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Cancers Jun 2024In this study, we aimed to identify the features of indeterminate choroidal melanocytic lesions visualized on optical coherence tomography angiography (OCTA) and to...
In this study, we aimed to identify the features of indeterminate choroidal melanocytic lesions visualized on optical coherence tomography angiography (OCTA) and to identify the predictors of growth. We retrospectively evaluated 86 patients with indeterminate lesions treated at our centre from 2016 to 2021. Clinical management involved active surveillance followed by brachytherapy if growth was detected. The lesions were classified into two groups according to whether they grew (small melanomas) or remained stable (choroidal nevi). Growth was detected in 19 (22.1%) lesions. All patients underwent OCTA at baseline. These images were compared to identify the possible predictors of growth. Significant between-group differences were observed in thickness ( = 0.00), greatest basal diameter ( = 0.00), number of risk factors ( = 0.00), symptoms ( = 0.001; relative risk [RR]: 4.3), orange pigment ( = 0.00; RR: 6.02), and ultrasonographic hollowness (Kappa sign); = 0.000; RR: 5.3). The melanomas had significantly more vessels with a diameter ≥ 76.3 µm ( = 0.02; RR: 2.46). The time to growth in these lesions was significantly shorter ( = 0.05) than in lesions with smaller vessels. These findings show that vessel diameter quantified by OCTA can help differentiate between choroidal nevi and small melanomas, when considered together with clinical risk factors.
PubMed: 38927873
DOI: 10.3390/cancers16122167 -
International Immunopharmacology Jun 2024Melanoma is a skin cancer originating from melanocytes. The global incidence rate of melanoma is rapidly increasing, posing significant public health challenges....
Melanoma is a skin cancer originating from melanocytes. The global incidence rate of melanoma is rapidly increasing, posing significant public health challenges. Identifying effective therapeutic agents is crucial in addressing this growing problem. Natural products have demonstrated promising anti-tumor activity. In this study, a plant flavonoid, taxifolin, was screened using Weighted Correlation Network Analysis (WGCNA) in combination with the Connectivity Map (CMAP) platform. Taxifolin was confirmed to inhibit the proliferation, migration, and invasion ability of melanoma A375 and MV-3 cells by promoting apoptosis. Additionally, it suppressed the Epithelial-Mesenchymal Transition (EMT) process of melanoma cells. Cyber pharmacological analysis revealed that taxifolin exerts its inhibitory effect on melanoma through the PI3K/AKT signaling pathway, specifically by downregulating the protein expression of p-PI3K and p-AKT. Notably, the addition of SC-79, an activator of the PI3K/AKT signaling pathway, reversed the effects of taxifolin on cell migration and apoptosis. Furthermore, in vivo experiments demonstrated that taxifolin treatment slowed tumor growth in mice without significant toxic effects. Based on these findings, taxifolin holds promise as a potential drug for melanoma treatment.
PubMed: 38924866
DOI: 10.1016/j.intimp.2024.112517 -
Hematology Reports Jun 2024Hypopigmentation disorders pose significant diagnostic challenges in dermatology, sometimes reflecting underlying hematological conditions. This review explores the... (Review)
Review
Hypopigmentation disorders pose significant diagnostic challenges in dermatology, sometimes reflecting underlying hematological conditions. This review explores the clinical presentations related to hypopigmentation in hematological disorders, focusing on vitiligo, morphea, and syndromic albinism. Vitiligo, an autoimmune disorder targeting melanocytes, involves interactions between genetic polymorphisms and immune responses, particularly regarding CD8+ T cells and IFN-γ. Drug-induced vitiligo, notably by immune checkpoint inhibitors and small-molecule targeted anticancer therapies, underscores the importance of immune dysregulation. Morphea, an inflammatory skin disorder, may signal hematological involvement, as seen in deep morphea and post-radiotherapy lesions. Syndromic albinism, linked to various genetic mutations affecting melanin production, often presents with hematologic abnormalities. Treatment approaches focus on targeting the immune pathways specific to the condition, and when that is not possible, managing symptoms. Understanding these dermatological manifestations is crucial for the timely diagnosis and management of hematological disorders.
