Pigment Cell & Melanoma Research最新文献

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.

Ectothermic vertebrates exhibit a diverse array of pigment cell types—chromatophores—that provide valuable opportunities to uncover mechanisms of fate specification and how they evolve. Like melanocytes of mammals, the melanophores of teleosts and other ectotherms depend on basic helix–loop–helix leucine zipper transcription factors encoded by orthologues of MITF. A different chromatophore, the iridescent iridophore, depends on the closely related transcription factor Tfec. Requirements for the specification of other chromatophore lineages remain largely uncertain. Here we identify a new allele of the zebrafish Mitf gene, mitfa, that results in a complete absence of not only melanophores but also yellow-orange xanthophores. Harboring a missense substitution in the DNA-binding domain identical to previously isolated alleles of mouse, we show that this new allele has defects in chromatophore precursor survival and xanthophore differentiation that extend beyond those of mitfa loss-of-function. Additional genetic analyses revealed interactions between Mitfa and Tfec as a likely basis for the observed phenotypes. Our findings point to collaborative roles for Mitfa and Tfec in promoting chromatophore development, particularly in xanthophore lineages, and provide new insights into evolutionary aspects of MITF functions across vertebrates.

Over the years, the cosmetic industry has shifted its focus from synthtic to natural compounds. This change is driven not only by the safety profile of natural ingredients but also by increased consumer awareness about the products they use. As a result, many natural skincare products have been launched in recent years. Hyperpigmentation disorders, such as melasma, age spots (solar lentigines), post-inflammatory hyperpigmentation, freckles, and acanthosis nigricans, are significant concerns. These conditions not only pose pathological issues but also affect individuals' self-esteem. Consequently, treating hyperpigmentation by reducing melanogenesis has become a key area of interest in cosmetology. Among various natural compounds, piceatannol (PCT) shows great potential in treating hyperpigmentation. The primary mechanism previously explored is the inhibition of the tyrosinase enzyme, which is one of the most researched strategies for combating melanogenesis. Additionally, PCT has been shown to downregulate MITF expression, a key gene responsible for the transcription of various melanogenic proteins and enzymes. However, beyond these two mechanisms, little is known about how PCT may inhibit melanogenesis. In this review, we aim to bridge that gap. We will explore and speculate on the possible upstream signaling pathways to MITF, such as Nrf, FOXO3a, CREB, MAPK signaling, etc., where PCT could potentially act to inhibit melanogenesis. This review will not only pave the way for future research related to PCT and hyperpigmentation but also highlight pathways that could be targeted for developing cosmetics and treatments for hyperpigmentation disorders.

This review explores the current literature on conjunctival melanoma, a rare and complex periocular neoplasm, emphasizing the absence of a standardized treatment protocol and the associated management challenges. It examines the clinical, genetic, and histological features of conjunctival melanoma, alongside diagnostic methodologies and treatment strategies, drawing on the most recent bibliographic data. The literature was systematically reviewed using the PubMed database, offering insights into future research directions and highlighting innovative treatment approaches, particularly for advanced-stage disease.

The skin microbiome plays a crucial role in maintaining skin health, defending the body against harmful pathogens, and interacting with melanoma. The composition of the skin microbiome can be affected by factors like age, gender, ethnicity, lifestyle, diet, and UV exposure. Certain bacteria like Staphylococcus and Veillonella are important for wound healing, while Cutibacterium acnes can play a role in dermatoses. UV radiation alters the skin microbiome, originates a “UV-resistome” and can lead to skin cancer initiation. Specifically, Staphylococcus epidermidis has shown protective effects against skin cancer, whereas Cutibacterium acnes can induce apoptosis in melanocytes postirradiation. The microbiome also interacts with melanoma treatment, affecting responses to immune checkpoint inhibitors. Strategies like bacteriotherapy, involving the manipulation of the gut microbiome but also the skin microbiome (with the gut–skin axis or through topical treatment) could improve treatment outcomes and show promise in melanoma therapy. Understanding the complex interplay between the skin microbiome, UV exposure, and melanoma development is crucial for developing personalized therapeutic approaches. Investigation into the skin microbiome and its potential role in melanoma progression continues to be an exciting area of research with implications for future therapeutic interventions.