Anti-oxidant treatment of muscle wasting and fatigue in tumor-bearing mice

荷瘤小鼠肌肉萎缩和疲劳的抗氧化治疗

基本信息

批准号：
8129899
负责人：
Yvonne Yumiko Clark
金额：
$ 3.56万
依托单位：
OHIO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-08-01 至 2013-10-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8129899
关键词：
Academic Medical Centers Affect Aftercare Aging Animal Cancer Model Animal Model Animals Antioxidants Area Behavior Biological Markers Cancer Etiology Cancer Patient Carcinoma Cardiac Catabolism Cell membrane Cells Chronic Clinical Clinical Trials Coenzyme Q10 Digestion Disease Distress Echocardiography Electron Transport Enzyme-Linked Immunosorbent Assay Fatigue Functional disorder Gastrocnemius Muscle Goals Healthcare Heart Neoplasms Heat shock proteins Human Inflammatory Inflammatory Response Interleukin-6 Intervention Laboratories Lead Limb structure Lipids Malignant Neoplasms Measures Mitochondria Modeling Mus Muscle Muscle Cells Muscle Proteins Muscle Weakness Muscle function Muscular Atrophy Myocardial Myocardial dysfunction Myocardium Myomatous neoplasm Myosin ATPase Nurses Organelles Oxidative Stress Pathway interactions Patients Persons Physical activity Play Production Protein Biosynthesis Proteins Quality of life Radiation therapy Reactive Oxygen Species Reporting Research Rodent Role Running Scientist Serum Skeletal Muscle Symptoms TNFRSF1A gene Techniques Testing Training Treatment-Related Cancer Tumor Necrosis Factor-alpha cancer therapy career chemotherapy cytokine effective therapy grasp heart function improved in vivo knowledge base muscle form muscle strength oxidative damage prevent protein degradation protein expression receptor skeletal muscle wasting social stress protein symptom management tumor tumor growth wasting

项目摘要

DESCRIPTION (provided by applicant): Fatigue is the most common and the most distressing symptom reported by cancer patients during and after anti-tumor treatments. There are no effective treatments for cancer related fatigue (CRF) and more information about its causes are needed in order to develop and test new treatments. A large body of evidence has shown that tumor growth increases serum levels of pro-inflammatory cytokines that increase expression and activity of catabolic pathways implicated in skeletal muscle wasting. Tumor growth and pro-inflammatory cytokines also increase production of reactive oxygen species (ROS) in muscle cells, which can also activate these same catabolic pathways of muscle wasting. The loss of muscle mass contributes to muscle weakness, while oxidative stress reduces contraction force in muscle cells. There is preliminary evidence in tumor-bearing rodents that oxidative stress and contractile dysfunction also occur in the myocardium. There is some evidence that pretreatment with an anti-oxidant prevents cytokine-induced catabolism and contractile dysfunction in muscle cells. Coenzyme Q10 (coQ10) is a naturally occurring anti-oxidant in mitochondria of cells that is depleted during the inflammatory response. The purpose of this study is to test the hypothesis that treatment with CoQ10 will reduce muscle wasting and improve contractile function of skeletal and heart muscle of tumor-bearing mice. The applicant will use laboratory techniques of ELISA, PCR, and echocardiography to evaluate muscle wasting and muscle function in tumor-bearing mice, and measures of wheel running activity and grip strength to model behaviors of fatigue and weakness. Symptom management is a research emphasis area of the NINR, and the findings of this study will contribute to the knowledge base needed to test clinical interventions to reduce fatigue in cancer patients. Demonstration of myocardial dysfunction in this animal model of tumor-induced fatigue will impact how clinicians evaluate and treat patients with CRF. The applicant will receive strong laboratory training in biomarkers of muscle wasting and muscle dysfunction, as well as clinical trials research to prepare her for a career as a nurse scientist in a large academic medical center. PUBLIC HEALTH RELEVANCE: Fatigue is the most common and most distressing symptom reported by cancer patients before and after treatment, negatively affecting their quality of life. Fatigue also increases the social and financial burden of health care for cancer patients. This study will examine the role of cardiac dysfunction, and the effect of anti-oxidant treatment in an animal model of cancer- related fatigue.

描述（由申请人提供）：疲劳是癌症患者在抗肿瘤治疗期间和之后报告的最常见和最令人痛苦的症状。没有有效的有关癌症相关疲劳（CRF）的治疗方法，需要更多有关其原因的信息，以开发和测试新的治疗方法。大量证据表明，肿瘤的生长增加了促炎性细胞因子的血清水平，从而增加了与骨骼肌浪费有关的分解代谢途径的表达和活性。肿瘤生长和促炎细胞因子还增加了肌肉细胞中活性氧（ROS）的产生，这也可以激活这些相同的肌肉浪费分解代谢途径。肌肉质量的丧失会导致肌肉无力，而氧化应激减少了肌肉细胞的收缩力。有初步的证据表明，肿瘤啮齿动物表明氧化应激和收缩功能障碍也发生在心肌中。有证据表明，用抗氧化剂预处理可防止细胞因子诱导的分解代谢和肌肉细胞的收缩功能障碍。辅酶Q10（COQ10）是在炎症反应期间耗尽的线粒体中天然存在的抗氧化剂。这项研究的目的是检验以下假设：COQ10的治疗将减少肌肉浪费并改善肿瘤小鼠骨骼和心肌的收缩功能。申请人将使用ELISA，PCR和超声心动图的实验室技术来评估肿瘤小鼠中的肌肉浪费和肌肉功能，并测量车轮跑步活动和抓地力，以模拟疲劳和虚弱的行为。症状管理是NINR的研究重点，这项研究的结果将有助于测试临床干预措施所需的知识库，以减少癌症患者的疲劳。在这种肿瘤诱导的疲劳动物模型中，心肌功能障碍的证明将影响临床医生评估和治疗CRF患者的方式。申请人将在肌肉浪费和肌肉功能障碍的生物标志物以及临床试验研究中接受强大的实验室培训，以准备她在大型学术医学中心担任护士科学家的职业。公共卫生相关性：疲劳是治疗前后癌症患者报告的最常见和最令人痛苦的症状，对他们的生活质量产生负面影响。疲劳还增加了癌症患者医疗保健的社会和经济负担。这项研究将检查心脏功能障碍的作用，以及抗氧化剂治疗在癌症相关疲劳模型中的作用。