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3,5,7-Trihydroxy-2-phenylchromen-4-one (THF) possesses a diverse range of pharmacological activities. Evidence suggests that THF exerts anticancer activity by distinct mechanisms of action. This study explores the anticancer potential of THF in human lung (A549) and skin (A431) cancer cells by employing different antiproliferative assays. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, neutral red uptake, sulphorhodamine B, and cell motility assays were used to confirm the anticancer potential of THF. Cell target-based and quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays were used to explore the effect of THF on the initiation, promotion and progression phase biomarkers of carcinogenesis. THF suppresses the activity of lipoxygenase-5 up to ~40% in both A549 and A431 cells and up to ~50% hyaluronidase activity in A549 cells. qRT-PCR assay reveals that THF inhibits the activity of phosphatidyl inositol-3 kinase/protein kinase B/mammalian target of rapamycin in both cell lines, which is responsible for the initiation of cancer. It also arrests the G2/M phase of the cell cycle in A431 cells and increases the sub-diploid population in both A549 and A431 cell lines which leads to cell death. Annexin V-FITC assay confirmed that THF induces apoptosis and necrosis in A431 and A549 cell lines. Further investigation revealed that THF not only enhances reactive oxygen species production but also modulates mitochondrial membrane potential in both cell lines. It significantly inhibits S-180 tumour formation at 5 and 10 mg/kg bw, i.p. dose. An acute skin toxicity study on mice showed that erythema and edema scores are within the acceptable range, besides acceptable drug-likeness properties and non-toxic effects on human erythrocytes. Conclusively, THF showed potent anticancer activity on skin and lung carcinoma cell lines, suppressed the level of the biomarkers and inhibited tumour growth in mice.
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Apoptosis , Neoplasias Pulmonares , Neoplasias Cutáneas , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/tratamiento farmacológico , Apoptosis/efectos de los fármacos , Animales , Ratones , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/tratamiento farmacológico , Células A549 , Regulación hacia Abajo/efectos de los fármacos , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/genética , Línea Celular Tumoral , Antineoplásicos/farmacologíaRESUMEN
Basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), and Merkel cell carcinoma (MCC) comprise the majority of nonmelanoma skin cancers. Advances have been made in treatment. Sentinel node biopsy should be considered for locally advanced, clinically node-negative cSCCs and MCCs. BCC patients failing traditional surgery and/or radiation are candidates for systemic hedgehog inhibitor therapy. Immune checkpoint inhibitor treatment is available for patients who failed traditional treatment with surgery and/or radiation or who are not candidates for these modalities. Specifically, cemiplimab is approved for advanced BCC; cemiplimab and pembrolizumab for advanced cSCC; and avelumab, pembrolizumab, and retifanlimab-dlwr for recurrent/metastatic MCC.
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Neoplasias Cutáneas , Humanos , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Manejo de la Enfermedad , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/terapia , Carcinoma Basocelular/tratamiento farmacológico , Carcinoma Basocelular/patología , Carcinoma Basocelular/terapiaRESUMEN
Squamous Cell Carcinoma (SCC) is a subtype of Non-Melanoma Skin Cancer, the most common group of malignancies worldwide. Photodynamic therapy (PDT) is a non-invasive treatment approved for specific subtypes of SCC. Some malignancies resist PDT, forming more aggressive tumors and multiple relapses. Thus, new approaches aimed at optimizing the response to PDT are needed. The mTORC1 inhibitor rapamycin, also known as Sirolimus (SRL), interferes with protein synthesis and cell metabolism. The use of SRL as an immunosuppressant is associated to lower rates of SCC in kidney-transplanted patients, which are frequently affected by this pathology. We have evaluated SRL pre-treatment efficacy to enhance the damage induced by PDT with Methyl 5-aminolevulinate in two different cutaneous SCC established cell lines (SCC13 and A431) in vitro and therapy sensitization in PDT-resistant cell lines. We tested for the first time the SRL + PDT combination in a SKH-1 mouse model of photocarcinogenesis, diminishing the frequency of lesions and restraining tumor growth. Molecular studies revealed that protoporphyrin IX and reactive oxygen species production induced by PDT were promoted by SRL pre-treatment. Lastly, SRL modifies the expression and intracellular location of NRF2, interfering with the downstream antioxidant response modulated by NQO1 and HO-1. In conclusion, we propose SRL as a potential adjuvant to enhance PDT efficacy for SCC treatment.
