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

基本信息

批准号：
10600856
负责人：
Teresa A Zimmers
金额：
$ 38.58万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
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/10600856
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 Central Nervous System Central Nervous System Neoplasms Chronic Chronic Disease Collaborations Data Dedications Desire for food Development Disease Encephalitis Endocrine Endothelium Event Evolution Fatigue Goals Growth Hippocampus 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 Neurocognitive Neurocognitive Deficit Neuroendocrinology Neurologic Neurons Pancreatic Ductal Adenocarcinoma Pathogenesis Pathologic Pathology Pathway interactions Patients Peripheral Pharmacologic Substance Physiological Population Prevention Process Production Proliferating Protein Secretion Proteins Publications Quality of life Reagent Receptor Signaling Research Research Design Role 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 melanocortin receptor 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 growth

项目摘要

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.

项目概要：疾病行为、代谢紊乱和认知能力下降在慢性全身性疾病患者中很常见疾病，并对生活质量和最终生存做出重大贡献。其他疾病引起的发病率包括厌食和嗜睡也会损害患者从挽救生命或延长生命中恢复的能力干预措施，并削弱积极应对潜在状况的动力。虽然两千多年前就描述了癌症患者的恶病质，其核心机制人们对这种疾病的背后知之甚少。此外，目前还没有有效的药物治疗。认知能力下降在所有慢性疾病中都很常见，并且可能是癌症的主诉患者，甚至在开始治疗之前。我们的实验室致力于揭示基本机制癌症会引发神经炎症，这是癌症患者恶病质和认知能力下降的关键驱动因素癌症。在本提案中，我们将重点了解系统性疾病的范围和机制诱导产生一种名为 lipocalin-2 的分子，该分子反过来作用于大脑，导致食欲不振和认知能力下降。该提案的意义在于它独特地结合了我们的历史焦点关于神经内分泌学和神经炎症，通过新的合作和努力来理解癌症患者厌食和神经认知下降的程度和机制。长期目标我们研究的目的是获得对急性疾病反应及其转变方式的机械理解研究所有癌症类型中的慢性神经炎症，以便开发更有效的治疗干预措施。