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

项目摘要： 疾病行为、代谢紊乱和心血管损害在患有以下疾病的患者中很常见： 慢性全身性疾病，并大大有助于生活质量和最终生存。其他疾病- 诱发的疾病，包括厌食和嗜睡，也损害了患者从生活中恢复的能力- 节省或延长干预措施，并减少积极与潜在的 条件尽管癌症患者的恶病质早在两千多年前就有描述， 这种疾病的潜在机制知之甚少。此外，目前没有有效的 药物治疗。心血管损害在所有慢性疾病中很常见， 在癌症患者中甚至在开始治疗之前就表现出不适。我们的实验室致力于 揭示了癌症引发神经炎症和随后的慢性炎症的基本机制， 激活癌症患者的全身应激反应。在这份提案中，我们将重点关注理解 系统性疾病引起慢性激活和改变的范围和机制， 交感神经系统这项建议的意义在于它独特地结合了我们的 历史上专注于神经内分泌学和神经炎症，新的合作和努力针对 了解心血管损伤和交感神经系统的程度和机制 癌症患者的可塑性。我们研究的长期目标是获得对 急性疾病反应以及它如何在所有癌症类型中转变为慢性神经炎症， 开发更有效的治疗干预措施。

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.