Salivary gland tumors (SGTs) comprise a group of rare neoplasms. Locally aggressive, recurrent and/or metastatic SGTs are notorious for their resistance to systemic therapy, making the need for carefully designed, prospective and randomized trials with useful predictive markers mandatory to define new effective therapeutic protocols. Histone Deacetylases (HDACs), are thought to play a crucial role in carcinogenesis. They affect the DNA structure, being also able to regulate its transcription, repair, and replication. This study aimed to evaluate—to our knowledge for the first time—the HDAC-1, -2, -4 and -6 immunohistochemical expression in SGTs and their potential use as prognostic biomarkers. Medical records and archival histopathological material of 58 (36 benign and 22 malignant) SGT patients were included in this study. The H-score was statistically correlated with the clinicopathological characteristics for all cases and patients’ survival rate in malignant SGTs. HDAC-2 positivity was significantly associated with more prolonged overall survival (OS) of patients with malignant SGTs (p = 0.028), while HDAC-2 positivity and no HDAC-6 expression were associated with prolonged OS of patients with HG malignant SGT (p = 0.003 and p = 0.043, respectively). Additionally, a high HDAC-2 H-score was significantly associated with longer OS for HG malignant SGT patients (p = 0.027). In our study, HDAC-2 expression is a marker for good prognosis, whereas HDAC-6 expression indicated poor prognosis; thus, an inhibitor of HDAC-6 may be used to improve patients’ survival.
Salivary gland tumors (SGTs) comprise a rare and heterogenous category of benign/malignant neoplasms with progressively increasing knowledge of the molecular mechanisms underpinning their pathogenesis, poor prognosis, and therapeutic treatment efficacy. Emerging data are pointing toward an interplay of genetic and epigenetic factors contributing to their heterogeneity and diverse clinical phenotypes. Post-translational histone modifications such as histone acetylation/deacetylation have been shown to actively participate in the pathobiology of SGTs, further suggesting that histone deacetylating factors (HDACs), selective or pan-HDAC inhibitors (HDACis), might present effective treatment options for these neoplasms. Herein, we describe the molecular and epigenetic mechanisms underlying the pathology of the different types of SGTs, focusing on histone acetylation/deacetylation effects on gene expression as well as the progress of HDACis in SGT therapy and the current status of relevant clinical trials.
Objective:In adults, short leukocyte telomere length (LTL) is associated with metabolic disorders such as diabetes and obesity. The causality remains unclear since longitudinal studies do not show influence of metabolic disorders on LTL attrition. These associations could stem from early life interactions between telomere dynamics and metabolic disorders. To test this hypothesis, we measured, in obese children and their controls, LTL and its evolution over time and their associations with metabolic parameters.Design and method:73 children aged 2–10 years (mean 7.6 ± 2.0) at inclusion were followed between 2 and 4 years (one visit/year). Anthropometric measurements (weight, height, waist and hip circumferences), a body composition analysis and a complete biology were performed annually. LTL was measured by Southern blot and LTL attrition was calculated. Scores for metabolic parameters were created based on the mean value of the parameter throughout the study.Results:Mean LTL attrition was 67 ± 8 bp/year. Baseline LTL correlated negatively with BMI score (p = 0.02), fat percentage score (p = 0.01), glycemia score (p = 0.0007), and insulinemia score (p = 0.02). These associations persisted after adjustment for age and sex. Trends for negative associations were observed between baseline LTL and waist/hip score (p = 0.07), and Hb1Ac score (p = 0.07). No association was found between LTL attrition and any of the metabolic parameters.Conclusions:In young children, metabolic parameters are negatively associated with LTL but not with LTL attrition. These results indicate that either short TL is the cause of metabolic disorders or that these metabolic disorders increased LTL attrition very early in life probably before the age of 5 years.
The adoption of healthy nutritional habits constitutes one of the most important determinants of healthy growth and development in childhood. Few studies in Greece have examined children’s diet quality using diet indices. The present study aimed to assess the diet quality of a large cohort of children and adolescents with overweight or obesity. Study participants (n = 1335), aged 2–18, were recruited through the Out-patient Clinic for the Prevention and Management of Overweight and Obesity in Childhood and Adolescence, Aghia Sophia Children’s Hospital, Athens, Greece. Anthropometric, socio-demographic, and behavioral data were collected using standard methods and equipment. The Diet Quality Index (DQI), which includes four subcomponents (i.e., dietary diversity, dietary quality, dietary equilibrium, and meal index), was calculated to assess each subject’s diet quality. According to the results of this study, children’s total DQI score was 63.1%. It was observed that 66.7% of the children had at least moderate diet quality (total DQI ≥ 59.34%). Boys had higher values of the total DQI and certain components of the DQI (i.e., dietary equilibrium score and meal index) compared to girls. Three out of ten children with overweight/obesity had poor diet quality (i.e., DQI ≤ 59.33). Younger children (2–5 years old) were found to have the lowest values of dietary equilibrium compared to older children (6–9 and 12–18 years old). Moreover, boys had higher values of the total DQI score and of specific components of this index (i.e., dietary equilibrium and meal index) compared to girls. Children living in urban areas had higher values in the dietary quality score compared to those living in rural areas. Children with overweight had higher values of the dietary quality score and the total DQI score compared to children with obesity. The present study highlighted that children and adolescents with overweight or obesity have poor diet quality. Multilevel and higher intensity interventions should be designed specifically for this group to achieve tangible outcomes.
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