Metabolic dysregulation during radiation-induced salivary gland dysfunction

摘要： 超过73%的头颈部癌症患者继续遭受口干症的慢性后果 在放疗完成后的几个月到几年内，这使这成为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 对这些患者来说仍然是一个严重的问题，并严重降低了他们的生活质量。辐射场- 诱发的唾液腺损伤严重受阻于缺乏详细描述 损伤的分子阶段。总体愿景(长期目标)是恢复患者的唾液腺功能。 放射治疗后，通过确定唾液腺的愈合阶段导致分层和 为他们的分期实施精确的治疗。这项提议将在三个时间段整合代谢变化 辐射诱发功能障碍的要点，为临床治疗奠定了机制基础 干预措施。我们假设唾液腺代谢的变化会导致功能表型的丧失。 在对唾液腺进行放射治疗后。这项工作的成果包括：1)代谢网络 随着IR的动态改变，2)新的代谢表型调节剂的鉴定 IR，3)代谢网络的变化与参与反应的细胞机制之间的联系 唾液腺对IR的损害。通过揭示干预措施，了解这一过程将产生积极影响 促进唾液腺功能恢复的穴位。

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.