1,721,036 research outputs found
Histone deacetylase inhibitors: recent insights from basic to clinical knowledge & patenting of anti-cancer actions
No full textDeregulation of cell death in cancer: Recent highlights
Full text linkThe aim of this Special Issue on the deregulation of cell death in cancer is to bring together recent perspectives on the relationship between tumorigenesis and programmed cell death (PCD) [...]
Trials with 'epigenetic' drugs: An update.
Full text link""Epigenetic inactivation of pivotal genes involved in correct cell growth is a hallmark of human pathologies, in particular cancer. These epigenetic mechanisms, including crosstalk between DNA methylation, histone modifications and non-coding RNAs, affect gene expression and are associated with disease progression. In contrast to genetic mutations, epigenetic changes are potentially reversible. Re-expression of genes epigenetically inactivated can result in the suppression of disease state or sensitization to specific therapies. Small molecules that reverse epigenetic inactivation, so-called epi-drugs, are now undergoing clinical trials. Accordingly, the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for cancer treatment have approved some of these drugs. Here, we focus on the biological features of epigenetic molecules, analyzing the mechanism(s) of action and their current use in clinical practice."
Gene transactivation and transrepression in myc-driven cancers
No full textMYC is a proto-oncogene regulating a large number of genes involved in a plethora of cellular functions. Its deregulation results in activation of MYC gene expression and/or an increase in MYC protein stability. MYC overexpression is a hallmark of malignant growth, inducing self-renewal of stem cells and blocking senescence and cell differentiation. This review summarizes the latest advances in our understanding of MYC-mediated molecular mechanisms responsible for its oncogenic activity. Several recent findings indicate that MYC is a regulator of cancer genome and epigenome: MYC modulates expression of target genes in a site-specific manner, by recruiting chromatin remodeling co-factors at promoter regions, and at genome-wide level, by regulating the expression of several epigenetic modifiers that alter the entire chromatin structure. We also discuss novel emerging therapeutic strategies based on both direct modulation of MYC and its epigenetic cofactors
Histone deacetylase inhibitors: a patent review (2009 - 2011).
No full text"Introduction: Given the involvement of histone deacetylases (HDACs) in regulation of gene expression, they are believed to be 'master regulators' of many diseases. Thus, HDAC inhibitors (HDACis) are able to modulate transcriptional activity. These molecules can induce cell cycle arrest, differentiation and apoptosis of tumor cells in culture and in animal models and therefore are emerging as an exciting new class of potential anti-cancer agents for the treatment of solid and hematological malignancies. Areas covered: The aim of this review is to provide an overview of current knowledge and molecular mechanisms of HDACis, and the most recent patents existing in the field of HDACis from 2009 until 2011. Expert opinion: In recent years, an increasing number of structurally diverse HDACis have been identified. In addition, non-cancer diseases, including neurodegeneration, metabolic, inflammatory and autoimmune disorders, infectious and cardiovascular diseases have also been proposed for an HDACi treatment. The growing body of evidence of the potential benefits of disease treatment based on the use of HDACis has led to a large number of patent applications throughout the world
NAA60 (HAT4): the newly discovered bi-functional Golgi member of the acetyltransferase family
No full textChromatin structural organization, gene expression and proteostasis are intricately regulated in a wide range of biological processes, both physiological and pathological. Protein acetylation, a major post-translational modification, is tightly involved in interconnected biological networks, modulating the activation of gene transcription and protein action in cells. A very large number of studies describe the pivotal role of the so-called acetylome (accounting for more than 80% of the human proteome) in orchestrating different pathways in response to stimuli and triggering severe diseases, including cancer. NAA60/NatF (N-terminal acetyltransferase F), also named HAT4 (histone acetyltransferase type B protein 4), is a newly discovered acetyltransferase in humans modifying N-termini of transmembrane proteins starting with M–K/M-A/M-V/M-M residues and is also thought to modify lysine residues of histone H4. Because of its enzymatic features and unusual cell localization on the Golgi membrane, NAA60 is an intriguing acetyltransferase that warrants biochemical and clinical investigation. Although it is still poorly studied, this review summarizes current findings concerning the structural hallmarks and biological role of this novel targetable epigenetic enzyme
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Sirtuins & disease: the road ahead
No full textSirtuins represent a promising new class of conserved histone deacetylases, originally identified in yeast. The activity of the sirtuin (SirT) family – made up of seven members (SirT1-7) – is NAD+ dependent. Sirtuins target a wide range of cellular proteins in nucleus, cytoplasm and mitochondria for post-translational modification by acetylation (SirT1, 2, 3 and 5) or ADP ribosylation (SirT4 and 6). Sirtuins regulate responses to stress and ensure that damaged DNA is not propagated, thus contrasting the accumulation of mutations. To date, sirtuins have emerged as potential therapeutic targets for treatment of human pathologies such as metabolic, cardiovascular and neurodegenerative diseases, and cancer. SirT1 is the founding member of this class of enzymes and is currently the best known of the group. SirT1 acts in various cellular processes, deacetylating both chromatin and non-histone proteins, and its role in cancer and aging has been extensively studied. SirT1 may play a critical role in tumor initiation and progression as well as drug resistance by blocking senescence and apoptosis, and by promoting cell growth and angiogenesis. Recently, growing interest in sirtuin modulation has led to the discovery and characterization of small molecules able to modify sirtuin activity. The present review highlights SirT mechanism(s) of action and deregulation in cancer, focusing on the therapeutic potential of SirT modulators both in cancer prevention and treatment
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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