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Microneedle-Assisted Topical Delivery of Photodynamically Active Mesoporous Formulation for Combination Therapy of Deep-Seated Melanoma
摘要: Topical treatment using photodynamic therapy (PDT) for many types of skin cancers has largely been limited by the inability of existing photosensitizers to penetrate into the deep skin tissue. To overcome these problems, we developed a mesoporous nanovehicle with dual loading of photosensitizers and clinically relevant drugs for combination therapy, while utilizing microneedle technology to facilitate their penetration into deep skin tissue. Sub-50 nm photodynamically active mesoporous organosilica nanoparticles were synthesized with photosensitizers covalently bonded to the silica matrix, which dramatically increased the quantum yield and photostability of these photosensitizers. The mesopores of the nanoparticles were further loaded with small-molecule inhibitors, i.e., dabrafenib and trametinib, that target the hyperactive mitogen-activated protein kinase (MAPK) pathway for melanoma treatment. As-prepared empty nanovehicle was cytocompatible with normal skin cells in the dark, while NIR-irradiated drug-loaded nanovehicle showed a synergistic killing effect on skin cancer cells mainly through reactive oxygen species and caspase-activated apoptosis. The nanovehicle could significantly inhibit the proliferation of tumor cells in a 3D spheroid model in vitro. Porcine skin fluorescence imaging demonstrated that microneedles could facilitate the penetration of nanovehicle across the epidermis layer of skin to reach deep-seated melanoma sites. Tumor regression studies in a xenografted melanoma mouse model confirmed superior therapeutic efficacy of the nanovehicle through combinational PDT and targeted therapy.
关键词: microneedle technology,mesoporous formulation,skin cancer,combination therapy,topical treatment
更新于2025-09-10 09:29:36
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LOW-LEVEL LIGHT-ASSISTED PHOTODYNAMIC THERAPY USING A WEARABLE CAP-LIKE DEVICE FOR THE TREATMENT OF ACTINIC KERATOSIS OF THE SCALP
摘要: Background: Daylight photodynamic therapy (dlPDT) is a painless and increasingly cost-effective treatment for actinic keratosis (AK). New protocols avoid incubation minimizing pain and adverse events. However, it is time-consuming and dependent on specific weather conditions. In patients with AK of the scalp, we evaluated the efficacy of indoor photodynamic therapy (PDT) using a wearable low-level light therapy (LLLT) device, without pre-incubation with a photosensitizing agent. Methods: In this pilot study, 27 patients with thin and moderately thick AK (Olsen Grades I-II) underwent a single 15-minute session of LLLT using a wearable cap-like device immediately after application of methyl-aminolevulinate (MAL) cream, with no prior preparation of the affected area. Treatment efficacy was quantified by measuring the reduction in AK lesion number and the AK quality of life (AKQoL) score. All AK lesions were mapped at baseline for follow-up 2 months later. Paired pre/post scalp biopsies from 5 patients were analysed using histological and immunohistochemical techniques (p53, p27, cyclin D1, p63, and Ki67 expression). Data were analysed using the Wilcoxon signed-rank test. Results: In all patients we observed a global reduction in the number of AK lesions (71%; p<0.0001) and AKQoL score (from 5.6 to 4.4; p=0.034) 2 months after treatment. Histology and immunohistochemistry of skin biopsies from 5 patients also revealed marked improvements after LLLT. No patients reported any pain during treatment. Conclusion: PDT using LLLT is a rapid, painless, and efficacious modality for the treatment of AK.
