65 research outputs found
Maria Concetta Carbone (in Piacente)
No full textVideo interview with Maria Concetta Carbone (in Piacente) as part of the Italian Cinema Audiences projec
Insight into immune profile associated with vitiligo onset and anti-tumoral response in melanoma patients receiving anti-PD-1 immunotherapy
No full textIntroductionImmunotherapy with checkpoint inhibitors is an efficient treatment for metastatic melanoma. Development of vitiligo upon immunotherapy represents a specific immune-related adverse event (irAE) diagnosed in 15% of patients and associated with a positive clinical response. Therefore, a detailed characterization of immune cells during vitiligo onset in melanoma patients would give insight into the immune mechanisms mediating both the irAE and the anti-tumor response. MethodsTo better understand these aspects, we analyzed T cell subsets from peripheral blood of metastatic melanoma patients undergoing treatment with anti-programmed cell death protein (PD)-1 antibodies. To deeply characterize the antitumoral T cell response concomitant to vitiligo onset, we analyzed T cell content in skin biopsies collected from melanoma patients who developed vitiligo. Moreover, to further characterize T cells in vitiligo skin lesion of melanoma patients, we sequenced T cell receptor (TCR) of cells derived from biopsies of vitiligo and primary melanoma of the same patient.Results and discussionStratification of patients for developing or not developing vitiligo during anti-PD-1 therapy revealed an association between blood reduction of CD8-mucosal associated invariant T (MAIT), T helper (h) 17, natural killer (NK) CD56bright, and T regulatory (T-reg) cells and vitiligo onset. Consistently with the observed blood reduction of Th17 cells in melanoma patients developing vitiligo during immunotherapy, we found high amount of IL-17A expressing cells in the vitiligo skin biopsy, suggesting a possible migration of Th17 cells from the blood into the autoimmune lesion. Interestingly, except for a few cases, we found different TCR sequences between vitiligo and primary melanoma lesions. In contrast, shared TCR sequences were identified between vitiligo and metastatic tissues of the same patient. These data indicate that T cell response against normal melanocytes, which is involved in vitiligo onset, is not typically mediated by reactivation of specific T cell clones infiltrating primary melanoma but may be elicited by T cell clones targeting metastatic tissues. Altogether, our data indicate that anti-PD-1 therapy induces a de novo immune response, stimulated by the presence of metastatic cells, and composed of different T cell subtypes, which may trigger the development of vitiligo and the response against metastatic tumor
A potential cause of asbestos-related granulomatosis due to adulterant contamination in a drug abuser
No full textDrug adulterants containing contaminants have been known to cause lung disease by inhalation or intravenous intake. Talcosis due to intravenous talc injection has been widely described in the literature, whereas the hypothesis of granulomatosis due to asbestos related to adulterated cocaine injection has not yet been explored. Herein, a case of pulmonary granulomatosis due to asbestos fibres related to cocaine injection in a young woman is described. Inorganic material in the lung was first individuated by light microscopy and last was identified using the SEM-EDX method. This case is unique since the occupational and passive inhalation of asbestos was excluded with absolute certainty
Dental pulp stem cells: osteogenic differentiation and genes expression
No full textDental pulp stem cells (DPSCs) are an adult stem cell population with high proliferative potential and the ability
to differentiate in many cell types, and this has led scientists to consider these cells to be an alternative source
of postnatal stem cells comparable to mesenchymal stem cells from bone marrow. In this work, we studied the
osteoblastic phenotype developed by DPSCs cultured in osteogenic medium. In particular, we analyzed the expression
of the typical osteoblast markers such as alkaline phosphatase, collagen type I, osteocalcin, osteopontin, as well as
mineralized matrix production. Furthermore, the gene expression during DPSC differentiation into osteoblastic
cells was studied by microarray technology. Using microarray and reverse transcriptase–polymerase chain reaction
(RT-PCR) analysis, we found that IGFBP-5, JunB, and NURR1 genes are upregulated during the differentiation of
DPSCs. These data indicate that opportunely differentiatedDPSCs show a correct osteoblastic phenotype. Therefore,
during the osteoblastic differentiation process, IGFBP-5, JunB, andNURR1gene expression is significantly increase
Osteogenic differentiation of dental follicle stem cells.
No full textBackground: Stem cells are defined as clonogenic cells capable of self-renewal and multi-lineage differentiation. A population of these cells has been identified in human Dental Follicle (DF).