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Carcinoma de Células Escamosas , Factor 2 Relacionado con NF-E2 , Fotoquimioterapia , Transducción de Señal , Sirolimus , Neoplasias Cutáneas , Factor 2 Relacionado con NF-E2/metabolismo , Fotoquimioterapia/métodos , Animales , Ratones , Sirolimus/farmacología , Sirolimus/uso terapéutico , Humanos , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Línea Celular Tumoral , Transducción de Señal/efectos de los fármacos , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Ácido Aminolevulínico/uso terapéutico , Ácido Aminolevulínico/farmacología , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Especies Reactivas de Oxígeno/metabolismo , FemeninoRESUMEN
Melanoma is a malignant tumor with the highest growth rate in the incidence and is the leading cause of death due to skin cancers. In Poland, approximately 1500 cases of melanoma are detected annually in advanced or metastatic stages. Intensive preventive measures can contribute to its early-stage diagnosis, consequently reducing the number of fatalities. The aim of the study was to assess the occurrence of melanoma risk factors among the residents of Silesia region and their knowledge about the diagnosis and prevention of this cancer. An original questionnaire was used in the study, and its completion was anonymous. The study was conducted among the residents of the Silesian Voivodeship. A total of 400 (100%) individuals were examined. Among them were 243 women and 157 men. The participants' ages ranged from 16 to 84 years (mean ageâ =â 34.38â ±â 18.39). The participants were burdened with melanoma development risk factors such as fair skin complexion (235; 58.75%), having more than 50 pigmented lesions (158; 39.50%) and sunburns (105; 26.25%). Over 40% (166; 41.50%) of the participants had never examined their pigmented lesions. A staggering 78% (311; 77.75%) of the respondents had never undergone dermatoscopic examination, and over 50% (215; 53.75%) did not know what this examination entailed. Just under 16% (63; 15.75%) of the participants stated that their family doctor had examined their pigmented lesions, and almost % (154; 97.47%) of those with numerous pigmented lesions had never been referred to a dermatologist for dermatoscopy. The surveyed residents of the Silesian Voivodeship were burdened with numerous risk factors for melanoma development, with the most common being fair skin complexion, having more than 50 pigmented lesions, and sunburns. The knowledge of the participants regarding the diagnosis and prevention of melanoma development was insufficient, thus highlighting the necessity for conducting systematic educational initiatives in the mentioned field. These initiatives should ultimately lead to the preservation of health and life, as well as the maintenance of its high quality.
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Melanoma , Neoplasias Cutáneas , Humanos , Masculino , Adulto , Femenino , Persona de Mediana Edad , Melanoma/prevención & control , Melanoma/diagnóstico , Melanoma/epidemiología , Polonia/epidemiología , Neoplasias Cutáneas/prevención & control , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/epidemiología , Anciano , Adulto Joven , Adolescente , Anciano de 80 o más Años , Factores de Riesgo , Conocimientos, Actitudes y Práctica en Salud , Encuestas y Cuestionarios , Detección Precoz del Cáncer/métodos , Detección Precoz del Cáncer/estadística & datos numéricosRESUMEN
This Corrigendum relates to the following article: https://doi.org/10.2340/actadv.v104.13381.
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Carcinoma de Células Escamosas , Queratoacantoma , Neoplasias Cutáneas , Humanos , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/inmunología , Neoplasias Cutáneas/metabolismo , Queratoacantoma/patología , Queratoacantoma/metabolismo , Queratoacantoma/inmunología , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/inmunología , Carcinoma de Células Escamosas/metabolismo , Masculino , Femenino , Anciano , Proteínas de Punto de Control Inmunitario/metabolismo , Persona de Mediana Edad , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/metabolismo , Inmunohistoquímica , Anciano de 80 o más AñosAsunto(s)
Anticuerpos Monoclonales Humanizados , Antineoplásicos Inmunológicos , Encefalitis , Melanoma , Humanos , Femenino , Melanoma/tratamiento farmacológico , Melanoma/secundario , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Encefalitis/inducido químicamente , Encefalitis/diagnóstico , Antineoplásicos Inmunológicos/efectos adversos , Neoplasias Cutáneas , Enfermedad de Hashimoto/complicaciones , Persona de Mediana EdadRESUMEN
A 5 yr old female spayed pit bull terrier mix was evaluated for development of multiple dermal nodules over the previous 2 wk with concurrent weight loss and lethargy. A definitive diagnosis of cutaneous epitheliotropic T-cell lymphoma was obtained through histopathology and immunohistochemistry. Treatment was initiated with 32.9 mg/m2 (1.2 mg/kg) of oral verdinexor twice per week, according to label guidance. One week after treatment initiation, clinical remission was noted with complete resolution of the cutaneous nodules. The dog has continued twice-weekly treatments without any interruption and remains in complete remission 17 mo following initiation of verdinexor therapy. This case provides evidence for the utility of verdinexor in the treatment of canine cutaneous epitheliotropic T-cell lymphoma.