关键词: helmet,skin cancer,low-level laser therapy,Actinic keratosis,photodynamic therapy,methylaminolevulinate
更新于2025-09-10 09:29:36
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Real-time measurement of outdoor worker’s exposure to solar ultraviolet radiation in Pretoria, South Africa
摘要: The city of Pretoria in South Africa receives considerable solar ultraviolet radiation (UVR) because of its low latitude (22–35°S) and relatively clear skies. Certain meteorological factors affect the amount of solar UVR that reaches the ground; the most dominant factors being stratospheric ozone, cloud cover and solar zenith angle. It is known that overexposure to solar UVR may lead to the development of adverse health conditions, the most significant being skin cancer. Outdoor workers spend a significant amount of time outside and are thus susceptible to this risk. In this case study, we estimated, for the first time, the real-time solar UVR exposure of an outdoor worker in Pretoria. Measurements were made on 27 and 28 May 2013 using a handheld ultraviolet index (UVI) meter calibrated against a science-grade biometer at the South African Weather Service in Pretoria. Personal exposure estimation was used to discern the pattern in diurnal and annual sunburn risk for the outdoor worker. Ambient UVR levels ranged from 0 UVI to 4.66 UVI and the outdoor worker’s potential exposure estimates regularly exceeded 80% of these levels depending on the time of day. The risk of sunburn was evident; however, actual incidents would depend on individual skin photosensitivity and melanin content, as well as sun protection used. Further research is needed to determine the personal exposure estimations of outdoor workers in other provinces in which solar UVR levels may be equally high, or higher than those in Pretoria.
关键词: sunburn,skin phototype,skin cancer,sun-protective measures,meteorological factors
更新于2025-09-09 09:28:46
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Photocarcinogenesis & Photoprotection || Ultraviolet Radiation (UVR): An Introduction
摘要: Radiant energy of sun is essential to perform metabolic processes of all flora and fauna on the earth. The electromagnetic radiations (EMR) emitted by sun extend from very long wavelength radiation, such as radiowaves (A ″′ 3 × 108 m), to very short wavelength radiation, such as cosmic rays (A ″′ 3 × 10?19 m). The EMR reaching at the earth surface contains wavelength from 290 to 4000 nm. However, the UV portion covers from 200 to 400 nm. The range from 200 to 400 nm is often arbitrarily categorized into UVA, UVB, and UVC radiation. Solar radiation less than 290 nm does not reach at the earth’s surface due to the presence of O3 layer in stratospheric zone. But, last from few decades due to anthropogenic activities, the concentration of ozone layer decreases on stratospheric zone. As a consequence of that, UVB radiation levels are rising to 1% a year. Thus, the deleterious health effects on human beings (skin aging, cataracts, skin cancer, and immune suppression) are enhanced by UVR.
关键词: Skin cancer,Ozone,UVR,Skin aging,EMR
更新于2025-09-09 09:28:46
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Diagnostic accuracy of ex vivo fluorescence confocal microscopy for Mohs surgery of basal cell carcinomas: a prospective study on 753 margins
摘要: Background: Frozen histological sections are currently used for intra-operative margin assessment during Mohs surgery. Fluorescence confocal microscopy (FCM) is a new tool, which offers a promising and faster alternative to frozen histology. Objective: The aim of the present study is to prospectively evaluate in a clinical setting, the accuracy of FCM as compared to frozen sections in BCC’s margin assessment. Methods: Patients with BCC, scheduled for Mohs surgery were prospectively enrolled. Freshly-excised surgical specimens were first examined through FCM and then frozen sections were evaluated. Permanent sections were finally obtained, in order to validate our sample technique. A blind re-evaluation was also performed for discordant cases between FCM and frozen sections. Sensitivity and specificity levels, as well as positive and negative predicting values were calculated and ROC curves were generated. Results: We enrolled 127 BCCs in as many patients (40.2% females). A total number of 753 sections were examined. All BCCs were located on the head and neck area. When evaluating the performance of FCM as compared to frozen sections 79.8% sensitivity, 95.8% specificity, 80.5% positive predicting and 95.7% negative predicting values were found (Area Under the Curve: .88, 95%CI .84-.92; P<.001). A total of 49 discordant cases between FCM and frozen sections evaluations were blindly re-evaluated, of which 24 were false positive and 25 false negative. The performance of FCM and frozen sections was also evaluated according to the final histopathological assessment. Conclusions: We found high levels of accuracy for FCM as compared to frozen sections evaluation, in intra-operative BCC’s margin assessment during Mohs surgery. Some technical issues still prevent a wide use of this technique, but new upcoming devices promise to overcome these limitations.
