SIRT1 in Secretory Organ Cancer

Mammalian silent information regulator 1 (SIRT1) is reported to play a role in cancers of the secretory organs, including thyroid, pancreatic endocrine, and ovarian tumors [1, 2, 3, 4]. A recent meta-analysis conducted on 37 selected studies of human cancers analyzed the correlations of overall survival (OS), disease-free survival (DFS) and relapse-free survival (RFS) with SIRT1 expression [5]. This study reported that SIRT1 overexpression was associated with a worse OS in liver and lung cancers, while it was not correlated with OS in breast cancer, colorectal cancer, or gastric carcinoma. Collectively, the meta-analysis revealed that an unfavorable OS was associated with SIRT1 expression for solid malignancies. Given the growing importance of this class of lysine/histone deacetylases in human endocrine malignancies, a rational and focused literature assessment is desirable in light of future clinical translations

Use of FTA® classic cards for epigenetic analysis of sperm DNA

FTA® technologies provide the most reliable method for DNA extraction. Although FTA technologies have been widely used for genetic analysis, there is no literature on their use for epigenetic analysis yet. We present for the first time, a simple method for quantitative methylation assessment based on sperm cells stored on Whatman FTA classic cards. Specifically, elution of seminal DNA from FTA classic cards was successfully tested with an elution buffer and an incubation step in a thermocycler. The eluted DNA was bisulfite converted, amplified by PCR, and a region of interest was pyrosequenced

Study on the role of clusterin in Hodgkin lymphoma

Clusterina è una proteina da stress ampiamente espressa nei tessuti e nei fluidi umani. Tuttavia vi sono poche informazioni riguardo alla sua funzione nei linfomi. In questo lavoro dimostriamo che la sua espressione in linee cellulari di linfoma di Hodgkin aumenta in risposta a diversi stimoli tra cui doxorubicina, interferon-gamma ed alte dosi di raggi X. La sua forma circolante è dosabile nel siero di pazienti affetti da linfoma di Hodgkin e sembra essere correlata con la persistenza del tessuto neoplastico ipercaptante dopo due cicli di chemioterapia.Clusterin is a molecular chaperon widely studied in cancers of epithelial origin. On the contrary, the information available on its functions in lymphomas are still quite poor. Here we demonstrate clusterin up-regulation in Hodgkin lymphoma derived cell lines as caused by doxorubicin, interferon-gamma and high doses of X-rays. We also present preliminary data on the quantitation of secretory clusterin in sera from Hodgkin lymphoma patients. The preliminary data show a correlation between the persistence of hypercaptating neoplastic mass and the increase in circulating clusterin

Cellular and Molecular Targets of Resveratrol on Lymphoma and Leukemia Cells

Resveratrol (RSV) is a well known chemopreventive molecule featuring anti-cancer properties. Our paper describes the main molecular targets of RSV linked to its antiproliferative activity on lymphoma and leukemia experimental models. It discusses further the most recent and most promising among these molecular targets for a translational application

The Multiple Mechanisms of Cell Death Triggered by Resveratrol in Lymphoma and Leukemia

Lymphoma and leukemia represent a serious threat to human health and life expectancy. Resveratrol is, among the natural-derived chemopreventive molecules, one of the most effective and better studied. In this paper the main mechanisms of cell death triggered by- or linked to- resveratrol are reviewed and discussed. The main focus is on lymphoma and leukemia experimental models where resveratrol has been tested and investigated at the cellular, molecular or physiological levels. The most relevant in vivo challenges involving resveratrol are also reported and analyzed in order to define the key features of this polyphenol and the potential for the treatment of hematologic tumors

Anti-Oxidant, Anti-Inflammatory and Anti-Angiogenic Properties of Resveratrol in Ocular Diseases