Dental Follicle Stem Cells (DFSCs) were found in pediatric unerupted wisdom teeth and have been shown to differentiate, under particular conditions, into various cell types of the mesenchymal tissues.
Aim: The aim of this study was to investigate if cells isolated from DF show stem features, differentiate toward osteoblastic phenotype and express osteoblastic markers.
Methods: We studied the immunophenotype of DFSCs by flow cytometric analysis, the osteoblastic markers of differentiated DFSCs were assayed by histochemical methods and real-time PCR.
Results: We demonstrated that DFSCs expressed a heterogeneous assortment of makers associated with stemness. Moreover DFSCs differentiated into osteoblast-like cells, producing mineralized matrix nodules and expressed the typical osteoblastic markers, Alkaline Phosphatase (ALP) and Collagen I (Coll I).
Conclusion: This study suggests that DFSCs may provide a cell source for tissue engineering of bone
The first skin cancer screening day at the Italian parliament: a Euromelanoma initiative
No full textBACKGROUND: The effort to decrease incidence/mortality of skin cancer should target not only the general public but also politicians and decision makers, to create a proper health policy. We report the results of the first Skin Cancer Screening Day at the Italian Parliament, organized to draw politicians' attention on skin cancer.
METHODS: A questionnaire was used to collect data on participants' characteristics and suspected skin cancers.
RESULTS: We screened 70 members of parliament (61.4% males, median age 54 years). Overall skin cancer suspicion rate was 14.5%. Suspicion rate, detection rate, and positive predictive values for melanoma were respectively 1.6, 1.6, and 100%, and for basal cell carcinoma 6.5, 1.6, and 25%. Highly educated, <54-year-old females reported sun-seeking behaviors.
CONCLUSIONS: The considerable suspicion rate produced by this screening is justified by the particular demographics of the study population. Italian members of parliament display sun-seeking behaviors similar to those previously described in the general public. Increasing politicians' attention on skin cancer is vital for sufficient resources to be allocated to prevention strategies. Expert medical groups and politicians should cooperate to create a proper, integrated policy on skin cancer
Molecular alterations in basal cell carcinoma subtypes
No full textAbstract A number of genes have been implicated in the pathogenesis of BCC in addition to the Hedgehog pathway, which is known to drive the initiation of this tumour. We performed in-depth analysis of 13 BCC-related genes (CSMD1, CSMD2, DPH3 promoter, PTCH1, SMO, GLI1, NOTCH1, NOTCH2, TP53, ITIH2, DPP10, STEAP4, TERT promoter) in 57 BCC lesions (26 superficial and 31 nodular) from 55 patients and their corresponding blood samples. PTCH1 and TP53 mutations were found in 71.9% and 45.6% of BCCs, respectively. A high mutation rate was also detected in CSMD1 (63.2%), NOTCH1 (43.8%) and DPP10 (35.1%), and frequent non-coding mutations were identified in TERT (57.9%) and DPH3 promoter (49.1%). CSMD1 mutations significantly co-occurred with TP53 changes (p = 0.002). A significant association was observed between the superficial type of BCC and PTCH1 (p = 0.018) and NOTCH1 (p = 0.020) mutations. In addition, PTCH1 mutations were significantly associated with intermittent sun exposure (p = 0.046) and the occurrence of single lesions (p = 0.021), while NOTCH1 mutations were more frequent in BCCs located on the trunk compared to the head/neck and extremities (p = 0.001). In conclusion, we provide further insights into the molecular alterations underlying the tumorigenic mechanism of superficial and nodular BCCs with a view towards novel rationale-based therapeutic strategies
High dickkopf-1 levels in sera and leukocytes from children with 21-hydroxylase deficiency on chronic glucocorticoid treatment
No full textChildren with 21-hydroxylase deficiency (21-OHD) need chronic glucocorticoid (cGC) therapy to replace congenital deficit of cortisol synthesis and this therapy is the most frequent and severe form of drug-induced-osteoporosis. We found in 21-OHD patients high serum and leukocyte levels of dickkopf-1 (DKK1), a secreted antagonist of the Wnt/β-catenin signaling pathway, known to be a key regulator of bone mass. In particular, we demonstrated by flow cytometry, confocal microscopy and real time PCR that monocytes, T lymphocytes and neutrophils from patients expressed high levels of DKK1, which may be related to the cGC therapy. In fact, we showed that dexamethasone treatment markedly induced the expression of DKK1 in a dose- and time-dependent manner in leukocytes. The serum from patients containing elevated levels of DKK1 can directly inhibit in vitro osteoblast differentiation and RANKL expression. We also found a correlation between both DKK1 and Receptor Activator of NF-kappaB Ligand (RANKL) or C-terminal telopeptides of Type I collagen (CTX) serum levels in 21-OHD patients on cGC treatment. Our data indicated that DKK1, produced by leukocytes, may contribute to the alteration of bone remodeling in 21-OHD patients on cGC treatment
Treatment adherence with diclofenac 3% gel among patients with multiple actinic keratoses: an integrated low-intensity intervention program versus standard-of-care
No full textBackground: Diclofenac 3% gel is a widely used topical treatment with proven efficacy in reducing the burden of Actinic Keratosis (AK), however clinical benefit might not fully translate in clinical practice as non-adherence is substantial for prolonged treatment regimens. We evaluated the efficacy of an integrated low-intensity intervention program versus standard-of-care on treatment adherence among patients with multiple AK receiving diclofenac in hyaluronic acid gel 3%.
