Browsing by Author "Southern, David"

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    Randomized controlled trial of fractionated laser resurfacing on aged skin as prophylaxis against actinic neoplasia
    (The American Society for Clinical Investigation, 2021) Spandau, Dan F.; Chen, Roy; Wargo, Jeffrey J.; Rohan, Craig A.; Southern, David; Zhang, Angela; Loesch, Mathew; Weyerbacher, Jonathan; Tholpady, Sunil S.; Lewis, Davina A.; Kuhar, Matthew; Tsai, Kenneth Y.; Castellanos, Amber J.; Kemp, Michael G.; Markey, Michael; Cates, Elizabeth; Williams, Amy R.; Knisely, Christina; Bashir, Sabina; Gabbard, Ryan; Hoopes, Robert; Travers, Jeffrey B.; Biochemistry and Molecular Biology, School of Medicine
    BACKGROUND: The loss of insulin-like growth factor 1 (IGF-1) expression in senescent dermal fibroblasts during aging is associated with an increased risk of nonmelanoma skin cancer (NMSC). We tested how IGF-1 signaling can influence photocarcinogenesis during chronic UVB exposure to determine if fractionated laser resurfacing (FLR) of aged skin, which upregulates dermal IGF-1 levels, can prevent the occurrence of actinic keratosis (AK) and NMSC. METHODS: A human skin/immunodeficient mouse xenografting model was used to test the effects of a small molecule inhibitor of the IGF-1 receptor on chronic UVB radiation. Subsequently, the durability of FLR treatment was tested on a cohort of human participants aged 65 years and older. Finally, 48 individuals aged 60 years and older with considerable actinic damage were enrolled in a prospective randomized clinical trial in which they underwent a single unilateral FLR treatment of one lower arm. Numbers of AKs/NMSCs were recorded on both extremities for up to 36 months in blinded fashion. RESULTS: Xenografting studies revealed that chronic UVB treatment with a topical IGF-1R inhibitor resulted in a procarcinogenic response. A single FLR treatment was durable in restoring appropriate UVB response in geriatric skin for at least 2 years. FLR resulted in sustained reduction in numbers of AKs and decreased numbers of NMSCs in the treated arm (2 NMSCs) versus the untreated arm (24 NMSCs). CONCLUSION: The elimination of senescent fibroblasts via FLR reduced the procarcinogenic UVB response of aged skin. Thus, wounding therapies are a potentially effective prophylaxis for managing high-risk populations.