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Computing uveal melanoma basal diameters: a comparative analysis of several novel techniques with improved accuracy
摘要： Background: We sought to compare the accuracy of standard and novel echographic methods for computing intraocular tumor largest basal diameter (LBD). Design: Multicenter, retrospective cohort study. Subjects: All patients presenting with new diagnosis of uveal melanoma (UM). Methods: Ultrasounds were obtained for all patients, and axial length (AL) was measured for a subset of patients. LBD was calculated as: (1) a single chord measured on B scan ultrasound (one-chord method [1CM]), or (2) by subdividing the basal diameter into two chords, which were summated (two-chord method [2CM]), or (3) by a mathematically-derived formula (MF) based on geometric relationships. The accuracy of each method was then compared, and sensitivity of each technique to factors such as tumor size and AL were analyzed. Main outcome measures: Accuracy, robustness, correctness of predicted plaque size. Results: 116 UMs were analyzed; 1CM-calculated LBD underestimated 2CM-calculated LBD by 7.5% and underestimated LBD by MF by 7.8%; 2CM and MF were tightly correlated (average LBD difference 0.038%). At larger LBDs, 1CM underestimated 2CM and MF by a much greater percentage (p < 0.001). By linear regression, 1CM underestimated LBD compared to 2CM by 0.8% and underestimated LBD compared to MF by 1.2% for every 1-mm LBD increase (p < 0.001 for each). Increasing the number of ultrasound chords beyond two did not significantly impact LBD calculations. For eyes with AL within two standard deviations of the mean, AL did not impact plaque selection using MF. 1CM would have led to selection of an undersized plaque in 41% of cases compared to 2CM and would have misclassified half of all eyes that actually required enucleation. For tumors with LBD < 12 mm, 1CM does not significantly underestimate LBD. Conclusions: Tumor LBD by 1CM is an inaccurate means of determining actual LBD, especially for larger tumors. Using either 2CM or MF is much more accurate, especially for tumors > 12 mm, where a single chord on ultrasound is more likely to lead to incorrect, undersized plaque selection. Our MF can be applied with great accuracy even in cases where the AL of the eye is not measured, using the population average AL (23.7 mm), and the formula LBD = 23.7 sin?1(chord length/23.7).
关键词： Ultrasonography,Plaque brachytherapy,Uveal melanoma,Ocular tumors
更新于2025-09-19 17:15:36
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Computational phantom study of frozen melanoma imaging at 0.45 terahertz
摘要： Terahertz radiation (THz) is highly absorbed by liquid water. This creates the possibility of medical imaging on the basis of the water content difference between normal and diseased tissue. The effective penetration of THz is limited, however, to a tissue depth of 0.2–0.3 mm at body temperature. A unique feature of the 0.1–2.0 THz frequency is that there is a high disparity between liquid water absorption and ice absorption, with ice being 100 times more permeable to the radiation than liquid water. This results in 90% of the radiation surviving to 1.0 mm in ice, permitting the imaging of frozen tissues to a depth of 5.0 mm. This method is practical as an in vivo procedure before or during surgical excision. Finite difference time domain (FDTD) computational modeling of frozen normal skin and frozen melanoma was undertaken using tissue phantoms. The study suggests that sufficient contrast exists to differentiate normal frozen skin and melanoma on the basis of the difference of water content alone. When the melanin pigment in melanomas is modeled as a significant absorber of THz, the contrast changes. Based on the modeling, further exploration of the “THz-skin freeze” imaging technique is justified. In the modeling, the boundary between the frozen tissue and non-frozen tissue is shown to be strongly reflective. If the reflective properties of the boundary are substantiated, the “THz-skin freeze” technique will have applications in other areas of skin diagnostics and therapeutics.