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Enfermedades de los Perros , Neoplasias Cutáneas , Animales , Perros , Enfermedades de los Perros/tratamiento farmacológico , Enfermedades de los Perros/patología , Femenino , Neoplasias Cutáneas/veterinaria , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Linfoma Cutáneo de Células T/veterinaria , Linfoma Cutáneo de Células T/tratamiento farmacológico , Linfoma Cutáneo de Células T/patología , Antineoplásicos/uso terapéuticoRESUMEN
BACKGROUND: Most primary cutaneous melanomas have pathogenesis driven by ultraviolet exposure and genetic mutations, whereas acral lentiginous melanoma (ALM) and metastatic melanoma are much less, if at all, linked with the former. Thus, we evaluated both ultraviolet related and non-ultraviolet related melanomas. Mutations in the MUC16 and TTN genes commonly occur concurrently in these melanoma patients, but their combined prognostic significance stratified by gender and cancer subtype remains unclear. METHODS: The cBioPortal database was queried for melanoma studies and returned 16 independent studies. Data from 2447 melanoma patients were utilized including those with ALM, cutaneous melanoma (CM), and melanoma of unknown primary (MUP). Patients were grouped based on the presence or absence of MUC16 and TTN mutations. Univariate Cox regression and Student's t-tests were used to analyze hazard ratios and total mutation count comparisons, respectively. RESULTS: TTN mutations, either alone or concurrently with MUC16 mutations, significantly correlated with worse prognosis overall, in both genders, and in CM patients. ALM patients with both mutations had better prognoses than CM patients, while ALM patients with neither mutation had worse prognosis than CM patients. For MUP patients, only MUC16 mutations correlated with worse prognosis. ALM patients with neither MUC16 nor TTN mutations had significantly more total mutations than MUP patients, followed by CM patients. CONCLUSION: TTN mutations are a potential marker of poor prognosis in melanoma, which is amplified in the presence of concurrent MUC16 mutations. ALM patients with neither gene mutations had worse prognosis, suggesting a protective effect of having both MUC16 and TTN mutations. Only MUC16 mutations conferred a worse prognosis for MUP patients. Comprehensive genetic profiling in melanoma patients may facilitate personalized treatment strategies to optimize patient outcomes.
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Conectina , Melanoma , Mutación , Neoplasias Cutáneas , Humanos , Melanoma/genética , Melanoma/mortalidad , Melanoma/patología , Femenino , Masculino , Pronóstico , Estudios Retrospectivos , Persona de Mediana Edad , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/patología , Conectina/genética , Antígeno Ca-125 , Factores Sexuales , Proteínas de la Membrana/genética , Anciano , Biomarcadores de Tumor/genética , AdultoRESUMEN
Line-field confocal optical coherence tomography (LC-OCT) is a new technology for skin cancer diagnostics. However, the interobserver agreement (IOA) of known image markers of keratinocyte carcinomas (KC), including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), as well as precursors, SCC in situ (CIS) and actinic keratosis (AK), remains unexplored. This study determined IOA on the presence or absence of 10 key LC-OCT image markers of KC and precursors, among evaluators new to LC-OCT with different levels of dermatologic imaging experience. Secondly, the frequency and association between reported image markers and lesion types, was determined. Six evaluators blinded to histopathologic diagnoses, assessed 75 LC-OCT images of KC (21 SCC; 21 BCC), CIS (12), and AK (21). For each image, evaluators independently reported the presence or absence of 10 predefined key image markers of KCs and precursors described in an LC-OCT literature review. Evaluators were stratified by experience-level as experienced (3) or novices (3) based on previous OCT and reflectance confocal microscopy usage. IOA was tested for all groups, using Conger's kappa coefficient (κ). The frequency of reported image marker and their association with lesion-types, were calculated as proportions and odds ratios (OR), respectively. Overall IOA was highest for the image markers lobules (κ = 0.68, 95% confidence interval (CI) 0.57;0.78) and clefting (κ = 0.63, CI 0.52;0.74), typically seen in BCC (94%;OR 143.2 and 158.7, respectively, p < 0.001), followed by severe dysplasia (κ = 0.42, CI 0.31;0.53), observed primarily in CIS (79%;OR 7.1, p < 0.001). The remaining seven image-markers had lower IOA (κ = 0.06-0.32) and were more evenly observed across lesion types. The lowest IOA was noted for a well-defined (κ = 0.07, CI 0;0.15) and interrupted dermal-epidermal junction (DEJ) (κ = 0.06, CI -0.002;0.13). IOA was higher for all image markers among experienced evaluators versus novices. This study shows varying IOA for 10 key image markers of KC and precursors in LC-OCT images among evaluators new to the technology. IOA was highest for the assessments of lobules, clefting, and severe dysplasia while lowest for the assessment of the DEJ integrity.