关键词: basal cell carcinoma,fluorescence confocal microscopy,Mohs surgery,skin cancer,ex vivo confocal microscopy
更新于2025-09-09 09:28:46
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[IEEE 2018 IEEE 20th International Conference on e-Health Networking, Applications and Services (Healthcom) - Ostrava (2018.9.17-2018.9.20)] 2018 IEEE 20th International Conference on e-Health Networking, Applications and Services (Healthcom) - Supervised Level Sets For Dermoscopic Image Segmentation
摘要: In this paper, we propose a novel segmentation method that has been used for segmenting lesions in dermoscopy images. This method uses the variational level sets formulation with a novel area term based on supervised learning that results in the global optimization of a cost function, that can potentially result in a robust segmentation of the images. This term uses a mixture of Gaussians that are trained from a set of training images, and evolves an active contour such that the difference between the learned models and the empirical distributions obtained from the evolving curve for both the lesion and the skin are minimized. In the end, our approach is validated on the publicly available PH2 dermoscopy imaging dataset and the results show that the proposed method outperforms the other state-of-the-art methods that have been considered in this paper.
关键词: Gaussian mixture models,Variational level sets,Segmentation,Skin cancer,Dermoscopy
更新于2025-09-09 09:28:46
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Original paper Efficacy and safety of electronic brachytherapy for superficial and nodular basal cell carcinoma
摘要: Purpose: Surface electronic brachytherapy (EBT) is an alternative radiotherapy solution to external beam electron radiotherapy and high-dose-rate radionuclide-based brachytherapy. In fact, it is also an alternative solution to surgery for a subgroup of patients. The objective of this work is to confirm the clinical efficacy, toxicity and cosmesis of a new EBT system, namely Esteya? in the treatment of nodular and superficial basal cell carcinoma (BCC). Material and methods: This is a prospective single-center, non-randomized pilot study to assess the efficacy and safety of EBT in nodular and superficial BCC using the Esteya? system. The study was conducted from June 2014 to February 2015. The follow up time was 6 months for all cases. Results: Twenty patients with 23 lesions were included. A complete response was documented in all lesions (100%). A low level of toxicity was observed after the 4th fraction in all cases. Erythema was the most frequent adverse event. Cosmesis was excellent, with more than 60% of cases without skin alteration and with subtle changes in the rest. Conclusions: Electronic brachytherapy with Esteya? appears to be an effective, simple, safe, and comfortable treatment for nodular and superficial BCC associated with excellent cosmesis. It could be a good choice for elderly patients, patients with contraindications for surgery (due to comorbidities or anticoagulant drugs) or patients where surgery would result in a more disfiguring outcome. A longer follow-up and more studies are needed to confirm these preliminary results.
关键词: electronic brachytherapy,skin brachytherapy,basal cell carcinoma,skin cancer
更新于2025-09-04 15:30:14
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Risk of skin cancer in psoriasis patients receiving long‐term narrowband ultraviolet phototherapy: results from a Taiwanese population‐based cohort study
摘要: Background: Narrow-band ultraviolet B (NB-UVB) phototherapy is a widely used treatment for various dermatoses. The risk of skin cancer following long term NB-UVB phototherapy has rarely been explored in skin phototypes III-V. Methods: We conducted a nationwide matched cohort study and identified a total of 22,891 psoriasis patients starting NB-UVB phototherapy from the Taiwan National Health Insurance Database during the period 2000-2013. Cumulative incidences of skin cancers were compared between subjects receiving less than 90 UVB treatments (S-cohort, N=13,260) and age- as well as propensity score-matched subjects receiving more than or equal to 90 UVB treatments (L-cohort, N=3,315). Results: There were no significant differences in the overall cumulative incidences of skin cancers between the two cohorts (log-rank t test, P = 0.691) during the follow-up periods. The S-cohort had a significantly lower prevalence of actinic keratosis when compared with the L-cohort (0.54% versus 1.00%, P=0.005). Conclusion: Long-term NB-UVB phototherapy does not increase skin cancer risk compared to short-term NB-UVB phototherapy in psoriasis patients with skin phototypes III-V.
