Search Results (45)

Cutaneous malignant melanoma remains one of the most aggressive forms of skin cancer, characterized by high metastatic potential and resistance to standard therapies. Emerging evidence suggests that transient receptor potential (TRP) channels, non-selective cation channels involved in calcium homeostasis, and cellular stress responses play a pivotal role in melanoma development and progression. This review highlights the physiological expression of key TRP subfamilies (TRPM1, TRPM7, TRPM8, TRPV1, TRPV4, and TRPM2) in melanocytes and discusses their dysregulation in melanoma cells. TRPM1 is implicated as a tumor suppressor, whereas TRPM7, TRPV1, and TRPV4 often function as both melanoma suppressor or oncogenic drivers, modulating proliferation, apoptosis, and metastasis. TRPM2, which is responsive to oxidative stress, supports melanoma cell survival under metabolic stress. The potential of TRP channels as diagnostic biomarkers and therapeutic targets is evaluated, with attention paid to current pharmacological approaches and research challenges. The complexity and context-dependency of TRP function in melanoma underscore the need for isoform-specific modulation and personalized therapeutic strategies. Full article

Melanoma is a type of skin cancer that originates in the melanocytes, the epidermis’ basal layer. The skin has traditionally been an attractive administration location for drug delivery in tumor therapy, and it is composed of three layers: the outermost stratum corneum (SC), the middle epidermis, and the deepest layer, the dermis. Melanoma can be treated using a variety of methods, such as chemotherapy, surgery, radiotherapy, and biological therapy, but all are expensive and have side effects. Furthermore, the SC is the primary barrier that contributes to the impermeability of the skin, which is a limitation in epidermal drug transport and can aid in achieving effective drug concentration with minimal side effects at the target location. Microneedles (MNs) are tiny needles that are easy to use, inexpensive, and non-toxic. In recent years, MNs have been significantly studied for the treatment of melanoma due to their excellent biocompatibility, minimal invasion, high patient compliance, simple penetration process, and high SC penetration rate. Most notably, MNs can provide efficient and seldom unpleasant delivery carriers and synergistic effectiveness by combining multi-model techniques with immunotherapy, gene therapy, photodynamic therapy (PDT), and photothermal treatment (PTT). This review will focus on biocompatibility, biodegradability, limitations, fabrication materials, release mechanisms, and delivery of the therapeutics of MNs for melanoma treatment. Full article

Optical coherence tomography (OCT) is a cellular-resolution imaging technique that can be used as non-invasive and real-time imaging and is useful for detecting early stages of diseases. Five in vitro skin cells were measured by the Mirau-based full-field OCT, including keratinocyte (HaCaT cell line), melanocyte, squamous cell carcinoma cell line (A431), and two melanoma cell lines, i.e., A375 and A2058. Deep learning algorithms (particularly convolutional neural networks, CNN) that extract features from images efficiently process the OCT’s complex images. We used four models to classify the images of five types of 2D-OCT skin cells. Based on the ResNet-15 model, the mean accuracy (average accuracy of 10-fold cross-validation) reaches 98.47%, and the standard deviation is only 0.28% with the data augmentation method. Interestingly, while two normal skin cell images mix and the other three cancer skin cell images mix, the model still works to identify normal and cancer cell features. The mean accuracy reaches 96.77%. Furthermore, we used k-fold analysis to detect the model reliability and adopt the Gradient-weighted Class Activation Mapping (GRAD-CAM) to explain the discrimination results. The deep learning algorithm is successfully and efficiently applied to discriminate the OCT skin cell images. Full article

Objective: Ex vivo confocal laser scanning microscopy (EVCM) is an emerging imaging technique, which offers rapid tissue examination. While the current literature shows promising results in the evaluation of non-melanoma skin cancer, only limited research exists on the application of EVCM in melanocytic lesions. This study aimed to assess the utility of EVCM in the characterization of melanocytic lesions and compare its findings with gold-standard histopathology. Methods: A total of 130 skin lesions, including 76 benign and 54 malignant melanocytic lesions, were prospectively collected and imaged using EVCM. Three blinded investigators were asked to identify characteristic morphologic features observed in the lesions and classify them into benign vs. malignant. The results were then compared with the corresponding histopathology. Sensitivity and specificity were calculated using contingency tables to assess the diagnostic performance. Results: The application of EVCM allowed for the visualization of cellular and tissue-level details, including cellular pleomorphism and atypical melanocytes. A comprehensive list of benign and malignant features identified by EVCM was compiled. Using these diagnostic criteria, the imaging of the inexperienced and dermatohistopathology-experienced investigator reached 67.7% concordance, and the imaging trained dermatologist obtained 69.2% agreement with dermatohistopathology in differentiating benign vs. malignant lesions. The imaging-trained dermatohistopathologist performed best with concordance up to 79.2%. Conclusions: In conclusion, EVCM is a promising technique for the rapid assessment of melanocytic lesions. Our study provides a comprehensive overview of morphologic EVCM features, which will contribute to the development of diagnostic algorithms for accurate diagnosis and appropriate treatment planning. Further studies are needed to evaluate its clinical utility and validate our diagnostic criteria. Full article

