Dasatinib Attenuates Fibrosis in Keloids by Decreasing Senescent Cell Burden.

Keloids are skin tumours caused by aberrant growth of dermal fibroblasts. Cellular senescence contributes to aging and various pathological conditions, including cancer, atherosclerosis, and fibrotic diseases. However, the effects of cellular senescence and senolytic drugs on keloids remain largely unknown. This study investigated senescent fibroblasts in keloids and assessed the effects of dasatinib on these cells. Tissues acquired from keloid removal surgery were analysed for senescence-associated ß-galactosidase-positive cells, p16 expression, and the effects of dasatinib treatment on keloids. Keloid tissue was xenotransplanted into mice, and the effect of intralesional dasatinib injection on keloid growth was observed. The results showed that the numbers of ß-galactosidase-positive and p16-expressing cells were higher in the keloids compared with in the controls. Dasatinib induced selective clearance of senescent cells and decreased procollagen expression in cultured keloid fibroblasts. In this xenotransplant keloid mouse model, intralesional injection of dasatinib reduced gross keloid tissue weight and the expression of both procollagen and p16. In addition, dasatinib-treated keloid fibroblasts conditioned medium reduced procollagen and p16 expression in cultured keloid fibroblasts. In conclusion, these results suggest that an increased number of senescent fibroblasts may play an important role in the pathogenesis of keloids. Therefore, dasatinib could be an alternative treatment for patients with keloids.

Adiponectin-Based Peptide (ADP355) Inhibits Transforming Growth Factor-ß1-Induced Fibrosis in Keloids.

Keloids, benign cutaneous overgrowths of dermal fibroblasts, are caused by pathologic scarring of wounds during healing. Current surgical and therapeutic modalities are unsatisfactory. Although adiponectin has shown an antifibrotic effect, its large size and insolubility limit its potential use in keloid treatment. We investigated the effect of a smaller and more stable adiponectin-based peptide (ADP355) on transforming growth factor ß1 (TGF-ß1)-induced fibrosis in a primary culture of keloid fibroblasts prepared from clinically obtained keloid samples. Xenograft of keloid tissues on athymic nude mice was used to investigate the effect of intralesional injection of ADP355. ADP355 significantly attenuated the TGF-ß1-induced expression of procollagen type 1 in keloid fibroblasts (p < 0.05). Moreover, it inhibited the TGF-ß1-induced phosphorylation of SMAD3 and ERK, while amplifying the phosphorylation of AMP-activated protein kinase (p < 0.05). Knockdown of adiponectin receptor 1 reversed the attenuation of procollagen expression in ADP355-treated TGF-ß1-induced fibrosis (p < 0.05). ADP355 also significantly reduced the gross weight and procollagen expression of keloid tissues in xenograft mice compared to control animals. These results demonstrate the therapeutic potential of the adiponectin peptide ADP355 for keloids.

Early detection of acral melanoma: A review of clinical, dermoscopic, histopathologic, and molecular characteristics.

Acral lentiginous melanoma is a distinct subtype of melanoma on acral skin. Patient presentation at later stages and delayed diagnosis by physicians contribute to a worse associated prognosis and survival rate. Despite our progress in understanding the key features of this disease, the diagnosis of early-stage acral melanoma is still challenging. It is essential to integrate clinical, dermoscopic, and histologic findings in the diagnosis of acral lentiginous melanoma. In addition, molecular studies can be helpful. In this review, we have summarized our current understanding of this disease entity from articles that were published between 1969 and 2018. We have outlined clinical and dermoscopic features as well as pathologic and molecular findings regarding acral melanoma and have presented an algorithm for diagnosis. Understanding and integrating these characteristics may assist clinicians in the early detection of acral melanomas.

Association between Breslow thickness and dermoscopic findings in acral melanoma.

BACKGROUND: Dermoscopy is a useful tool for the diagnosis of acral melanomas (AMs). However, little is known about the influence of tumor thickness on the dermoscopic findings of AM. OBJECTIVE: To investigate the affect Breslow thickness (BT) has on the dermoscopic patterns of AM. METHODS: Data on cases of AM on the glabrous skin were collected from 4 university hospitals. We investigated the frequency of each dermoscopic feature of AM according to the BT. Statistical analysis was performed to investigate the association between the specific dermoscopic patterns and BT. RESULTS: Multivariable analysis revealed that the colors red (odds ratio [OR] 16.482, 95% confidence interval [CI] 3.605-99.016); blue (OR 7.092; 95% CI 1.707-37.435); and white (OR 5.048, 95% CI 1.152-22.897) were more common in AM with BT >2 mm than those with BT ≤2 mm. Regarding patterns, atypical vascular (OR 34.589, 95% CI 6.458-305.852); blue-white veils (OR 9.605, 95% CI 1.971-72.062); and ulcers (OR 5.084, 95% CI 1.145-24.152) were more frequently detected in cases with BT >2 mm than those with BT ≤2 mm. LIMITATIONS: A retrospective study design and small sample size. CONCLUSION: This study showed an association between dermoscopic patterns and tumor thickness among patients with AM. Dermoscopy can be a useful adjuvant tool for predicting BT in AM.