45 research outputs found

    The aberrant expression of the mesenchymal variant of FGFR2 in the epithelial context inhibits autophagy

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    Signaling of the epithelial splice variant of fibroblast growth factor receptor 2 (FGFR2b) triggers both differentiation and autophagy, while the aberrant expression of the mesenchymal FGFR2c isoform in epithelial cells induces impaired differentiation, epithelial mesenchymal transition (EMT) and tumorigenic features. Here we analyzed in the human keratinocyte cell line, as well as in primary cultured cells, the possible impact of FGFR2c forced expression on the autophagic process. Biochemical and quantitative immunofluorescence analysis, coupled to the use of autophagic flux sensors, specific substrate inhibitors or silencing approaches, showed that ectopic expression and the activation of FGFR2c inhibit the autophagosome formation and that AKT/MTOR is the downstream signaling mainly involved. Interestingly, the selective inhibition of AKT or MTOR substrates caused a reversion of the effects of FGFR2c on autophagy, which could also arise from the imbalance of the interplay between AKT/MTOR pathway and JNK1 signaling in favor of JNK1 activation, BCL-2 phosphorylation and possibly phagophore nucleation. Finally, silencing experiments of depletion of ESRP1, responsible for FGFR2 splicing and consequent FGFR2b expression, indicated that the switching from FGFR2b to FGFR2c isoform could represent the key event underlying the inhibition of the autophagic process in the epithelial context. Our results provide the first evidence of a negative impact of the out-of-context expression of FGFR2c on autophagy, suggesting a possible role of this receptor in the modulation of the recently proposed negative loop between autophagy and EMT during carcinogenesis

    Seborrheic keratoses mimicking melanoma unveiled by in vivo reflectance confocal microscopy

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    Background: Seborrheic keratoses (SebK) with atypical dermoscopy presentation are increasingly reported. These lesions do not exhibit typical dermoscopy features of SebK and sometimes mimic melanoma, thus complicating the differential diagnosis. Reflectance confocal microscopy (RCM) is a non-invasive tool, which allows an in vivo imaging of the skin. Objective: To evaluate the agreement between RCM classification and histological diagnoses, and the reliability of well-known RCM criteria for SebK in the identification of SebK with atypical dermoscopy presentation. Methodology: We retrospectively analysed at RCM excised lesions presenting in dermoscopy 651 score at revisited 7-point checklist. The study population consisted of cases showing no melanocytic RCM findings. Lesions were investigated for distinct non-melanocytic RCM features, blinded from histopathology diagnoses. Histopathology matching was then performed before statistical analysis. Results: The study consisted of 117 cases, classified at RCM as SebK (71 cases), dermatofibroma (DF; 18 cases), basal cell carcinoma (BCC; 13 cases), squamous cell carcinoma (SCC; 2 cases), and \u201cnon specific\u201d (13 cases). Overall K strength of agreement at histopathology matching proved 0.76. Of the 71 cases classified at RCM with SebK, agreement was achieved in 97%. Conclusions: RCM classification proved high agreement with histopathology for SebK with atypical dermoscopy presentations, allowing an early differential diagnosis. RCM features in this group of lesions were similar to those described for typical cases of SebK, and may assist clinician therapy decision making, whilst avoiding unnecessary excisions

    Improving the aging of the neck: combined treatments

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    INTRODUCTION, OBJECTIVES, PURPOSE OF THE STUDY The request for less aggressive procedures to treat skin laxity of face and neck is increasing. Only a few approaches are available for aesthetic treatments of the neck. Several factors are known to be involved in aging process: skin laxity and photodamage, fat tissue deposition, variation of muscle tone. MATERIALS AND METHODS Clinical evaluation of the patient. Classification and selection of the patient and targeted therapies: from microbotox, bio-stimulation, high intensity focused ultrasound to traction thread. Inclusion criteria: people aged >18 years old; moderate skin laxity and horizontal wrinkles of the neck. Exclusion criteria: severe diseases; skin laxity showing a high grade of severity and severe fat tissue deposition. Different treatments in multiple sessions. Controls at T0 + T30 + T90. Measurement and analysis: standard digital photo. Evaluation of results and satisfaction of patients. RESULTS The targeted approach focused on the correction of specific expressions of the ageing of the neck, showing a variable grading, is effective. The association of target therapy results to satisfy patient expectations. CONCLUSIONS In the field of aesthetic medicine we have available various techniques such as microbotox, bio-stimulation, high intensity focused ultrasound and traction thread. One treatment does not exclude the others. The combination of the two treatment it is possible to optimize the results. The targeted treatment and an appropriate selection of patients are essential to reach satisfactory results in the treatment of imperfections related to the process of ageing of the neck

