Search Results (560)

Ultraviolet B (UVB) radiation is a key factor in the overproduction of melanin in the skin. Melanocytes produce melanin through melanogenesis to protect the skin from UVB radiation-induced damage. However, excessive melanogenesis can lead to hyperpigmentation and increase the risk of malignant melanoma. Tyrosinase is the rate-limiting enzyme in melanogenesis; it catalyzes the oxidation of tyrosine to 3,4-dihydroxy-L-phenylalanine and subsequently to dopaquinone. Thus, inhibiting tyrosinase is a promising strategy for preventing melanogenesis and skin hyperpigmentation. White mulberry (Morus alba L.) is rich in antioxidants, and mulberry fruit extracts have been used as cosmetic skin-lightening agents. However, data on the capacity of mulberry fruit extracts to inhibit tyrosinase under UVB radiation-induced melanogenic conditions remain scarce, especially in an in vivo model. In this study, we evaluated the effects of a mulberry crude extract (MCE) on UVB radiation-induced melanogenesis in B16F10 melanoma cells and zebrafish embryos. The MCE significantly reduced tyrosinase activity and melanogenesis in a dose-dependent manner without inducing cytotoxicity. These effects are likely attributable to the antioxidant constituents of the extract. Our findings highlight the potential of this MCE as an effective tyrosinase inhibitor for the prevention of UVB radiation-induced skin hyperpigmentation. Full article

In this review, we explore the complexities of objectively assessing the response to immunotherapy in mycosis fungoides (MF), a prevalent form of cutaneous T-cell lymphoma. The core challenge lies in distinguishing between reactive and malignant lymphocytes amidst treatment, particularly given the absence of uniform pathological biomarkers for MF. We highlight the vital role of emerging histological technologies, such as multispectral imaging and spatial transcriptomics, in offering a more profound insight into the tumor microenvironment (TME) and its dynamic response to immunomodulatory therapies. Drawing on parallels with melanoma—another immunogenic skin cancer—our review suggests that methodologies and insights from melanoma could be instrumental in refining the approach to MF. We specifically focus on the prognostic implications of various TME cell types, including CD8+ tumor-infiltrating lymphocytes, natural killer (NK) cells, and histiocytes, in predicting therapy responses. The review culminates in a discussion about adapting and evolving treatment response quantification strategies from melanoma research to the distinct context of MF, advocating for the implementation of novel techniques like high-throughput T-cell receptor gene rearrangement analysis. This exploration underscores the urgent need for continued innovation and standardization in evaluating responses to immunotherapies in MF, a field rapidly evolving with new therapeutic strategies. Full article

Segmentation of skin lesions in dermoscopic images is critical for the accurate diagnosis of skin cancers, particularly malignant melanoma, yet it is hindered by irregular lesion shapes, blurred boundaries, low contrast, and artifacts, such as hair interference. Conventional deep learning methods, typically based on UNet or Transformer architectures, often face limitations in regard to fully exploiting lesion features and incur high computational costs, compromising precise lesion delineation. To overcome these challenges, we propose SGNet, a structure-guided network, integrating a hybrid CNN–Mamba framework for robust skin lesion segmentation. The SGNet employs the Visual Mamba (VMamba) encoder to efficiently extract multi-scale features, followed by the Dual-Domain Boundary Enhancer (DDBE), which refines boundary representations and suppresses noise through spatial and frequency-domain processing. The Semantic-Texture Fusion Unit (STFU) adaptively integrates low-level texture with high-level semantic features, while the Structure-Aware Guidance Module (SAGM) generates coarse segmentation maps to provide global structural guidance. The Guided Multi-Scale Refiner (GMSR) further optimizes boundary details through a multi-scale semantic attention mechanism. Comprehensive experiments based on the ISIC2017, ISIC2018, and PH2 datasets demonstrate SGNet’s superior performance, with average improvements of 3.30% in terms of the mean Intersection over Union (mIoU) value and 1.77% in regard to the Dice Similarity Coefficient (DSC) compared to state-of-the-art methods. Ablation studies confirm the effectiveness of each component, highlighting SGNet’s exceptional accuracy and robust generalization for computer-aided dermatological diagnosis. Full article