Background/Objectives: With regard to excision of pigmented lesions for detection of malignant melanoma (MM), the number needed to treat (NNT) describes the number of melanocytic nevi that need to be biopsied/excised to detect one MM. The aim should be a low NNT. Methods: Single-center data analysis, including dermatohistopathological records of all nevi and MM cases during 2004–2013 at the Department of Dermatology, University Hospital Regensburg (UKR), was performed. We calculated the NNT, correlating it with the patient’s age and referring physician. The MM to MM in situ ratio was calculated to quantify early detection. As a secondary objective, we stratified into a pre- and post-2008 dataset, coinciding with the introduction of statutory skin cancer screening in Germany. Results: The overall NNT of 118,668 pigmented lesions was 17.2. We found a linear decrease in NNT towards older patients (R² = 62%; p < 0.001). The impact of skin cancer screening in 2008 was marked by a reduction in biopsies/excisions, a shift in age distribution, and a decrease in the NNT from 20.3 to 14.7. Office-based dermatologists had an NNT of 22.3, UKR-based dermatologists had an NNT of 8.0, and non-dermatologists had an NNT of 16.5. Conclusions: The age-related decrease in the NNT emphasizes the importance of age stratification for pigmented lesions. The NNT differed between professional settings. The implementation of skin cancer screening in 2008 was associated with a reduced NNT. Full article

Melanoma (malignant melanoma, MM) is an aggressive malignant skin cancer with an increasing incidence rate. The complete pathogenesis of MM in not clear. Due to DNA damage, mutations, dysregulation of growth factors, inactivation of tumor suppressor genes, and activation of oncogenes, excessive uncontrolled growth of abnormal melanocytes occurs in melanomas. Caspases are a group of proteolytic enzymes that participate in several processes important in regulating mechanisms at the cellular level. They play a role in cell homeostasis and programmed cell death (apoptosis) and in the regulation of non-apoptotic cell death processes. Dysregulation of caspase activation plays a role in the etiology of cancers, including melanoma. Caspases can initiate and execute apoptosis and are involved in regulating cell death and controlling tumor growth. These enzymes also inhibit tumor growth by cleaving and inactivating proteins that are involved in cell proliferation and angiogenesis. Moreover, caspases are involved in the activation of immune processes through the processing and presentation of tumor antigens, which facilitates recognition of the tumor by the immune system. The role of caspases in melanoma is complex, and they may inhibit melanoma growth and progression. This work aims to review the current knowledge of the role of individual caspases in melanoma pathogenesis. Full article

Keratinocytes are major cellular components of the skin and are strongly involved in its homeostasis. Oncogenic events, starting mainly from excessive sun exposure, lead to the dysregulation of their proliferation and differentiation programs and promote the initiation and progression of non-melanoma skin cancers (NMSCs). Primary melanomas, which originate from melanocytes, initiate and develop in close interaction with keratinocytes, whose role in melanoma initiation, progression, and immune escape is currently being explored. Recent studies highlighted, in particular, unexpected modes of communication between melanocytic cells and keratinocytes, which may be of interest as sources of new biomarkers in melanomagenesis or potential therapeutic targets. This review aims at reporting the various contributions of keratinocytes in skin basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), and melanoma, with a greater focus on the latter in order to highlight some recent breakthrough findings. The readers are referred to recent reviews when contextual information is needed. Full article

The occurrence of second primary malignancies is becoming increasingly important among cancer survivors. Melanoma, an aggressive neoplasm originating from the melanocytes, is responsible for most skin cancer-related deaths. This review aims to explore the risk of melanoma occurrence as a second primary cancer after the most common subtypes of hematologic neoplasia, a malignant disease originating from myeloid or lymphocytic cell lineages. Chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL) are among the most associated subtypes with melanoma development. We also discuss the underlying hypotheses that may explain the associations between these malignancies and the impact of melanoma on survival. The review emphasizes the importance of increasing awareness of melanoma risk in hematologic cancer survivors, as it can lead to prompt recognition, improved skin surveillance, and better survival outcomes. Full article

