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

A chat about actinic keratosis:Examining capabilities and user experience of ChatGPT as a digital health technology in dermato-oncology

Background: The potential applications of artificial intelligence (AI) in dermatology are evolving rapidly. Chatbots are an emerging trend in healthcare that rely on large language models (LLMs) to generate answers to prompts from users. However, the factuality and user experience (UX) of such chatbots remain to be evaluated in the context of dermato-oncology. Objectives: To examine the potential of Chat Generative Pretrained Transformer (ChatGPT) as a reliable source of information in the context of actinic keratosis (AK) and to evaluate clinicians' attitudes and UX with regard to the chatbot. Methods: A set of 38 clinical questions were compiled and entered as natural language queries in separate, individual conversation threads in ChatGPT (OpenAI, default GPT 3.5). Questions pertain to patient education, diagnosis, and treatment. ChatGPT's responses were presented to a panel of 7 dermatologists for rating of factual accuracy, currency of information, and completeness of the response. Attitudes towards ChatGTP were explored qualitatively and quantitatively using a validated user experience questionnaire (UEQ). Results: ChatGPT answered 12 questions (31.6%) with an accurate, current, and complete response. ChatGPT performed best for questions on patient education, including pathogenesis of AK and potential risk factors, but struggled with diagnosis and treatment. Major deficits were seen in grading AK, providing up-to-date treatment guidance, and asserting incorrect information with unwarranted confidence. Further, responses were considered verbose with an average word count of 198 (SD 55) and overly alarming of the risk of malignant transformation. Based on UEQ responses, the expert panel considered ChatGPT an attractive and efficient tool, scoring highest for speed of information retrieval, but deemed the chatbot inaccurate and verbose, scoring lowest for clarity. Conclusions: While dermatologists rated ChatGPT high in UX, the underlying LLMs that enable such chatbots require further development to guarantee accuracy and concision required in a clinical setting.</p

Keratinocyte cancer

Keratinocyte cancer (KC) cases have risen by 172% in Denmark over the last decade and the lifetime risk of developing KC is at least 22%. This highlights the need for innovative strategies in KC prevention, diagnosis, and treatment. To reduce incidence, new prevention methods are crucial. New diagnostics using non-invasive scanning can streamline patient care, especially for low-risk tumours and patients with multiple tumours. New treatments can be more effective and with fewer side effects. Together, these initiatives can improve the patient journey and ease the burden on healthcare resources, as argued in this review.</p