PubMed: 38921184
DOI: 10.3390/hematolrep16020036 -
Current Issues in Molecular Biology May 2024Melanocytes, located in the epidermis' basal layer, are responsible for melanin pigment production, crucial for skin coloration and protection against UV...
Melanocytes, located in the epidermis' basal layer, are responsible for melanin pigment production, crucial for skin coloration and protection against UV radiation-induced damage. Melanin synthesis is intricately regulated by various factors, including the Wnt signaling pathway, particularly mediated by the microphthalmia-associated transcription factor (MITF). While MITF is recognized as a key regulator of pigmentation, its regulation by the Wnt pathway remains poorly understood. This study investigates the role of Sfrp5pepD, a peptide antagonist of the Wnt signaling pathway, in modulating melanogenesis and its potential therapeutic implications for pigmentary disorders. To tackle this issue, we investigated smaller peptides frequently utilized in cosmetics or pharmaceuticals. Nevertheless, there is a significant scarcity of reports on peptides associated with melanin-related signal modulation or inhibiting melanin production. Results indicate that Sfrp5pepD effectively inhibits Wnt signaling by disrupting the interaction between Axin-1 and β-catenin, thus impeding downstream melanogenic processes. Additionally, Sfrp5pepD suppresses the interaction between MITF and β-catenin, inhibiting their nuclear translocation and downregulating melanogenic enzyme expression, ultimately reducing melanin production. These inhibitory effects are validated in cell culture models suggesting potential clinical applications for hyperpigmentation disorders. Overall, this study elucidates the intricate interplay between Wnt signaling and melanogenesis, highlighting Sfrp5pepD as a promising therapeutic agent for pigmentary disorders. Sfrp5pepD, with a molecular weight of less than 500 Da, is anticipated to penetrate the skin unlike SFRPs. This suggests a strong potential for their use as cosmetics or transdermal absorption agents. Additional investigation into its mechanisms and clinical significance is necessary to enhance its effectiveness in addressing melanin-related skin conditions.
PubMed: 38920996
DOI: 10.3390/cimb46060324 -
Wellcome Open Research 2023Schwannoma is a nerve sheath tumour arising from differentiated Schwann cells, and melanocytic schwannoma (MS) is a rare variant where the Schwan cells produce melanin...
Schwannoma is a nerve sheath tumour arising from differentiated Schwann cells, and melanocytic schwannoma (MS) is a rare variant where the Schwan cells produce melanin pigment. MS is typically associated with spinal nerve roots and there have been only ~20 reports of cutaneous or subcutaneous MS to-date in humans. In canines, there have only been two reports of MS, both associated with spinal root nerves. In this report, we describe a 7-year-old Weimaraner cross breed dog that presented with two pigmented lesions on the eyelids. The lesions were surgically removed and histological analysis revealed well-circumscribed, non-encapsulated, expansile, neoplasms that were displacing most of the dermis and adnexa. The first lesion was composed of spindloid cells arranged in short interlacing streams with large amounts of pale eosinophilic cytoplasm that sometimes contained fine melanin granules. In areas there were spindle cells arranged in verocay bodies which led to a diagnosis of MS. In contrast, the second lesion was composed of polygonal cells arranged in thick sheets with large amounts of pale eosinophilic cytoplasm that sometimes contained fine melanin granules. The diagnosis was melanocytoma (which is one of the macroscopic differential diagnoses for MS). Whilst melanocytoma is a commonly occurring cutaneous lesion in canines and surgical removal is considered curative, due to little being known about MS in dogs, the outcome remained guarded, as MS in humans has an unpredictable nature, and recurrence and metastasis have been reported.
PubMed: 38911282
DOI: 10.12688/wellcomeopenres.19694.2 -
Cureus May 2024Pigmented lesions in the oral cavity can arise from the accumulation of external substances or internal pigments, resulting in black or brown discoloration. The etiology...
