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skin cancer

Multisubunit Reconstruction of a Medial Canthal and Nasal Defect.

No abstract found

skin cancer

Combined Transpetrosal Approach: 2-Dimensional Operative Video.

This approach is suitable for petroclival lesions medial to V cranial nerve that extend in both middle and posterior fossa. It provides multiple surgical corridors with minimal brain retraction.

skin cancer

How to score the impact of treatment on cutaneous neurofibromas in clinical trials.

No abstract found

skin cancer

Apocrine cystadenoma: A long-standing apocrine hidrocystoma with an adenomatous proliferation.

Apocrine cystadenoma is a rare, benign adenomatous cystic neoplasm, the pathogenesis of which is not fully understood. We sought to characterize the clinical, dermatoscopic, and histopathologic features of apocrine cystadenoma and its relationship to hidrocystoma.

skin cancer

Recurrent and metastatic cellular cutaneous fibrous histiocytoma: A case report and literature review.

Cutaneous fibrous histiocytoma (FH) is considered a benign dermal tumor. The cellular variant is rare and poorly documented. Besides presenting a high risk of local recurrence, it has a low but serious metastatic potential. We present a case of metastatic cellular FH and also review the literature on this tumor, given its unusual metastatic development. A 47-year-old male patient presented with a lesion in the anterior surface of the right thigh, which has been present since adolescence but had grown during last year. Anatomopathological evaluation revealed a cellular FH, and the lesion was completely removed. Six months later, tumor recurrence with multiple compartment muscle involvement and pulmonary metastasis were detected. Both lesions were completely resected and after 3 years of follow-up, the patient is asymptomatic and free of the disease. We conclude that FH should be carefully sampled to detect variants with high local recurrence rates or with some metastatic risk such as the cellular one. We recommend wide surgical resection and a close follow-up including chest x-rays or thorax computed tomography (CT) in all cellular FH cases with local recurrence.

skin cancer

Immunotherapy-induced eczema treated with dupilumab.

No abstract found

skin cancer

DPYSL4 is a Prognostic Indicator Linked to Immune Infiltration in Gastric Cancer.

Dihydropyrimidinase like 4 (DPYSL4), expressed little in normal tissues, was reported as one of the gene family members to predict prognosis in melanoma; however, there are no reports about the link between DPYSL4 expression in gastric cancer and the tumor immune microenvironment.

skin cancer

Liver metastasis of breast carcinoma: An unusual presentation and growth pattern.

Breast carcinoma is one of the tumors that frequently metastasize to the liver. Extramedullary hematopoiesis (EMH) usually occurs due to insufficient medullary hematopoiesis. In this case report, we present a female patient with sinusoidal breast carcinoma metastasis and extramedullary hematopoiesis in liver biopsy. A 63-year-old female patient with history of breast carcinoma was admitted to our center with respiratory distress. Pleural effusion was detected and thoracentesis was planned. Treatment was given after detection of non-mycobacterial tuberculosis bacillus in the thoracentesis fluid. Antibiotherapy was terminated due to elevation of liver enzymes and bilirubin. The patient's clinical status was evaluated and treatment was re-initiated. The patient did not have any mass lesion in the liver. Tru-cut biopsy was performed to evaluate a possible tuberculosis involvement in the liver. The diagnosis of metastatic breast carcinoma located in the sinusoidal area and cholestatic liver with extramedullary hematopoiesis foci was given using the histomorphological, immunohistochemical and histochemical findings. Radiological evaluation has an important role in staging of malignancies. However, it should be kept in mind that hepatic metastases may present without formation of a mass lesion, and unexpected laboratory results of cases without abnormal radiological features should raise the suspicion of a metastasis. Such materials should be evaluated in detail by making multiple serial sections in the pathology laboratory. Rare metastatic tumor growth patterns not causing a mass lesion such as sinusoidal or portal pattern, should also be kept in mind.

skin cancer

Epidermal inclusion cyst embedded in benign fibrous histiocytic lesion with prominent epithelioid morphology.

Benign fibrous histiocytoma also known as dermatofibroma is one of the common mesenchymal neoplasms. It commonly develops in young adult with female predominance and predilection for the extremities, particularly lower extremities. Implantation of epidermis in the dermis or subcutaneous tissues may lead to the formation of epidermal inclusion cyst, which is the most common type of epithelial cyst. Development of epidermal inclusion cyst within a benign fibrous histiocytoma is a rare occurrence. This is a unique case of two unrelated lesions.

skin cancer

The role of R21 expression in differential diagnosis of melanocytic lesions.

Cyclic adenosine monophosphate (cAMP) is an intracellular signal transmitter involved in the regulation of melanocyte growth, proliferation, and melanogenesis. R21 is a monoclonal antibody against the soluble adenylyl cyclase (sAC) protein. Various nuclear and cytoplasmic R21 expression patterns in melanocytic lesions have been previously reported. Pan-nuclear staining was defined as specific for melanoma and was found supportive in the assessment of surgical margins.

skin cancer

Cutaneous eccrine spiradenoma: Insights into cytomorphological features via fine needle aspiration biopsy and a comprehensive literature review.

No abstract found

skin cancer

Vitamin D - a scoping review for Nordic nutrition recommendations 2023.

Vitamin D is an essential nutrient. Its role in calcium and phosphorous metabolism, and in the development and maintenance of a healthy skeleton is well documented. In addition, there is some evidence for vitamin D decreasing total mortality and cancer mortality modestly, but not cancer incidence. Vitamin D is unique, as both diet and sun induced production in skin are sources to this vitamin. Individual vitamin D status is thus a sum of both sun exposure and dietary intakes. The discovery of vitamin D receptors and the activation of biological active vitamin D in numerous tissues and organs in the body has given support to hypothesis on vitamin D having extra-skeletal functions. The scientific literature on vitamin D and several health outcomes is high in numbers and has been increasing exponentially the last two decades. However, despite this large body of scientific publications and improvement in study quality, vitamin D supplementation has not shown to give additional health benefits when status is in sufficient range (i.e. circulating 25 hydroxyvitamin D >50 nmol/L). Well-designed studies on insufficient or deficient individuals are lacking. The totality of evidence does not support that increased intake of vitamin D beyond current recommendation will have additional beneficial health effects.

skin cancer

Revisiting the safety profile: Understanding the link between Methotrexate and skin cancer in psoriasis patients.

No abstract found

skin cancer

A single-center retrospective analysis of prognoses in patients with melanoma brain metastases and effectiveness of treatment in Japan.

Melanoma brain metastasis (MBM) has a poor prognosis, although recent treatments, including immune checkpoint inhibitors and targeted therapy, have improved the prognosis. However, these systemic therapies have been reported to be less efficient for Asian patients. We investigated the survival of Asian patients with MBM and the effectiveness of systemic therapies.

skin cancer

Analyzing the Impact of Image Denoising and Segmentation on Melanoma Classification Using Convolutional Neural Networks.

Early skin cancer detection and its treatment are crucial for reducing death rates worldwide. Deep learning techniques have been used successfully to develop an automatic lesion detection system. This study explores the impact of pre-processing steps such as data augmentation, contrast enhancement, and segmentation on improving the convolutional neural network (CNN) performance for lesion classification. The classification network was designed from scratch by uniquely organizing its layers and using a different number of kernels, depth of the network, size, and hyperparameters. In addition, the network's performance was improved by pre-processing and segmentation steps. The proposed network was compared with the current state-of-the-art to demonstrate its best performance on the benchmark HAM10000 lesion dataset. The experimental study revealed that the classification network using denoised+segmented data achieved an accuracy (ACC), precision (PRE), recall (REC), specificity (SPE), and F-score of 93.40%, 93.45%, 94.51%, 92.08%, and 93.98%, respectively. To conclude, classification performance can be improved by incorporating pre-processing and segmentation steps.

skin cancer

DEPAS: De-novo Pathology Semantic Masks using a Generative Model.

The integration of artificial intelligence (AI) into digital pathology has the potential to automate and improve various tasks, such as image analysis and diagnostic decision-making. Yet, the inherent variability of tissues, together with the need for image labeling, lead to biased datasets that limit the generalizability of algorithms trained on them. One of the emerging solutions for this challenge is synthetic histological images. Debiasing real datasets require not only generating photorealistic images but also the ability to control the cellular features within them. A common approach is to use generative methods that perform image translation between semantic masks that reflect prior knowledge of the tissue and a histological image. However, unlike other image domains, the complex structure of the tissue prevents a simple creation of histology semantic masks that are required as input to the image translation model, while semantic masks extracted from real images reduce the process's scalability. In this work, we introduce a scalable generative model, coined as DEPAS (De-novo Pathology Semantic Masks), that captures tissue structure and generates high-resolution semantic masks with state-of-the-art quality. We demonstrate the ability of DEPAS to generate realistic semantic maps of tissue for three types of organs: skin, prostate, and lung. Moreover, we show that these masks can be processed using a generative image translation model to produce photorealistic histology images of two types of cancer with two different types of staining techniques. Finally, we harness DEPAS to generate multi-label semantic masks that capture different cell types distributions and use them to produce histological images with on-demand cellular features. Overall, our work provides a state-of-the-art solution for the challenging task of generating synthetic histological images while controlling their semantic information in a scalable way.

skin cancer

Multi-Level Swin Transformer Enabled Automatic Segmentation and Classification of Breast Metastases.