关键词： imaging,freezing,melanoma,skin,terahertz
更新于2025-09-19 17:15:36
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Regulation of NADPH-dependent Nitric Oxide and reactive oxygen species signalling in endothelial and melanoma cells by a photoactive NADPH analogue
摘要： Nitric Oxide (NO) and Reactive oxygen species (ROS) are endogenous regulators of angiogenesis-related events as endothelial cell proliferation and survival, but NO/ROS defect or unbalance contribute to cancers. We recently designed a novel photoactive inhibitor of NO-Synthases (NOS) called NS1, which binds their NADPH site in vitro. Here, we show that NS1 inhibited NO formed in aortic rings. NS1-induced NO decrease led to an inhibition of angiogenesis in a model of VEGF-induced endothelial tubes formation. Beside this effect, NS1 reduced ROS levels in endothelial and melanoma A375 cells and in aorta. In metastatic melanoma cells, NS1 first induced a strong decrease of VEGF and blocked melanoma cell cycle at G2/M. NS1 decreased NOX4 and ROS levels that could lead to a specific proliferation arrest and cell death. In contrast, NS1 did not perturb melanocytes growth. Altogether, NS1 revealed a possible cross-talk between eNOS- and NOX4 – associated pathways in melanoma cells via VEGF, Erk and Akt modulation by NS1 that could be targeted to stop proliferation. NS1 thus constitutes a promising tool that modulates NO and redox stresses by targeting and directly inhibiting eNOS and, at least indirectly, NADPH oxidase(s), with great potential to control angiogenesis.
关键词： ROS,endothelium,NADPH analogue,Angiogenesis,melanoma,cell proliferation,Cellular signaling
更新于2025-09-19 17:15:36
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The Efficiency of Verteporfin as a Therapeutic Option in Pre-Clinical Models of Melanoma
摘要： Yes Associated Protein 1 (YAP) and Transcriptional coactivator with PDZ-Binding Motif (TAZ) have gained notoriety for their ability to drive tumor initiation and progression in a wide variety of cancers, including melanoma. YAP and TAZ act as drivers of melanoma through its interaction with the TEAD family of transcription factors. Verteporfin is a benzoporphyrin derivative that is used clinically for photodynamic treatment of macular degeneration. Recently it has emerged as a potential inhibitor of YAP/TAZ-TEAD interaction independent of light activation. In this study we determine if verteporfin has clinical potential by testing this compound on human melanoma cell cultures and in a clinically significant mouse model, BrafCA; Tyr-CreERT2; Ptenf/f, which parallels human melanoma in terms of disease progression, genetics, and histopathology. In culture, Verteporfin treatment induces a rapid drop in YAP and TAZ protein levels and cell numbers. In the transgenic model, utilizing drug levels that correspond to previously determined safe doses in human patients and with a dosing regimen calculated in this study, Verteporfin did not inhibit melanoma initiation or progression in comparison to mock treated controls. Taken together, our study suggests that although Verteporfin induces YAP/TAZ degradation in melanoma cell lines, Verteporfin was not effective as a YAP/TAZ-TEAD specific inhibitor of melanoma in our studies that aimed to mimic conditions found in clinic in terms of treatment regimen and disease model.
关键词： TAZ,Verteporfin,hippo pathway,mouse models,melanoma,YAP
更新于2025-09-19 17:15:36
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Anti-cancer effect of gallic acid in presence of low level laser irradiation: ROS production and induction of apoptosis and ferroptosis
摘要： Background: There are different treatments for breast cancer and melanoma that mostly have some side effects. One of the therapeutic strategies is the use of natural components. Phenol components are a class of antioxidants in plants that have many biological functions like anticancer effects. Gallic acid (GA) is a natural polyhydroxy phenolic compound and commonly found in various foods. In the present study, GA effects alone and in combination with low-level laser irradiation on human dermal fibroblast cell line (HDF), human non-tumorigenic breast epithelial cell line (MCF10A), breast cancer cell line (MDA-MB-231) and melanoma cancer cell line (A375) was under the investigation. Methods: The normal and cancerous cell lines were exposed to 660 nm low-level laser with 3 J/cm2 for 90 s. Then, the cells were treated with different concentrations of GA for 24 h. In another study, the cell lines firstly were treated with GA and then exposed to low-level laser irradiation. The effects of GA and low-level laser on cell survival and apoptosis were examined using MTT assay, light microscopy, ROS production assay, fluorescence microscopy (AO/EB double staining) and flow cytometry. Results: The results showed that pre-treatment with low-level laser and then GA reduced the survival of breast cancer cells and melanoma more than the first treatment with GA and then low-level laser irradiation. Our findings showed that ROS production in cells treated with both low-level laser and GA was more than the cells treated with GA alone. The apoptosis and ferroptosis assays confirmed the MTT results which combination treatment with low-level laser and then GA increase the cell death probably via apoptosis and ferroptosis cell death mechanisms compared to GA alone. Conclusions: This study suggests that low-level laser irradiation alone is not able to cause death in human normal and cancerous cells. Preirradiation followed by GA treatment did not change the cell viability in human normal significantly but reduces the cell survival of cancer cells more than GA alone.