Malignant cutaneous melanoma is among the most aggressive forms of skin cancer, characterized by high metastatic potential and frequent resistance to standard therapies. Hydroxytyrosol, a phenolic compound derived from extra virgin olive oil, has shown promising anticancer properties in various models, yet its effects in 3D melanoma systems remain poorly understood. In this study, we used paired 3D spheroid models of non-tumorigenic (HEMa) and melanoma (C32) to assess the therapeutic potential of hydroxytyrosol. To evaluate the anti-tumoral effect of hydroxytyrosol, we performed cytotoxicity, metastasis, invasiveness, cell cycle arrest, apoptotic, and proteomic assays. Hydroxytyrosol treatment significantly impaired spheroid growth, reduced cell viability, and induced cell cycle arrest and apoptosis in C32 spheroids, with minimal cytotoxicity observed in HEMa models. Proteomic profiling further demonstrated that hydroxytyrosol selectively downregulated a network of oncogenic proteins, including ERBB2, ERBB3, ERBB4, VEGFR-2, and WIF-1, along with suppression of downstream PI3K-Akt and MAPK/ERK signaling pathways. In conclusion, compared to dabrafenib, hydroxytyrosol exerted a broader range of molecular effects and was more selective toward tumor cells. These findings support the use of hydroxytyrosol as a multi-targeted agent capable of attenuating melanoma progression through suppression of kinase signaling and tumor-stromal interactions. Full article

Malignant melanoma (MM) affects not only humans but also animals, with gray horses being particularly predisposed to acquiring the disease. Multiomics have greatly advanced the understanding of human MM. In contrasty little is known regarding the pathogenesis of gray-horse melanoma and the unique phenomenon of melanoma “dormancy” in some animals. To help close this gap in knowledge, melanoma tissue and intact skin collected from gray horses were subjected to transcriptome analysis using RNAseq. In the next step, cultured primary tumor cells and normal skin fibroblasts were established from gray horses, and their protein expression profiles were determined. The obtained data unambiguously identified gray-horse melanoma (ghM) as a malignant tumor, as reflected by the overrepresentation of pathways typically activated in human melanoma and other human cancers. These included the RAS/RAF/MAPK, the IRS/IGF1R, and the PI3K/AKT signaling networks. In addition, the obtained data suggest that the key molecules RAC1, RAS, and BRAF, which are frequently mutated in human melanoma, may also contain activating mutations in ghM, whilst PTEN may harbor loss-of-function mutations. This issue will be subject to downstream analyses determining the mutational status in ghM to further advance the understanding of this frequent disease in gray horses. Full article

Gene therapy involves introducing genetic material into cells to treat or prevent disease and offers highly targeted and potentially curative approaches for both inherited and acquired conditions. The skin is an especially suitable organ for gene therapy due to its accessibility, ease of sampling, rapid cell turnover, and the possibility for localized treatment with minimal systemic exposure. Gene therapy is being actively explored across a range of dermatological conditions, including recessive dystrophic epidermolysis bullosa, ichthyosis, psoriasis, chronic wounds, and melanoma, with therapeutic strategies encompassing viral vectors, non-viral delivery systems, gene editing technologies, RNA-based treatments, and cell-based approaches. These diverse methods aim to correct genetic defects, modulate immune responses, promote tissue repair, or selectively target malignant cells. This review examines the advancements and potential of gene therapies in addressing complex skin diseases, providing hope for improved patient outcomes and long-term care. Full article

Transient receptor potential classical or cation channels (TRPCs) are integral to tumor biology, particularly in maintaining Ca²⁺ homeostasis within cancer cells. TRPC5, a pH-sensitive member of this family, may act as a signaling molecule in the altered microenvironment of solid tumors, which are characterized by an inverted pH-gradient—with decreased extracellular and increased intracellular pH—that promotes tumor progression. This study addresses a gap in the field, as there is currently limited research on TRPC5, particularly regarding its potential role as a tumor marker. While TRPCs are known to be involved in cancer biology, the specific role of TRPC5 in solid tumors, including its potential role as a diagnostic marker, remains largely unexplored. This study is the first to examine TRPC5 expression profiles in common skin cancers, including basal cell carcinoma (BCC), squamous cell carcinoma (SCC), malignant melanoma (MM), and nevus cell nevi (NCN). Our findings reveal that the frequency of TRPC5 expression in BCC is significantly lower compared to SCC and epidermal portions of NCN and MM. These results suggest that TRPC5 could serve as an immunohistochemical marker to distinguish SCC from BCC. Additionally, this study lays the groundwork for future research into the role of TRPC5 in tumor progression and metastasis, especially since BCCs, which rarely metastasize, are predominantly negative for TRPC5. Full article

