Investigating Correlates and Therapeutics of Fatigue in Cancer Patients

研究癌症患者疲劳的相关性和治疗方法

• 批准号: 10013012
• 负责人: Leorey Saligan
• 金额: $ 171.14万
• 依托单位: NATIONAL INSTITUTE OF NURSING RESEARCH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10013012
• 关键词: Action Potentials; Affective; Alcohol consumption; Animals; Anxiety; Behavioral; Biological Markers; Blood specimen; Cancer Fatigue; Cancer Patient; Cardiovascular Physiology; Chronic Disease; Clinic; Clinical Research; Cognitive; Communities; Coupling; Data; Dimensions; Disease; Emotional; Energy Metabolism; Enrollment; Etiology; Exertion; Failure; Fatigue; Functional disorder; Gene Expression; Glutamates; Glycolysis; IL8 gene; Immunotherapy; Impairment; In Vitro; Individual; Inflammation; Inflammatory; Insulin-Like Growth Factor I; Interleukin-6; Investigation; Laboratories; Life Experience; Literature; Longitudinal Studies; Malignant Neoplasms; Malignant neoplasm of prostate; Measures; Mental Depression; Molecular; Molecular Genetics; Muscle; Muscle Fibers; National Cancer Institute; Neuraxis; Observational Study; Oxygen Consumption; Pain; Participant; Patient Care; Patient Self-Report; Patients; Performance at work; Peripheral; Personal Satisfaction; Physiological; Primary Health Care; Psyche structure; Psychosocial Factor; Research; Rest; Risk; Risk Factors; Role; Sensory; Serotonergic System; Skeletal Muscle; Symptoms; TNF gene; Therapeutic; Time; Tissue Sample; Tobacco use; United States National Institutes of Health; Validation; base; cancer therapy; chemotherapy; cognitive function; cost; cytokine; diet and exercise; disabling symptom; economic outcome; experience; experimental study; health economics; health related quality of life; hormone therapy; lifestyle factors; multidisciplinary; muscle strength; negative affect; neural stimulation; peripheral blood; prospective; receptor; recruit; relating to nervous system

Fatigue is a multidimensional symptom that impacts 38% of community-based individuals and 42% of primary care patients. It is one of the most common and most debilitating symptoms in chronic illness and in cancer. It has significant repercussions on both direct and indirect health economic outcomes, costing an estimated annual lost productive time of US$330 million mostly due to reduced work performance. In cancer, fatigue had the greatest negative impact on daily activity, physical well-being/function, and relationships with significant others. Fatigue is described as a persistent, subjective sense of tiredness that interferes with usual functioning. It can be distinguished from normal everyday tiredness, because it is more frequent, unrelenting, unpredictable, and unresolved by rest. Fatigue may be influenced by a combination of physiological factors (e.g., inflammation or central nervous system dysfunction), psychosocial factors (e.g., depression or anxiety), and lifestyle factors (e.g., diet, exercise, alcohol use, tobacco use, or social role). Fatigue also co-occurs with other symptoms (e.g., pain, depression) contributing to symptom burden, which negatively affects health-related quality of life of patients. The etiology of fatigue is unknown, but it is believed to have central and peripheral components. Central fatigue is hypothesized to result from a decrease in central nervous system drive brought about by serotonergic pathways limiting muscle fiber recruitment during exertion reducing muscle glycolysis, oxygen consumption, and cardiovascular function. Peripheral fatigue is the inability of a particular muscle to perform a task even with an increased neural drive. This is thought to be caused by an action potential failure, cross-bridge formation impairment, or excitation contraction coupling failure amidst increased neural stimulation. The interplay between central and peripheral types of fatigue remains unclear although an increasing body of literature has indicated a potential interaction of both mechanisms. The research team continues to enroll participants for their studies that investigate the molecular-genetic correlates, as well as possible therapeutics of cancer-related fatigue. The group recently made significant discoveries related to the activation of glutamatergic receptors associated with cancer therapy that trigger inflammation that may explain the fatigue experience related to cancer therapy. Further validation is being conducted through clinical studies, animal projects and in vitro experiments. The PI is working closely with collaborators from the Multidisciplinary Prostate Cancer Clinics of the National Cancer Institute to continue to recruit study participants. The study team is also collaborating with several NIH core laboratories to further their investigations.

疲劳是一种多维症状，影响了38％的基于社区的人和42％的初级保健患者。它是慢性疾病和癌症中最常见，最令人衰弱的症状之一。它对直接和间接的健康经济成果都产生了重大影响，估计每年损失的生产时间为3.3亿美元，主要是由于工作绩效降低。在癌症中，疲劳对日常活动，身体健康/功能以及与其他重要人物的关系产生了最大的负面影响。疲劳被描述为一种持续的，主观的疲倦感，会干扰通常的功能。它可以与普通的日常疲倦区分开，因为它更频繁，不柔韧，不可预测且无法解决。疲劳可能会受到生理因素（例如炎症或中枢神经系统功能障碍），社会心理因素（例如抑郁症或焦虑症）和生活方式因素（例如饮食，运动，锻炼，酒精使用，烟草使用或社会角色）的影响。疲劳还与其他症状（例如疼痛，抑郁症）共同出现，导致症状负担，这会对患者的健康相关生活质量产生负面影响。疲劳的病因尚不清楚，但据信具有中央和外围成分。假设中枢疲劳是由于抑制肌肉纤维招募在减少肌肉糖酵解，氧合消耗和心血管功能的肌肉纤维招募所带来的中枢神经系统驱动器导致的降低而导致的。外围疲劳是即使神经驱动增加，特定肌肉也无法执行任务。这被认为是由动作潜在失败，跨桥的形成障碍或激发收缩偶联失败在增加神经刺激中引起的。尽管文献越来越多，但疲劳的中央类型之间的相互作用仍不清楚，这表明两种机制的潜在相互作用。 研究小组继续为参与者提供研究，以研究分子遗传学相关性以及与癌症相关疲劳的可能治疗学。该小组最近发现了与癌症治疗相关的谷氨酸能受体激活有关的大量发现，这些发现会引发炎症，这可能解释了与癌症治疗有关的疲劳经历。正在通过临床研究，动物项目和体外实验进行进一步的验证。 PI正在与国家癌症研究所多学科前列腺癌诊所的合作者紧密合作，以继续招募研究参与者。研究团队还与几个NIH核心实验室合作，以进一步进行调查。