Detection of metastatic breast cancer lesions is a challenging task in breast cancer treatment. The recent advancements in deep learning gained attention owing to its robustness, particularly in addressing automated segmentation and classification issues in medical images. In this paper, we proposed a modified Swin Transformer model (mST) integrated with a novel Multi-Level Adaptive Feature Fusion (MLAFF) Module. We constructed a modified Swin Transformer network comprising of a Local Transferable MSA (LT-MSA) and a Global Transferable MSA (GT-MSA) in addition to a Feed Forward Network (FFN). Our novel Multi-Level Adaptive Feature Fusion (MLAFF) module iteratively combines the features throughout multiple transformers. We utilized a pre-trained deep learning model U-Net and trained it on mammography utilizing Transfer Learning for automated segmentation. The proposed method, mST-MLAFF, is used for breast cancer classification into normal, benign, and malignant classes. Our model outperformed comparison methods based on U-Net and Swin Transformer in breast metastatic lesion segmentation on the seven benchmark datasets, namely INBreast, DDSM, MIAS, CBIS-DDSM, MIMBCD-UI, KAU-BCMD, and Mammographic Masses. Our model achieved 98% Dice-Similarity coefficient (DSC) for segmentation and an average of 94.5% accuracy for classification, whereas U-Net based model achieved 92% DSC and Swin Transformer achieved 93% DSC. Extensive performance evaluation of our model on benchmark datasets shows the potential of our model for breast cancer classification.Clinical relevance- This research work is focused on assisting the radiologist in the early detection and classification of breast cancer. A single mammography image is analyzed in less than a minute for automated segmentation and classification into malignant and benign classes.

skin cancer

[Diagnoseverzögerung, komorbide Hidradenitis suppurativa und die prognostische Bedeutung bakterieller Kulturen bei Folliculitis decalvans: eine Kohortenstudie].

Folliculitis decalvans (FD) ist eine primäre neutrophile vernarbende Alopezie, die häufig zu irreversiblem Haarverlust führt. Daten zu Epidemiologie, klinischen Merkmalen, Folgen und prognostischen Faktoren sind nur eingeschränkt verfügbar. ZIEL: Die Beurteilung einer Patientenkohorte mit FD sowie die Charakterisierung schwerer Krankheitsverläufe und prognostischer Faktoren, die eine Remission verhindern.

skin cancer

Dissecting cellular states of infiltrating microenvironment cells in melanoma by integrating single-cell and bulk transcriptome analysis.

Cellular states of different immune cells can affect the activity of the whole immune microenvironment.

skin cancer

Mosquito control exposures and breast cancer risk: analysis of 1071 cases and 2096 controls from the Ghana Breast Health Study.

Epidemiologic data on insecticide exposures and breast cancer risk are inconclusive and mostly from high-income countries. Using data from 1071 invasive pathologically confirmed breast cancer cases and 2096 controls from the Ghana Breast Health Study conducted from 2013 to 2015, we investigated associations with mosquito control products to reduce the spread of mosquito-borne diseases, such as malaria. These mosquito control products were insecticide-treated nets, mosquito coils, repellent room sprays, and skin creams for personal protection against mosquitos. Multivariable and polytomous logistic regression models were used to estimate odds ratios (OR

skin cancer

From patient tissue correlates to molecular mechanisms of cancer immune evasion: the emerging role of CD58 and PD-L1 co-regulation via CMTM6.

Immune evasion is a hallmark of cancer, yet the underlying mechanisms are often unknown in many patients. Using single-cell transcriptomics analysis, we previously identified the co-stimulator CD58 as part of a cancer cell-intrinsic immune checkpoint resistance signature in patient melanoma tissue. We subsequently validated CD58 loss as a driver of immune evasion using a patient-derived co-culture model of cancer and cytotoxic tumor-infiltrating lymphocytes in a pooled single-cell perturbation experiment, where we additionally observed concurrent upregulation of PD-L1 protein expression in melanoma cells with CD58 loss. In our most recent study, we uncovered the mechanisms of immune evasion mediated by CD58 loss, including impaired T cell activation and infiltration within tumors, as well as inhibitory signaling by PD-L1 via a shared regulator, CMTM6. Thus, cancer cell-intrinsic reduction of CD58 represents a multi-faceted determinant of immune evasion. Furthermore, its reciprocal interaction with PD-L1 via CMTM6 provides critical insights into how co-inhibitory and co-stimulatory immune cues are regulated.

skin cancer

Modeling cardiac fibroblast heterogeneity from human pluripotent stem cell-derived epicardial cells.

Cardiac fibroblasts play an essential role in the development of the heart and are implicated in disease progression in the context of fibrosis and regeneration. Here, we establish a simple organoid culture platform using human pluripotent stem cell-derived epicardial cells and ventricular cardiomyocytes to study the development, maturation, and heterogeneity of cardiac fibroblasts under normal conditions and following treatment with pathological stimuli. We demonstrate that this system models the early interactions between epicardial cells and cardiomyocytes to generate a population of fibroblasts that recapitulates many aspects of fibroblast behavior in vivo, including changes associated with maturation and in response to pathological stimuli associated with cardiac injury. Using single cell transcriptomics, we show that the hPSC-derived organoid fibroblast population displays a high degree of heterogeneity that approximates the heterogeneity of populations in both the normal and diseased human heart. Additionally, we identify a unique subpopulation of fibroblasts possessing reparative features previously characterized in the hearts of model organisms. Taken together, our system recapitulates many aspects of human cardiac fibroblast specification, development, and maturation, providing a platform to investigate the role of these cells in human cardiovascular development and disease.

skin cancer

Protocol for a systematic review of reviews on training primary care providers in dermoscopy to detect skin cancers.

Globally, incidence, prevalence and mortality rates of skin cancers are escalating. Earlier detection by well-trained primary care providers in techniques such as dermoscopy could reduce unnecessary referrals and improve longer term outcomes. A review of reviews is planned to compare and contrast the conduct, quality, findings and conclusions of multiple systematic and scoping reviews addressing the effectiveness of training primary care providers in dermoscopy, which will provide a critique and synthesis of the current body of review evidence.

skin cancer

Retrospective Analysis of Radiation-Induced Complications of Uveal Melanoma Patients Treated With Brachytherapy in the Era of Anti-VEGF.

To associate clinical factors and radiation doses delivered by iodine-125 plaque brachytherapy to visual outcomes and development of radiation-induced ocular complications in patients with uveal melanoma in the era of anti-vascular endothelial growth factor (anti-VEGF) injections.

skin cancer

Photodynamic therapy for nodular basal cell carcinoma up to 5mm located on high-risk area: Effectiveness and long-term follow-up results.

Response rates evaluation of photodynamic therapy (PDT) for nodular basal cell carcinoma (BCC) treatment located on high-risk and low-risk areas of the face.

skin cancer

Microfluidic development and biological evaluation of targeted therapy-loaded biomimetic nano system to improve the metastatic melanoma treatment.

Optimizing current therapies is among next steps in metastatic melanoma (MM) treatment landscape. The innovation of this study is the design of production process by microfluidics of cell membrane (CM)-modified nanoparticles (NPs), as an emerging biomimetic platform that allows for reduced immune clearance, long blood circulation time and improved specific tumor targeting. To achieve melanoma selectivity, direct membrane fusion between synthetic liposomes and CMs extracted from MM cell line was performed by microfluidic sonication approach, then the hybrid liposomes were loaded with cobimetinib (Cob) or lenvatinib (Lenva) targeting agents and challenged against MM cell lines and liver cancer cell line to evaluate homotypic targeting and antitumor efficacy. Characterization studies demonstrated the effective fusion of CM with liposome and the high encapsulation efficiency of both drugs, showing the proficiency of microfluidic-based production. By studying the targeting of melanoma cells by hybrid liposomes versus liposomes, we found that both NPs entered cells through endocytosis, whereas the former showed higher selectivity for MM cells from which CM was extracted, with 8-fold higher cellular uptake than liposomes. Hybrid liposome formulation of Cob and Lenva reduced melanoma cells viability to a greater extent than liposomes and free drug and, notably, showed negligible toxicity as demonstrated by bona fide haemolysis test. The CM-modified NPs presented here have the potential to broaden the choice of therapeutic options in MM treatment.

skin cancer

Age at Natural Menopause, Reproductive Lifespan, and the Risk of Late-Onset Psoriasis and Psoriatic Arthritis in Women: A Prospective Cohort Study.

