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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

基本信息

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
项目类别：
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

项目摘要

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.

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