D as a proxy for intra-prostatic vitamin D levels using the expressed prostatic secretion from 260 prostatectomy specimen; 2) estimate the effect of vitamin D on rates of proliferation and apoptosis in 240 prostate tumors by evaluating percentage of cancer cells undergoing proliferation and apoptosis as a function of vitamin D tertile using a Ki-67 and a direct TUNEL assay on formalin fixed paraffin embedded tissue; 3) evaluate for changes in relative gene expression in the vitamin D metabolic pathway with tumor progression in fifty low grade tumors (Gleason < 6) versus fifty high grade tumors (Gleason 8-10).

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