Pathophysiological profiling of vocal fold hyperkeratosis

声带角化过度的病理生理学分析

基本信息

批准号：
10365122
负责人：
SHERRY A TANUMIHARDJO
金额：
$ 54.23万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-01-01 至 2026-12-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10365122
关键词：
Ablation Adjuvant Therapy All-Trans-Retinol American Area Biological Assay Biological Markers Biology Biopsy Cadaver Cells Cellular biology Chemicals Chylomicrons Clinical Clinical Trials Consensus Data Dietary intake Dilution Techniques Disease Dose Dysphonia Epithelial Epithelial Cells Excision Extrahepatic Family Fibrosis Frequencies Functional disorder Goals Health Health Care Costs Histopathology Human Hyperkeratosis Impairment Intervention Isotopes Keratin Kinetics Larynx Lasers Lesion Leukoplakia Literature Liver Measures Mediating Medical Metabolism Modeling Morbidity - disease rate Mucous Membrane Nature Nutrient Occupational Operative Surgical Procedures Patients Performance Practice Guidelines Quality of life Rattus Recurrence Research Retinoids Retinol Binding Proteins Risk Site Societies Supplementation Surface Techniques Testing Time Tissues Translational Research United States United States Food and Drug Administration Vitamin A Vitamin A Deficiency Voice analog base candidate marker clinical application dietary disorder control experimental study iatrogenic injury improved molecular marker mucosal uptake novel marker novel strategies pre-clinical preservation regional difference stellate cell trafficking uptake vitamin A analog vocal cord

项目摘要

Project Summary/Abstract Vocal fold (VF) hyperkeratosis – an accumulation of epithelial surface keratin resulting in clinical leukoplakia – is primarily managed using destructive techniques that risk iatrogenic injury, fibrosis, and voice impairment. Given the potential morbidity of biopsy and lesion removal, there is a compelling need for new approaches to the workup and treatment of VF leukoplakic disorders that are non-destructive and grounded in disease pathophysiology. In the current application, we propose translational research that will advance this goal. Our preliminary data indicate that the essential nutrient vitamin A is a key regulator of epithelial health and that systemic vitamin A deficiency can directly contribute to hyperkeratosis. Based on evidence of vitamin A’s importance to VF stellate and epithelial cell biology, and its direct relevance to VF hyperkeratosis, we propose three Specific Aims that will advance this research area towards greater clinical applicability by: (i) assessing the systemic vitamin A status and lesion histopathology of patients with VF hyperkeratosis, and (ii) examining vitamin A trafficking to, and uptake by, normal and hyperkeratotic VF mucosa in a rat model. Our overarching goal is to determine if there is a pathophysiologic rationale for vitamin A supplementation in the treatment of VF hyperkeratosis. Such a therapy would be transformative – both as a first-line approach for patients who require conservative management, as well as an adjuvant therapy in patients for whom surgical treatment is indicated.

项目概要/摘要声带 (VF) 角化过度——上皮表面角蛋白的积累导致临床症状白斑——主要使用破坏性技术进行治疗，有医源性损伤、纤维化和声音风险鉴于活检和病灶切除的潜在发病率，迫切需要新的方法。室颤白斑病的检查和治疗方法是非破坏性的并且基于在当前的应用中，我们提出了转化研究来推进这一点。我们的初步数据表明，必需营养素维生素 A 是上皮健康的关键调节剂。根据维生素的证据，全身性维生素 A 缺乏可直接导致角化过度。 A 对 VF 星状和上皮细胞生物学的重要性，及其与 VF 角化过度的直接相关性，我们提出三个具体目标，通过以下方式推动该研究领域获得更大的临床适用性：(i) 评估 VF 角化过度患者的全身维生素 A 状态和病变组织病理学，以及 (ii) 在大鼠模型中检查维生素 A 向正常和角化过度的 VF 粘膜的运输和吸收。总体目标是确定补充维生素 A 是否存在病理生理学原理这种疗法将是革命性的——既可以作为治疗 VF 角化过度的一线方法。需要保守治疗的患者，以及需要手术治疗的患者表明治疗。