Histone code, human growth and cancer

Epigenetics refers to all heritable changes, which are not dependent on alterations of DNA primary structure [1]. Among them, histone post-translational modifications (HPTMs) play a crucial role in regulating gene expression. Histones are core chromatin components, organized in cylindrical structures. The nucleosome is the fundamental chromatin unit: it is made of appreciatively 150 bp. DNA wrapped around a cylindrical histone core [2]. Histone N-terminal tails protrude from this compact structure, and may be modified by several HPTMs (acetylation, methylation, phosphorylation…). Each modification occurs on a specific residue, and is mediated by an enzymatic complex. Since HPTMs dictate DNA-chromatin binding and gene activity, it has been proposed that a complex histone code orchestrates gen

Neuroendocrine prostate cancer: long noncoding RNAs to treat an incurable cancer – an interview with Dr Francesco Crea

Francesco Crea speaks to Lucy Chard, Commissioning Editor. Dr Crea’s lab studies the role of epigenetic factors and noncoding RNA in cancer initiation and progression. While working at the National Cancer Institute (USA), Dr Crea has demonstrated that polycomb-targeting drugs eradicate prostate cancer stem cells. While working at the BC Cancer Agency (Canada), Dr Crea discovered and patented PCAT18, a long noncoding RNA involved in prostate cancer metastasis. Dr Crea has received awards from the American Society of Clinical Oncology, from the Prostate Cancer Program and from Prostate Cancer Foundation BC. He is also an Editorial Board member for Epigenomics. His team is currently working on developing new biomarkers and therapeutic targets for incurable prostate and breast cancers

Targeting SARS-CoV-2 using polycomb inhibitors as antiviral agents

SARS-CoV-2, a betacoronavirus is the infectious viral agent causing the current pandemic of COVID-19. The disease causes acute respiratory distress syndrome, an inflammatory response which is the major cause of mortality of this disease. The current pandemic has been projected to cause hundreds of thousands of deaths worldwide. Currently, even with social distancing control strategies in place, the predicted death toll is still within the hundreds of thousands. It is therefore of paramount importance to explore any possible diagnostic and therapeutic option that may reduce the burden of disease. The definitive solution to this global crisis will likely come from the development of an effective vaccine which is likely to take longer than one year. In the meantime, it is important to evaluate a variety of therapeutic targets which can improve the prognosis of patients with severe COVID-19 infections, particularly to reduce the need for intensive care units, which have been quickly overwhelmed in many countries

EZH2 Single Nucleotide Variants (SNVs): Diagnostic and Prognostic Role in 10 Solid Tumor Types

The enhancer of zeste homolog 2 (EZH2) gene encodes a histone methyltransferase that is a catalytic subunit of the Polycomb repressive complex 2 (PRC2) group of proteins that act to repress gene expression. The EZH2 locus is rarely mutated in solid tumors and there is no comprehensive study of EZH2 single nucleotide variants (SNVs) associated with cancer susceptibility, prognosis and response to therapy. Here, for the first time, we review the functional roles of EZH2 DNA variants and propose a putative etiological role in 10 various solid tumors including: esophageal, hepatocellular, oral, urothelial, colorectal, lung and gastric cancers. In particular, we found that the C allele of the EZH2 variant rs3757441 is associated with increased EZH2 RNA expression and poorer prognosis (advanced stage) in at least two malignancies such as colorectal and hepatocellular carcinoma. This suggests that the C allele may be a functional risk variant in multiple malignant tumors. We therefore propose that the rs3757441 single nucleotide variant (SNV) be genotyped and real-time PCR assays be performed in large cohort studies in order to confirm this preliminary finding that could be useful for clinical practice

Clinical significance of Polycomb gene expression in brain tumors

Polycomb group (PcG) proteins are crucial for neural cancer stem cell (NCSC) self-renewal. However, the relative expression levels of PcG genes in different subtypes of brain tumors, their prognostic role and their effects on cellular pathways have not been investigated. For this purpose, we queried the Oncomine database and found that 4 PcG genes (EZH2, RBBP7, SUZ12, YY1) are specifically expressed in brain tumors. EZH2 expression increases with tumor grade in adult and pediatric brain tumors, and is a poor prognostic factor. In glioblastoma, EZH2 inhibits differentiation, and activates cancer-, cell cycle- and cellular movement-related genes. In keeping with previously published data, our results suggest that EZH2 is both a prognostic factor and a promising therapy target in brain tumors

Treatment-emergent neuroendocrine prostate cancer: molecularly driven clinical guidelines

An increasingly recognized mechanism of prostate cancer resistance is the transdifferentiation from adenocarcinoma to treatment-emergent neuroendocrine prostate cancer (t-NEPC), an extremely aggressive malignancy. The incidence of t-NEPC has been increasing in recent years, in part due to novel treatments that target the androgen receptor pathway. While clinicians historically had very few options for t-NEPC detection and treatment, recent research has uncovered key diagnostic tools and therapeutic targets that can be translated into improved patient care. In this article, we will outline the clinical features of t-NEPC and its molecular pathogenesis. Importantly, we will also discuss recently uncovered molecularly based strategies aimed at improving the diagnosis and treatment of t-NEPC. Finally, we will propose a unified algorithm that integrates clinical and molecular information for the clinical management of t-NEPC

speciation of poly amino carboxylic compounds in seawater

AbstractIn this work quantitative data on the interaction of EDTA and EGTA with the major inorganic components of seawater are reported. Protonation constants and alkali and alkaline earth metal complex formation constants are reported at different ionic strengths (0< l/mol L−1≤1). These formation data were obtained from potentiometric measurements in several single and mixed electrolyte media (such as artificial seawater). Potentiometric measurements in artificial seawater (containing Na+, K+, Mg2+, Ca2+, Cl−and SO42−) were analysed by using the single salt approximation (the artificial seawater being considered as a single salt BA whose ions have fractional charge -zanion = zcation = 1.117). Several species BpHrL (L = EDTA or EGTA) are formed and their formation constants are reported at different salinities. Present results, together with similar data on the complexing capability of NTA, DTPA and TTHA towards inorganic components of natural fluids, allowed to find general conclusions on the important c..

An Unusual Treatment of Atrial Fibrillation Percutaneous Exclusion of a Large Coronary Aneurysm

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