PQ6: Lipocalin-2 as a therapeutic target for prevention of cancer cachexia

PQ6：Lipocalin-2 作为预防癌症恶病质的治疗靶点

• 批准号: 10379260
• 负责人: Daniel L. Marks
• 金额: $ 38.58万
• 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: 2021-04-01 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10379260
• 关键词: Acute; Address; Adipose tissue; Agonist; Amplifiers; Animals; Anorexia; Attenuated; Automobile Driving; Bacterial Infections; Behavior; Behavioral; Blood - brain barrier anatomy; Body Weight decreased; Bone Marrow; Brain; Cachexia; Cancer Patient; Cells; Chronic; Chronic Disease; Collaborations; Data; Desire for food; Development; Disease; Encephalitis; Endocrine; Endothelium; Event; Evolution; Fatigue; Goals; Growth; Hippocampus (Brain); Hypothalamic structure; Immune; Impaired cognition; In Vitro; Inflammation; Inflammatory; Inflammatory Response; Injury; Intervention; Iron; LCN2 gene; Laboratories; Lethargies; Life; Malignant Neoplasms; Melanocortin 4 Receptor; Metabolic; Metabolism; Morbidity - disease rate; Motivation; Muscle; Muscular Atrophy; Myeloid Cells; Neuraxis; Neurocognitive; Neurocognitive Deficit; Neuroendocrinology; Neurologic; Neurons; Pancreatic Ductal Adenocarcinoma; Pathogenesis; Pathologic; Pathology; Pathway interactions; Patients; Peripheral; Pharmacologic Substance; Physiological; Play; Population; Prevention; Process; Production; Proteins; Publications; Quality of life; Reagent; Research; Research Design; Role; Savings; Series; Sick Role; Signal Pathway; Signal Transduction; Sterility; Stroke; Sympathetic Nervous System; Symptoms; Systemic disease; Testing; Therapeutic Intervention; Tissues; Toxic effect; appetite loss; cancer cachexia; cancer prevention; cancer therapy; cancer type; cell transformation; design; drug development; in vivo; mortality risk; motivated behavior; mouse model; neural circuit; neuroinflammation; neurotoxic; neurotoxicity; new therapeutic target; novel; nutrition; pathogen; recruit; resilience; response; sensor; therapeutic target; therapeutically effective; tumor; tumor growth

Project Summary: Illness behaviors, metabolic disturbances, and cognitive decline 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. Cognitive decline 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, a key driver of cachexia and cognitive decline in patients with cancer. In this proposal, we will focus on understanding the scope and mechanism by which systemic illness induces the production of a molecule called lipocalin-2, that in turn acts on the brain to cause loss of appetite and cognitive decline. 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 anorexia and neurocognitive decline 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.

项目摘要： 慢性全身患者常见疾病行为，代谢障碍和认知能力下降很常见 疾病，并为生活质量和最终生存做出了重大贡献。其他疾病引起的病毒 包括厌食症和嗜睡还损害了患者从挽救生命或延长的能力 干预措施，减少积极与潜在条件作斗争的动机。虽然 癌症患者中的恶病质被描述了两千多年前的中心机制 这种疾病的基础知之甚少。此外，目前没有有效的药物 治疗。认知能力下降在所有慢性疾病中都是常见的，并且可能是癌症的投诉 患者，甚至在开始治疗之前。我们的实验室致力于阐明基本机制 癌症会触发神经炎症，这是病虫气的关键驱动力和患者的认知能力下降 癌症。在此提案中，我们将专注于理解系统性疾病的范围和机制 诱导一个称为lipocalin-2的分子的产生，该分子反过来作用于大脑，以引起食欲的丧失 和认知能力下降。该提议的重要性在于我们历史重点的独特结合 关于神经内分泌学和神经炎症，采用了新的合作和努力，致力于理解 癌症患者厌食和神经认知能力下降的程度和机制。长期目标 我们的研究是对急性疾病反应以及如何过渡的机械理解 为了开发更有效的治疗干预措施，进入所有癌症类型的慢性神经炎症。