Early detection of cancer via biomarkers is vital for improving patient survival rates. In the case of skin cancers, low-molecular-weight biomarkers can penetrate the skin barrier, enabling non-invasive sampling at an early stage. This study focuses on detecting tryptophan (Trp) and kynurenine (Kyn) on the surface of reconstructed 3D melanoma and melanocyte models. This is examined in connection with IDO-1 and IL-6 expression in response to IFN-γ or UVB stimulation, both crucial factors of the melanoma tumor microenvironment (TME). Using a polystyrene scaffold, full-thickness human skin equivalents containing fibroblasts, keratinocytes, and melanocytes or melanoma cells were developed. The samples were stimulated with IFN-γ or UVB, and Trp and Kyn secretion was measured using HPLC-PDA and HPLC-MS. The expression of IDO-1 and IL-6 was measured using RT-qPCR. Increased Trp catabolism to Kyn was observed in IFN-γ-stimulated melanoma and melanocyte models, along with higher IDO-1 expression. UVB exposure led to significant changes in Kyn levels but only in the melanoma model. This study demonstrates the potential of skin surface Trp and Kyn monitoring to capture TME metabolic changes. It also lays the groundwork for future in vivo studies, aiding in understanding and monitoring skin cancer progression. Full article

Nonmelanocytic skin cancers (NMSCs) are currently the most common group of human cancers and include all tumors that are not melanomas. Increased exposure to sunlight over the past few years, the lack of regular and proper use of sunscreen, the aging of the population, and better screening techniques are the reasons for the escalation in their diagnosis. Squamous cell carcinoma (SCC) comprises nearly 37% of the tumors in this group and can originate from actinic keratosis (AK), which usually presents as pink, often scaly plaques, usually located on the face or scalp. Advances in dermatoscopy, as well as the development of other non-invasive skin imaging modalities such as high-frequency ultrasound (HFUS), reflectance confocal microscopy (RCM), and optical coherence tomography (OCT), have allowed for greatly increased sensitivity in diagnosing these lesions and monitoring their treatment. Since AK therapy is usually local, and SCCs must be removed surgically, non-invasive imaging methods enable to correctly qualify difficult lesions. This is especially important given that they are very often located on the face, and achieving an appropriate cosmetic result after treatments in this area is very important for the patients. In this review, the authors describe the use of non-invasive skin imaging methods in the diagnosis of actinic keratosis. Full article

Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) are the most frequently occurring non-melanocytic skin cancers. The objective of our study is to present the pathophysiology of BCC and cSCC and its direct relationship with the histopathological diagnostics and the differential diagnostics of these types of cancer, based on the morphological characteristics, immunohistochemical profile, and genetic alterations. The qualitative study was based on emphasizing the morphological characteristics and immunohistochemistry profiles of BCC and cSCC and the differential diagnostics based on the tissue samples from the Clinical Pathology Department of Mures Clinical County Hospital between 2020 and 2022. We analyzed the histopathological appearances and immunohistochemical profiles of BCC and cSCC in comparison with those of Bowen disease, keratoacanthoma, hyperkeratotic squamous papilloma, metatypical carcinoma, pilomatricoma, trichoblastoma, Merkel cell carcinoma, pleomorphic dermal sarcoma (PDS), and melanoma. Our study showed the importance of the correct histopathological diagnosis, which has a direct impact on the appropriate treatment and outcome for each patient. The study highlighted the histopathological and morphological characteristics of NMSCs and the precursor lesions in HE and the immunohistochemical profile for lesions that may make the differential diagnosis difficult to establish. Full article

Background: Teledermatology is employed in the diagnosis and follow-up of skin cancer and its use was intensified during and after the COVID-19 pandemic. At the same time, demographic changes result in an overall increase in non-melanoma skin cancer and skin precancerous lesions. The aim of this study was to elucidate the role of teledermatology in comparison to conventional face-to-face dermatology for such lesions and determine the advantages and limitations of this workflow for patients and physicians. Methods: Research was performed using relevant keywords in MEDLINE and CENTRAL. Relevant articles were chosen following a predetermined standardized extraction form. Results: Diagnostic accuracy and interrater/intrarater agreement can be considered comparable—although lower—than in-person consultation. Improvement of particular features such as image quality, medical history availability, and teledermoscopy can further increase accuracy. Further aspects of limitations and advantages (mean time-to-assessment, time-to-treatment, cost-effectiveness) are discussed. Conclusions: Teledermatology has comparable diagnostic accuracy with face-to-face dermatology and can be utilized both for the effective triage of non-melanocytic epithelial tumors and precancerous lesions, as well as the follow-up. Easy access to dermatologic consultation with shorter mean times to diagnostic biopsy and/or treatment coupled with cost-effectiveness could compensate for the lower sensitivity of teledermatology and offer easier access to medical care to the affected populations. Full article

