PQ6: Therapeutic approaches for autonomic and neuroendocrine dysfunction in cancer cachexia

PQ6：癌症恶病质自主神经和神经内分泌功能障碍的治疗方法

• 批准号: 10490306
• 负责人: Daniel L. Marks
• 金额: $ 42.41万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-10 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10490306
• 关键词: Acute; Address; Adipose tissue; Adrenergic Agents; Adrenergic Receptor; Animals; Anorexia; Atrophic; Attenuated; Behavior; Behavioral; Body Weight decreased; Cachexia; Cancer Patient; Cardiac; Cardiovascular system; Catabolism; Chronic; Chronic Disease; Chronic stress; Clinical Trials Design; Collaborations; Corticosterone; Corticotropin-Releasing Hormone; Data; Disease; Energy Metabolism; Evolution; Exhibits; Fatigue; Functional disorder; Genetic; Glucocorticoids; Goals; Human; Hypothalamic structure; Impairment; Inflammatory; Intervention; Laboratories; Lead; Lethargies; Life; Malignant Neoplasms; Metabolic; Metabolic dysfunction; Metabolic syndrome; Metabolism; Modeling; Morbidity - disease rate; Motivation; Mus; Muscle; Muscular Atrophy; Nerve; Neuroendocrinology; Neurons; Neurosecretory Systems; Neurotransmitters; Norepinephrine; Observational Study; Organ; Organism; Output; Pancreatic Ductal Adenocarcinoma; Pathologic; Pathway interactions; Patients; Peripheral; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacology; Phase II Clinical Trials; Phenotype; Physical Function; Physiological; Plasma; Pre-Clinical Model; Prevention; Quality of life; Reagent; Research; Role; Savings; Sick Role; Signal Transduction; Skeletal Muscle; Stress; Sympathetic Nervous System; Systemic disease; Testing; Therapeutic; Therapeutic Intervention; Tissues; acute stress; behavioral phenotyping; behavioral response; biological adaptation to stress; cancer cachexia; cancer type; clinical translation; defined contribution; density; design; exercise intolerance; experience; functional decline; hypothalamic-pituitary-adrenal axis; metabolic phenotype; mortality risk; mouse model; neuroinflammation; new therapeutic target; novel; novel therapeutics; pancreatic cancer patients; pancreatic ductal adenocarcinoma model; prospective; response; synergism; systemic inflammatory response; therapeutically effective; tumor; tumor growth; wasting

Project Summary: Illness behaviors, metabolic disturbances, and cardiovascular compromise are common in patients with chronic systemic diseases, and contribute substantially to quality of life and ultimate survival. Other illness- induced morbidities including anorexia and lethargy also compromise the ability of patients to recover from life- saving or extending interventions, and diminish the motivational drive to aggressively battle the underlying condition. Although cachexia in cancer patients was described more than two thousand years ago, the central mechanisms underlying this disorder are poorly understood. Furthermore, there is currently no effective pharmaceutical treatment. Cardiovascular impairment is common in all chronic diseases, and can be a presenting complaint in cancer patients, even prior to initiation of therapy. Our laboratory is dedicated to unraveling the basic mechanisms whereby cancer triggers neuroinflammation and subsequent chronic activation of systemic stress responses in patients with cancer. In this proposal, we will focus on understanding the scope and mechanism by which systemic illness induces chronic activation and alteration in the sympathetic nervous system. The significance of this proposal resides in its unique combination of our historical focus on neuroendocrinology and neuroinflammation, with new collaborations and efforts directed at understanding the extent and mechanisms of cardiovascular impairment and sympathetic nervous system plasticity in patients with cancer. The long-term goal of our research is to gain mechanistic understanding of the acute illness response and how it is transitioned into chronic neuroinflammation in all cancer types, in order to develop more effective therapeutic interventions.

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