Pigmented lesions in the oral cavity can arise from the accumulation of external substances or internal pigments, resulting in black or brown discoloration. The etiology can be categorized as physiologic, reactive, neoplastic, idiopathic, or indicative of systemic illness. Several systemic drugs have been linked to the development of oral and/or cutaneous pigmentation, either by stimulating the production of melanin or by the accumulation of the drug or its byproducts. The medications most commonly associated with this condition include antimalarials, hormones, oral contraceptives, phenothiazines, chemotherapeutics, amiodarone, minocycline, zidovudine, clofazimine, and ketoconazole. The aim of this case report is to illustrate the drug-induced appearance of multiple melanotic macules in an 89-year-old female patient. The patient was referred to the Department of Oral Medicine and Pathology, School of Dentistry, Aristotle University of Thessaloniki, Greece, complaining of the recent and constant appearance of black spots in her oral cavity. Her medical history revealed a multitude of prescribed drugs, with citalopram being the most recently prescribed one, approximately one year prior to the examination. The clinical examination revealed multiple melanotic macules, on the upper and lower lip as well as on the hard and soft palate. Based on these findings, a biopsy of a melanotic macule of the lip was carried out. The histopathological examination showed that the basal layer of the stratified squamous epithelium exhibited hyperpigmentation (melanin-pigmented basal cells). In addition, scattered melaninophages were noted in lamina propria. Psychotropic drugs associated with cutaneous hyperpigmentation include citalopram. Therefore, our case constitutes an exception since citalopram induced intraoral and perioral, instead of cutaneous, hyperpigmentation.
PubMed: 38910786
DOI: 10.7759/cureus.60889 -
Acta Neuropathologica Communications Jun 2024Neurofibromatosis Type 1 (NF1) is caused by loss of function variants in the NF1 gene. Most patients with NF1 develop skin lesions called cutaneous neurofibromas (cNFs)....
snRNA-seq of human cutaneous neurofibromas before and after selumetinib treatment implicates role of altered Schwann cell states, inter-cellular signaling, and extracellular matrix in treatment response.
Neurofibromatosis Type 1 (NF1) is caused by loss of function variants in the NF1 gene. Most patients with NF1 develop skin lesions called cutaneous neurofibromas (cNFs). Currently the only approved therapeutic for NF1 is selumetinib, a mitogen -activated protein kinase (MEK) inhibitor. The purpose of this study was to analyze the transcriptome of cNF tumors before and on selumetinib treatment to understand both tumor composition and response. We obtained biopsy sets of tumors both pre- and on- selumetinib treatment from the same individuals and were able to collect sets from four separate individuals. We sequenced mRNA from 5844 nuclei and identified 30,442 genes in the untreated group and sequenced 5701 nuclei and identified 30,127 genes in the selumetinib treated group. We identified and quantified distinct populations of cells (Schwann cells, fibroblasts, pericytes, myeloid cells, melanocytes, keratinocytes, and two populations of endothelial cells). While we anticipated that cell proportions might change with treatment, we did not identify any one cell population that changed significantly, likely due to an inherent level of variability between tumors. We also evaluated differential gene expression based on drug treatment in each cell type. Ingenuity pathway analysis (IPA) was also used to identify pathways that differ on treatment. As anticipated, we identified a significant decrease in ERK/MAPK signaling in cells including Schwann cells but most specifically in myeloid cells. Interestingly, there is a significant decrease in opioid signaling in myeloid and endothelial cells; this downward trend is also observed in Schwann cells and fibroblasts. Cell communication was assessed by RNA velocity, Scriabin, and CellChat analyses which indicated that Schwann cells and fibroblasts have dramatically altered cell states defined by specific gene expression signatures following treatment (RNA velocity). There are dramatic changes in receptor-ligand pairs following treatment (Scriabin), and robust intercellular signaling between virtually all cell types associated with extracellular matrix (ECM) pathways (Collagen, Laminin, Fibronectin, and Nectin) is downregulated after treatment. These response specific gene signatures and interaction pathways could provide clues for understanding treatment outcomes or inform future therapies.