关键词: skin phototype,nationwide cohort study,skin cancer,narrowband ultraviolet B phototherapy
更新于2025-09-04 15:30:14
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Highly conformal CT based surface mould brachytherapy for non-melanoma skin cancers of earlobe and nose
摘要: Purpose: Brachytherapy (BT), due to rapid dose fall off and minor set-up errors, should be superior to external beam radiotherapy (EBRT) for treatment of lesions in difficult locations like nose and earlobe. Evidences in this field are scarce. We describe computed tomography (CT) based surface mould BT for non-melanoma skin cancers (NMSC), and compare its conformity, dose coverage, and tissue sparing ability to EBRT. Material and methods: We describe procedure of preparation of surface mould applicator and dosimetry parameters of BT plans, which were implemented in 10 individuals with NMSC of nose and earlobe. We evaluated dose coverage by minimal dose to 90% of planning target volume (PTV) (D90), volumes of PTV receiving 90-150% of prescribed dose (PD) (VPTV90-150), conformal index for 90 and 100% of PD (COIN90, COIN100), dose homogeneity index (DHI), dose nonuniformity ratio (DNR), exposure of organs. Prospectively, we created CT-based photons and electrons plans. We compared conformity (COIN90, COIN100), dose coverage of PTV (D90, VPTV90, VPTV100), volumes of body receiving 10-90% of PD (V10-V90) of EBRT and BT plans. Results: We obtained mean BT-DHI = 0.76, BT-DNR = 0.23, EBRT-DHI = 1.26. We observed no significant differences in VPTV90 and D90 between BT and EBRT. Mean BT-VPTV100 (89.4%) was higher than EBRT-VPTV100 (71.2%). Both COIN90 (BT-COIN90 = 0.46 vs. EBRT-COIN90 = 0.21) and COIN100 (BT-COIN100 = 0.52 vs. EBRT-COIN100 = 0.26) were superior for BT plans. We observed more exposure of normal tissues for small doses in BT plans (V10, V20), for high doses in EBRT plans (V70, V90). Conclusions: Computed tomography-based surface mould brachytherapy for superficial lesions on irregular surfaces is a highly conformal method with good homogeneity. Brachytherapy is superior to EBRT in those locations in terms of conformity and normal tissue sparing ability in high doses.
关键词: skin cancer,ear,mould,nose,brachytherapy
更新于2025-09-04 15:30:14
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[IEEE 2018 IEEE International Conference on Computational Electromagnetics (ICCEM) - Chengdu (2018.3.26-2018.3.28)] 2018 IEEE International Conference on Computational Electromagnetics (ICCEM) - Terahertz Wave Scattering by Skin Cancer Tissues
摘要: This paper presents an approximate method for analysis of scattering by skin cancer tissues at Terahertz. The complex dielectric parameters of skin tissues are based on the double Debye model. The cancer tissue is taken to be a weak disturbance to the bulk skin organ. Born approximation is used to calculate the scattering field by the equivalent volume currents of cancer tissues in a layered configuration. Discrete complex image method is employed to evaluate the Sommerfeld-type integral. Numerical results show that the proposed approach is efficient and viable.
关键词: Born approximation,Terahertz scattering,skin cancer tissues,double Debye model
更新于2025-09-04 15:30:14