Biological & Environmental Mediators of Vitamin D and Aggressive Prostate Cancer

生物

• 批准号: 8727995
• 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/8727995
• 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; PC3 cell line; 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; 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).

描述（由申请人提供）： Murphy，AdamB。维生素D和侵略性前列腺癌的生物学和环境介质！候选人：亚当·墨菲（Adam Murphy）博士是一位学术泌尿科医师，两年前完成了居留权。亚当的目标是加深他的基础科学技能，成为一位全面的翻译科学家。他是由指导的国防部医师研究培训奖的最后一年，重点介绍了维生素D和相关的遗传多态性在前列腺癌荒地差异中的作用。 Kittles博士是DOD赠款准备亚当（Adam）领导相关协议和基于社区项目的主要导师。拟议方案提供的职业发展将加深他对免疫组织化学，标本加工，激光捕获微观截止，组织库，基因分型和基因表达分析的了解。当前的翻译项目着重于验证血清和前列腺维生素D作为抗癌剂，在人类前列腺癌肿瘤中具有治疗潜力。培训计划包括遗传流行病学，临床试验将激发他成为独立的翻译研究人员。环境：亚当在泌尿科系的杰西·布朗·弗吉尼亚州医学中心和西北大学有双重任命。此外，亚当现在在伊利诺伊大学芝加哥大学的研究员身份。一年多以前，安德烈·K·巴拉（Andre K.墨菲博士已与正确的研究人员和一个研究协调员在3个芝加哥地区机构进行了适当的合作。墨菲博士还为所有在杰西·布朗·弗吉尼亚州（Jesse Brown VA）的新诊断为前列腺癌的男性提供了每周的前列腺癌教育诊所，以提供教育，简化治疗途径并促进杰西·布朗泌尿外科诊所内的研究招募。研究：墨菲博士的研究方案集中在数据库分析，基本遗传数据分析和基于社区的参与式项目上。为了进行翻译，墨菲博士将通过该项目提供的培训和指导加深他的基础科学技能。摘要：维生素D在正常前列腺上皮细胞，前列腺癌细胞系和动物模型中具有抗癌特性。已知活化的维生素D，1,25二羟基维生素D，可减少增殖并促进前列腺癌细胞系中的凋亡。在几项流行病学研究中，维生素D缺乏症与前列腺癌的风险增加有关，在一些研究中，侵略性疾病。但是，由于正常前列腺具有羟基酶来激活和代谢维生素D。前列腺酶的维生素D水平可能无法准确反映前列腺中的维生素D水平。前列腺蛋白D。前列腺癌细胞系通常显示出伴有肿瘤进展的1-α羟基酶活性。因此，我们寻求1）使用260个前列腺切除术标本的表达前列腺分泌来验证血清维生素D作为局内维生素D水平的代理； 2）通过评估使用KI-67的维生素D tertile的癌症，估计维生素D对240个前列腺肿瘤增殖和凋亡率的影响，并使用Ki-67的效果，并在福尔马林固定石质上进行直接TUNEL分析组织; 3）评估维生素D代谢途径中相对基因表达的变化，五十个低级肿瘤（Gleason <6）与五十个高级肿瘤（Gleason 8-10）中的肿瘤进展变化。