关键词： Breast cancer,Apoptosis,Low level laser irradiation,Ferroptosis,Melanoma cancer,Gallic acid
更新于2025-09-19 17:13:59
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Laser Interstitial Thermal Therapy for Metastatic Melanoma After Failed Radiation Therapy: A Case Series
摘要： Laser interstitial thermal therapy (LITT) is a growing technology to treat a variety of brain lesions. It offers an alternative to treatment options, such as open craniotomy and stereotactic radiosurgery. OBJECTIVE: To analyze our experience using LITT for metastatic melanoma. METHODS: This is a retrospective chart review of the patients from our institution. Our case series involves 5 patients who had previously failed radiation treatment. RESULTS: Our patients have low complication rates and short hospital stays. Both are considerably lower when compared to the literature for metastatic melanoma. CONCLUSION: LITT is a safe therapy, with few complications and short hospital stays.
关键词： Melanoma,LITT,Laser interstitial thermal therapy
更新于2025-09-19 17:13:59
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Low-level laser irradiation potentiates anticancer activity of p-coumaric acid against human malignant melanoma cells
摘要： p-Coumaric acid (PCA) is a kind of phenolic compound, and as one of the cinnamic acid derivatives, it has many biological functions such as antioxidants, anti-inflammatory, antiplatelet, and anticancer activity. Low-level laser irradiation has received increasing interest in the fields of tissue regeneration and wound healing. In this study, the effect of low-level laser irradiation on human fibroblast cells (human dermal fibroblast) and human melanoma cancer cells (A375 and SK-MEL-37) treated with PCA was investigated. The human dermal fibroblast, A375, and SK-MEL-37 cells were exposed to low-level laser at 660-nm wavelength with 3 J/cm2 for 90 s, and then the cells were treated with different concentrations of PCA (0–1000 μg/ml for 24 h), separately. In another experiment, first the cells were treated by PCA and then irradiated with low-level laser as described before. The effect of various irradiation energy (1–6 J/cm2) on the melanoma cells, which were then treated by PCA, was studied. The cell viability using MTT assay and lactate dehydrogenase assay was determined. Morphological changes owing to apoptosis induction by irradiation and PCA were detected by fluorescence microscopy using acridine orange/ethidium bromide double staining. The results showed that pretreatment with low-level laser irradiation and then PCA reduced the survival and growth of melanoma cells more than the early treatment with PCA and then low-level laser irradiation. Lactate dehydrogenase activity was reduced significantly by preirradiation and then PCA treatment in comparison with the dark group in melanoma cells. The cell cytotoxicity at different irradiation energy and then IC50 concentration of PCA was increased up to 3 J/cm2 and then decreased following increasing irradiation energy. The morphology study with light microscopy and apoptotic assay using acridine orange/ethidium bromide dual staining confirmed the MTT results. This study showed that low-level laser irradiation alone is not able to kill human normal fibroblast and human melanoma cancer cells. Preirradiation followed by treatment with PCA did not change the cell viability in human fibroblast significantly but reduced the cell viability in melanoma cells presumably through the apoptosis pathway.
关键词： p-coumaric acid,human melanoma cancer,lactate dehydrogenase,low-level light therapy
更新于2025-09-12 10:27:22
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Validation of an integrated dermoscopic scoring method in a European teledermoscopy web platform: the <i> <scp>iDS</scp> core </i> project for early detection of melanoma
摘要： Background. Although live and teledermoscopic examination have been successfully used to achieve non-invasive diagnosis of melanocytic skin lesions (MSLs), early melanoma (EM) and atypical nevi (AN) continue to be a challenge, and none of the various algorithms proposed have been sufficiently accurate. We designed a scoring classifier diagnostic method, the iDScore, that combines clinical data of the patient with dermoscopic features of the MSL. Objective. To test the accuracy of the iDScore in differentiating EM from AN in a teledermoscopy setting, and to compare it with intuitive diagnosis, the ABCD rule and the seven-point checklist. Materials and methods. A dedicated teledermoscopy web platform was designed. This involved: 1) collecting a large integrated clinical-historical-dermoscopic dataset of difficult MSLs from eight European dermatology centres; 2) on-line testing, education and training in using the iDScore. A total of 904 images were combined with age, sex, lesion diameter and body site data and evaluated on the platform by 111 participants with four levels of skill in dermoscopy. Each testing session consisted of 30 blind cases to examine consecutively by the above four methods. “Management decisions” and personal participant data were also recorded. Results. iDScore aided-diagnosis achieved satisfactory diagnostic accuracy for all lesions, irrespective of centre of affiliation, showing an average AUC of 0.776 in all participant testing sessions. All skill groups improved their accuracy by 10-16% with respect to intuitive diagnosis and the other methods, showing high concordance and avoiding wrong management decisions. Conclusion. We demonstrated the validity of the iDScore method for managing suspicious MSLs in a large multicentric dataset and a teledermoscopic setting. The platform designed for the iDScore project provides ready support for physicians of any dermoscopy skill level and is useful for education and training.