Methods: We designed an open label, randomized, parallel group, interventional, multicenter, longitudinal cohort study including patients with multiple, grade I/II AKs. Visits were scheduled for end of treatment (T4), follow-up 1 (T5) and follow-up 2 (T6) at 90, 180 and 365 days from baseline, respectively. Patients in the intervention group received additional visits at 30 and 60 days from baseline, a brief health education intervention, an enhanced patient-physician communication, a weekly SMS reminder to medication prescriptions.
Results: Patients were equally allocated between intervention (intervention group [IG], N=86) and control group (CG, N=86); at baseline, both groups had similar socio-demographic and clinical characteristics. Change scores from baseline showed a slight increment in quality of life related to AK in both groups (CG: ΔT4 - T1=-0.079; IG: ΔT4 - T1=-0.006; p=0.39) and in quality of physicianpatient interaction reported by IG (ΔT3 - T2=0.18; p<.0001). Adherence rate was not statistically different between IG and CG (28.4% vs 40.7%; p=0.11). Patients reported similar satisfaction for effectiveness, convenience and side effects of treatment. Clinical conditions improved over time and results did not differ between groups; complete clearance rate at 1 year was 18% and 29% for CG and IG, respectively.
Conclusions: Our findings showed no difference in adherence rate between the two groups, suggesting that enhanced follow-up interventions and health care education may not be sufficient drivers to promote adherence among this clinical population. Further studies are needed to explore barriers to adherence with treatments for AKs
Prevalence and risk factors of actinic keratosis in patients attending Italian dermatology clinics
No full textBackground: Actinic keratosis (AK) is a common keratinocyte intraepidermal neoplasia. Objective: To assess AK prevalence and potential risk factors in patients attending Italian general dermatology clinics. Materials & methods: This retrospective study was conducted on clinical data from consecutive white outpatients aged â¥30 years, attending 24 general dermatology clinics between December 2014 and February 2015. AK prevalence (entire population) and multivariate risk factor analysis (patients with current/previous AK and complete data) are presented. Results: AK prevalence in 7,284 patients was 27.4% (95% CI: 26.4-28.4%); 34.3% in men and 20.0% in women (p70 years), history of other non-melanoma skin cancers (OR: 2.7 [2.2-3.3]), residence in southern Italy/Sardinia (OR: 2.6 [2.1-3.0]), working outdoors >6 hours/day (OR: 1.9 [1.4-2.4]), male gender (OR: 1.7 [1.4-2.0]), facial solar lentigos (OR: 1.6 [1.4-1.9]), light hair colour (OR: 1.5 [1.2-1.8]), prolonged outdoor recreational activities (OR: 1.4 [1.2-1.7]), light eye colour (OR: 1.3 [1.1-1.6]), skin type I/II (OR: 1.3 [1.1-1.6]), and alcohol consumption (OR: 1.2 [1.0-3.3]). BMI â¥25.0 (OR: 0.6 [0.5-0.7]), regular sunscreen use (OR: 0.7 [0.6-0.8]), and a lower level of education (OR: 0.8 [0.7-1.0]) were independent protective factors. Conclusions: AK prevalence was high in Italian dermatology outpatients. We confirm several well-known AK risk factors and reveal possible novel risk and protective factors. Our results may inform on the design and implementation of AK screening and educational programmes
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