Pigment Cell & Melanoma Research最新文献

We have identified a chemically induced mouse mutation which increases the eumelanic hair pigmentation. We identify a coding mutation, A3533G, resulting in an amino acid substitution Y1133C, in the Gnas gene encoding the G_αs subunit of the tripartite G-protein, consistent with an activation of signalling via MC1R. In addition heterozygous mutant females are significantly lighter than wild type littermates. In cultured melanocytes, derived from mutant mice crossed to C57BL6 mice carrying Cdkn2a^tm1Rdp, basal pigmentation is higher than wild type melanocytes derived from litter mates. However, the addition of exogenous NDP-MSH does not increase pigmentation in mutant melanocytes in contrast to the pigmentation response of non-mutant melanocytes. The mutant and wild type cells respond in the same way to agouti signalling protein (ASP), consistent with ASP signalling mediated through a pathway other than G_αs-protein.

Pigment cells not only are intrinsic factors to determine animal patterns, but also play vital roles in numerous behavioral and physiological processes as well as health, such as melanomas originating from melanocytes. Model organisms are commonly used to study pigment cell development and the mechanisms underlying related diseases, with zebrafish and mice, and Xenopus being well-established examples. Xenopus tropicalis, a diploid amphibian model, offers advantages such as high fecundity and easily observable pigment cell development. Recent advancements in gene-editing techniques have increased its prominence in research on pigment cell biology and melanoma pathogenesis. Here, we compare the skin pigment cell distribution as well as the skin structure in X. tropicalis, zebrafish, mice, and humans and point out the potential value of using X. tropicalis to model human skin diseases, such as melanoma.

Uveal melanoma (UM) is an aggressive intraocular malignancy. Despite effective control of primary tumors, ~50% of UM patients develop metastases, with the liver being the predominant secondary site. BAP1 deficiency, present in ~80% of metastatic UM cases, is strongly associated with increased metastatic risk and poor prognosis. In silico analysis of UM patient samples suggests that reduced BAP1 is linked to enhanced expression of genes involved in fatty acid processing; therefore, we hypothesize that BAP1 deficiency primes UM cells for survival in the hepatic microenvironment by enhancing lipid tolerance and oxidative stress responses. Our findings demonstrate BAP1-mutant UM resist lipotoxicity, whereas BAP1-competent UM exhibit sensitivity due to lipid peroxide accumulation—a hallmark of ferroptotic-like stress, and a response that can be mitigated by ferroptosis inhibition. Using an ex vivo liver slice model, we found that disrupting lipid metabolism with atorvastatin, an HMG-CoA reductase inhibitor, reduced tumor burden of BAP1-mutant UM. Moreover, we demonstrate a positive correlation between BAP1 and an epigenetic regulator of lipid homeostasis, ASXL2. Notably, ASXL2 depletion in BAP1-competent UM phenocopies the lipotoxicity resistance observed in BAP1-mutant UM—an effect that may be mediated by altered PPAR expression. This study reveals a novel mechanism linking BAP1 expression to lipid sensitivity via ASXL2, providing insights into liver tropism and potential therapeutic avenues for metastatic uveal melanoma.

Evaluating measurement properties (MPs) of Patient Reported Outcome Measures (PROMs) in vitiligo is essential for evidence-based recommendations and identifying research gaps. This study assesses the quality of PROMs used in vitiligo. A systematic search of PubMed, Embase, and the Cochrane Library (up to 20 February 2024) included studies on PROM analysis or development, excluding those validating other tools. Quality assessments followed the COSMIN guidelines. PROMs with the highest number MPs rated sufficient (supported by moderate/high Quality of Evidence [QoE]) were reported per construct category, and information related to content validity specifically was provided. Forty articles on 24 PROMs (=161 MP studies) were analyzed. In the QoL group, the VIT, VLQI, VIP-FS, and ViPPO had the highest number of MPs rated sufficient (n = 3). For severity-related constructs, the Self-Assessment Vitiligo Extent Score (SA-VES) had the most MPs rated sufficient (n = 3). For treatment-related PROMs, the BMQ had the highest number MPs rated sufficient (n = 2). Content validity was limitedly assessed in 12 different PROMs. Comprehensive MP assessment and further validation of vitiligo PROMs are necessary to make definitive conclusions. These systematic reviews are registered at PROSPERO (CRD42020216338). Only English publications were included, which may limit the scope. Additionally, systematic searches conducted by different reviewers in consecutive updates may introduce subjectivity.

Vitiligo is the most common skin depigmentation disease, affecting 0.1%–2% of people in the world. 3.5%–20.5% of segmental patients account for the total number of vitiligo patients. It has been clinically observed that segmental vitiligo patients are more likely to generate white hair, which may be related to neuroendocrine factors. The color of human skin and hair is affected by the number and functional status of melanocytes. Vitiligo affects patients' physical and mental health due to the shame it causes from the white patches and hair. This article reviews the underlying mechanisms of segmental vitiligo with white hair based on skin and hair follicle melanocytes. The article attempts to propose possible targets for the treatment of this disease.

Oral melanoma is an aggressive neoplasm arising from melanocytes in the mucosal epithelium, accounting for 0.2%–0.8% of all melanomas. Unlike cutaneous melanoma, it is not associated with UV exposure, and its pathogenesis involves complex genetic and molecular alterations. This neoplasm predominantly affects older adults (≥ 60 years). Clinically, lesions often present as macular or nodular with an exophytic growth pattern, sometimes ulcerated, and exhibit varied pigmentation. Diagnosis is further complicated by non-pigmented (amelanotic) variants that can resemble other oral pigmentations. Wide surgical excision remains the mainstay treatment, often combined with chemotherapy; however, recurrence and distant metastasis remain high. While immunotherapy has shown promise in other melanoma subtypes, its efficacy in oral melanoma remains uncertain. Treatment in older adults is particularly challenging due to comorbidities and treatment-related morbidity. This review summarizes the epidemiology, clinical features, and current treatment strategies for oral melanoma in older adults. Key advances in the molecular mechanisms underlying this neoplasm are also outlined. As a strategic approach, integrating oral melanoma screening into routine geriatric dental care, supported by diagnostic algorithms, may improve early detection, prognosis, and survival outcomes in this vulnerable population.

Recent advances in avian melanogenesis have pinpointed multiple genetic loci associated with color polymorphisms, predominantly in the plumage of chickens, quails, and pigeons. However, the genetic basis of melaninization in parrot plumage remains elusive. Previously, we showed that mutations in the melanosomal ion-transporter SLC45A2 lead to a complete loss of blue structural color in green parrot feathers, leaving only yellow psittacofulvin. Yet, several color morphs involving partial or complete melanin reduction are common in captive-bred parrots that have not been studied. To bridge this gap, we investigated two new color morphs of parrot plumage: non-sex-linked recessive lutino (NSL), which entirely inhibits blue structural coloration, and the sex-linked recessive cinnamon, which reduces the intensity of blue structural coloration. Our genotypic analysis revealed that tyrosinase (TYR) variants are responsible for the NSL phenotype in Fischer's lovebird and green-cheeked parakeet, while tyrosinase related protein 1 (TYRP1) variants are associated with the cinnamon phenotype in the rose-ringed parakeet. When transfected into HEK293T cells, the candidate substitutions significantly affected tyrosinase enzymatic activity. This study underscores tyrosinase and related enzymes' role in parrot feather coloration, enhancing our understanding of avian melanogenesis as well as the conserved functions of melanogenic components across different species.