Randomized controlled trial of fractionated laser resurfacing on aged skin as prophylaxis against actinic neoplasia.

BACKGROUNDThe 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.METHODSA 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.RESULTSXenografting 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).CONCLUSIONThe 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.TRIAL REGISTRATIONClinicalTrials.gov (NCT03906253).FUNDINGNational Institutes of Health, Veterans Administration.

Keratinocyte-derived microvesicle particles mediate ultraviolet B radiation-induced systemic immunosuppression.

A complete carcinogen, ultraviolet B (UVB) radiation (290-320 nm), is the major cause of skin cancer. UVB-induced systemic immunosuppression that contributes to photocarcinogenesis is due to the glycerophosphocholine-derived lipid mediator platelet-activating factor (PAF). A major question in photobiology is how UVB radiation, which only absorbs appreciably in the epidermal layers of skin, can generate systemic effects. UVB exposure and PAF receptor (PAFR) activation in keratinocytes induce the release of large numbers of microvesicle particles (MVPs; extracellular vesicles ranging from 100 to 1000 nm in size). MVPs released from skin keratinocytes in vitro in response to UVB (UVB-MVPs) are dependent on the keratinocyte PAFR. Here, we used both pharmacologic and genetic approaches in cells and mice to show that both the PAFR and enzyme acid sphingomyelinase (aSMase) were necessary for UVB-MVP generation. Our discovery that the calcium-sensing receptor is a keratinocyte-selective MVP marker allowed us to determine that UVB-MVPs leaving the keratinocyte can be found systemically in mice and humans following UVB exposure. Moreover, we found that UVB-MVPs contained bioactive contents including PAFR agonists that allowed them to serve as effectors for UVB downstream effects, in particular UVB-mediated systemic immunosuppression.

Single Ablative Fractional Resurfacing Laser Treatment For Forearm Actinic Keratoses: 6-Month Follow-Up Data From An Intrapatient Comparison Between Treated and Untreated Sites.

BACKGROUND AND OBJECTIVES: Actinic keratoses (AK) are common pre-cancerous lesions, which are associated with ultraviolet light exposure and aging. Wounding therapies such as fractionated laser resurfacing (FLR) have been previously demonstrated to effectively treat facial AK. However, the effectiveness of FLR on other sites commonly afflicted with AK has not been studied in detail. Previously, our group has reported that treatment of aged skin with wounding therapies including dermabrasion and ablative fractionated resurfacing results in the removal of senescent fibroblasts and normalizing the pro-carcinogenic acute ultraviolet B radiation responses associated with aged skin. The current studies were designed to test the effectiveness of FLR of the forearm skin of subjects aged 60 and older to remove AKs. STUDY DESIGN/MATERIALS AND METHODS: Between February 2018 and March 2019, 30 subjects were enrolled in a study, in which they underwent a single FLR treatment of one extremity including the dorsal forearm, wrist, and dorsal hand. The number of AKs was recorded on both extremities at baseline, 3 and 6 months in a blinded fashion. Side effects of the FLR were documented. RESULTS: A single FLR treatment resulted in a 62% reduction in the absolute number of AK in the treated arm at 6 months post-treatment. The laser treatment was well-tolerated without major complications. CONCLUSIONS: These studies demonstrate that FLR using settings, which have demonstrated to remove senescent fibroblasts and normalize the pro-carcinogenic UVB-response of aged skin is a potentially effective and safe field therapy treatment that should be studied for long-term efficacy for use in treating upper extremity AKs. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.