Skin cancer, including melanoma and non-melanoma cancers (basal and squamous cell carcinomas), is the most common type of cancer. UV radiation, family history, and genetic predisposition are the main risk factors. Although surgical excision is the standard treatment, essential oils are attracting growing interest for their anti-cancer effects. This study tested the effects of Juniperus excelsa M. Bieb. (Cupressaceae), Lavandula vera DC. (Lamiaceae), and Salvia fruticosa (Mill). (Lamiaceae) essential oils extracted from Middle Eastern medicinal plants on HaCaT (normal), A5 (benign), and II4 (low-grade malignant) keratinocytes. Essential oils were extracted from Juniperus excelsa, Lavandula vera, and Salvia libanotica using steam distillation and then were chemically analyzed. The oils were sterilized, dissolved in DMSO, and prepared at concentrations of 0.75, 0.5, and 0.25 mg/mL. Human keratinocyte (HaCaT), benign (A5), and malignant (II4) cell lines were cultured in DMEM and treated with the essential oils for 24 or 48 h. Cell viability was assessed using the Trypan Blue Exclusion Test, while cell proliferation was evaluated using the MTT assay. Statistical analysis was performed using ANOVA with appropriate post hoc tests, considering p < 0.05 as significant. The results show that J. excelsa is cytotoxic but lacks selectivity, limiting its efficacy. In contrast, L. vera and S. fruticosa preferentially target malignant cells, particularly at low concentrations, while sparing normal cells. These oils have dose-dependent anticancer effects, with L. vera efficacy increasing as the concentration increases. In conclusion, L. vera and S. fruticosa are promising candidates for the treatment of skin cancer, although further in vivo studies are required. Full article

Background/Objectives: Skin cancer remains a significant global health issue, driving the development of new treatment strategies to improve clinical outcomes and prevent recurrence. Traditional monotherapies often face obstacles such as bioactive resistance, prompting interest in combination therapies that enhance efficacy, while minimizing side effects. This study investigated the use of a co-nanoparticle approach of iron oxide nanoparticles (NPs) surface-functionalized with curcumin (Cur-FeONPs) delivered with prolonged-release interferon alpha (IFNα)-loaded PLGA NPs (IFNα-PLGANPs) for the synergistic treatment of malignant melanoma tested in A375 cells. Methods: Extensive in vitro characterization studies of the Cur-FeONPs and IFNα-PLGANPs were performed, including zeta-size profiling, morphological studies, and structural validation, in addition to cytotoxicity assessments on A375 melanoma and NIH-3T3 fibroblast cells. Results: The Cur-FeONP and IFNα-PLGANPs synthesis processes yielded NPs with an average size of 111.0 nm and 97.0 nm, respectively. Morphological and structural validation studies determined the successful synthesis of the nanoparticulate systems, with cell viability analyses displaying significant cytotoxicity against A375 melanoma cells for the combination treatment, when compared to the individual platforms, with a minimal effect on NIH-3T3 fibroblast cells. Conclusions: The results of this study present a promising synergistic approach for enhanced anticancer activity in A375 melanoma skin cancer cells, providing a potential platform for future preclinical and clinical studies. Full article

