Acral melanoma occurring on the palms, soles, and nails is the most common subtype of cutaneous melanoma in Asians. Genetic alterations in acral melanoma and acral melanocytic nevus are not well known. We performed next-generation sequencing and evaluated the correlations between genetic information and the clinicopathologic characteristics from 85 Korean patients with acral melanocytic neoplasms. Of the 64 patients with acral melanoma, most had lesions at the T2 stage or higher, and the heel was the most common anatomical site of melanoma (n = 34 [53.1%]). The five most common mutations were BRAF (22 [34.4%]), NRAS (14, [21.9%]), NF1 (11, [17.2%]), GNAQ (12, [17.2%]), and KIT (7, [10.9%]). In the 21 acral melanocytic nevi, those five gene mutations were also common. Copy number variations were also frequently detected in 75% of acral melanomas and 47.6% of acral melanocytic nevi, and amplification was more common than deletion in both lesions. BRAF mutation was associated with round epithelioid cells and NRAS and NF1 mutations with bizarre cells. NF1 and GNAQ mutations showed elongated and spindle cells with prominent dendrites in acral melanomas. KIT mutations were common in amelanotic acral melanoma. This study suggests that common mutated genes are associated with distinct cytomorphological features in acral melanocytic lesions.
While daylight photodynamic therapy (PDT) is a simpler and more tolerable treatment procedure for both clinicians and patients, it has never been applied for acne treatment. In this study, we evaluated efficacy, safety and histological changes of facial acne after application of the novel variant of 5-aminolevulinate (ALA)-ester, 1.5% 3-butenyl ALA-bu gel, using daylight only as the potential visible light source. Forty-six acne patients were randomly assigned to either ALA-bu or vehicle application group in a double-blind fashion. Both groups applied the allocated gel to facial acne lesions every other day for 12 weeks. At the final 12 week, both inflammatory and non-inflammatory acne lesions had decreased significantly by 58.0% and 34.1% in the ALA-bu group, respectively. Only a few patients expressed mild adverse effects. In the histopathological analysis, attenuated inflammatory cell infiltrations were observed and immunostaining intensities for interleukin-8, interleukin-1β, matrix metalloproteinase-9 and phosphorylated nuclear factor-κB were reduced concomitantly. Changes of their mRNA expression demonstrated comparable patterns. In conclusion, this ambulatory PDT was effective, very well tolerated and convenient for treating inflammatory acne lesions. Experimental results correlated well with clinical results. This novel regimen would provide a viable option for acne therapy.
Rosacea is a common chronic inflammatory skin condition. Although several epidemiological and etiologic studies with large sample sizes have been conducted on Caucasians, such data regarding Asian populations are lacking. A total of 580 patients diagnosed with rosacea were enrolled from October 2014 to February 2015 at 14 general hospitals. Questionnaires, including the standard classification and grading system, were used for evaluation. The average age of the patients was 47.9 years. While 83.8% of patients revealed a single subtype, 16.2% of patients revealed mixed subtypes showing two or more subtypes simultaneously. Erythematotelangiectatic rosacea (ETR) was the most prevalent subtype. ETR combined with papulopustular rosacea showed the highest proportion in the mixed subtype group. Mild severity was revealed in 71.9% of patients. The most common aggravating factor was emotional changes (51.7%), followed by stress (48.4%). Approximately half of the patients (47.4%) showed relatively low awareness of rosacea. By identifying the epidemiological and etiologic features in Korea, we can suggest valuable clinical avenues for research, education and awareness among rosacea patients.
Cathelicidin (LL-37), Toll-like receptor 2 (TLR-2) and kallikreins (KLKs) are key inflammatory mediators in rosacea. Laser or light-based devices have been successfully used for rosacea. We investigated the effects of light-emitting diodes (LEDs) on LL-37, KLKs, TLR-2 and protease activity in cultured normal human epidermal keratinocytes (NHEKs) and rosacea-like mouse skin (RLMS). LL-37, KLK5, KLK7 and vitamin D receptor were induced by 1α, 25-dihydroxyvitamin D (VD ) and TLR-2 by Ad-CMV transfection in cultured NHEKs. NHEKs were subjected to LED irradiation at differing wavelengths (480-940 nm) and fluences (1-40 J/cm ). Inflammatory mediators were analysed with RT-PCR and real-time PCR and protease activity analysis and immunocytofluorescence staining were performed for NHEKs. Changes in RLMS induced by LL-37 peptide were evaluated with real-time PCR, immunohistochemical staining and enzyme-linked immunosorbent assay. In NHEKs, LED at 630 and 940 nm significantly attenuated LL37, KLK5 and TLR-2 mRNA expressions. Protease activity was significantly suppressed at 630, 850 and 940 nm. In the RLMS, LL-37, KLK5 and PAR-2 mRNA expressions significantly decreased at 24 and 48 hours after LED irradiation was performed three times at 630 and 940 nm. mCAMP and IL-8 protein levels and protease activity after LED irradiation were lower than those in RLMS control groups. LED at 630 and 940 nm downregulated TLR-2, KLK5 and LL-37 expressions and protease activity in NHEK and RLMS. Thus, LEDs may be promising for rosacea treatment. However, clinical trials are required for further study.
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