1,615 publications from this institution
<p>Fisher exact test for each combination of mutated pathways, comparing responders vs. non-responders at diagnosis</p>
<p>Differences in cell type abundance upon AZA treatment according to hematological improvement (HI) and marrow complete response (mCR)</p>
Members of the Polycomb-group (PcG) family of proteins, including EZH2 (enhancer of zeste homolog 2), are involved in establishing epigenetic silencing of developmental genes in adult and embryonic stem cells, and their deregulation has been implicated in cancer. In a recent report, EZH2-mediated epigenetic repression of DNA damage repair in breast tumor initiating cells (BTICs) was identified as a mechanism that could promote expansion of BTICs, and may contribute to cancer progression.
Both appropriate DNA methylation and histone modifications play a crucial role in the maintenance of normal cell function and cellular identity. In cancerous cells these "epigenetic belts" become massively perturbed, leading to significant changes in expression profiles which confer advantage to the development of a malignant phenotype. DNA (cytosine-5)-methyltransferase 1 (Dnmt1), Dnmt3a and Dnmt3b are the enzymes responsible for setting up and maintaining DNA methylation patterns in eukaryotic cells. Intriguingly, DNMTs were found to be overexpressed in cancerous cells, which is believed to partly explain the hypermethylation phenomenon commonly observed in tumors. However, several lines of evidence indicate that further layers of gene regulation are critical coordinators of DNMT expression, catalytic activity and target specificity. Splice variants of DNMT transcripts have been detected which seem to modulate methyltransferase activity. Also, the DNMT mRNA 3'UTR as well as the coding sequence harbors multiple binding sites for trans-acting factors guiding post-transcriptional regulation and transcript stabilization. Moreover, microRNAs targeting DNMT transcripts have recently been discovered in normal cells, yet expression of these microRNAs was found to be diminished in breast cancer tissues. In this review we summarize the current knowledge on mechanisms which potentially lead to the establishment of a DNA hypermethylome in cancer cells.
The design of a tax system is a daunting task. Economies have become increasingly complex, which makes the design of taxes has to take into account behavioral taxpayers' responses - including mobility -, but also tax planning issues. Additionally, increasing inequality trends put more pressure on design. This complex framework increases the need of complete and constantly updated information about the functioning of the system to carry out welfare-enhancing reforms and having stable sources of public funding. It seems now the moment the Spanish tax system takes advantage of all sources of information to undertake a necessary reform. For this ambitious purpose, we aim at providing a novel source of information: the (objective) opinion of tax professionals. From a survey all over Spain, tax professionals unanimously conclude the current tax system is unfair, while the main inefficiencies, rather than due to traditional responses, come out as a consequence of tax planning and tax mobility. We hope the complete results of the survey are a useful source of information.
