40 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

    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

    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

    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

    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

    Presentazione dermoscopica atipica di lesioni non melanocitarie benigne: quale aiuto dal confocale?

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    Sono sempre più frequenti i report di lesioni cutanee benigne che simulano clinicamente il melanoma; in questi casi spesso mancano i criteri clinico-dermoscopici tipici. Abbiamo analizzato retrospettivamente in microscopia laser confocale (RCM) lesioni che presentassero in dermoscopia punteggio ≥1 alla revisited 7-point checklist, focalizzandoci su quelle prive di criteri melanocitari. Ogni caso è stato indagato quindi per la presenza di caratteristiche RCM non melanocitarie. La selezione ha permesso di raccogliere 117 lesioni a presentazione dermoscopica atipica, classificate al confocale come benigne (71 cheratosi seborroiche e 18 dermatofibromi), maligne (13 basaliomi e 2 spinaliomi), e “non specifiche” (13). Il valore K relativo al matching complessivo con l’istologia è risultato elevato (0.76); per cheratosi seborroiche e dermatofibromi la concordanza è risultata del 97% e 89% rispettivamente. I risultati ottenuti su un gruppo di lesioni di difficile inquadramento clinico, confermano l’utilità del confocale nella diagnosi differenziale non invasiva tra patologie benigne e maligne

    Identifying the factors that influence surgeon's compliance with excisional margins of non-melanoma skin cancer

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    The rising incidence of Non Melanoma Skin Cancers (NMSC) leads to a high number of surgical procedures worldwide. The strict compliance with international guidelines with regard to excisional margins may help decrease the number of re-excision procedures and reduce the risk of NMSC recurrence. The aim of this study was to investigate the prevalence of excisional margins as recommended by the European Academy of Dermatology and Venereology (EADV) and the European Dermatology Forum (EDF) guidelines, and the factors (demographic or clinical) that influence surgeons' compliance with these guidelines.This was a prevalence study looking at surgical excisions of NMSCs performed over a period of 2 years (2011-2012). A sample size of 1669 patients was considered. Definition of excisional margins recommended by the international guidelines (EADV and EDF) were used as point of reference for the analysis. Tumor and histologic specimen size were calculated ex vivo by 5 different pathologists. The size of skin specimens was measured with a major axis and a minor axis. The same was done for the tumor present on the skin specimens. The differences between the major and minor axes of surgical specimen and tumor were calculated. These differences were subsequently divided by two, hypothesizing that the lesion had the same distance from the margins of the surgical specimen. The differences obtained were named "Delta", the formulas applied being the following: Delta major = (major axis specimen-major axis tumor)/2; Delta minor = (minor axis specimen -minor axis tumor)/2.Results show a significant statistical difference, associated with factors such as: Age of the patient, anatomical localization of the tumor, histological diagnosis, and surgeons' experience.The identification of these factors sheds light on clinicians' practice and decision-making regarding excisional margins. Hopefully a higher level of adherence to the guidelines can be achieved in the future
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