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Carcinoma Basocelular , Carcinoma de Células Escamosas , Queratinocitos , Queratosis Actínica , Variaciones Dependientes del Observador , Neoplasias Cutáneas , Tomografía de Coherencia Óptica , Humanos , Neoplasias Cutáneas/diagnóstico por imagen , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/diagnóstico , Tomografía de Coherencia Óptica/métodos , Carcinoma Basocelular/diagnóstico por imagen , Carcinoma Basocelular/patología , Carcinoma Basocelular/diagnóstico , Carcinoma de Células Escamosas/diagnóstico por imagen , Carcinoma de Células Escamosas/patología , Queratinocitos/patología , Queratosis Actínica/diagnóstico por imagen , Queratosis Actínica/patología , Queratosis Actínica/diagnóstico , Microscopía Confocal/métodos , Lesiones Precancerosas/diagnóstico por imagen , Lesiones Precancerosas/patología , Femenino , Masculino , Anciano , Persona de Mediana EdadRESUMEN
Melanoma of the skin is the 17th most common cancer worldwide. Early detection of suspicious skin lesions (melanoma) can increase 5-year survival rates by 20%. The 7-point checklist (7PCL) has been extensively used to suggest urgent referrals for patients with a possible melanoma. However, the 7PCL method only considers seven meta-features to calculate a risk score and is only relevant for patients with suspected melanoma. There are limited studies on the extensive use of patient metadata for the detection of all skin cancer subtypes. This study investigates artificial intelligence (AI) models that utilise patient metadata consisting of 23 attributes for suspicious skin lesion detection. We have identified a new set of most important risk factors, namely "C4C risk factors", which is not just for melanoma, but for all types of skin cancer. The performance of the C4C risk factors for suspicious skin lesion detection is compared to that of the 7PCL and the Williams risk factors that predict the lifetime risk of melanoma. Our proposed AI framework ensembles five machine learning models and identifies seven new skin cancer risk factors: lesion pink, lesion size, lesion colour, lesion inflamed, lesion shape, lesion age, and natural hair colour, which achieved a sensitivity of 80.46 ± 2.50 % and a specificity of 62.09 ± 1.90 % in detecting suspicious skin lesions when evaluated using the metadata of 53,601 skin lesions collected from different skin cancer diagnostic clinics across the UK, significantly outperforming the 7PCL-based method (sensitivity 68.09 ± 2.10 % , specificity 61.07 ± 0.90 % ) and the Williams risk factors (sensitivity 66.32 ± 1.90 % , specificity 61.71 ± 0.6 % ). Furthermore, through weighting the seven new risk factors we came up with a new risk score, namely "C4C risk score", which alone achieved a sensitivity of 76.09 ± 1.20 % and a specificity of 61.71 ± 0.50 % , significantly outperforming the 7PCL-based risk score (sensitivity 73.91 ± 1.10 % , specificity 49.49 ± 0.50 % ) and the Williams risk score (sensitivity 60.68 ± 1.30 % , specificity 60.87 ± 0.80 % ). Finally, fusing the C4C risk factors with the 7PCL and Williams risk factors achieved the best performance, with a sensitivity of 85.24 ± 2.20 % and a specificity of 61.12 ± 0.90 % . We believe that fusing these newly found risk factors and new risk score with image data will further boost the AI model performance for suspicious skin lesion detection. Hence, the new set of skin cancer risk factors has the potential to be used to modify current skin cancer referral guidelines for all skin cancer subtypes, including melanoma.