Although a peak incidence of psoriasis in women aged around 60 years has been observed, the link between reproductive lifespan and late-onset psoriatic diseases is underexplored. This study aims to elucidate the association between reproductive lifespan and the risk of late-onset psoriasis and psoriatic arthritis (PsA). Utilizing the UK Biobank data, we conducted a prospective cohort study in postmenopausal women without baseline psoriatic diseases. The exposure variables included age at natural menopause (ANM) and duration from menarche to menopause, termed reproductive years. The outcome variables were incident psoriasis and PsA. We employed Cox regression analysis, factoring in polygenic risk scores for psoriatic diseases and recognized risk factors. We found that later ANM and longer reproductive years were significantly associated with decreased risks of late-onset psoriasis and PsA in a dose-dependent manner (P<.05). ANM after age 55 years led to a 34 and 46% risk reduction in late-onset psoriasis and PsA, respectively, compared with ANM before age 45 years (P<.001). The population-attributable risks of ANM were 17.4% for late-onset psoriasis and 21.6% for PsA. In conclusion, reproductive lifespan, with its inherent homeostasis, plays a pivotal yet overlooked role in late-onset psoriatic diseases. Investigations into estrogen-centric causes and sex-specific interventions are imperative.

skin cancer

Identifying critical quality metrics in Mohs Surgery: A national expert consensus process.

Amid a movement toward value-based healthcare, increasing emphasis has been placed on outcomes and cost of medical services. To define and demonstrate the quality of services provided by Mohs surgeons, it is important to identify and understand the key aspects of Mohs micrographic surgery (MMS) that contribute to excellence in patient care.

skin cancer

Metrics for Mohs: Responsible use of a potentially helpful tool.

No abstract found

skin cancer

Chemoimmunotherapy for Untreated Lung Cancer Brain Metastases: Systemic Before Local Therapy?

No abstract found

skin cancer

Membrane-bound Merkel cell polyomavirus middle T protein constitutively activates PLCγ1 signaling through Src-family kinases.

Merkel cell polyomavirus (MCV or MCPyV) is an alphapolyomavirus causing human Merkel cell carcinoma and encodes four tumor (T) antigen proteins: large T (LT), small tumor (sT), 57 kT, and middle T (MT)/alternate LT open reading frame proteins. We show that MCV MT is generated as multiple isoforms through internal methionine translational initiation that insert into membrane lipid rafts. The membrane-localized MCV MT oligomerizes and promiscuously binds to lipid raft-associated Src family kinases (SFKs). MCV MT-SFK interaction is mediated by a Src homology (SH) 3 recognition motif as determined by surface plasmon resonance, coimmunoprecipitation, and bimolecular fluorescence complementation assays. SFK recruitment by MT leads to tyrosine phosphorylation at a SH2 recognition motif (pMT

skin cancer

Tumor Cell Lysate-Based Multifunctional Nanoparticles Facilitate Enhanced mRNA Delivery and Immune Stimulation for Melanoma Gene Therapy.

Messenger ribonucleic acid (mRNA)-based gene therapy has great potential for cancer gene therapy. However, the effectiveness of mRNA in cancer therapy needs to be further improved, and the delivery efficiency and instability of mRNA limit the application of mRNA-based products. Both the delivery efficiency can be elevated by cell-penetrating peptide modification, and the immune response can be enhanced by tumor cell lysate stimulation, representing an advantageous strategy to expand the effectiveness of mRNA gene therapy. Therefore, it is vital to exploit a vector that can deliver high-efficiency mRNA with codelivery of tumor cell lysate to induce specific immune responses. We previously reported that DMP cationic nanoparticles, formed by the self-assembly of DOTAP and mPEG-PCL, can deliver different types of nucleic acids. DMP has been successfully applied in gene therapy research for various tumor types. Here, we encapsulated tumor cell lysates with DMP nanoparticles and then modified them with a fused cell-penetrating peptide (TAT-iRGD) to form an MLSV system. The MLSV system was loaded with encoded Bim mRNA, forming the MLSV/Bim complex. The average size of the synthesized MLSV was 191.4 nm, with a potential of 47.8 mV. The MLSV/mRNA complex promotes mRNA absorption through caveolin-mediated endocytosis, with a transfection rate of up to 68.6% in B16 cells. The MLSV system could also induce the maturation and activation of dendritic cells, obviously promoting the expression of CD80, CD86, and MHC-II both

skin cancer

Effect of a Perioperative Educational Video in Patients Undergoing Mohs Reconstruction: A Randomized Clinical Trial.

Skin cancer is the most common type of cancer in the United States, and most are treated with Mohs micrographic surgery (MMS) by fellowship-trained dermatologic surgeons. Complex reconstruction in cosmetically and functionally sensitive areas often requires a plastic surgery consult. The uncertainty regarding reconstructive options and cosmetic appearance is difficult emotionally and cognitively for patients.

skin cancer

A positive feedback loop between ZEB2 and ACSL4 regulates lipid metabolism to promote breast cancer metastasis.

Lipid metabolism plays a critical role in cancer metastasis. However, the mechanisms through which metastatic genes regulate lipid metabolism remain unclear. Here, we describe a new oncogenic-metabolic feedback loop between the epithelial-mesenchymal transition transcription factor ZEB2 and the key lipid enzyme ACSL4 (long-chain acyl-CoA synthetase 4), resulting in enhanced cellular lipid storage and fatty acid oxidation (FAO) to drive breast cancer metastasis. Functionally, depletion of ZEB2 or ACSL4 significantly reduced lipid droplets (LDs) abundance and cell migration. ACSL4 overexpression rescued the invasive capabilities of the ZEB2 knockdown cells, suggesting that ACSL4 is crucial for ZEB2-mediated metastasis. Mechanistically, ZEB2-activated ACSL4 expression by directly binding to the ACSL4 promoter. ACSL4 binds to and stabilizes ZEB2 by reducing ZEB2 ubiquitination. Notably, ACSL4 not only promotes the intracellular lipogenesis and LDs accumulation but also enhances FAO and adenosine triphosphate production by upregulating the FAO rate-limiting enzyme CPT1A (carnitine palmitoyltransferase 1 isoform A). Finally, we demonstrated that ACSL4 knockdown significantly reduced metastatic lung nodes in vivo. In conclusion, we reveal a novel positive regulatory loop between ZEB2 and ACSL4, which promotes LDs storage to meet the energy needs of breast cancer metastasis, and identify the ZEB2-ACSL4 signaling axis as an attractive therapeutic target for overcoming breast cancer metastasis.

skin cancer

BRAF and MEK inhibitor combinations induce potent molecular and immunological effects in NRAS-mutant melanoma cells: Insights into mode of action and resistance mechanisms.

About 25% of melanoma harbor activating NRAS mutations, which are associated with aggressive disease therefore requiring a rapid antitumor intervention. However, no efficient targeted therapy options are currently available for patients with NRAS-mutant melanoma. MEK inhibitors (MEKi) appear to display a moderate antitumor activity and also immunological effects in NRAS-mutant melanoma, providing an ideal backbone for combination treatments. In our study, the MEKi binimetinib, cobimetinib and trametinib combined with the BRAF inhibitors (BRAFi) encorafenib, vemurafenib and dabrafenib were investigated for their ability to inhibit proliferation, induce apoptosis and alter the expression of immune modulatory molecules in sensitive NRAS-mutant melanoma cells using two- and three-dimensional cell culture models as well as RNA sequencing analyses. Furthermore, NRAS-mutant melanoma cells resistant to the three BRAFi/MEKi combinations were established to characterize the mechanisms contributing to their resistance. All BRAFi induced a stress response in the sensitive NRAS-mutant melanoma cells thereby significantly enhancing the antiproliferative and proapoptotic activity of the MEKi analyzed. Furthermore, BRAFi/MEKi combinations upregulated immune relevant molecules, such as ICOS-L, components of antigen-presenting machinery and the "don't eat me signal" molecule CD47 in the melanoma cells. The BRAFi/MEKi-resistant, NRAS-mutant melanoma cells counteracted the molecular and immunological effects of BRAFi/MEKi by upregulating downstream mitogen-activated protein kinase pathway molecules, inhibiting apoptosis and promoting immune escape mechanisms. Together, our study reveals potent molecular and immunological effects of BRAFi/MEKi in sensitive NRAS-mutant melanoma cells that may be exploited in new combinational treatment strategies for patients with NRAS-mutant melanoma.

skin cancer

Fibroblast Growth Factor Receptor 2 Overexpression in Multiple Familial Trichoepithelioma.

No abstract found

skin cancer

Systemic therapy timing and use in patients with advanced melanoma at the end of life: A retrospective cohort study.

Novel systemic therapies for advanced melanoma improve survival, but carry potential serious side effects and high costs. This study aimed to assess the timing and use of systemic therapies in the months before death. Patients diagnosed with advanced melanoma (July 2017-June 2020) who died before July 2020 were selected from the Netherlands Cancer Registry. We evaluated the timing of systemic therapies within 30 days and 3 months before death, and studied patient and tumor characteristics associated with systemic therapy use between diagnosis and death. Out of 1097 patients 68% received systemic therapy. Almost 25% and 10% started a new therapy within 90 days and within 30 days before death, respectively. Female sex, elevated LDH, BRAF mutation, poor ECOG performance status (≥3), and high comorbidity index reduced the odds of receiving immune therapy. Poor performance status and high comorbidity decreased the odds for both therapies. A considerable number of patients started systemic therapy shortly before death, emphasizing the importance of considering potential benefits and drawbacks through shared decision-making.

skin cancer

Characterization of CD4 T-cell phenotype in human leukocyte antigen class II-positive acral melanoma.

