Cancer-Related Fatigue and the Adaptive Response to Oxidative Stress

癌症相关的疲劳和对氧化应激的适应性反应

• 批准号: 9751397
• 负责人: Kristin Ashley Dickinson
• 金额: $ 24.9万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9751397
• 关键词: Acute; Address; Apoptosis; Area; Autophagocytosis; Award; Bioinformatics; Biologic Development; Biological; Biological Assay; Blood Cells; Blood specimen; Cancer Etiology; Cellular Stress; Cellular Stress Response; Chemotherapy-Oncologic Procedure; Chronic; Clinical; Clinical Research; Data; Detection; Electron Transport Complex III; Enzymes; Event; Expression Profiling; External Beam Radiation Therapy; Extramural Activities; Fatigue; Funding; Gene Expression; Genes; Genetic; Genetic Markers; Goals; Homeostasis; In Vitro; Individual; Institutional Review Boards; Investigation; Knowledge; Laboratories; Laboratory Research; Lead; Link; Malignant Neoplasms; Methods; Mitochondria; Modeling; Nature; Necrosis; Nonmetastatic; Nurses; Oxidative Phosphorylation; Oxidative Stress; Pathway interactions; Patients; Performance; Phenotype; Principal Investigator; Production; Prognostic Marker; Questionnaires; Radiation; Radiation exposure; Reactive Oxygen Species; Reporting; Research; Research Personnel; Research Proposals; Research Training; Risk; Role; Scientist; Symptoms; Tissue-Specific Gene Expression; Training; base; biological adaptation to stress; cancer risk; cancer therapy; career; career development; clinically significant; cost; differential expression; experience; follow-up; genetic analysis; interdisciplinary collaboration; meetings; men; novel; oncology; peripheral blood; precision medicine; prognostic; programs; response; side effect; skills; standard of care; symptom science; therapeutic target; translational scientist

The candidate proposes a career development Pathway to Independence Award to further advance her laboratory and clinical research skills in the area of symptom science research. Each aim of the proposal is supported by didactic coursework, research training experiences, scientific meetings and seminars, and a detailed dissemination plan. The candidate’s ultimate career goal is to become an independent, extramurally-funded nurse scientist with expertise in biological underpinnings of cancer-related fatigue (CRF), one of the most commonly reported side effects of cancer and its treatment. The etiology of CRF is poorly understood and there is no clear, single, clinical definition. The purpose of this proposal is to identify cellular stress response genes that define a unique external beam radiation therapy (EBRT)-related fatigue phenotype. The K99 period of the proposal will focus on identifying a cluster of cellular stress response genes from the peripheral blood cells of men who are at risk to develop acute clinically-significant fatigue during EBRT for non-metastatic prostate cancer (NM-PC) and validating the functional role of these differentially expressed genes in cellular energy production using an in vitro radiation-induced cell stress model. The R00 period will identify a cluster of cell stress response genes from peripheral blood cells of men who are at risk to develop persistent clinically-significant fatigue months after completion of EBRT for NM-PC and to identify genes at EBRT completion that can serve as prognostic markers of persistent fatigue. Questionnaire data assessing CRF and peripheral blood samples for genetic analysis will be collected during EBRT and following EBRT completion. The overall goal of this K99/R00 research proposal is to provide the candidate with expertise in advancing symptom science through the performance and interpretation of genetic assays under the guidance of an experienced team of scientists. The findings from the K99/R00 investigations will optimize precision medicine in oncology by identifying prognostic genetic markers that can define a unique EBRT-related fatigue phenotype, as well as identify biologically-relevant therapeutic targets to manage EBRT-related fatigue.

候选人提出职业发展途径独立奖，以进一步推动她 症状科学研究领域的实验室和临床研究技能。提案的每一个目标都是 由教学课程、研究培训经验、科学会议和研讨会以及 详细的传播计划。候选人的最终职业目标是成为一名独立的、获得外部资助的人 一位护士科学家，在癌症相关疲劳（CRF）的生物学基础方面具有专业知识， 最常报告的癌症及其治疗的副作用。CRF的病因学知之甚少， 没有明确、单一的临床定义。这个建议的目的是确定细胞应激反应 定义独特的外部束放射治疗（EBRT）相关疲劳表型的基因。 K99时期的建议将集中在确定一组细胞应激反应基因 来自有发生急性临床显著疲劳风险的男性的外周血细胞 EBRT用于非转移性前列腺癌（NM-PC），并验证这些差异的功能作用 使用体外辐射诱导的细胞应激模型在细胞能量产生中表达基因。R00 该项目将从有风险的男性外周血细胞中鉴定出一组细胞应激反应基因， 在完成NM-PC的EBRT后数月出现持续性临床显著性疲乏，并确定 EBRT完成时的基因，可以作为持续性疲劳的预后标志物。问卷数据 在EBRT期间和之后，将收集用于评估CRF和进行遗传分析的外周血样本 EBRT完成。本K99/R 00研究提案的总体目标是为候选人提供 通过执行和解释基因检测来推进症状科学的专业知识 一个经验丰富的科学家团队的指导。K99/R 00调查的结果将优化 通过识别可以定义独特EBRT相关的预后遗传标记， 疲劳表型，以及确定生物学相关的治疗靶点，以管理EBRT相关的 疲劳