关键词： skill levels,early melanoma,non-invasive diagnosis,teledermoscopy
更新于2025-09-11 14:15:04
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Lesions Mimicking Melanoma at Dermoscopy Confirmed Basal Cell Carcinoma: Evaluation with Reflectance Confocal Microscopy
摘要： Background: Atypical basal cell carcinoma (BCC), characterized by equivocal dermoscopic features typical of malignant melanoma (MM), can be difficult to diagnose. Reflectance confocal microscopy (RCM) enables in vivo imaging at nearly histological resolution. Objectives: To evaluate with RCM atypical melanocytic lesions identified in dermoscopy, according to common RCM criteria for the differential diagnosis of BCC, and to identify representative RCM parameters for superficial (sBCCs) and nonsuperficial (nsBCCs) basal cell carcinomas (BCCs). Methods: A retrospective analysis of consecutive patients evaluated with RCM, selecting excised lesions classified at dermoscopy with ≥1 score from the revisited 7-point checklist, mimicking melanoma, registered between 2010 and 2016. Cluster analysis identified BCC subclassifications. Results: Of 178 atypical lesions, 34 lesions were diagnosed as BCCs with RCM. Lesions were confirmed BCCs with histopathology. Dermoscopic features included atypical network (55.9%) and regression structures (35.5%) associated with sBCCs, and an atypical vascular pattern (58.8%) and irregular blotches (58.8%) with nsBCCs. Hierarchical cluster analysis identified 2 clusters: cluster 1 (100% sBCCs) was characterized by the presence of cords connected to the epidermis (90%, p < 0.001), tumor islands located in the epidermis (100%, p < 0.001), smaller vascular diameter (100%, p < 0.001) and solar elastosis (90%, p = 0.017), and cluster 2 (nsBCCs 85%) was defined by the dermic location of tumor islands (87.5%, p < 0.001) with branch-like structures (70.8%, p = 0.007) and surrounding collagen (83.3%, p = 0.012), peripheral palisading (83.3%, p = 0.012) and coiled vascular morphology (79.2%, p < 0.001) with a larger vascular diameter (50%, p < 0.001). Conclusions: RCM is able to diagnose BCCs mimicking melanoma at dermoscopy and seems able to identify sBCCs and nsBCCs.
关键词： Melanoma,Basal cell carcinoma,Reflectance confocal microscopy,Dermoscopy,Noninvasive diagnosis
更新于2025-09-10 09:29:36
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[IEEE 2018 IEEE 20th International Conference on e-Health Networking, Applications and Services (Healthcom) - Ostrava, Czech Republic (2018.9.17-2018.9.20)] 2018 IEEE 20th International Conference on e-Health Networking, Applications and Services (Healthcom) - Learning Based Segmentation of Skin Lesion from Dermoscopic Images
摘要： Segmentation is the pre-requisite process in most of the computer aided diagnosis systems for medical imaging. Presence of different artifacts makes segmentation of skin lesion very difficult. Abnormal growth of artifacts can appear as false positives and can degrade the performance of the diagnosis systems. It can be avoided only when false structures are removed while extracting the lesion. To address this issue, this paper proposes deep leaning for skin lesion segmentation. Within this framework, automated skin lesion segmentation is proposed which achieves high accuracy segmentation of skin lesion. Our proposed architecture is 31 layers deep with same filter size. The validity of the proposed techniques is tested on two publically available databases of PH2 and ISIC 2017. Experimental results show the efficiency of the proposed approaches. The proposed method gives Dice Coefficient of 92.3% for PH2 Dataset while Dice Coefficient of 85.5% for ISIC 2017 Dataset.
关键词： Dice Coefficient,Deep Learning,Melanoma,Dermoscopy,Automatic segmentation,Convolution Neural Network
更新于2025-09-10 09:29:36