No abstract found

skin cancer

Delineating effect of headgroup and preparation method on transfection versus toxicity of DNA-loaded lipid nanocarriers.

skin cancer

Antibody landscape of C57BL/6 mice cured of B78 melanoma via a combined radiation and immunocytokine immunotherapy regimen.

Sera of immune mice that were previously cured of their melanoma through a combined radiation and immunocytokine immunotherapy regimen consisting of 12 Gy of external beam radiation and the intratumoral administration of an immunocytokine (anti-GD2 mAb coupled to IL-2) with long-term immunological memory showed strong antibody-binding against melanoma tumor cell lines via flow cytometric analysis. Using a high-density whole-proteome peptide array (of 6.090.593 unique peptides), we assessed potential protein-targets for antibodies found in immune sera. Sera from 6 of these cured mice were analyzed with this high-density, whole-proteome peptide array to determine specific antibody-binding sites and their linear peptide sequence. We identified thousands of peptides that were targeted by these 6 mice and exhibited strong antibody binding only by immune (after successful cure and rechallenge), not naïve (before tumor implantation) sera and developed a robust method to detect these differentially targeted peptides. Confirmatory studies were done to validate these results using 2 separate systems, a peptide ELISA and a smaller scale peptide array utilizing a slightly different technology. To the best of our knowledge, this is the first study of the full set of germline encoded linear peptide-based proteome epitopes that are recognized by immune sera from mice cured of cancer via radio-immunotherapy. We furthermore found that although the generation of B-cell repertoire in immune development is vastly variable, and numerous epitopes are identified uniquely by immune serum from each of these 6 immune mice evaluated, there are still several epitopes and proteins that are commonly recognized by at least half of the mice studied. This suggests that every mouse has a unique set of antibodies produced in response to the curative therapy, creating an individual "fingerprint." Additionally, certain epitopes and proteins stand out as more immunogenic, as they are recognized by multiple mice in the immune group.

skin cancer

Single-cell sequencing analysis related to sphingolipid metabolism guides immunotherapy and prognosis of skin cutaneous melanoma.

We explore sphingolipid-related genes (SRGs) in skin melanoma (SKCM) to develop a prognostic indicator for patient outcomes. Dysregulated lipid metabolism is linked to aggressive behavior in various cancers, including SKCM. However, the exact role and mechanism of sphingolipid metabolism in melanoma remain partially understood.

skin cancer

Prognostic value of body composition on survival outcomes in melanoma patients receiving immunotherapy.

The influence of body composition on the effectiveness of immune checkpoint inhibitors (ICIs) in patients with melanoma is still uncertain in clinical practice. Therefore, the objective of this study was to examine the potential association between body composition and clinical outcomes in patients with melanoma undergoing ICIs treatment.

skin cancer

FANCI serve as a prognostic biomarker correlated with immune infiltrates in skin cutaneous melanoma.

As a member of tumor, Skin cutaneous melanoma (SKCM) poses a serious threat to people's health because of its strong malignancy. Unfortunately, effective treatment methods for SKCM remain lacking. FANCI plays a vital role in the occurrence and metastasis of various tumor types. However, its regulatory role in SKCM is unclear. The purpose of this study was to explore the association of FANCI with SKCM.

skin cancer

Development of a flow cytometric panel to assess prognostic biomarkers in fine needle aspirates of canine cutaneous or subcutaneous mast cell tumors.

Mast cell tumor (MCT) is a common skin cancer in dogs that has a wide range of clinical behaviors. The purpose of this study was to develop a novel multicolor flow cytometry (FC) panel that will enable the quantification of candidate prognostic markers (Ki-67 and pKIT) in fine needle aspirate (FNA) samples prior to surgical removal of the tumors. FNA of canine MCTs and the NI-1 cell line were utilized to develop a FC panel that includes a viability dye (FVS620, BD Biosciences; 7-AAD, Invitrogen) and the following primary conjugated antibodies: CD117-PE (ACK45, BD Biosciences), pKIT-A647 (polyclonal bs-3242R, BIOSS) and Ki-67-FITC (20Raj1, eBioscience; MIB-1, DAKO). A total of nine FNA samples of canine MCTs were collected, seven out which produced sufficient cells for FC analysis. The Ki-67 antibody clone 20Raj1 produced a positive signal when applied to blood leukocytes but failed to provide robust labeling of neoplastic mast cells. The Ki-67 antibody clone MIB-1 delivered a superior staining quality in both the NI-1 cells and primary MCT cells. CD117-PE signal was adequate post fixation and permeabilization and in the combination of 7-AAD. pKIT produced non-specific staining and was not suitable for this multicolor FC panel. In conclusion, FNA samples of canine MCTs can often yield adequate cell numbers for FC analysis, and a multicolor FC panel was developed that can detect Ki-67 in canine mast cells. This would permit further studies into the potential use of this panel for canine cutaneous and subcutaneous MCT prognostication purposes.

skin cancer

Treating locally advanced and metastatic cutaneous squamous cell carcinoma with anti-PD-1 drugs: Real-world experience in 72 patients.

No abstract found

skin cancer

Advances in melanoma: epidemiology, diagnosis, and prognosis.

Unraveling the multidimensional complexities of melanoma has required concerted efforts by dedicated community of researchers and clinicians battling against this deadly form of skin cancer. Remarkable advances have been made in the realm of epidemiology, classification, diagnosis, and therapy of melanoma. The treatment of advanced melanomas has entered the golden era as targeted personalized therapies have emerged that have significantly altered the mortality rate. A paradigm shift in the approach to melanoma classification, diagnosis, prognosis, and staging is underway, fueled by discoveries of genetic alterations in melanocytic neoplasms. A morphologic clinicopathologic classification of melanoma is expected to be replaced by a more precise molecular based one. As validated, convenient, and cost-effective molecular-based tests emerge, molecular diagnostics will play a greater role in the clinical and histologic diagnosis of melanoma. Artificial intelligence augmented clinical and histologic diagnosis of melanoma is expected to make the process more streamlined and efficient. A more accurate model of prognosis and staging of melanoma is emerging based on molecular understanding melanoma. This contribution summarizes the recent advances in melanoma epidemiology, classification, diagnosis, and prognosis.

skin cancer

Exploring the molecular mechanism of Licorice rose beverage anti-melasma based on network pharmacology, molecular docking technology and in vivo and in vitro experimental verification.

Melasma is a pigmentation disease with refractory and high recurrence risk. Therefore, finding effective treatment has become the focus of research. This study aimed to reveal the mechanism of Licorice rose beverage (LRB) in treating melasma from the perspective of network pharmacology and in vitro and in vivo experimental techniques. Network pharmacological studies have shown that Isolicoflavonol, quercetin, and kaempferol are the main active components of anti-melasma and tyrosinase is the main target. Molecular docking studies have shown that these compounds have a good affinity for these targets. In vitro tyrosinase inhibition experiments showed that LRB could significantly inhibit tyrosinase activity. In vivo studies showed that LRB could significantly improve skin damage and skin pigmentation, reduce the activities of serum and skin tyrosinase in model mice, increase the activity of SOD in serum, and reduce the content of MDA in mice, showing a good effect of anti-melasma. In conclusion, these findings reveal the molecular mechanism of LRB in treating melasma and provide the scientific basis for this product's development and clinical application.

skin cancer

5-Fluorouracil-Loaded Hyaluronic Acid-Coated Niosomal Vesicles: Fabrication and Ex Vivo Evaluation for Skin Drug Delivery.

5-Fluorouracil (5-FU) is one of the most potent drugs against solid tumors. However, its parenteral administration is associated with systemic toxicity, while its topical application has limited percutaneous absorption. To overcome these limitations, the current study undertakes the formulation of 5-FU as niosomal vesicles that were coated with hyaluronic acid to improve its targeting efficiency for cancer cells. The niosomes were prepared by the thin-film hydration method using cholesterol as physiological lipid and nonionic surfactants (Tween 80 and Span 80) in the ratio of 1:1. The niosomal vesicles were characterized for their size, size distribution, viscosity, surface tension, density, and drug entrapment efficiency. The vesicles were within the particle size range of 337-478 nm with relatively homogeneous particle size distribution (PDI ≤ 0.5). The ζ-potential and drug entrapment efficiency of coated formulations (F2 and F4) were comparatively higher than corresponding noncoated formulations (F1 and F3). The release behavior of 5-FU from niosomal vesicles using a dialysis membrane depicts that initial burst drug release was higher for F1 and F3 due to their smaller particle size in comparison to their coated counterparts. However, the release was more controlled for F4 due to the larger particle size, higher viscosity, and entrapped fraction of the formulation. The permeation of the drug through the rat's skin was comparatively higher in the case of noncoated formulations than their coated counterparts (

skin cancer

Mechanistic insight of

An excessive amount of multidrug-resistant

skin cancer

Screening for Mutations in Hereditary Cancer Susceptibility Genes in a Region with High Endogamy in Brazil.

skin cancer

The role of cellular senescence in skin aging and age-related skin pathologies.