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Inteligencia Artificial , Melanoma , Neoplasias Cutáneas , Humanos , Neoplasias Cutáneas/diagnóstico , Melanoma/diagnóstico , Factores de Riesgo , Masculino , Persona de Mediana Edad , Femenino , Metadatos , Detección Precoz del Cáncer/métodos , Adulto , Anciano , Aprendizaje Automático , Medición de Riesgo/métodosRESUMEN
BACKGROUND: Cutaneous melanoma (CM) is associated with a higher mortality rate than most other skin cancers. The purpose of this expert consensus panel was to review the published literature on new technological advancements for the diagnosis and prognosis for CM and provide updated guidance on their usage. METHODS: A comprehensive literature search of PubMed, Scopus, and Google Scholar was completed for English-language original research articles on the topics of non-invasive diagnostic and prognostic testing for CM, including gene expression profiling (GEP) and electrical impedance spectroscopy (EIS). A panel of 10 dermatologists with significant expertise in the treatment of CM gathered to review the articles and create consensus statements. A modified Delphi process was used to approve each statement and a strength of recommendation was assigned using widely recognized Strength of Recommendation Taxonomy criteria. RESULTS: The literature search produced 200 articles that met the criteria. A screening of the studies resulted in 19 articles. These were distributed to all panelists for review prior to a roundtable discussion. The panel unanimously voted to adopt 7 consensus statements and recommendations, 5 of which were given a strength of "A", 1 of which was given a strength of "B," and 1 of which was given a strength of "C". CONCLUSION: The 2-GEP test and EIS can aid in the precise diagnosis of clinically indeterminate lesions and the 23-GEP test can be used when histopathology is equivocal. The 31-GEP test can enhance prognostic assessment beyond AJCC8 staging and improve clinical decision-making. J Drugs Dermatol. 2024;23(9):774-781. doi:10.36849/JDD.8365R1.
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Consenso , Espectroscopía Dieléctrica , Melanoma , Neoplasias Cutáneas , Humanos , Melanoma/diagnóstico , Melanoma/genética , Melanoma/patología , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/genética , Pronóstico , Espectroscopía Dieléctrica/métodos , Perfilación de la Expresión Génica , Técnica DelphiRESUMEN
BACKGROUND: To assess the distribution characteristics of immune infiltration and lymphovascular invasion in breast cancer skin recurrence patients. METHODS: We retrospectively analyzed the clinicopathological data of patients who underwent radical surgery for primary breast cancer and experienced skin recurrence between January 2001 and April 2019. Immune and lymphovascular biomarkers were quantified in primary breast cancers, skin lesions and visceral metastatic lesions. Differences in biomarkers distribution between matched tissues were statistically analyzed using the Wilcoxon signed-rank test and Kruskal-Wallis one-way ANOVA. RESULTS: A total of 71 female breast cancer patients were reviewed in this study. Our study found that the expression levels of various lymphocyte immune markers in primary tumor specimens were higher than those in skin recurrences. The expression of CD8, CD57 and CD31 in primary breast cancer was higher than those in the skin. Compared to visceral metastatic lesions, D2-40 was highly expressed in the skin, while CD8 tended to decrease. In the skin specimens, the expression of CD8 (P < 0.001), FOXP3 (P = 0.006) and CD68 (P < 0.001) in the intratumoral area was higher, while the expression of CD57 (P < 0.001) was higher in the peritumoral area. Analyzing specimens from the same patient at different time points of skin progression, it was found that the expression of peritumoral CD4 decreased (P = 0.044) as the disease progressed. The low expression of D2-40 and CD163 in the skin lesions suggested a decrease in DFS. CONCLUSION: The immune microenvironment of breast cancer skin recurrence may be in a state of suppression, and this suppression may intensify with disease progression. The pattern of skin recurrence may be more inclined toward lymphatic invasion. Our study provides new insights into the biological behaviors of this disease and its response to immunotherapy.
