Validation of Mesoscopic Imaging to Predict Cutaneous Carcinogenesis and its Therapeutic Response

验证细观成像预测皮肤癌发生及其治疗反应

• 批准号: 10595503
• 负责人: Jeffrey B. Travers
• 金额: --
• 依托单位: DAYTON VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-10-01 至 2023-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10595503
• 关键词: Actinic keratosis; Acute; Age; Aging; Area; Biochemical; Biological Models; Biopsy; Blood Vessels; Blood Volume; Caring; Cause of Death; Characteristics; Chronic; Clinic; Clinical; Clinical Treatment; Colon Carcinoma; Cream; Cutaneous; DNA Repair Enzymes; DNA Sequence Alteration; Dermabrasion; Dermal; Dermatology; Diagnosis; Diagnostic; Effectiveness; Elderly; Exhibits; Fibroblasts; Financial Hardship; Fluorouracil; General Population; Goals; Healthcare Systems; Hemoglobin; Histologic; Histology; Hot Spot; Human; IL8 gene; Image; Incidence; Insulin-Like Growth Factor I; Interleukin-6; Intervention; Lasers; Malignant Neoplasms; Malignant neoplasm of esophagus; Malignant neoplasm of lung; Maps; Measurement; Methodology; Modeling; Monitor; Morbidity - disease rate; Mutation; Neoplasms; Optics; Organ Transplantation; Organ failure; PUVA Photochemotherapy; Patients; Phenotype; Physiological; Pilot Projects; Prediction of Response to Therapy; Prevention; Proliferating; Reporting; Research; Research Personnel; Risk; Risk Factors; Site; Skin; Skin Cancer; Skin Carcinoma; Solid; Source; Spatial Frequency Domain Imaging; Spottings; Stains; Sun Exposure; TNF gene; TP53 gene; Testing; Thymidine; Time; Tissues; Transplant Recipients; UV Radiation Exposure; Ultraviolet B Radiation; Validation; Veterans; body system; cancer type; carcinogenesis; chemotherapy; cohort; cytokine; dimer; early detection biomarkers; experience; high risk; high risk population; imaging platform; imaging system; improved; insight; keratinocyte; mortality; mutant; neoplastic; non-invasive imaging; novel; patient response; preclinical study; predicting response; premalignant; quantitative imaging; radiation response; risk prediction; risk stratification; senescence; skin photodamage; spectrograph; tool; transcriptome; treatment response; wound

PROJECT SUMMARY Actinic neoplasia (precancerous actinic keratosis and non-melanoma skin cancer) is the most common type of human neoplasia, and the most common diagnosis in VA dermatology clinics. We and other groups have characterized the mechanisms by which aging and ultraviolet B radiation (UVB) contribute to actinic neoplasia. In particular, human skin at high risk for actinic neoplasia exhibits biochemical features, including decreased keratinocyte expression of DNA repair enzymes, increased numbers of senescent fibroblasts with lower levels of fibroblast IGF-1, and increased fibroblast cytokines including IL-6, IL-8 and TNF. Moreover, at risk skin responds to UVB by generating basal keratinocytes proliferating while still harboring DNA mutations. This revised VA Merit application will leverage our recent findings that a noninvasive, multi-spectral, mesoscopic imaging platform could potentially identify clinically normal-appearing skin at risk for actinic neoplasia. This proposal also provides evidence that mesoscopic imaging could have use in quantifying field carcinogenesis. To that end, two specific aims will test the hypothesis that mesoscopic imaging will be able to discern skin with biochemical and functional characteristics of tissue at high risk for actinic neoplasia. The first aim consists of two parts. In the first part, mesoscopic imaging will be used to predict areas of at-risk vs. normal skin, which will be tested with biopsies and non-invasive transcriptome analysis to compare imaging parameter-based predictions against biochemical, histological and functional features associated with skin at high risk for actinic neoplasia. In the second part of Aim 1 we will take advantage of our recent findings that wounding of photo- damaged geriatric skin with fractionated laser resurfacing normalizes the actinic neoplastic biochemical/histological changes. We will leverage these findings by conducting mesoscopic imaging of laser- wounded vs unwounded skin in geriatric subjects with photo-damaged skin. The second aim will test the ability of mesoscopic imaging to quantify the effectiveness of topical photodynamic therapy (PDT) performed or chemotherapy agent 5-fluorouracil cream on subjects with multiple actinic keratosis requiring field therapy. Additionally, subjects at high risk for actinic neoplasia not treated with field therapy will be monitored longitudinally in clinics by serial mesoscopic imaging. These three strategies in Aim 2 will test if this noninvasive imaging can predict where actinic keratosis will arise and assess if mesoscopic imaging has use in the clinic for quantifying skin at-risk for actinic neoplasia and actinic keratosis. The overall goal is to establish a fast, wide- field, multi-spectral imaging system that can provide quantitative imaging parameters for monitoring human skin non-invasively. If successful, these studies will validate a valuable clinical tool that can stratify risk of actinic neoplasia even when skin appears clinically normal. Moreover, this non-invasive, image-based contrast mapping approach could serve to propel research in field cancerization using skin as a model system, which could be adapted to other organ systems such as colon, esophagus and lung cancers. These studies will improve the care of veterans served in our dermatology clinics. This proposal will also provide valuable tools for both the study and monitoring of many cancer types found in US Veterans.

项目总结