Melanoma e tessuto adiposo peritumorale: studio preliminare sul ruolo delle adipocitochine nella caratterizzazione e prognosi di malattia

Nelle 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

Psoriasis 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

Coexistence of systemic lupus erythematosus, Hashimoto’s thyroiditis, and bilateral breast cancer in the same patient: a random association?

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Biologic Therapy in Psoriasis: Safety Profile

This 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?

Estrogens 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

Primary Dermal Melanoma: A Rare Clinicopathological Variant Mimicking Metastatic Melanoma

none6Primary dermal melanoma (PDM) is a rare distinct variant of cutaneous melanoma, predominantly occurring on the extremities of young or middle-aged adults. In comparison to conventional melanoma, PDM is characterized by unexpectedly prolonged survival and long-term survival. Thus, correct identification of this variant is crucial to avoid potential misdiagnosis and establish correct treatment and follow-up. In addition, no consensus and specific guidelines exist on the management of this peculiar subtype of cutaneous melanoma.noneSimonetti, Oriana; Molinelli, Elisa; Brisigotti, Valerio; Brancorsini, Donatella; Talevi, Davide; Offidani, AnnamariaSimonetti, Oriana; Molinelli, Elisa; Brisigotti, Valerio; Brancorsini, Donatella; Talevi, Davide; Offidani, Annamari