Aging is the result of a gradual functional decline at the cellular, and ultimately, organismal level, resulting in an increased risk of developing a variety of chronic illnesses, such as cardiovascular disease, stroke, cancer and diabetes. The skin is the largest organ of the human body, and the site where signs of aging are most visible. These signs include thin and dry skin, sagging, loss of elasticity, wrinkles, as well as aberrant pigmentation. The appearance of these features is accelerated by exposure to extrinsic factors such as ultraviolet (UV) radiation or pollution, as well as intrinsic factors including time, genetics, and hormonal changes. At the cellular level, aging is associated with impaired proteostasis and an accumulation of macromolecular damage, genomic instability, chromatin reorganization, telomere shortening, remodelling of the nuclear lamina, proliferation defects and premature senescence. Cellular senescence is a state of permanent growth arrest and a key hallmark of aging in many tissues. Due to their inability to proliferate, senescent cells no longer contribute to tissue repair or regeneration. Moreover, senescent cells impair tissue homeostasis, promote inflammation and extracellular matrix (ECM) degradation by secreting molecules collectively known as the "senescence-associated secretory phenotype" (SASP). Senescence can be triggered by a number of different stimuli such as telomere shortening, oncogene expression, or persistent activation of DNA damage checkpoints. As a result, these cells accumulate in aging tissues, including human skin. In this review, we focus on the role of cellular senescence during skin aging and the development of age-related skin pathologies, and discuss potential strategies to rejuvenate aged skin.

skin cancer

Adverse events in patients with advanced urothelial carcinoma treated with erdafitinib: a retrospective pharmacovigilance study.

skin cancer

Linea Nigra: Case Report of a Woman With a Pregnancy-Associated Linear Streak of Cutaneous Hyperpigmentation on Her Abdomen From the Umbilicus to the Pubic Symphysis.

Linea nigra is a distinctive presentation of asymptomatic cutaneous hyperpigmentation on the abdomen that usually extends from the umbilicus to the pubic symphysis. It is frequently observed as a physiologic change associated with pregnancy. A primigravida 19-year-old woman began to develop skin darkening during week 24 of gestation. She delivered a healthy infant. Three months postpartum, the hyperpigmentation had not resolved. After the benign characteristics of her cutaneous hyperpigmentation were explained, the patient decided to clinically monitor the dark linear streak. Similar to this patient, clinical studies of pregnant women have observed the incidence of pregnancy-associated linea nigra to range from 32% to 92%; in contrast to this woman, partial or complete spontaneous resolution of the skin darkening commonly occurs after delivery of the newborn. During gestation, the development of linea nigra has been postulated to be caused by elevated estrogen, progesterone, and/or melanocyte-stimulating hormone levels. Linea nigra is not restricted to gestational females; it has also been noted in newborns and children. In addition, it has also been observed in men who had either benign prostate hyperplasia or prostate cancer. In summary, linea nigra is often an acquired longitudinal streak of benign cutaneous hyperpigmentation on the abdomen; when linea nigra is pregnancy-associated, the skin darkening often partially or completely resolves, spontaneously after delivery.

skin cancer

Intracranial infection accompanied sweet's syndrome in a patient with anti-interferon-γ autoantibodies: A case report.

Several reports of adult-onset immunodeficiency syndrome have been associated with anti-interferon-gamma (IFN-γ) autoantibodies (AIGAs). However, it is rare to find AIGAs with intracranial infections.

skin cancer

Impact of primary organ site of involvement by peripheral T-cell lymphoma not otherwise specified on survival.

Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is a rare, highly heterogeneous group of mature T-cell neoplasms that historically has been associated with poor outcomes. We sought to investigate the influence of primary disease site on PTCL-NOS outcomes using a large national cancer registry.

skin cancer

Orbital apocrine hidrocystoma. Report of two cases.

We report the clinical features and the management of two cases of orbital hidrocystoma in the setting of an enlarging orbital mass.

skin cancer

Treatment practices and response in kaposiform hemangioendothelioma: A multicenter cohort study.

Kaposiform hemangioendothelioma (KHE) and tufted angioma (TA) are rare vascular tumors in children historically associated with significant morbidity and mortality. This study was conducted to determine first-line therapy in the absence of available prospective clinical trials.

skin cancer

Novel lncRNA Gm33149 modulates metastatic heterogeneity in melanoma by regulating the miR-5623-3p/Wnt axis via exosomal transfer.

The high mortality rate associated with melanoma primarily results from metastasis and recurrence. However, the precise mechanisms driving these processes remain poorly understood. Intercellular communication between cancer cells and non-cancer cells significantly influences the tumor microenvironment and plays a crucial role in metastasis. Therefore, our current study aims to investigate the role and mechanism of long non-coding RNAs (lncRNAs) in regulating the interaction between melanoma cancer stem cells (CSCs) and non-CSCs during the metastatic colonization process. This study has characterized a novel lncRNA called Gm33149. Importantly, we provide evidence for the first time that Gm33149, originating from highly metastatic melanoma stem cells (OL-SD), can be packaged into exosomes and transferred to low-metastatic nonstem cells (OL). Once internalized by OL cells, Gm33149 exerts its function through a competitive endogenous RNA mechanism (ceRNA) involving miR-5623-3p. Specifically, Gm33149 competitively binds to miR-5623-3p, thereby activating the Wnt signaling pathway and promoting the acquisition of a more aggressive metastatic phenotype by OL cells. In summary, our findings suggest that targeting lncRNA Gm33149 within extracellular vesicles could potentially serve as a therapeutic strategy for the treatment of metastatic melanoma. Schematic representation of the mechanisms underlying the pro-metastatic activity of lncRNA Gm33149 mediated by exosomal transfer. The figure illustrates the key mechanisms involved in the pro-metastatic activity of lncRNA Gm33149 through exosomal transfer. Melanoma stem cells (OLSD) release exosomes containing lncRNA Gm33149. These exosomes are taken up by non-stem melanoma cells (OL), delivering lncRNA Gm33149 to the recipient cells. Within OL cells, lncRNA Gm33149 functions as a competitive endogenous RNA (ceRNA), sequestering miR-5623-3p. This sequestration prevents miR-5623-3p from binding to its target genes, thereby activating the Wnt signaling pathway. The activated Wnt signaling pathway enhances the migration, invasion, and metastatic colonization capabilities of OL cells. The transfer of lncRNA Gm33149 via exosomes contributes to OL cells acquiring "metastatic competency" while promoting their metastatic colonization. These findings underscore the importance of lncRNA Gm33149 in intercellular communication and the metastatic progression of melanoma.

skin cancer

HGF facilitates methylation of MEG3, potentially implicated in vemurafenib resistance in melanoma.

Melanoma, a frequently encountered cutaneous malignancy characterized by a poor prognosis, persists in presenting formidable challenges despite the advancement in molecularly targeted drugs designed to improve survival rates significantly. Unfortunately, as more therapeutic choices have developed over time, the gradual emergence of drug resistance has become a notable impediment to the effectiveness of these therapeutic interventions. The hepatocyte growth factor (HGF)/c-met signaling pathway has attracted considerable attention, associated with drug resistance stemming from multiple potential mutations within the c-met gene. The activation of the HGF/c-met pathway operates in an autocrine manner in melanoma. Notably, a key player in the regulatory orchestration of HGF/c-met activation is the long non-coding RNA MEG3.

skin cancer

Single-Cell and Spatial Transcriptome Analysis of Dermal Fibroblast Development in Perinatal Mouse Skin: Dynamic Lineage Differentiation and Key Driver Genes.

Several single-cell RNA studies of developing mouse skin have elucidated the molecular and cellular processes involved in skin development. However, they have primarily focused on either the fetal or early postnatal period, leaving a gap in our understanding of skin development. In this study, we conducted a comprehensive time-series analysis by combining single-cell RNA-sequencing datasets collected at different stages of development (embryonic days 13.5, 14.5, and 16.5 and postnatal days 0, 2, and 4) and validated our findings through multipanel in situ spatial transcriptomics. Our analysis indicated that embryonic fibroblasts exhibit heterogeneity from a very early stage and that the rapid determination of each lineage occurs within days after birth. The expression of putative key driver genes, including Hey1, Ebf1, Runx3, and Sox11 for the dermal papilla trajectory; Lrrc15 for the dermal sheath trajectory; Zfp536 and Nrn1 for the papillary fibroblast trajectory; and Lrrn4cl and Mfap5 for the fascia fibroblast trajectory, was detected in the corresponding, spatially identified cell types. Finally, cell-to-cell interaction analysis indicated that the dermal papilla lineage is the primary source of the noncanonical Wnt pathway during skin development. Together, our study provides a transcriptomic reference for future research in the field of skin development and regeneration.

skin cancer

Paris polyphylla saponins II inhibits invasive, migration and epithelial-mesenchymal transition of melanoma cells through activation of autophagy.

