Keratinocyte Carcinoma and Photoprevention:The Protective Actions of Repurposed Pharmaceuticals, Phytochemicals and Vitamins

SIMPLE SUMMARY: Keratinocyte carcinoma is the most common type of cancer. Sun exposure and ultraviolet radiation are significant contributors to the development of carcinogenesis, mediated by DNA damage, increased oxidative stress, inflammation, immunosuppression and dysregulated signal transduction. Photoprevention involves using different compounds to delay or prevent ultraviolet radiation-induced skin cancer. In this review, we look at new avenues for systemic photoprevention that are based on pharmaceuticals, plant-derived phytochemicals and vitamins. We also investigate the mechanisms underlying these strategies for preventing the onset of carcinogenesis. ABSTRACT: Ultraviolet radiation (UVR) arising from sun exposure represents a major risk factor in the development of keratinocyte carcinomas (KCs). UVR exposure induces dysregulated signal transduction, oxidative stress, inflammation, immunosuppression and DNA damage, all of which promote the induction and development of photocarcinogenesis. Because the incidence of KCs is increasing, better prevention strategies are necessary. In the concept of photoprevention, protective compounds are administered either topically or systemically to prevent the effects of UVR and the development of skin cancer. In this review, we provide descriptions of the pathways underlying photocarcinogenesis and an overview of selected photoprotective compounds, such as repurposed pharmaceuticals, plant-derived phytochemicals and vitamins. We discuss the protective potential of these compounds and their effects in pre-clinical and human trials, summarising the mechanisms of action involved in preventing photocarcinogenesis

Исследование желаемого образа семьи молодежи, проживающей в больших, средних и малых городах

Funding: EPSRC EP/J01771X, Royal Society Wolfson Research Merit AwardBackground Topical Photodynamic therapy (PDT) is an effective treatment for superficial non-melanoma skin cancers (NMSC) and dysplasia. During PDT light activates the photosensitiser (PpIX), metabolised from a topical pro-drug. A combination of PpIX, light and molecular oxygen results in inflammation and cell death. However, the outcomes of the treatment could be better. Insufficient biosynthesis of PpIX may be one of the causes of incomplete response or recurrence. Measuring surface fluorescence is usually employed as a means of studying PpIX formation. The aim of this work was to develop a device and a method for convenient fluorescence imaging in clinical settings to gather information on PpIX metabolism in healthy skin and NMSC with a view to improving PDT regimes. Methods A handheld fluorescence camera and a time course imaging method was developed and used in healthy volunteers and patients diagnosed with basal cell carcinoma (BCC) and actinic keratosis (AK). The photosensitiser (precursor) creams used were 5-aminolaevulinic acid (ALA; Ameluz®) and methyl aminolevulinate (MAL; Metvix®). Pain was assessed using a visual analogue score immediately after the PDT. Results Fluorescence due to PpIX increases over three hours incubation in healthy skin and in lesional BCC and AK. Distribution of PpIX fluorescence varies between the lesion types and between subjects. There was no significant correlation between PpIX fluorescence characteristics and pro-drug, diagnosis or pain experienced. However, there was a clear dependence on body site. Conclusion The device and the method developed can be used to assess the characteristics of PpIX fluorescence, quantitative analysis and time course. Our findings show that body site influences PpIX fluorescence which we suggest may be due to the difference in skin temperature at different body sites.PostprintPeer reviewe