Preferentially Expressed Antigen in Melanoma (PRAME), a member of the cancer/testis antigen family, is central to the field of skin cancer diagnostics and therapeutics. As a nuclear receptor and transcriptional regulator, PRAME plays a critical role in inhibiting retinoic acid signalling, which is essential for cell differentiation and proliferation. Its aberrant overexpression in various malignancies, particularly cutaneous melanoma, is associated with more aggressive tumour phenotypes, positioning PRAME as both a diagnostic and prognostic marker. In melanoma, PRAME is typically highly expressed, in contrast to its weak or absent expression in benign nevi, thereby improving the accuracy of differential diagnoses. The diagnostic value of PRAME extends to various lesions. It is significantly expressed in uveal melanoma, correlating to an increased risk of metastasis. In acral melanomas, especially those with histopathological ambiguity, PRAME helps to improve diagnostic accuracy. However, its expression in spitzoid and ungual melanocytic lesions is inconsistent and requires a comprehensive approach for an accurate assessment. In soft tissue sarcomas, PRAME may be particularly helpful in differentiating melanoma from clear cell sarcoma, an important distinction due to their similar histological appearance but different treatment approaches and prognosis, or in detecting dedifferentiated and undifferentiated melanomas. In non-melanoma skin cancers such as basal cell carcinoma, squamous cell carcinoma, and Merkel cell carcinoma, the variable expression of PRAME can lead to diagnostic complexity. Despite these challenges, the potential of PRAME as a therapeutic target in melanoma is significant. Emerging immunotherapies, including T-cell-based therapies and vaccines targeting PRAME, are being investigated to exploit its cancer-specific expression. Ongoing research into the molecular role and mechanism of action of PRAME in skin cancer continues to open new avenues in both diagnostics and therapeutics, with the potential to transform the management of melanoma and related skin cancers. Full article

Hypertension is known to be a multifactorial disease associated with abnormalities in neuroendocrine, metabolic, and hemodynamic systems. Poorly controlled hypertension causes more than one in eight premature deaths worldwide. Hydrochlorothiazide (HCT) and furosemide (FUR), being first-line drugs in the treatment of hypertension, are among others the most frequently prescribed drugs in the world. Currently, many pharmacoepidemiological data associate the use of these diuretics with an increased risk of adverse phototoxic reactions that may induce the development of melanoma and non-melanoma skin cancers. In this study, the cytotoxic and phototoxic potential of HCT and FUR against skin cells varied by melanin pigment content was assessed for the first time. The results showed that both drugs reduced the number of metabolically active normal skin cells in a dose-dependent manner. UVA irradiation significantly increased the cytotoxicity of HCT towards fibroblasts by approximately 40% and melanocytes by almost 20% compared to unirradiated cells. In the case of skin cells exposed to FUR and UVA radiation, an increase in cytotoxicity by approximately 30% for fibroblasts and 10% for melanocytes was observed. Simultaneous exposure of melanocytes and fibroblasts to HCT or FUR and UVAR caused a decrease in cell viability, and number, which was confirmed by microscopic assessment of morphology. The phototoxic effect of HCT and FUR was associated with the disturbance of redox homeostasis confirming the oxidative stress as a mechanism of phototoxic reaction. UVA-irradiated drugs increased the generation of ROS by 10–150%, and oxidized intracellular thiols. A reduction in mitochondrial potential of almost 80% in melanocytes exposed to HCT and UVAR and 60% in fibroblasts was found due to oxidative stress occurrence. In addition, HCT and FUR have been shown to disrupt the cell cycle of normal skin cells. Finally, it can be concluded that HCT is the drug with a stronger phototoxic effect, and fibroblasts turn out to be more sensitive cells to the phototoxic effect of tested drugs. Full article

Non-melanocytic skin cancers represent an important public health problem due to the increasing incidence and the important local destructive potential. Thus, the early diagnosis and treatment of precancerous lesions (actinic keratoses) is a priority for the dermatologist. In recent years, non-invasive skin imaging methods have seen an important development, moving from simple observational methods used in clinical research, to true diagnostic and treatment methods that make the dermatologist’s life easier. Given the frequency of these precancerous lesions, their location on photo-exposed areas, as well as the long treatment periods, with variable, imprecise end-points, the need to use non-invasive imaging devices is increasingly evident to complete the clinical observations in the diagnosis and treatment of these lesions, with the aim of increasing accuracy and decreasing the adverse effects due to long treatment duration. This is the first review that brings together all skin imaging methods (dermoscopy, reflectance confocal microscopy, ultrasonography, dermoscopy-guided high frequency ultrasonography, and optical coherence tomography) used in the evaluation of actinic keratoses and their response to different treatment regimens. Full article