Malignant melanoma is a kind of malignant tumor derived from normal epidermal melanocytes or original nevus cells. It has a high degree of malignancy, rapid progress, dangerous condition, and poor prognosis. In recent years, the innovation of traditional Chinese medicine has broadened the scope and effect of tumor treatment. It is a hotspot and breakthrough to find new anti-tumor invasion and migration drugs from natural plants or traditional Chinese medicine. This study explored the role of PPII in promoting autophagy to inhibit EMT of melanoma cells, the role of the PI3K/Akt signaling pathway in the invasion and migration of melanoma cells induced by PPII. We found that PPII effectively inhibited the proliferation, invasion and migration of melanoma B16 and B16F10 in vitro, and induced autophagy. We also established the xenograft tumor and metastatic tumor model of C57BL/6 mice with B16F10 cells. Results showed that PPII effectively inhibited the growth of transplanted tumors, induced autophagy and inhibited the expression level of EMT related protein; Metastasis experiment showed that PPII inhibited the invasion and migration of B16F10, the effect of inhibiting lung metastasis is the most significant. Further mechanism studies showed that the inhibition of PPII on melanoma invasion and migration is related to its induction of autophagy and then inhibition of EMT.

skin cancer

Presenting features of indolent primary cutaneous B-cell lymphomas: Distinguishing clinical and histopathologic features.

No abstract found

skin cancer

Final analysis of phase II results with cemiplimab in metastatic basal cell carcinoma after hedgehog pathway inhibitors.

Metastatic basal cell carcinoma (mBCC) is a rare condition with no effective second-line treatment options. Cemiplimab is an immune checkpoint inhibitor that blocks the binding of programmed cell death-1 (PD-1) to its ligands, programmed death-ligand 1 (PD-L1) and programmed death-ligand 2 (PD-L2). Here, we present the final analysis of cemiplimab in patients with mBCC after first-line hedgehog pathway inhibitor (HHI) treatment (NCT03132636).

skin cancer

Mutational landscape of advanced extramammary Paget disease with comprehensive genomic profiling tests: A cohort study in a Japanese real-world setting.

No abstract found

skin cancer

Can a Single-Stage Approach Using a Dermal Regeneration Template Lead to Satisfactory Scalp Defect Reconstruction After Skin Cancer Excision?

Large-defect reconstructive surgeries for skin cancer can be performed using different approaches. Integra Dermal Regeneration Template (DRT, Integra Life Sciences, Princeton, New Jersey, the United States) is a membrane utilized to fill skin defects, followed by second-stage surgery with a full-thickness skin graft or flap.

skin cancer

New Perspectives for Patients with Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg-Type.

No abstract found

skin cancer

Epidermis lesion detection via optimized distributed capsule neural network.

Skin cancer, encompassing various forms such as melanoma, basal cell carcinoma, and others, remains a significant global health concern, often proving fatal if not diagnosed and treated in its early stages. The challenge of accurately diagnosing skin cancer, particularly melanoma, persists even for experienced dermatologists due to the intricate and unpredictable nature of its symptoms. To address the need for more accurate and efficient skin cancer detection, a novel Golden Hawk Optimization-based Distributed Capsule Neural Network (GHO-DCaNN) is proposed. This novel technique leverages advanced computational methods to improve the reliability and precision of skin cancer diagnosis. An optimized clustering-based segmentation approach is introduced, integrating the innovative Sewer Shad Fly Optimization (SSFO), which combines elements of both mayfly and moth flame optimization. This integration enhances the accuracy of lesion boundary delineation and feature extraction. The core of the innovation lies in the optimized distributed capsule neural network, which is trained using the Hybrid GHO. This optimizer, inspired by the behaviors of the golden eagle and fire hawk, ensures the effectiveness of epidermis lesion detection, pushing the boundaries of skin cancer diagnosis methods. The achievements based on the metrics, like specificity, sensitivity, and accuracy show 97.53%, 99.05%, and 98.83% for 90% of training and 97.83%, 99.50%, and 99.06% for k-fold of 10, respectively.

skin cancer

Articles from 2022 to 2023 to Inform Your Cancer Practice: Melanoma.

Modern effective systemic therapy for melanoma includes two important classes of treatment: immune checkpoint inhibitors (ICIs), comprising inhibitors of cytotoxic T-lymphocyte antigen 4, programmed cell death receptor 1, and lymphocyte-activation gene 3; and small molecule BRAF/MEK inhibitor therapy. These treatments have revolutionized the management of patients with advanced melanoma and have dramatically improved clinical outcomes. The melanoma treatment landscape continues to evolve as outcome data from completed trials continue to mature and as newer studies begin to report data. In 2022 and 2023, longer-term follow-up data for established single-agent ICI therapy has been published improving our understanding of both efficacy and durability of treatment responses. A trial of a novel combination ICI therapy has demonstrated enhanced efficacy, and a study examining the order/sequence of ICI therapy versus BRAF/MEK inhibitor therapy for first-line treatment of metastatic melanoma showed that survival is improved when patients start with ICI therapy. As the indications for these therapies have expanded to the adjuvant and neoadjuvant space, we also saw the publication of 5-year results of adjuvant therapy in resected stage III patients, new data on the role of adjuvant therapy in resected stage IIB and IIC patients, and, finally, a practice-changing trial demonstrating improved outcomes using a neoadjuvant approach for patients with macroscopic disease amenable to surgical resection. In this article, we review these articles and highlight key elements for surgical oncologists.

skin cancer

RPTOR mutation: a novel predictor of efficacious immunotherapy in melanoma.

Identifying biomarkers to evaluate the therapeutic effect of immune checkpoint inhibitors (ICIs) is crucial. Regulatory Associated Protein of MTOR Complex 1 (RPTOR), one of the genes in the mTOR pathway, plays a role in regulating tumor progression. However, the connection between RPTOR mutation and the efficacy of ICIs in melanoma remains unclear. The data of ICIs-treated melanoma patients in discovery (n = 384) and validation (n = 320) cohorts were obtained from cBioPortal databases. The genomic data in the two cohorts was used to investigate the connection between RPTOR mutation and immunotherapy efficacy. The underlying mechanisms were explored based on data from the The Cancer Genome Atlas (TCGA)-skin cutaneous melanoma (SKCM) cohort. Compared to melanoma patients with RPTOR wildtype (RPTOR-WT), RPTOR-mutation (RPTOR-Mut) patients achieved prolonged overall survival (OS) in both discovery cohort (median OS of 49.3 months vs. 21.7 months; HR = 0.41, 95% CI: 0.18-0.92; P = 0.026) and validation cohorts (not reached vs. 42.0 months; HR = 0.34, 95% CI: 0.11-1.06; P = 0.049). RPTOR-Mut melanoma patients exhibited a higher objective response rate (ORR) than RPTOR-WT patients in the discovery cohort (55.0% vs. 29.0%, P = 0.022). RPTOR-Mut patients exhibited higher TMB than RPTOR-WT patients in both discovery and validation cohorts (P < 0.001). RPTOR-Mut melanoma patients had an increased number of DNA damage response (DDR) mutations in TCGA-SKCM cohort. Immune cell infiltration analysis suggested that activated CD4 memory T cells were more enriched in RPTOR-Mut tumors. RPTOR-Mut melanoma patients had higher expression levels of immune-related genes than the RPTOR-WT patients. Our results suggest that RPTOR mutation could serve as a predictor of effective immunotherapy for melanoma.

skin cancer

Improved Staging of Ciliary Body and Choroidal Melanomas Based on Estimation of Tumor Volume and Competing Risk Analyses.

The current, 8th edition of the American Joint Committee on Cancer (AJCC) anatomic classification and staging model for uveal melanoma does not fully separate survival estimates for patients with advanced stages of the disease (e.g., IIIB and IIIC). Furthermore, some tumors in higher size categories have a smaller volume than tumors in lower categories. Therefore, we developed a novel model for prognostication of metastatic mortality based on estimations of tumor volume.

skin cancer

Alpelisib decreases nevocytes of congenital melanocytic nevi.

Multiple, large or giant congenital melanocytic nevi (CMN) are uncommon and affected patients can show progressive growth and thickening, associate neurocutaneous melanocytosis or develop melanoma. Current treatment modalities are mostly complex surgeries that frequently do not solve the disease and its risks completely. Thus, investigation on new treatment options for CMN and its complications must continue. MAPK pathway inhibitors are being investigated, also targeting PI3K-AKT. Omipalisib (PI3K inhibitor, with no indications approved yet) has been studied for CMN in vitro and in mice with promising results. However, alpelisib, a PI3K inhibitor approved with an adequate safety profile for patients with severe manifestations of PROS (PIK3CA-Related Overgrowth Spectrum), had not yet been tested for CMN.

skin cancer

Multiple myeloma, haematologic malignancy and immunosuppressant and immunomodulatory medications are associated with sebaceous carcinoma, a pharmacovigilance study of the FDA adverse event reporting system.

Sebaceous carcinoma (SC) is a rare skin cancer with significant associated morbidity and mortality. A known association exists between immunosuppression, in particular solid organ transplant patients (SOTR), and SC. However, the comparative reporting odds ratios (ROR) of different immunosuppressive medications and SC are incompletely defined.

skin cancer

Vulvar cancer incidence and net survival in Sweden 1960 to 2019: A population-based national study.

Vulvar cancer is a rare gynecological cancer affecting mostly older women. The aim of this population-based study was to investigate the incidence and net survival of vulvar cancer in Swedish women from 1960 to 2019.

skin cancer

Oncological aspects related to non-surgical treatment of basal cell carcinoma. Comments on: chemotherapeutical treatment of basal cell carcinoma with bleomycin via microinfusion of the drug into the skin (MMP®).

