Sociobiological Responses to Stress in Prostate Cancer Survivors

研究项目1：项目总结 下丘脑-垂体-肾上腺轴的失调被认为是一种机制， 社会和生物因素造成了癌症结果的种族差异。一个长期的和升高的 糖皮质激素（GC）反应后的社会压力预测肿瘤的生长速度和发展 在组织学和病因学上类似于人类疾病的啮齿动物癌症。GC的反应是一个关键 非稳态负荷的生物标志物，其是对压力源的生物反应的量度。许多非洲裔美国人 经历紧张的生活事件和环境，包括经济，歧视和其他压力因素。 这些心理社会因素可能导致非洲人经历的有据可查的较差结果。 美国男性前列腺癌患者然而，应激反应（SR），或一个人的生理和心理 对压力源的反应是高度个性化的，依赖于心理和社会决定因素， 以及遗传因素。MUSC的研究人员将研究SR在免疫发展中的作用。 参与前列腺疫苗试验的受试者对前列腺癌的反应。审判本身将是 进行记录痘病毒疫苗（PROSTVAC）对癌症生长和免疫的影响， 根治性直肠癌切除术后患者的反应。MUSC研究人员将能够研究这些 受试者确定压力和压力源的水平，以及使用经验证的心理学方法的可行性。 方法来描述这些参数在老年男性。本研究的具体目的是：（1）开展一项 PROSTVAC疫苗在根治性直肠癌切除术后高复发风险受试者中的II期临床试验 前列腺癌作为一个平台，以评估SR对开发有效的抗肿瘤药物的影响 免疫应答;（2）基于以下指标测量有复发风险前列腺癌患者的应激反应性： 社会经济地位，糖皮质激素受体（GR）多态性，对社会压力的感知， 非稳态负荷;和（3）比较临床和 疫苗效果的免疫学指标。这项临床试验将提供一个“真实的世界”的免疫治疗设置 以及前列腺癌患者在经历急性癌症时的免疫反应发展- 相关的紧张性刺激（例如，复发风险）。此外，本研究还将提供关于 频率和种类的压力在前列腺癌幸存者，他们的生理反应，以验证 实验室应激源，以及SR与临床、基因组和免疫学参数之间的关系 在免疫治疗中很重要。

RESEARCH PROJECT 1: PROJECT SUMMARY Dysregulation of the hypothalamic-pituitary-adrenal axis has been suggested as a mechanism through which social and biological factors contribute to racial disparities in cancer outcomes. A prolonged and elevated glucocorticoid (GC) response following a social stressor predicts tumor growth rates and the development of rodent cancers that histologically and etiologically resembles human disease. The GC response is a key biomarker for allostatic load, which is a measure of biological responses to stressors. Many African Americans experience stressful life events and circumstances, including economic, discriminatory, and other stressors. These psychosocial factors may contribute to the well-documented poorer outcomes experienced by African American men with prostate cancer. However stress reactivity (SR), or one's physiological and psychological responses to a stressor, is highly individualized and dependent on psychological and social determinants as well as genetic factors. Investigators at MUSC will investigate the role of SR in the development of immune responses to prostate cancer among subjects participating in a prostate vaccine trial. The trial itself will be conducted to document the effects of a poxvirus vaccine (PROSTVAC) on the cancer growth and immune responses of patients immediately after radical prostatectomy. MUSC investigators will be able to study these subjects to determine the levels of stress and stressors and the feasibility of using validated psychologic methods to characterize these parameters in older men. The specific aims of this study are to: (1) conduct a Phase II clinical trial of PROSTVAC vaccine in subjects at high risk of relapse after radical prostatectomy for prostate cancer as a platform to evaluate the effects of SR on the development of an effective anti-tumor immune response; (2) measure stress reactivity among prostate cancer patients at risk for relapse based on socioeconomic status, glucocorticoid receptor (GR) polymorphisms, perceptions of social stressors, and allostatic load; and (3) compare the magnitude and distribution of stress responses with clinical and immunologic measures of vaccine effect. This clinical trial will provide a “real world” setting of immunotherapy and immune response development in prostate cancer patients as they are experiencing an acute cancer- related stressor (e.g., risk for recurrence). In addition, this research will provide novel empirical data on the frequency and kinds of stress in prostate cancer survivors, their physiological responses to a validated laboratory stressor, and the associations between SR and clinical, genomic, and immunologic parameters important in immunotherapy.