Resveratrol (3,4′,5 trihydroxy-trans-stilbene) is one of the best known phytophenols with pleiotropic properties. It is a phytoalexin produced by vine and it leads to the stimulation of natural plant defenses but also exhibits many beneficial effects in animals and humans by acting on a wide range of organs and tissues. These include the prevention of cardiovascular diseases, anti-cancer potential, neuroprotective effects, homeostasia maintenance, aging delay and a decrease in inflammation. Age-related macular degeneration (AMD) is one of the main causes of deterioration of vision in adults in developed countries This review deals with resveratrol and ophthalmology by focusing on the antioxidant, anti-inflammatory, and anti-angiogenic effects of this molecule. The literature reports that resveratrol is able to act on various cell types of the eye by increasing the level of natural antioxidant enzymatic and molecular defenses. Resveratrol anti-inflammatory effects are due to its capacity to limit the expression of pro-inflammatory factors, such as interleukins and prostaglandins, and also to decrease the chemo-attraction and recruitment of immune cells to the inflammatory site. In addition to this, resveratrol was shown to possess anti-VEGF effects and to inhibit the proliferation and migration of vascular endothelial cells. Resveratrol has the potential to be used in a range of human ocular diseases and conditions, based on animal models and in vitro experiments

Methylation Heterogeneity and Gene Expression of SPG20 in Solid Tumors

Introduction. The downregulation of the Spastic Paraplegia-20 (SPG20) gene is correlated with a rare autosomal recessive disorder called Troyer Syndrome. Only in recent years has SPG20 been studied and partially characterized in cancer. SPG20 has been shown to be hypermethylated in colorectal cancer, gastric cancer, non-Hodgkin’s lymphoma and hepatocellular carcinoma. In this study, we analyze the methylation status and the gene expression of SPG20 in different tumors of various histological origins. Methods. We analyzed the data generated through Infinium Human Methylation 450 BeadChip arrays and RNA-seq approaches extrapolated from The Cancer Genome Atlas (TCGA) database. The statistics were performed with R 4.0.4. Results. We aimed to assess whether the hypermethylation of this target gene was a common characteristic among different tumors and if there was a correlation between the m-values and the gene expression in paired tumor versus solid tissue normal. Overall, our analysis highlighted that SPG20 open sea upstream the TSS is altogether hypermethylated, and the tumor tissues display a higher methylation heterogeneity compared to the solid tissue normal. The gene expression evidences a reproducible, higher gene expression in normal tissues. Conclusion. Our research, based on data mining from TCGA, evidences that colon and liver tumors display a consistent methylation heterogeneity compared to their normal counterparts. This parallels a downregulation of SPG20 gene expression in tumor samples and suggests a role for this multifunctional protein in the control of tumor progression

Methylation changes of SIRT1, KLF4, DAPK1 and SPG20 in B-lymphocytes derived from follicular and diffuse large B-cell lymphoma

Diffuse large-B cell lymphomas (DLBCL) and follicular lymphomas (FL) are the most represented subtypes among mature B-cell neoplasms and originate from malignant B lymphocytes. Methylation represents one of the major epigenetic mechanisms of gene regulation. Silent information regulator 1 (SIRT1) is a class III lysine-deacetylase playing several functions and considered to be a context-dependent tumor promoter. We present the quantitative methylation, gene expression and tissue distribution of SIRT1 and some key mediators related to lymphoma pathogenesis in B lymphocytes purified from biopsies of follicular hyperplasias, FL and DLBCL. SIRT1 mRNA levels are higher in FL than follicular hyperplasias and DLBCL. B cell lymphoma 6 (BCL6) positively correlates with SIRT1. SIRT1 promoter shows a methylation decrease in the order: follicular hyperplasia - FL - DLBCL. Kruppel-like factor 4 (KLF4), Death-associated protein kinase 1 (DAPK1) and Spastic Paraplegia 20 (SPG20) methylation increase significantly in FL and DLBCL compared to follicular hyperplasias. Gene expression of DAPK1 and SPG20 inversely correlates with their degree of methylation. Our findings evidence a positive correlation between SIRT1 and BCL6 expression increase in FL. SIRT1 methylation decreases in FL and DLBCL accordingly and this parallels the increase of KLF4, DAPK1 and SPG20 methylation