No abstract found

skin cancer

Systematic Review and Meta-analysis of Minimally Invasive Procedures for Surgical Inguinal Nodal Staging in Penile Carcinoma.

There are several procedures for surgical nodal staging in clinically node-negative (cN0) penile carcinoma.

skin cancer

Co-delivery of lapatinib and 5-fluorouracil transfersomes using transpapillary iontophoresis for breast cancer therapy.

Combination chemotherapy, involving the intervention of two or more anti-neoplastic agents has been the cornerstone in breast cancer treatment, owing to the applications it holds in contrast to the mono-therapy approach. This research predominantly focussed on proving the synergy between Lapatinib (LPT) and 5-Fluorouracil (5-FU) and further enhancing its localized permeation via transfersome-loaded delivery and iontophoresis to treat breast tumors. The IC

skin cancer

BRD9 status is a major contributor for cysteine metabolic remodeling through MST and EAAT3 modulation in malignant melanoma.

Cutaneous melanoma (CM) is the most aggressive skin cancer, showing globally increasing incidence. Hereditary CM accounts for a significant percentage (5-15 %) of all CM cases. However, most familial cases remain without a known genetic cause. Even though, BRD9 has been associated to CM as a susceptibility gene. The molecular events following BRD9 mutagenesis are still not completely understood. In this study, we disclosed BRD9 as a key regulator in cysteine metabolism and associated altered BRD9 to increased cell proliferation, migration and invasiveness, as well as to altered melanin levels, inducing higher susceptibility to melanomagenesis. It is evident that BRD9 WT and mutated BRD9 (c.183G>C) have a different impact on cysteine metabolism, respectively by inhibiting and activating MPST expression in the metastatic A375 cell line. The effect of the mutated BRD9 variant was more evident in A375 cells than in the less invasive WM115 line. Our data point out novel molecular and metabolic mechanisms dependent on BRD9 status that potentially account for the increased risk of developing CM and enhancing CM aggressiveness. Moreover, our findings emphasize the role of cysteine metabolism remodeling in melanoma progression and open new queues to follow to explore the role of BRD9 as a melanoma susceptibility or cancer-related gene.

skin cancer

Incidence and profile of skin cancers in patients following ultraviolet phototherapy without psoralens: A retrospective cohort study.

Psoralen + ultraviolet-A (PUVA) is associated with photocarcinogenesis. However, carcinogenic risk with other ultraviolet phototherapies remains unclear.

skin cancer

Has-miR-300-GADD45B promotes melanoma growth via cell cycle.

Response to oncogenic factors like UV, GADD45 family in skin participates in scavenging ROS, DNA repair and cell cycle control. Because of this, the previous study of the chronic UVB injury model has found that hsa-miR-300 can conduct intercellular transport by exosomes and target regulation of GADD45B. Whether the hsa-miR-300-GADD45B still regulates tumor development by cell cycle pathway is unclear. Through transcriptomic analysis of primary (n=39) and metastatic (n=102) melanoma, it was confirmed that in metastatic samples, some of the 97 down-regulated genes participate in maintaining skin homeostasis while 42 up-regulated genes were enriched in cancer-related functions. Furthermore, CDKN1A, CDKN2A, CXCR4 and RAD51 in the melanoma pathway, were also differentially expressed between normal skin and melanoma. CDKN1A and CDKN2A were also found to be involved in TP53-dependent cell cycle regulation. In conclusion, it was speculated that CDKN1A, CDKN2A, TP53, GADD45B and hsa-miR-300 may have regulatory relationships. It was demonstrated that there is a bidirectional regulation between hsa-miR-300 and TP53. In addition, miR-300 can regulate CDKN1A by GADD45B/TP53 and promote melanoma growth by accelerating the cell cycle transition from G1/S to G2 phase.

skin cancer

Sunburn, sunbeds and melanoma skin cancer: a story behind the statistics.

No abstract found

skin cancer

Formulation of herbal based hair colour from

Synthetic oxidative hair dyes available in the market contain a combination of peroxide and ammonia. In addition, people who use synthetic dyes are at risk for skin burns, irritation to the eye and also lead to cancer. Hence, herbal-based hair dyes are safe to use. In the traditional system of medicine, different parts of

skin cancer

Specific dermoscopic findings in glomeruloid haemangioma for diagnosis of POEMS syndrome.

No abstract found

skin cancer

EUSCAP: A Euromelanoma project to investigate skin cancer risk factors in Europe.

No abstract found

skin cancer

Hypericin-Based Photodynamic Therapy Displays Higher Selectivity and Phototoxicity towards Melanoma and Squamous Cell Cancer Compared to Normal Keratinocytes In Vitro.

The aim of this study was to explore the potential of hypericin, a naturally occurring photosensi-tizer, for photodynamic therapy (PDT) in skin cancer, investigating its phototoxic effects and mechanisms of action in cancer cells compared to normal skin keratinocytes, squamous cell cancer (SCC-25) cells and melanoma (MUG-Mel2) cells. Hypericin was applied at concentrations ranging from 0.1-40 μM to HaCaT, SCC-25, and MUG-Mel2 cells. After 24 h of incubation, the cells were exposed to orange light at 3.6 J/cm

skin cancer

Elevated Serum Gastrin Is Associated with Melanoma Progression: Putative Role in Increased Migration and Invasion of Melanoma Cells.

Micro-environmental factors, including stromal and immune cells, cytokines, and circulating hormones are well recognized to determine cancer progression. Melanoma cell growth was recently shown to be suppressed by cholecystokinin/gastrin (CCK) receptor antagonists, and our preliminary data suggested that melanoma patients with

skin cancer

Synthesis and In Vitro Evaluation as Potential Anticancer and Antioxidant Agents of Diphenylamine-Pyrrolidin-2-one-Hydrazone Derivatives.

The title compounds were synthesized by the reaction of 5-oxo-1-(4-(phenylamino)phenyl)pyrrolidine-3-carbohydrazide with various aldehydes bearing aromatic and heterocyclic moieties and acetophenones, and their cytotoxicity was tested via MTT assay against human triple-negative breast cancer MDA-MB-231, human melanoma IGR39, human pancreatic carcinoma Panc-1, and prostate cancer cell line PPC-1. Furthermore, the selectivity of compounds towards cancer cells compared to fibroblasts was also investigated. Four compounds were identified as the most promising anticancer agents out of a series of pyrrolidinone-hydrazone derivatives bearing a diphenylamine moiety. These compounds were most selective against the prostate cancer cell line PPC-1 and the melanoma cell lines IGR39, with EC

skin cancer

Antitumor Effect of Poplar Propolis on Human Cutaneous Squamous Cell Carcinoma A431 Cells.

Propolis is a gelatinous substance processed by western worker bees from the resin of plant buds and mixed with the secretions of the maxillary glands and beeswax. Propolis has extensive biological activities and antitumor effects. There have been few reports about the antitumor effect of propolis against human cutaneous squamous cell carcinoma (CSCC) A431 cells and its potential mechanism. CCK-8 assays, label-free proteomics, RT-PCR, and a xenograft tumor model were employed to explore this possibility. The results showed that the inhibition rate of A431 cell proliferation by the ethanol extract of propolis (EEP) was dose-dependent, with an IC

skin cancer

Unraveling the Potential of Organic Oregano and Tarragon Essential Oils: Profiling Composition, FT-IR and Bioactivities.

Oregano and tarragon are widely cultivated culinary herbs used for food seasoning, having familiar characteristic aromas appreciated by the wide public. The aim of this research was to characterize essential oils (EOs) from locally sourced organic oregano and tarragon (Cluj, Romania) and study their bioactivity potential. Results showed that oregano EO had a sesquiterpene dominant profile responsible for strong bands between 2800 and 3000 cm

skin cancer

Primary Thyroid Dysfunction Is Prevalent in Hidradenitis Suppurativa and Marked by a Signature of Hypothyroid Graves' Disease: A Case-Control Study.

Hidradenitis suppurativa (HS) is a chronic skin disease that can have an association with endocrine disorders. There is conflicting information in the literature regarding the role of the thyroid gland in HS. This study aimed to close this knowledge gap and investigate how thyroid disease is involved in patients with HS. We carried out a case-control study with a total of 160 patients, of whom 108 were patients with HS and 52 were controls matched for age and sex. Parametric and non-parametric methods were used to analyze the results. We calculated structural parameters of thyroid homeostasis to detect subclinical thyroid disease, non-thyroid disease syndrome and other forms. The severity of HS was not associated with thyroid hormone levels and antibodies (

skin cancer

Tunneled Island Flaps for the Reconstruction of Nasal Defects: A 21-Case Series.

