Defining an Integrated Allostatic Load Index with Immune and Tumor Microenvironment Factors

定义具有免疫和肿瘤微环境因素的综合稳态负荷指数

• 批准号: 9145866
• 负责人: RICHARD R. DRAKE
• 金额: $ 25.71万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-08 至 2021-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9145866
• 关键词: African American; Age; Archives; Behavior; Biological; Biological Assay; Biological Markers; Biological Process; Cancer Control; Cells; Chronic stress; Clinical Management; Complex; Data; Decision Making; Development; Diagnostic Neoplasm Staging; Disease; Disease Progression; Early Diagnosis; Epidemiology; Equilibrium; Gleason Grade for Prostate Cancer; Glucocorticoids; Goals; Guidelines; IL8 gene; Image; Immune; Immune Sera; Immune system; Inflammatory; Interleukin-6; Link; Malignant neoplasm of prostate; Maps; Mass Spectrum Analysis; Medical; Minority; Molecular; Outcome; Pathway interactions; Performance; Physiological; Play; Polysaccharides; Population; Prostate-Specific Antigen; Prostatic Neoplasms; Recurrence; Research; Research Personnel; Research Project Grants; Resources; Risk; Role; Sampling; Serum; Social Conditions; South Carolina; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Stress; Surface; Testing; Tissues; Tumor Volume; Tumor stage; Universities; allostatic load; base; biological adaptation to stress; biomarker panel; cancer biomarkers; cancer health disparity; cancer initiation; clinical decision-making; cohort; contextual factors; cytokine; early detection biomarkers; immune function; indexing; innovation; male health; men; precision medicine; psychologic; racial disparity; response; screening; social; socioeconomics; stressor; tumor; tumor microenvironment; tumor progression; two-dimensional

RESEARCH PROJECT 2- PROJECT SUMMARY The goal of this MUSC TCC project is to develop more precise biomarkers of prostate cancer initiation and progression, and determine how to treat and manage prostate cancer among minority men within the context of their biological risk for poor outcomes and social, psychological, and physiological (i.e., allostatic load/AL) stressors. This will be done using several new innovative experimental approaches directly on archived tissues unique to MUSC, using a rich resource cohort of samples (n=570) representing approximately one third African American (AA) subjects. Based on the epidemiology of prostate cancer among AA men (already described in the proposal), considerable efforts have been made to promote early detection through screening with prostate specific antigen (PSA) testing. Recently, however, screening guidelines have shifted from performance of annual screening starting at age 50 to informed decision-making as new data have emerged about the efficacy of PSA testing. As early detection plays a less prominent role in prostate cancer control, it becomes even more important to identify biological pathways that are activated in the initiation and progression of disease and develop more effective biomarkers for early detection. Several prior studies have shown that there is a complex interplay between the tumor microenvironment and the immune system that contributes to the development of more aggressive prostate cancer among AA men. However, biological processes related to immune functioning operate within and are influenced by social contextual factors. Thus, identifying biological mechanisms without understanding the ways in which they are associated with social determinants is necessary, but not sufficient to long-term efforts to reduce racial disparities in prostate cancer outcomes through early detection and clinical management of disease. An emerging hypothesis central to this application about cancer health disparities is that social conditions and psychological responses to social stressors influence biological processes that are important to the initiation and progression of cancer. In this project, MUSC investigators will examine this hypothesis through a transdisciplinary study that defines the molecular mechanisms involved in the initiation and progression of prostate cancer by evaluating the tumor microenvironment interactions between the immune system, the tumor glycome, social determinants and AL. These investigators will determine whether the combination of distinct tumor and stroma N-glycans in prostate cancers of AA men promotes a more pro-tumor inflammatory/immune microenvironment. They will also examine the relationship between these biological processes and social determinants that include isolation, perceived stress, and chronic socioeconomic stressors. They hypothesize that a combination of stress- inducing social determinants, distinct N-glycans, impaired immune/inflammatory balance contributes to more aggressive prostate cancers in the AA population.

研究项目2-项目摘要 这个MUSC TCC项目的目标是开发更精确的前列腺癌启动和 进步，并确定如何在少数族裔男性中治疗和管理前列腺癌 他们对不良结果以及社会，心理和生理学的生物学风险 压力源。这将使用直接在存档组织上的几种新的创新实验方法来完成 MUSC独有的，使用丰富的样品队列（n = 570）代表大约三分之一的非洲人 美国（AA）主题。基于AA男性的前列腺癌的流行病学（已经在 提案），通过与 前列腺特异性抗原（PSA）测试。但是，最近，筛查指南已从性能转变 从50岁开始的年度筛查，随着新数据的出现，以了解决策 PSA测试的功效。随着早期检测在前列腺癌控制中起不太突出的作用，它变成了 确定在开始和进展中激活的生物学途径更为重要 疾病并开发更有效的生物标志物来早期检测。几项先前的研究表明 肿瘤微环境与免疫系统之间存在复杂的相互作用，这有助于 AA男性中更具侵略性的前列腺癌的发展。但是，生物过程 与免疫功能相关的内部运作并受社会背景因素的影响。因此，识别 生物学机制而不了解与社会决定因素相关的方式 是必要的，但不足以长期努力减少前列腺癌预后的种族差异 通过疾病的早期检测和临床管理。该应用程序的新兴假设 关于癌症健康差异是社会状况和对社会压力源的心理反应 影响对癌症开始和进展至关重要的生物学过程。在这个项目中， MUSC研究人员将通过一项跨学科研究来检验这一假设，该研究定义了分子 通过评估肿瘤参与前列腺癌的启动和进展的机制 免疫系统，肿瘤糖，社会决定因素和AL之间的微环境相互作用。 这些研究人员将确定前列腺中不同肿瘤和基质N-聚糖的组合是否 AA男子的癌症促进了更促肿瘤的炎症/免疫微环境。他们也会 检查这些生物过程与社会决定因素之间的关系，包括隔离， 感知的压力和慢性社会经济压力源。他们假设应力的结合 诱导社会决定因素，独特的N-聚糖，免疫/炎症平衡受损有助于更多 AA人群中的侵略性前列腺癌。