Metabolic dysregulation during radiation-induced salivary gland dysfunction

辐射引起的唾液腺功能障碍期间的代谢失调

• 批准号: 10254415
• 负责人: KIRSTEN H LIMESAND
• 金额: $ 19.19万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-04 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10254415
• 关键词: 6-Phosphofructokinase; Acute; Affect; Animal Model; Antioxidants; Apical; Area; Biochemical Pathway; Bioinformatics; Biological Markers; Biological Specimen Banks; Biology; Biopsy; Cell physiology; Cells; Chronic; Citric Acid Cycle; Clinical; Complex; Conflict (Psychology); DNA Repair; Data; Defect; Disease; Effectiveness; Enzymes; Foundations; Functional disorder; Genetic Transcription; Genus Hippocampus; Goals; Head and Neck Cancer; Homeostasis; Intervention; Kinetics; Knowledge; Lead; Macronutrients Nutrition; Metabolic; Metabolic Pathway; Metabolism; Modeling; Molecular; Nuclear; Outcome; Oxygen Consumption; Pathway Analysis; Pathway interactions; Patients; Pentosephosphate Pathway; Phase; Phenotype; Problem Solving; Process; Quality of life; Radiation; Radiation therapy; Reaction; Regulation; Reporting; Research Personnel; Saliva; Salivary Gland Tissue; Salivary Glands; Serum; Stratification; Technology; Therapeutic; Therapeutic Intervention; Time; Tissues; Transcription Coactivator; Urine; Vision; Work; Xerostomia; aminoacid biosynthesis; cancer therapy; common treatment; experimental study; extracellular; functional loss; head and neck cancer patient; healing; lipid metabolism; loss of function; metabolic phenotype; metabolomics; multidisciplinary; novel; novel therapeutic intervention; novel therapeutics; nucleotide metabolism; patient stratification; preference; radiation effect; radiation response; repaired; response; restoration; saliva sample; salivary acinar cell; side effect; skills; stressor; therapeutically effective; transcriptomics

Abstract: More than 73% of head and neck cancer patients continue to suffer from the chronic consequences of xerostomia months to years after the completion of radiotherapy making this one of the most compelling issues in salivary gland biology. Despite technological advancements in cancer therapies, collateral damage to salivary glands remains a significant problem for these patients and severely diminishes their quality of life. The field of radiation- induced salivary gland damage is severely hampered by the lack of a comprehensive model detailing the molecular stages of damage. The overall vision (long-term goal) is to restore salivary gland function in patients following radiotherapy by identifying healing stages in salivary glands that lead to the stratification and administration of precise therapeutics for their stage. This proposal will integrate metabolic changes at three time points of radiation-induced dysfunction that build a mechanistic foundation to bridge to clinical therapeutic interventions. We hypothesize that changes in salivary gland metabolism enable the loss of function phenotype following radiation treatment of salivary glands. The outcomes from this work include: 1) Metabolic networks that are kinetically altered following IR, 2) Identification of novel regulators of the metabolic phenotype following IR, 3) Linkage of changes in metabolic networks with cellular mechanisms that are involved in the response of salivary glands to IR damage. Understanding this process would have a positive impact by revealing intervention points that promote restoration of salivary gland function.

抽象的： 超过73％ 放疗后的几个月到几年，这是唾液中最引人注目的问题之一 腺体生物学。尽管癌症治疗方面的技术进步，但唾液腺的附带损害 对于这些患者而言，仍然是一个重要的问题，并严重降低了他们的生活质量。辐射领域 由于缺乏详细介绍的全面模型，诱发的唾液腺损伤受到了严重阻碍 损害的分子阶段。总体视觉（长期目标）是恢复患者的唾液腺功能 通过鉴定唾液腺中的愈合阶段，导致分层和 为其舞台进行精确治疗。该建议将在三次整合代谢变化 辐射引起的功能障碍的点，建立了桥接临床治疗的机械基础 干预措施。我们假设唾液腺代谢的变化使功能表型丧失 辐射治疗唾液腺。这项工作的结果包括：1）代谢网络 IR之后的动力学改变，2）鉴定代谢表型的新型调节剂之后 ir，3）代谢网络变化与细胞机制的链接，这些机制与响应有关 唾液腺造成红外损伤。了解这一过程将通过揭示干预措施产生积极的影响 促进唾液腺功能恢复的点。