Topics: Humans; Schwann Cells; Skin Neoplasms; Benzimidazoles; Extracellular Matrix; Signal Transduction; Neurofibroma; Female; Male; RNA-Seq; Middle Aged; Adult; Neurofibromatosis 1; Protein Kinase Inhibitors; Transcriptome
PubMed: 38907342
DOI: 10.1186/s40478-024-01821-z -
Archives of Dermatological Research Jun 2024High-frequency ultrasound has been used to visualize depth and vascularization of cutaneous neoplasms, but little has been synthesized as a review for a robust level of... (Review)
Review
High-frequency ultrasound has been used to visualize depth and vascularization of cutaneous neoplasms, but little has been synthesized as a review for a robust level of evidence about the diagnostic accuracy of high-frequency ultrasound in dermatology. A narrative review of the PubMed database was performed to establish the correlation between ultrasound findings and histopathologic/dermoscopic findings for cutaneous neoplasms. Articles were divided into the following four categories: melanocytic, keratinocytic/epidermal, appendageal, and soft tissue/neural neoplasms. Review of the literature revealed that ultrasound findings and histopathology findings were strongly correlated regarding the depth of a cutaneous neoplasm. Morphological characteristics were correlated primarily in soft tissue/neural neoplasms. Overall, there is a paucity of literature on the correlation between high-frequency ultrasound and histopathology of cutaneous neoplasms. Further studies are needed to investigate this correlation in various dermatologic conditions.
Topics: Humans; Skin Neoplasms; Ultrasonography; Skin; Dermoscopy; Melanoma
PubMed: 38904763
DOI: 10.1007/s00403-024-03179-7 -
International Journal of Surgery Case... Jul 2024Seborrheic keratosis (SK) is a common benign epidermal tumor usually presenting as small, non-pigmented lesions on the skin. However, giant SK presenting as a pigmented...
INTRODUCTION AND IMPORTANCE
Seborrheic keratosis (SK) is a common benign epidermal tumor usually presenting as small, non-pigmented lesions on the skin. However, giant SK presenting as a pigmented variant is a rare occurrences, with limited documented cases in medical literature.
CASE PRESENTATION
Here, we present a case report of a 70 year old female patient with an unusual giant warty cutaneous lesion prompting excisional biopsy. Histopathological examination revealed pigmented proliferative basaloid cell and pseudohorn cysts, characteristic of SK. Notably, the lesion exhibited pigmentation, adding to the rarity of the giant forms of SK case.
CLINICAL DISCUSSION
Giant pigmented seborrheic keratosis (GPSK) is an uncommon form that shares clinical and dermatoscopic features, frequently causing misdiagnosis as malignant melanoma.
CONCLUSION
Thus this report underscores the importance recognizing such atypical presentations of SK and highlights the need for histological evaluation to diagnose such variants.
PubMed: 38901381
DOI: 10.1016/j.ijscr.2024.109916 -
ELife Jun 2024Transport and localization of melanosome at the periphery region of melanocyte are depended on myosin-5a (Myo5a), which associates with melanosome by interacting with...
Transport and localization of melanosome at the periphery region of melanocyte are depended on myosin-5a (Myo5a), which associates with melanosome by interacting with its adaptor protein melanophilin (Mlph). Mlph contains four functional regions, including Rab27a-binding domain, Myo5a GTD-binding motif (GTBM), Myo5a exon F-binding domain (EFBD), and actin-binding domain (ABD). The association of Myo5a with Mlph is known to be mediated by two specific interactions: the interaction between the exon-F-encoded region of Myo5a and Mlph-EFBD and that between Myo5a-GTD and Mlph-GTBM. Here, we identify a third interaction between Myo5a and Mlph, that is, the interaction between the exon-G-encoded region of Myo5a and Mlph-ABD. The exon-G/ABD interaction is independent from the exon-F/EFBD interaction and is required for the association of Myo5a with melanosome. Moreover, we demonstrate that Mlph-ABD interacts with either the exon-G or actin filament, but cannot interact with both of them simultaneously. Based on above findings, we propose a new model for the Mlph-mediated Myo5a transportation of melanosomes.
Topics: Melanosomes; Myosin Type V; Animals; Mice; Adaptor Proteins, Signal Transducing; Protein Binding; Humans; Myosin Heavy Chains; Melanocytes
PubMed: 38900147
DOI: 10.7554/eLife.93662