    Skin above the knees: treatments for a difficult area

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    INTRODUCTION, OBJECTIVES, PURPOSE OF THE STUDY The interest for non-invasive techniques for skin rejuvenation is increasing. However, lax skin above the knee is often forgotten. As a matter of fact, there were not so many options for its treatment. The aim of our study is to present the application of selected rejuvenation techniques and to define their efficacy and safety. MATERIALS AND METHODS Clinical evaluation of the patient. Classification and selection of the patient and targeted therapies: from calcium hydroxyapatite to microfocused ultrasound. Inclusion criteria: people aged >18 years old; skin laxity. Exclusion criteria: severe diseases and severe skin laxity. Treatment in single or multiple sessions. Controls at T0 + T30 + T90. Measurement and analysis: standard digital photo. Evaluation of results and satisfaction of patients. RESULTS The targeted approach focused on the correction of specific morphologic variations of the skin above the knee, showing a variable grading, is effective and able to satisfy patient expectations. The treatment was well tolerated; we reported only a few adverse events: local reactions (erythema, oedema, swelling). All these effects last few days. CONCLUSIONS The treatment of the skin above the knee is challenging. Our protocols have shown good results in this difficult area and a good tolerability profile. A good selection of patients is mandatory in order to achieve the best result

    BRAFV600E mutated and wild type melanomas: dermoscopy and reflectance confocal microscopy characterization

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    The advent of modern molecular approaches was of crucial importance for the identification of melanoma genetic signatures, opening new horizons in the treatment of metastatic disease with molecular targeted therapies. Similarly the melanoma diagnosis is aided by reflectance confocal microscopy (RCM): a promising technique that allows non-invasive imaging from the skin surface to the upper dermis with quasi-histologic resolution. The most common melanoma mutation involves the gene BRAF and it is represented by the BRAFV600E, however, V600K, V600R and V600D mutations are also known. Because different genetic aberrations categorize melanoma subtypes with distinct clinical characteristics, it is reasonable to hypothesize that a distinctive molecular signature corresponds to specific morphologic patterns. A comparison between the dermoscopic patterns of BRAF p.V600E, BRAF p.V600K and wild-type BRAF primary melanomas was assessed from a collection of 12 lesions (4 primary melanomas per each BRAFV600 mutated status and 4 wt). In 9 cases the RCM images were available and the frequency of the RCM descriptors was examined. The RCM analysis showed that the presence of plump bright cells, collagen bundles and inflammatory cells in the dermis were frequently observed even when dermoscopy showed no regression features. Our study showed that regression phenomena and the associated dermoscopic and RCM descriptors could help the clinician to discriminate between the different BRAF mutated status, providing key information for patient screening, management and follow-up

    Congenital Glioblastoma multiforme and eruptive disseminated Spitz nevi

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    Background: Glioblastoma multiforme (GBM) is the deadliest malignant primary brain tumor in adults. GBM develops primarily in the cerebral hemispheres but can develop in other parts of the central nervous system. Its congenital variant is a very rare disease with few cases described in literature. Case presentation: We describe the case of a patient with congenital GBM who developed eruptive disseminated Spitz nevi (EDSN) after chemotherapy. Few cases of EDSN have been described in literature and this rare clinical variant, which occurs predominantly in adults, is characterized by multiple Spitz nevi in the trunk, buttocks, elbows and knees. There is no satisfactory treatment for EDSN and the best therapeutic choice is considered the clinical observation of melanocytic lesions. Conclusion: We recommend a close follow-up of these patients with clinical observation, dermoscopy and reflectance confocal microscopy (RCM). However, we suggest a surgical excision of the lesions suspected of being malignant
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