Current Issue : April-June Volume : 2022 Issue Number : 2 Articles : 5 Articles
Enhancer RNAs (eRNAs), a subclass of noncoding RNAs from enhancers, have been demonstrated to exhibit important regulatory effects on the expressions of various genes. However, the role of eRNAs in skin cutaneous melanoma (SKCM) remained largely unclear. In this study, we aimed to explore the expression and prognostic value of an enhancer RNA TEX41 in SKCM as well as the associations between TEX41 and tumor-infiltrating immune cells (TICs). We observed that TEX41 expression was distinctly increased in SKCM specimens compared with normal skin specimens using GEPIA. Survival assays based on TGCA datasets revealed that patients with low TEX41 expressions displayed a longer overall survival than those with high TEX41 expression. CIBERSORT datasets revealed that TEX41 was related to 8 types of TICs (macrophages M1, T cells regulatory, plasma cells, mast cells resting, T cells CD8, dendritic cells resting, and T cells follicular helper). Three kinds of TICs were negatively related to TEX41 expressions, including macrophages M2, NK cells resting, and macrophages M0. The expressions of TEX41 were involved in five KEGG pathways, including transcriptional misregulation in cancer, SNARE interactions in vesicular transport, mitophagy-animal, melanoma, melanogenesis, and progesterone-mediated oocyte maturation. Overall, TEX41 can be used as a novel biomarker for the prognosis of SKCM patients and is associated with TICs, indicating it as a therapeutic target for SKCM....
The skin is the outermost barrier protecting the body from pathogenic invasion and environmental insults. Its breakdown initiates the start of skin inflammation. The epidermal growth factor (EGFR) on keratinocytes protects this barrier, and its dysfunction leads to atopic dermatitis-like skin disease. One of the initial cytokines expressed upon skin barrier breach and during atopic dermatitis is TSLP. Here, we describe the expression and secretion of TSLP during EGFR inhibition and present an ex-vivo model, which mimics the early events after barrier insult. Skin explants floated on culture medium at 32 C released TSLP in parallel to the activation of the resident Langerhans cell network. We could further show the up-regulation and activation of the AP-1 family of transcription factors during atopic-like skin inflammation and its involvement in TSLP production from the skin explant cultures. Inhibition of the c-Jun N-terminal kinase pathway led to a dose-dependent blunting of TSLP release. These data indicate the involvement of AP-1 during the early stages of atopic-like skin inflammation and highlight a novel therapeutic approach by targeting it. Therefore, skin explant cultures mimic the early events during skin barrier immunity and provide a suitable model to test therapeutic intervention....
The impact of age on the clinical benefit of anti-PD1 immunotherapy in advanced melanoma patients has been evolving recently. Due to a reduced immune function in elderly patients, young patients with a robust immune system are theoretically expected to benefit more from the treatment approach. However, in contrast to this hypothesis, recent studies in patients with metastatic melanoma have demonstrated that immunotherapy, especially with anti-PD1 treatment, is less effective in patients below 65 years, on average, with significantly lower responses and reduced overall survival compared to patients above 65 years of age. Besides, data on young patients are even more sparse. Hence, in this review, we will focus on age-dependent differences in the previously described resistance mechanisms to the treatment and discuss the development of potential combination treatment strategies for enhancing the anti-tumor efficacy of anti-PD1 or PDL1 treatment in young melanoma patients....
Dietary nutrition intake is essential for human beings and influences various physiological and pathological actions in the human body. Among various nutritional factors, dietary intake of omega‐3 polyunsaturated fatty acids (PUFAs) has been shown to have various beneficial effects against inflammatory diseases. In addition to their therapeutic potency against inflammation, omega‐3 PUFAs have also been shown to have anti‐tumor effects via various mechanisms, such as cell arrest and apoptosis. To date, limited information is available on these effects in cutaneous malignancies. In this review, we focused on the effect of omega‐3 PUFAs on skin cancers, especially malignant melanoma, basal cell carcinoma, lymphoma, and squamous cell carcinoma and discussed the detailed molecular mechanism of the omega‐3 PUFA‐mediated anti‐tumor response. We also explored the molecular mechanisms mediated by epigenetic modifications, cell adhesion molecules, and anti‐tumor immune responses....
Background: The current vitamin D deficiency epidemic is accompanied by an increase in endemic skin cancer. There are still multiple controversies. This review aims to give practical recommendations regarding vitamin D among people at risk or with a personal history of skin cancer. Methods: Narrative review including human research articles published between 2011 and 2021, elaborated bearing in mind an epidemiological, patient-centered approach. Results: Ultraviolet (UV) exposure (neither artificial nor natural) is not the ideal source to synthesize vitamin D. There is conflicting epidemiological evidence regarding vitamin D, non-melanoma skin cancer (NMSC), and cutaneous melanoma (CMM), confounded by the effect of sun exposure and other factors. Conclusions: Current evidence is controversial, and there are no widely applicable strategies. We propose three practical recommendations. Firstly, sun protection recommendations should be kept among people at risk or with a personal history of skin cancer. Secondly, vitamin D should preferably be sourced through diet. In patients with melanoma or at risk of cutaneous cancer, serum vitamin D checks are warranted to detect and avoid its insufficiency....
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