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Neoplasias de la Mama , Linfocitos Infiltrantes de Tumor , Recurrencia Local de Neoplasia , Neoplasias Cutáneas , Humanos , Femenino , Neoplasias de la Mama/patología , Neoplasias de la Mama/inmunología , Neoplasias de la Mama/metabolismo , Neoplasias Cutáneas/inmunología , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/metabolismo , Persona de Mediana Edad , Estudios Retrospectivos , Recurrencia Local de Neoplasia/inmunología , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/metabolismo , Anciano , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismo , Adulto , Metástasis Linfática/patología , Metástasis Linfática/inmunología , Biomarcadores de Tumor/metabolismo , Microambiente Tumoral/inmunología , Invasividad Neoplásica , PronósticoRESUMEN
BACKGROUND: Skin cancer is one of the highly occurring diseases in human life. Early detection and treatment are the prime and necessary points to reduce the malignancy of infections. Deep learning techniques are supplementary tools to assist clinical experts in detecting and localizing skin lesions. Vision transformers (ViT) based on image segmentation classification using multiple classes provide fairly accurate detection and are gaining more popularity due to legitimate multiclass prediction capabilities. MATERIALS AND METHODS: In this research, we propose a new ViT Gradient-Weighted Class Activation Mapping (GradCAM) based architecture named ViT-GradCAM for detecting and classifying skin lesions by spreading ratio on the lesion's surface area. The proposed system is trained and validated using a HAM 10000 dataset by studying seven skin lesions. The database comprises 10 015 dermatoscopic images of varied sizes. The data preprocessing and data augmentation techniques are applied to overcome the class imbalance issues and improve the model's performance. RESULT: The proposed algorithm is based on ViT models that classify the dermatoscopic images into seven classes with an accuracy of 97.28%, precision of 98.51, recall of 95.2%, and an F1 score of 94.6, respectively. The proposed ViT-GradCAM obtains better and more accurate detection and classification than other state-of-the-art deep learning-based skin lesion detection models. The architecture of ViT-GradCAM is extensively visualized to highlight the actual pixels in essential regions associated with skin-specific pathologies. CONCLUSION: This research proposes an alternate solution to overcome the challenges of detecting and classifying skin lesions using ViTs and GradCAM, which play a significant role in detecting and classifying skin lesions accurately rather than relying solely on deep learning models.
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Algoritmos , Aprendizaje Profundo , Dermoscopía , Neoplasias Cutáneas , Humanos , Dermoscopía/métodos , Neoplasias Cutáneas/diagnóstico por imagen , Neoplasias Cutáneas/clasificación , Neoplasias Cutáneas/patología , Interpretación de Imagen Asistida por Computador/métodos , Bases de Datos Factuales , Piel/diagnóstico por imagen , Piel/patologíaRESUMEN
BACKGROUND: Keratinocyte cancer (KC) in Australia poses a unique healthcare challenge due to its high prevalence and the requirement for multidisciplinary management of many cases. Advances in radiation therapy (RT) have increased its use in treating different keratinocyte cancer presentations. Understanding the indications for RT and the role that general practitioners (GPs) play in the treatment pathway are imperative to ensure best patient outcomes. OBJECTIVE: This review examined the efficacy, advances and treatment considerations of RT for the management of keratinocyte cancer, and role of the GP in the treatment pathway. DISCUSSION: Radiation therapy offers effective alternatives to, or adjuvants for, surgery in existing keratinocyte cancer treatments in appropriate cases. The evolving RT landscape necessitates GPs to be well informed for effective case identification, referral and management. This includes understanding RT advances, protocols, treatment reactions and managing patient expectations. Continuing education in this space is important for GPs to understand the suitability of RT for their patients.
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Médicos Generales , Queratinocitos , Neoplasias Cutáneas , Humanos , Neoplasias Cutáneas/radioterapia , Australia , Carcinoma de Células Escamosas/radioterapia , Carcinoma Basocelular/radioterapiaRESUMEN
Merkel cell polyomavirus (MCPyV) is a significant contributor to the development of Merkel cell carcinoma (MCC), an aggressive skin cancer with high recurrence and a low survival rate. In fact, it is the deadliest skin cancer. The precise routes of transmission for MCPyV-positive MCC remain unclear, but several factors may trigger its development. Conventional treatments for MCC are not highly effective, especially in patients with metastasis, with a clear need for new treatment options. Gene-targeted therapies hold great promise for the treatment of MCC, including the use of siRNA and CRISPR/Cas (C/Cas) but critically none have yet been translated into clinical trials. Validating this approach is the fact that several siRNA products are already FDA licenced, while C/Cas has entered clinical trial, albeit for conditions other than MCC. There are many challenges that must be overcome to move from preclinical research to the clinic. In this review, we provide a comprehensive summary of the current understanding of MCC, with a particular focus on MCPyV-positive MCC, and the status of gene-targeted therapies. Additionally, we discuss the major obstacles that impede MCC research and explore future prospects.
