1,721,017 research outputs found
Melanoma e tessuto adiposo peritumorale: studio preliminare sul ruolo delle adipocitochine nella caratterizzazione e prognosi di malattia
Full text linkNelle ultime decadi, è andato delineandosi il concetto di organo adiposo, conferendo al tessuto adiposo una funzione endocrina attiva espletata mediante la secrezione di molteplici citochine e chemochine. Queste sembrano detenere infatti un ruolo chiave non solo nel mantenimento dell'omeostasi energetica ma anche nella patogenesi di malattie metaboliche ed infiammatorie e nella crescita e progressione di numerose neoplasie tra le quali il melanoma. In questo studio sperimentale preliminare abbiamo analizzato l'espressione, a livello del tessuto adiposo sottocutaneo peritumorale mediante qPCR, delle principali adipocitochine (Tumor Nescrosis Factor alpha (TNF-alpha), Interleukin-6 (IL-6), Plasminogen Activator Inhibitor 1 (PAI1), Leptina (LEP), Insulin-like Growth factor 1 (IGF1), Vascular Endothelial Growth Factor A (VEGF-A), Nicotinamide phosphoribosyltransferase (NAMPT), C-X-C Motif Chemokine Ligand 1 (CXCL1) e C-X-C Motif Chemokine Ligand 8 (CXCL8)) ritenute coinvolte, sulla base dei dati presenti in letteratura, nei processi di cancerogenesi e metastatizzazione. Lo studio è stato condotto prendendo in analisi una popolazione composta da pazienti affetti da melanoma, confrontando i dati ottenuti con l'espressione delle stesse citochine nel tessuto adiposo sottocutaneo in 2 gruppi controllo composti rispettivamente da nevi melanocitari e cisti epidemoidi. Abbiamo correlato i risultati ottenuti con i principali fattori prognostici di malattia per comprendere la loro espressione in relazione alla severità di patologia. Abbiamo osservato un aumento statisticamente significativo dell'espressione di PAI1, NAMPT, LEP e CXCL1 a livello del tessuto peritumorale dei campioni di melanoma rispetto ai gruppi controlli ed una correlazione degli stessi con lo stadio patologico di malattia ed in particolare con lo spessore di Breslow (il fattore prognostico più importante nella stadiazione patologica di melanoma). Il limite principale dello studio è rappresentato dal fatto che la popolazione risulta composta da un numero esiguo di pazienti. Studi su casistiche più ampie saranno necessari per confermare i risultati parziali ottenuti. Nel complesso, i risultati preliminari di questo lavoro evidenziano che la sovraespressione di alcune adipochine e chemochine in particolare PAI1, NAMPT, LEP e CXCL1 non solo a livello della lesione melanomatosa ma anche nel tessuto adiposo peritumorale può rappresentare un evento chiave nella crescita e soprattutto nell’aggressività locale della neoplasia e apre pertanto l'ipotesi di un ruolo oncogenico diretto di queste molecole e del tessuto adiposo sottocutaneo nella tumoregenesi del melanoma.In the last decades, the concept of adipose organ has emerged, giving adipose tissue an active endocrine function carried out through the secretion of multiple cytokines and chemokines having a key role not only in maintaining energy homeostasis but also in the pathogenesis of metabolic and inflammatory diseases and in the growth and progression of numerous neoplasms including melanoma.
In this preliminary experimental study, we analyzed the expression in the peritumor subcutaneous adipose tissue by qPCR of the most significant adipocytokines involved in the processes of carcinogenesis and metastasis such as Tumor Nescrosis Factor alpha (TNF-alpha), Interleukin- 6 (IL-6), Plasminogen Activator Inhibitor 1 (PAI1), Leptin (LEP), Insulin-like Growth factor 1 (IGF1), Vascular Endothelial Growth Factor A (VEGF-A), Nicotinamide phosphoribosyltransferase (NAMPT), CXC Motif Chemokine Ligand 1 (CXCL1) and CXC Motif Chemokine Ligand 8 (CXCL8) in a population of melanoma patients by comparing the data obtained with the expression of the same cytokines in the subcutaneous adipose tissue of 2 control groups composed respectively of melanocytic nevi and epidemoid cysts. We correlated the results obtained with the main disease prognostic factors to understand their expression in relation to the severity of the disease.
We observed a statistically significant increase in the expression of PAI1, NAMPT, LEP and CXCL1 at the level of the peritumor tissue of the melanoma samples compared to the control groups and a correlation of the same with the pathological stage of the disease and in particular with the Breslow thickness (the most important prognostic factor in the pathological staging of melanoma).
The main limitation of the study is represented by the small cohort of patients. Studies on larger case series will be necessary to confirm the partial results obtained.
