Treatment of Functional Deficits IN tongue muscles induced by radiation and chemoradiation treatment

放射和放化疗引起的舌肌功能缺陷的治疗

• 批准号: 10320009
• 负责人: John A Russell
• 金额: $ 35万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10320009
• 关键词: Address; Affect; Animal Model; Area; Biochemical; Biological; Biological Assay; Biology; Blood capillaries; Cephalic; Chronic; Clinical; Clinical Research; Clinical Services; Communication; Conflict (Psychology); Deglutition; Development; Etiology; Evidence based treatment; Exercise; Fibrosis; Foundations; Functional disorder; Guidelines; Head and Neck Cancer; Head and Neck Muscle; Head and neck structure; Heterogeneity; Human; Impairment; Institute of Medicine (U.S.); Knowledge; Lead; Linear Regressions; Malignant Neoplasms; Mastication; Measures; Methods; Modality; Modeling; Morbidity - disease rate; Morphology; Movement; Muscle; Muscle Contraction; Muscle Fibers; Muscle Weakness; Muscle function; Myosin Heavy Chains; Neuromuscular Junction; Normal tissue morphology; Operative Surgical Procedures; Organ; Patients; Phenotype; Physiological; Population; Probability; Property; Quality of life; Radiation; Radiation therapy; Rattus; Research; Research Design; Sampling; Series; Skeletal Muscle; Speech; Structure; Testing; Therapeutic Intervention; Time; Tissues; Tongue; Translations; Treatment Effectiveness; Vascular System; Voice; Work; analog; base; cancer therapy; chemoradiation; chemotherapy; clinically relevant; density; exercise program; exercise training; experimental study; functional outcomes; head and neck cancer patient; improved; improved functioning; innovation; muscular structure; muscular system; negative affect; neuromuscular stimulation; optimal treatments; prevent; radiation effect; remediation; response; satellite cell; service delivery; translational study; treatment effect; treatment optimization; tumor

ABSTRACT Radiotherapy and chemoradiation for head and neck cancer treatment exposes normal tissues to radiation, which has many devastating effects and often results in difficulty with communication and swallowing. While muscle weakness and fibrosis are possible etiologies for disruptions in critical communicative and deglutition functions following radiation, very little research has been performed on underlying biological changes within muscles of the head and neck following radiation, or possible treatments for these lasting negative effects. Skeletal muscles can adapt at multiple levels of structure and function to changing demands. Exercise training of the tongue, or enhanced muscle contraction via neuromuscular electrical stimulation (NMES) may be beneficial for preventing or reversing muscle tissue damage. However, controlled research examining these putative benefits has not been performed and optimal treatment modalities have not been established. Our hypothesis is that radiotherapy and chemoradiation-induced decline in speech and swallowing function is largely due to alterations in tongue muscle structure and function. Further, we hypothesize that tongue exercise or NMES will result in phenotypic changes in extrinsic tongue muscles that will improve tongue muscle function. To examine these clinically-relevant issues, we will use a rat model to test two different tongue treatment paradigms (tongue exercise; NMES) for remediation of radiotherapy and chemoradiation- induced muscle damage. The proposed research has two specific aims: 1) To determine how treatment modality affects morphological, biochemical, and physiological changes in radiotherapy and chemoradiation- induced muscle damage of the tongue, 2) To discover how tongue exercise and/or NMES treatment affects functional measures of deglutition following radiotherapy/chemoradiation. This work is innovative and significant because the mechanisms by which tongue exercise or NMES can prevent or treat the effects of radiation- or chemoradiation-induced communication and swallowing dysfunction is largely unexplored. Our animal model and treatments are analogs to treatments used in human patients and follow the Institute of Medicine guidelines for increasing probability of translation. Further, this work is highly significant in providing a basis for understanding the mechanisms underlying the potential of therapeutic interventions for radiation- and chemoradiation-induced cranial impairments. Translation of findings will assist with increasing the effectiveness of treatments for radiation- and chemoradiation-induced tongue muscle impairments that are so prevalent in patients with head and neck cancer.

抽象的 头颈癌治疗的放疗和放化疗会使正常组织暴露在辐射下， 这会产生许多破坏性影响，并常常导致沟通和吞咽困难。尽管 肌肉无力和纤维化是关键沟通和吞咽障碍的可能病因 辐射后的功能，很少有研究对其潜在的生物变化进行研究 放射治疗后头部和颈部的肌肉，或针对这些持久负面影响的可能治疗方法。 骨骼肌可以在结构和功能的多个层面上适应不断变化的需求。运动训练 舌头的刺激，或通过神经肌肉电刺激（NMES）增强肌肉收缩可能是 有益于预防或逆转肌肉组织损伤。然而，对照研究检验了这些 假定的益处尚未发挥，最佳治疗方式尚未确定。我们的 假设是放疗和放化疗引起的言语和吞咽功能下降 很大程度上是由于舌头肌肉结构和功能的改变。此外，我们假设舌头 运动或 NMES 将导致外在舌头肌肉的表型变化，从而改善舌头 肌肉功能。为了研究这些临床相关问题，我们将使用大鼠模型来测试两种不同的 用于修复放射治疗和放化疗的舌头治疗范例（舌头锻炼；NMES） 诱发肌肉损伤。拟议的研究有两个具体目标：1）确定如何治疗 方式影响放疗和放化疗的形态、生化和生理变化 诱发舌头肌肉损伤，2) 发现舌头锻炼和/或 NMES 治疗如何影响 放疗/放化疗后吞咽的功能性测量。这项工作具有创新性和 意义重大，因为舌头运动或 NMES 可以预防或治疗以下影响的机制： 放射或放化疗引起的沟通和吞咽功能障碍在很大程度上尚未被探索。我们的 动物模型和治疗方法与人类患者使用的治疗方法类似，并遵循研究所 增加翻译概率的医学指南。此外，这项工作对于提供 理解放射治疗干预潜力的机制的基础 放化疗引起的颅骨损伤。研究结果的转化将有助于提高 治疗放疗和放化疗引起的舌肌损伤的有效性 多见于头颈癌患者。