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Carcinoma de Células de Merkel , Terapia Genética , Poliomavirus de Células de Merkel , Infecciones por Polyomavirus , Humanos , Poliomavirus de Células de Merkel/genética , Carcinoma de Células de Merkel/virología , Carcinoma de Células de Merkel/terapia , Carcinoma de Células de Merkel/genética , Infecciones por Polyomavirus/virología , Infecciones por Polyomavirus/terapia , Terapia Genética/métodos , Neoplasias Cutáneas/terapia , Neoplasias Cutáneas/virología , Neoplasias Cutáneas/genética , Animales , Infecciones Tumorales por Virus/virología , Infecciones Tumorales por Virus/terapia , ARN Interferente Pequeño/genéticaRESUMEN
PURPOSE: Long-term use of hydrochlorothiazide increases the risk of non-melanoma skin cancer. We aimed to evaluate potential changes in the use of hydrochlorothiazide in Switzerland after a direct healthcare professional communication (DHPC) in November 2018 by Swissmedic. METHODS: We performed interrupted time-series analyses using a large Swiss healthcare claims database (2015-2021). Within monthly intervals, we quantified the total number of claims and the total dispensed 'defined daily doses' (DDD) for preparations containing (1) hydrochlorothiazide, (2) angiotensin-converting enzyme (ACE) inhibitors and angiotensin-II-receptor blockers (ARB), (3) calcium-channel blockers (CCB) and (4) thiazide-like diuretics per 10 000 persons. Using segmented linear regression, we quantified the pre-DHPC trend, the immediate change and the post-DHPC change in trend for total claims and DDD for the four drug classes weighted for the demographic distribution of the Swiss population. RESULTS: ACE inhibitors and ARB were the most frequently claimed antihypertensive drugs with 300-400 claims per 10 000 persons, which increased by 5.4% during the study period. The average number of hydrochlorothiazide claims (157/10 000 persons in 2015) declined by 35% between 2015 and 2021. The decrease started prior to the DHPC, but the DHPC was associated with an immediate 6.1% decline and an accelerated decline in claims over time after the DHPC (similar results for DDD). This coincided with a 23% increase in claims of CCB (dihydropyridine type) over 7 years, whereas use of other antihypertensives increased less. CONCLUSION: Our results suggest that the DHPC by Swissmedic in 2018 accelerated a pre-existing decline in the use of hydrochlorothiazide in Switzerland.
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Antihipertensivos , Hidroclorotiazida , Análisis de Series de Tiempo Interrumpido , Neoplasias Cutáneas , Humanos , Suiza/epidemiología , Hidroclorotiazida/efectos adversos , Antihipertensivos/efectos adversos , Neoplasias Cutáneas/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Anciano , Bases de Datos Factuales/estadística & datos numéricos , Adulto , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Antagonistas de Receptores de Angiotensina/efectos adversos , Hipertensión/tratamiento farmacológico , Hipertensión/epidemiologíaRESUMEN
The internal mammary artery perforator (IMAP) flap has been widely used for chest wall and neck reconstruction. The color of its skin paddle closely resembles that of facial skin, making it attractive for facial reconstruction. However, there has been insufficient investigations reporting the use of free IMAP flap. Furthermore, even in such studies, somewhat invasive procedures, including rib cartilage resection, were employed to ensure sufficient pedicle length, potentially increasing donor morbidity. Our report presents two cases of successful facial defect reconstruction using a free IMAP flap harvested with minimal donor site damage, showing its feasibility. In the first case, a 48-year-old male underwent wide excision for a malignant melanoma on his right cheek, resulting in a 4 × 4.5 cm full-thickness defect. A free IMAP flap with a 2.5 cm pedicle, was harvested without rib cartilage resection, preserving IMA main trunk, and transferred with anastomosed to the angular vessels within the defect. The second patient presented with a 4.5 × 3.5 cm basal cell carcinoma on the left cheek, necessitating wide excision and leaving a 6 × 5 cm defect. A free IMAP flap was harvested with the same approach and successfully reconstructed the defect with connected to the superficial temporal vessels using vascular bridge. Both patients were discharged complication-free, with no recurrence during 24 and 15 months of follow-up, respectively. They were highly satisfied with the final skin color and texture outcomes. Harvesting a free IMAP flap while minimizing donor morbidity may offer an attractive option for facial reconstruction.