Early detection and continuous monitoring of diseases are critical to improving patient outcomes, treatment adherence, and diagnostic accuracy. Traditional melanoma diagnosis relies primarily on visual assessment and biopsy, with reported accuracies ranging from 50% to 90% and significant inter-observer variability. Among emerging diagnostic technologies, Raman spectroscopy has demonstrated considerable promise for non-invasive disease detection, particularly in early-stage skin cancer identification. A portable, real-time Raman spectroscopy system could significantly enhance diagnostic precision, reduce biopsy reliance, and expedite diagnosis. However, miniaturization of Raman spectrometers for portable use faces significant challenges, including weak signal intensity, fluorescence interference, and inherent trade-offs between spectral resolution and the signal-to-noise ratio. Recent advances in silicon photonics present promising solutions by facilitating efficient light collection, enhancing optical fields via high-index-contrast waveguides, and allowing compact integration of photonic components. This work introduces a numerical analysis of an integrated digital Fourier transform spectrometer implemented on a silicon-nitride (SiN) platform, specifically designed for Raman spectroscopy. The proposed system employs a switch-based digital Fourier transform spectrometer architecture coupled with a single optical power meter for detection. Utilizing a regularized regression method, we successfully reconstructed Raman spectra in the 800 cm⁻¹ to 1800 cm⁻¹ range, covering spectra of both benign and malignant skin lesions. Our results demonstrate the capability of the proposed system to effectively differentiate various skin cancer types, highlighting its feasibility as a non-invasive diagnostic sensor. Full article

Introduction: While not considered a genuine tumorigenic pathogen, the human cytomegalovirus (CMV) has been associated with a wide assortment of malignancies, including breast cancer (BC). In recent years, increasing evidence has been detailing the potential anti-oncogenic capabilities of CMV. Works in the literature addressing the issue are scarce, and a global approach elucidating the role of CMV in breast cancer is lacking. Aim: We inquired into the association between CMV and BC on a global level and surveyed the related literature. Material and Methods: Virus–tumor interaction was examined by correlating country-specific CMV seroprevalence and the age-standardized BC incidence rates for 73 countries, as provided by the International Agency for Research on Cancer (IARC). Statistical analysis was conducted using Spearman’s correlation, along with univariate and multivariate linear regression analysis. The literature review included works available in the PubMed^® database until and including February 2025. Results: The worldwide incidence of BC correlated strongly and inversely with CMV prevalence the world over (p < 0.001, Spearman ρ = −0.553). This association was upheld after univariate and multivariate linear regression, extending to other tumors such as skin melanoma and kidney cancer (p < 0.001). Conclusions: In this study, we draw attention to a previously unexplored global inverse relationship between the prevalence of CMV and the incidence of BC, which suggests a potential oncoprotective role for this pathogen. Although the association itself does not imply causality, these data provide an intriguing possibility of observing CMV as a tentative factor of protection against this malignancy. Full article

Background: Uveal melanoma (UM) is a relatively rare malignancy, yet it remains the most common primary intraocular cancer in adults. Several risk factors have been identified, including light iris color, fair skin tone, and cutaneous freckles. Methods: The aim of this article was an overview of the treatment methods for uveal melanoma, with a particular focus on emerging therapies such as tebentafusp and da-rovasertib. The research method was a review of the latest literature. Results: Genetic studies have uncovered key mutations in GNAQ and GNA11, which significantly contribute to UM pathogenesis. Treatment selection depends on tumor location and disease stage. In localized disease, radiotherapy—especially brachytherapy—is commonly used and generally effective. However, the prognosis worsens significantly once distant metastases, most often to the liver, develop, as no standard systemic therapy has demonstrated high efficacy in this setting. Recent years have seen the emergence of promising therapies, including tebentafusp, which stimulates immune responses against gp100-expressing melanoma cells, and darovasertib, a potent PKC inhibitor that targets MAPK pathway activation driven by GNAQ/GNA11 mutations. Both agents have shown encouraging tolerability; tebentafusp has demonstrated clinical benefit in Phase II and III trials, while darovasertib is still under investigation. Additionally, melphalan-based liver-directed therapy, particularly via hepatic arterial infusion (approved by the FDA), has shown potential in controlling liver-dominant disease in metastatic UM. This localized approach may provide significant benefit for patients with limited extrahepatic spread. Conclusions: Future research should focus on optimizing these novel strategies—tebentafusp, darovasertib, melphalan, and combination therapies—and on expanding our understanding of UM’s molecular drivers to enable the development of more effective, personalized treatments. Full article

