有馬 豪

The skin is a tissue highly susceptible to damage from various stressors, including reactive oxygen species, UV radiation and chemical exposure. While damaged cells are often repaired, some sustain irreversible damage and become senescent. Although the body possesses mechanisms to remove these senescent cells, they accumulate with age for reasons that remain unclear. The close relationship between chronic inflammation and cellular senescence has recently become a major focus of research. Here, we sought to analyse the mechanisms driving age-related chronic inflammation and its impact on the accumulation of senescent cells. Our analysis of the cytokine IL-17A, a key factor in chronic inflammation, revealed that its levels increase in the skin with age. We also discovered that regulatory T cells (Treg cells), which typically act to suppress IL-17A, begin to secrete it as they age. Moreover, we found that IL-17A enhances the resistance of senescent cells to apoptosis. These results propose a model in which the age-related rise in the inflammatory factor IL-17A fosters an environment where senescent cells resist clearance, thereby promoting their accumulation.

Lichen sclerosus et atrophicus (LSA) is a chronic, progressive inflammatory disorder with a risk of malignant transformation to squamous cell carcinoma (SCC). This study investigated the role of activation-induced cytidine deaminase (AID) in UV-independent SCC arising from LSA. We retrospectively analyzed 19 female patients, including 5 SCC cases. AID expression was significantly associated with SCC development, pruritus, and shorter disease duration. AID was detected in SCC lesions and adjacent LSA tissues, mainly in basal cells. Reduced AID expression was observed in higher-stage tumors, suggesting its potential as a prognostic indicator. The use of topical corticosteroids was less common in AID-positive patients, suggesting a possible association. These findings suggest a possible inverse association between topical corticosteroid use and AID expression.

BACKGROUND: Preservation of plantar subcutaneous fat is crucial for cushioning in the surgical treatment of acral melanoma of the sole. However, no studies exist on the relationship between deep margins and prognosis. We aimed to retrospectively compare the prognoses of different deep margins (within or beyond the subcutaneous fat) in patients with invasive acral melanoma of the sole who underwent wide local excision. METHODS: In this multi-institutional retrospective study, survival was compared between 2 groups of patients: those with tumors excised within (S group) and those beyond the subcutaneous fat (D group). RESULTS: In total, 464 patients were included. Cox multivariable analyses showed that the depth of the deep excision margin was not associated with local recurrence-free survival, overall survival, or distant metastasis-free survival (hazard ratios of 1.20, P = .36; 1.10, P = .66; and 1.42, P = .05, respectively). However, excision beyond the subcutaneous fat was negatively associated with disease-free survival (hazard ratio 1.45, P = .02). After propensity score matching (both groups, n = 139), no significant differences were observed in survival outcomes between the S and D groups (5-year local recurrence-free survival: 72.8 vs 66.8%, P = .55; 5-year disease-free survival: 55.3 vs 43.7%, P = .24; 5-year overall survival: 76.2 vs 73.2%, P = .52; 5-year distant metastasis-free survival: 63.3 vs 54.1%, P = .13). Subgroup analysis of American Joint Committee on Cancer stages revealed no significant differences in survival outcomes between the 2 groups at any stage. CONCLUSION: Wide local excision beyond the subcutaneous fat was not associated with survival benefit of acral melanoma of the sole. Excision within the subcutaneous fat may represent the optimal deep margin.

The skin, the body's largest organ, covers the entire body and consists of three layers: the epidermis, dermis, and subcutaneous tissue. Its structure and properties vary by body region. Although homeobox (HOX) genes are implicated in mechanisms contributing to regional skin property differences, their influence is not completely understood. In this study, we focused on the relationships between HOX gene expression to regional differences in dermal structure and skin elasticity. Our results revealed significantly higher HOXA cluster expression in skin tissues and cells derived from the body in comparison to those derived from the face. Among HOXA genes highly expressed in the body, HOXA9 was found to regulate dermal fibroblast proliferation and extracellular matrix (ECM)-related gene expression, both associated with skin elasticity. Furthermore, HOXA9 was shown to affect cell proliferation and ECM-related gene expression through IGF-1 signaling. Collectively, our findings suggest that HOXA genes are expressed differently in different body regions, variably affecting dermal structure and cellular functions, thus contributing to regional variation in skin.