Overall, the preliminary results of this study show that the overexpression of adipokines and chemokines in particular PAI1, NAMPT, LEP and CXCL1 not only at the level of the melanomatous lesion but also in the peritumoral adipose tissue, may represent a key event in growth and especially in the local aggressiveness of the neoplasm and therefore opens the hypothesis of a direct oncogenic role of these molecules and of the subcutaneous adipose tissue in the tumorigenesis of melanoma
Psoriasis, non-alcoholic fatty liver disease, and cardiovascular disease: Three different diseases on a unique background
No full textPsoriasis is a chronic inflammatory immune-mediated skin disease, frequently associated with systemic comorbidities. According to recent data, patients with psoriasis show a greater prevalence of metabolic syndrome, which confers a higher cardiovascular risk. The link between these pathological conditions appears to be a chronic low-grade inflammatory status. The aim of this review is to focus on the multiple epidemiological and physio-pathogenetic aspects linking non-alcoholic fatty liver disease, psoriasis, and cardiovascular disease
Biologic Therapy in Psoriasis: Safety Profile
No full textThis review focuses on the emerging concepts concerning the efficacy profile of biological drugs in psoriasis ranging from moderate to severe, and attempts to provide the most recent individual positioning of biologics in treating psoriasis. Biologic agents targeting towards specific immune mediators have emerged as treatment options for patients with moderate to-severe plaque psoriasis unresponsive or intolerant to traditional systemic agents. Data on the safety of biologics are available for up to 5 years in psoriasis and are on the whole reassuring. National registries are still evolving and will provide data on safety, to help the long-term monitoring of patients with psoriasis ongoing biological treatment. Although several biologics have demonstrated good efficacy and tolerability in short-term trials, treatment guidelines recommend them as third line therapies due to relative lack of long-term safety data, especially for those who have been commercialized recently. Here, we have reviewed the long-term safety data obtained from National Registries, randomized controlled trials, open-label extension studies and meta-analyses on etanercept, infliximab, adalimumab, and ustekinumab in the treatment of adults with moderate to severe plaque psoriasis
Coexistence of systemic lupus erythematosus, Hashimoto's thyroiditis, and bilateral breast cancer in the same patient: a random association?
No full textEstrogens influence many physiological processes and play a crucial role in the development of several diseases, including autoimmune disorders and hormone-sensitive cancers. Systemic lupus erythematosus is one of the most common systemic autoimmune rheumatic diseases affecting young and middle-aged females. The coexistence of multiple autoimmune disorders is well recognized, whereas the association between systemic lupus erythematosus and malignancies, especially hormone-sensitive cancers, remains enigmatic. We report the unusual case of a middle-aged woman that presented with concomitance of lupus erythematosus, Hashimoto's thyroiditis, and bilateral breast cancer
Biologic Therapy in Immune Mediated Inflammatory Disease: Basic Science and Clinical Concepts
No full textDuring the last decades, the advent of biological therapies has revolutionized the management of several immune-mediated inflammatory disorders, as inflammatory bowel diseases, autoimmune arthritis and psoriasis, which significantly impact both quality of life and health care economics. Biological therapies currently available can be divided into two main categories: the tumor necrosis factor-α antagonists (infliximab, adalimumab, etanercept, golimumab, certolizumab pegol) and interleukin 12/23 monoclonal antibodies (ustekinumab). Biologics, reducing TNFα bioavailability or inhibiting proximal regulators of inflammatory cascade, represent an established therapeutic strategy of inflammatory autoimmune diseases, with remarkable efficacy and a safety profile that is extensively examined and monitored. The biology and the immunological effects of TNFα, IL-12, IL-23 and related signalling pathways are accurately summarized. The dosing regimens, methods of administration, pharmacodynamics profiles, and side effects of the currently licensed TNFα antagonists and IL12/IL23 inhibitor are discussed in detail
Biologic Therapy in Inflammatory and Immunomediated Skin Diseases: Safety Profile
No full textBiologic treatments have modified the therapeutic armamentarium in the treatment of many dermatological and non- dermatological diseases and data on literature have widely focused on the efficacy and safety of TNF-alpha inhibitors in psoriasis. Although the etiopathogenesis has not completely elucidated, inflammation appears the lait motif unifying the immune-pathogenesis of diverse skin disease, as atopic dermatitis, alopecia areata and hidradenitis suppurativa. Actually, data on the off-label use of biologics in cutaneous immune-mediated inflammatory diseases are scarce and restricted to anecdotal cases and case series. The present review aims to evidence the major off- label use of TNF-alpha inhibitors in dermatology
Biologic Therapy in Psoriasis (Part II): Efficacy and Safety of New Treatment Targeting IL23/IL-17 Pathways
No full text
IL-17, IL-23, and p73 expression in cutaneous melanoma: a pilot study
No full textThe incidence of cutaneous malignant melanoma is increasing worldwide, resulting in the demand for clinically useful prognostic biomarkers, especially for invasive and metastatic disease. We studied the immunohistochemical expression of interleukin-17 (IL-17), IL-23, and p73 in 35 malignant melanomas and compared them with benign melanocytic nevi and Spitz nevi, correlating them with clinical-pathological variables. A higher and statistically significant difference (P<0.05) in the intensity and percentage of stained cells of IL-17 and IL-23 was found in the melanoma group than in ordinary benign nevi that did not correlate with Breslow thickness nor Clark level. Moreover, p73 staining and percentage of stained cells was significantly higher (P<0.05) in all the melanomas studied, with a peculiar cytoplasmatic distribution. Our findings could suggest a possible IL-17, IL-23, and p73 involvement in cutaneous melanomas with a hypothetical impact on melanoma invasiveness
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