Pathophysiological profiling of vocal fold hyperkeratosis

声带角化过度的病理生理学分析

• 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
• 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

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.

项目摘要/摘要 声带（VF）高性病 - 上皮表面角蛋白的积累，导致临床 白细胞 - 主要是使用风险造成造成损伤，纤维化和声音的破坏性技术进行管理的 损害。鉴于活检和病变的潜在发病率，因此需要新的 无限期且扎根的VF白细胞疾病的工作和治疗方法 疾病病理生理学。在当前的应用程序中，我们提出了转化研究，以推动这一点 目标。我们的初步数据表明，必需的营养维生素A是上皮健康的关键调节剂 这种全身性维生素A缺乏可以直接导致过度促进性。基于维生素的证据 A对VF恒星和上皮细胞生物学的重要性及其与VF高伴病的直接相关性，我们 提案三个具体的目标，可以将该研究领域推向更大的临床适用性：（i） 评估VF过度性高性病患者的系统性维生素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的贩运和摄取正常和过度性VF粘膜。我们的 总体目标是确定是否存在补充维生素A的病理生理原理 治疗VF过度性过度。这种疗法将具有变革性 - 既是作为一线方法 需要保守管理的患者，以及手术的患者可调节疗法 表示治疗。