Background/Objectives: Cowden syndrome (or PTEN hamartoma tumor syndrome) (CS/PHTS) belongs to a group of inherited disorders associated with the development of multiple hamartomas. The clinical presentation of patients may include dysmorphic facial features, macrocephaly, developmental delay, and multiple benign and malignant tumors of various localizations. At the same time, only thyroid cancer is thought to have an increased risk in childhood. Skin lesions in CS/PHTS occur in 90–100% of patients and include multiple tricholemmoma, papilloma, acral keratosis, pigmentation changes, as well as rarer forms like vascular malformations, fibromas, neuromas, melanoma, and basal cell carcinoma. Methods: Next-generation sequencing and Sanger sequencing were used to search for PTEN genetic variants. A histological and immunohistochemical examination of tumor biopsies and skin lesions was performed. Results: A total of 13 patients from six families with CS/PHTS, including 10 children, were described. Seven pediatric patients belonged to families with paternal transmission of the PTEN pathogenic variants, while three others were de novo cases. Atypical manifestations in CS/PHTS were diffuse large B-cell lymphoma in one adult, a renal cell carcinoma, three germ cell tumors, and a linear epidermal nevus in pediatric patients. A literature review of the identified pathogenic variants in the PTEN gene was performed, assessing their clinical significance and analyzing the traditional and modified diagnostic criteria as applied to the pediatric population. Conclusions: Taking into account the low incidence of CS/PHTS, the data presented significantly expand our current understanding of this disease and guide physicians to consider a wider range of possible malignant neoplasms in pediatric patients with CS/PHTS. Full article

Background/Objectives: Melanoma is an aggressive skin cancer with high metastatic potential and poor prognosis in advanced stages. Hesperidin, a natural flavonoid, has shown anticancer properties across various malignancies. This study aimed to evaluate the antiproliferative and pro-apoptotic effects of Hesperidin, alone and in combination with Cisplatin, on the human epidermoid carcinoma cell line A431. Materials and Methods: A431 cells were cultured under standard conditions and treated with different concentrations of Hesperidin and Cisplatin for 48 h. Cell viability was assessed using the MTT assay. Apoptosis was evaluated by Annexin V-FITC/PI staining and caspase-3/7 activity assays. Expression levels of Bax, caspase-3/7, and survivin were measured by RT-qPCR. Results: Hesperidin significantly reduced cell viability at both 24 and 48 h. Annexin V/PI staining revealed increased apoptosis, with the highest apoptotic ratio in the Hesperidin + Cisplatin group (p < 0.001). Caspase-3/7 activity was markedly elevated in Hesperidin-treated cells. RT-qPCR showed upregulation of Bax and caspase-3/7 and downregulation of survivin. Conclusions: Hesperidin demonstrated significant cytotoxic and pro-apoptotic effects in A431 cells. When combined with Cisplatin, a synergistic enhancement of apoptosis was observed. These findings support the potential of Hesperidin as a complementary agent in carcinoma therapy, pending further in vivo and clinical validation. Full article

Janus kinase inhibitors, including tofacitinib, filgotinib, and upadacitinib, have emerged as effective therapeutic options for the management of inflammatory bowel diseases (IBDs). By targeting the JAK-STAT signaling pathway, these agents modulate immune responses and reduce inflammation. However, concerns regarding the potential risk of malignancy associated with their use have gained significant attention. The JAK-STAT pathway is not only critical for inflammatory signaling but also plays a pivotal role in cellular growth, differentiation, and tumor surveillance. Observational studies and clinical trial data in rheumatoid arthritis have reported malignancies, including non-melanoma skin cancer and solid tumors, in patients receiving JAK inhibitors, with evidence suggesting variable risks depending on the selectivity of the agent. Current evidence does not suggest an increased risk of oncogenesis in patients with IBDs. Balancing therapeutic efficacy with long-term safety requires ongoing vigilance; patient stratification based on risk factors; and tailored monitoring strategies to mitigate potential adverse effects, including malignancies, during JAK inhibitor therapy. Long-term follow-up data of up to 10 years offer reassuring evidence that JAK inhibitor therapy in IBD patients does not confer an increased risk of malignancies, supporting their continued use within appropriate clinical settings. Full article