(1) Background: The reconstruction of cutaneous defects following surgical procedures in the nasal pyramid presents a challenge due to the limited amount of available tissue. In cases of larger defects, skin from adjacent units is used. Traditionally, two-stage surgical flaps have been employed for reconstructing these defects. Tunnelized island flaps allow for the one-stage surgical reconstruction of nasal pyramid defects, using tissue from the forehead or cheek for the flap. (2) Methods: Descriptive retrospective study of 21 consecutive patients who underwent surgery for defects on the nasal pyramid using tunnelized island flaps. (3) Results: Surgical reconstruction was performed in 21 patients with basal cell carcinomas, 14 of them using the melolabial island flap and 7 using the paramedian forehead island flap. In all cases except one, clear histological margins were obtained. Immediate complications were mild and minor. It is worth noting the trapdoor effect complication, which improved over time in most cases, resulting in a satisfactory cosmetic outcome. No tumor recurrences were observed during an average follow-up period of 17.7 months. (4) Conclusions: Tunnelized island flaps allow for single-stage reconstruction of nasal pyramid defects, yielding excellent cosmetic results by utilizing adjacent skin. This procedure demands a certain level of skill but is associated with minimal complications, making it a valuable alternative in reconstructive dermatological surgery.

skin cancer

From Vibrations to Visions: Raman Spectroscopy's Impact on Skin Cancer Diagnostics.

Raman spectroscopy, a non-invasive diagnostic technique capturing molecular vibrations, offers significant advancements in skin cancer diagnostics. This review delineates the ascent of Raman spectroscopy from classical methodologies to the forefront of modern technology, emphasizing its precision in differentiating between malignant and benign skin tissues. Our study offers a detailed examination of distinct Raman spectroscopic signatures found in skin cancer, concentrating specifically on squamous cell carcinoma, basal cell carcinoma, and melanoma, across both in vitro and in vivo research. The discussion extends to future possibilities, spotlighting enhancements in portable Raman instruments, the adoption of machine learning for spectral data refinement, and the merging of Raman imaging with other diagnostic techniques. The review culminates by contemplating the broader implications of these advancements, suggesting a trajectory that may significantly optimize the accuracy and efficiency of skin cancer diagnostics.

skin cancer

Expression of p53, p63, p16, Ki67, Cyclin D, Bcl-2, and CD31 Markers in Actinic Keratosis, In Situ Squamous Cell Carcinoma and Normal Sun-Exposed Skin of Elderly Patients.

Age and cumulative exposure to ultraviolet (UV) light are primary contributors to skin cancer development. Regulatory proteins within the cell cycle are essential for the homeostasis of squamous epithelium.

skin cancer

Phytochemical and Nutraceutical Screening of Ethanol and Ethyl Acetate Phases of Romanian

skin cancer

Progress in Antimelanoma Research of Natural Triterpenoids and Their Derivatives: Mechanisms of Action, Bioavailability Enhancement and Structure Modifications.

Melanoma is one of the most dangerous forms of skin cancer, characterized by early metastasis and rapid development. In search for effective treatment options, much attention is given to triterpenoids of plant origin, which are considered promising drug candidates due to their well described anticancer properties and relatively low toxicity. This paper comprehensively summarizes the antimelanoma potential of natural triterpenoids, that are also used as scaffolds for the development of more effective derivatives. These include betulin, betulinic acid, ursolic acid, maslinic acid, oleanolic acid, celastrol and lupeol. Some lesser-known triterpenoids that deserve attention in this context are 22

skin cancer

Cancer-Preventive Activity of

Skin cancer is the 5th most common cancer in Western countries with a surge in case occurrences making it a global burden on healthcare systems. The present study aims to evaluate the cancer-preventive activity of an ethanolic extract of

skin cancer

A Review of Recent Advances in Computer-Aided Detection Methods Using Hyperspectral Imaging Engineering to Detect Skin Cancer.

Skin cancer, a malignant neoplasm originating from skin cell types including keratinocytes, melanocytes, and sweat glands, comprises three primary forms: basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and malignant melanoma (MM). BCC and SCC, while constituting the most prevalent categories of skin cancer, are generally considered less aggressive compared to MM. Notably, MM possesses a greater capacity for invasiveness, enabling infiltration into adjacent tissues and dissemination via both the circulatory and lymphatic systems. Risk factors associated with skin cancer encompass ultraviolet (UV) radiation exposure, fair skin complexion, a history of sunburn incidents, genetic predisposition, immunosuppressive conditions, and exposure to environmental carcinogens. Early detection of skin cancer is of paramount importance to optimize treatment outcomes and preclude the progression of disease, either locally or to distant sites. In pursuit of this objective, numerous computer-aided diagnosis (CAD) systems have been developed. Hyperspectral imaging (HSI), distinguished by its capacity to capture information spanning the electromagnetic spectrum, surpasses conventional RGB imaging, which relies solely on three color channels. Consequently, this study offers a comprehensive exploration of recent CAD investigations pertaining to skin cancer detection and diagnosis utilizing HSI, emphasizing diagnostic performance parameters such as sensitivity and specificity.

skin cancer

Neoadjuvant Approaches to Non-Melanoma Skin Cancer.

Surgery and external-beam radiation therapy are the primary treatment modalities for locally advanced NMSC, but they can lead to impairment of function and disfigurement in sensitive areas such as the head and neck. With the advent of targeted systemic therapies and immunotherapy, physicians have explored the ability to offer neoadjuvant therapy for NMSC in order to reduce surgically induced morbidity. Provided herein is a guide to current applications of neoadjuvant systemic therapies for NMSC and future directions.

skin cancer

CAR NK Cell Therapy for the Treatment of Metastatic Melanoma: Potential & Prospects.

Melanoma is among the most lethal forms of cancer, accounting for 80% of deaths despite comprising just 5% of skin cancer cases. Treatment options remain limited due to the genetic and epigenetic mechanisms associated with melanoma heterogeneity that underlie the rapid development of secondary drug resistance. For this reason, the development of novel treatments remains paramount to the improvement of patient outcomes. Although the advent of chimeric antigen receptor-expressing T (CAR-T) cell immunotherapies has led to many clinical successes for hematological malignancies, these treatments are limited in their utility by their immune-induced side effects and a high risk of systemic toxicities. CAR natural killer (CAR-NK) cell immunotherapies are a particularly promising alternative to CAR-T cell immunotherapies, as they offer a more favorable safety profile and have the capacity for fine-tuned cytotoxic activity. In this review, the discussion of the prospects and potential of CAR-NK cell immunotherapies touches upon the clinical contexts of melanoma, the immunobiology of NK cells, the immunosuppressive barriers preventing endogenous immune cells from eliminating tumors, and the structure and design of chimeric antigen receptors, then finishes with a series of proposed design innovations that could improve the efficacy CAR-NK cell immunotherapies in future studies.

skin cancer

Basosquamous Carcinoma: Comprehensive Clinical and Histopathological Aspects, Novel Imaging Tools, and Therapeutic Approaches.

Basosquamous carcinoma (BSC), an uncommon and aggressive nonmelanoma skin cancer exhibiting characteristics ranging from basal cell carcinoma (BCC) to squamous cell carcinoma (SCC), is a subject of controversy in terms of its classification, pathogenesis, histologic morphology, biologic behavior, prognosis, and management. This narrative review is based on an electronic search of English-language articles in PubMed that included the terms "basosquamous carcinoma" and/or "metatypical carcinoma of the skin" in their titles. The review aims to succinctly present and assess current data on the epidemiology, clinical presentation, dermoscopic, LC-OCT, and histopathologic characteristics, as well as the genetics and management of BSC, providing insight into this intriguing entity. As a conclusion, dermoscopy, deep incisional biopsies, and immunohistologic techniques should be applied in clinically suspicious lesions to achieve an early diagnosis and better prognosis of this tumor. Surgical treatments, including wide excision and Mohs' micrographic surgery, remain the treatment of choice. Finally, Hedgehog pathway inhibitors and checkpoint inhibitors, must be thoroughly investigated with large controlled trials, since they may offer an alternative solution to irresectable or difficult-to-treat locally advanced cases of basosquamous carcinoma.

skin cancer

Clinical manifestations of telomere biology disorders in adults.

Telomere biology disorders (TBDs) are a spectrum of inherited bone marrow failure syndromes caused by impaired telomere function due to pathogenic germline variants in genes involved in telomere maintenance. TBDs can affect many organ systems and are often thought of as diseases of childhood. However, TBDs may present in mid- or even late adulthood with features similar to but not always the same as the childhood-onset TBDs. Adult-onset TBDs are often cryptic with isolated pulmonary, liver, or hematologic disease, or cancer, and may lack the classic disease-defining triad of abnormal skin pigmentation, nail dysplasia, and oral leukoplakia. Diagnostics include detection of very short leukocyte telomeres and germline genetic testing. Notably, adult-onset TBDs may show telomeres in the 1st to 10th percentile for age, and some cases may not have an identifiable genetic cause. TBD genetic etiology includes all modes of inheritance, with autosomal dominant the most frequent in adult-onset disease. Variable symptom onset due to incomplete penetrance, variable expressivity, and genetic anticipation add to the diagnostic challenges. Adult-onset TBDs are likely underrecognized, but their correct identification is of utmost importance, since affected patients are faced with numerous clinical complications, including but not limited to an increased risk of malignancies requiring close surveillance for early detection. Currently lung, liver, or hematopoietic cell transplants are the only curative therapeutic approaches but can be complicated by comorbidities, despite improved medical care. This review highlights the challenges of identifying adult-onset TBDs and addresses currently recommended clinical screening measures and therapy options.