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Personalized epigenetics

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https://www.readbyqxmd.com/read/29343412/implementing-genome-driven-personalized-cardiology-in-clinical-practice
#1
REVIEW
Ares Pasipoularides
Genomics designates the coordinated investigation of a large number of genes in the context of a biological process or disease. It may be long before we attain comprehensive understanding of the genomics of common complex cardiovascular diseases (CVDs) such as inherited cardiomyopathies, valvular diseases, primary arrhythmogenic conditions, congenital heart syndromes, hypercholesterolemia and atherosclerotic heart disease, hypertensive syndromes, and heart failure with preserved/reduced ejection fraction. Nonetheless, as genomics is evolving rapidly, it is constructive to survey now pertinent concepts and breakthroughs...
January 14, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29342453/fine-particulate-air-pollution-and-the-expression-of-micrornas-and-circulating-cytokines-relevant-to-inflammation-coagulation-and-vasoconstriction
#2
Renjie Chen, Huichu Li, Jing Cai, Cuicui Wang, Zhijing Lin, Cong Liu, Yue Niu, Zhuohui Zhao, Weihua Li, Haidong Kan
BACKGROUND: MicroRNAs (miRNAs) are a key factor in epigenetic regulation of gene expression, but miRNA responses to fine particulate matter (PM2.5) air pollution and their potential contribution to cardiovascular effects of PM2.5 are unknown. OBJECTIVE: We explored the potential influence of PM2.5 on the expression of selected cytokines relevant to systemic inflammation, coagulation, and vasoconstriction, and on miRNAs that may regulate their expression. METHODS: We designed a double-blind, randomized crossover study in which true and sham air purifiers were used to expose 55 healthy young adult students in Shanghai, China, to reduced or ambient levels of indoor PM2...
January 17, 2018: Environmental Health Perspectives
https://www.readbyqxmd.com/read/29340618/mitochondrial-toxicity
#3
Joel N Meyer, Jessica H Hartman, Danielle F Mello
Recent decades have seen a rapid increase in reported toxic effects of drugs and pollutants on mitochondria. Researchers have also documented many genetic differences leading to mitochondrial diseases, currently reported to affect ∼1 person in 4,300, creating a large number of potential gene-environment interactions in mitochondrial toxicity. We briefly review this history, and then highlight cutting-edge areas of mitochondrial research including the role of mitochondrial reactive oxygen species in signaling; increased understanding of fundamental biological processes involved in mitochondrial homeostasis (DNA maintenance and mutagenesis, mitochondrial stress response pathways, fusion and fission, autophagy and biogenesis, and exocytosis); systemic effects resulting from mitochondrial stresses in specific cell types; mitochondrial involvement in immune function; the growing evidence of long-term effects of mitochondrial toxicity; mitochondrial-epigenetic cross-talk; and newer approaches to test chemicals for mitochondrial toxicity...
January 11, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29340131/acute-myeloid-leukemia-genetic-alterations-and-their-clinical-prognosis
#4
REVIEW
Francisco Alejandro Lagunas-Rangel, Venice Chávez-Valencia, Miguel Ángel Gómez-Guijosa, Carlos Cortes-Penagos
Acute myeloid leukemia (AML) is a group of hematological diseases, phenotypic and genetically heterogeneous, characterized by abnormal accumulation of blast cells in the bone marrows and peripheral blood. Its incidence rate is approximately 1.5 per 100,000 in infants younger than 1 year of age and 25 per 100,000 persons in octogenarians. Traditionally, cytogenetic markers are used to stratify patients in three risk categories: favorable, intermediate and unfavorable. However, the forecast stratification and the treatment decision for patients with normal karyotype shows difficulties due to the high clinical heterogeneity...
October 1, 2017: International Journal of Hematology-oncology and Stem Cell Research
https://www.readbyqxmd.com/read/29336995/a-search-for-molecular-mechanisms-underlying-male-idiopathic-infertility
#5
REVIEW
An Bracke, Kris Peeters, Usha Punjabi, David Hoogewijs, Sylvia Dewilde
Infertility affects approximately 15% of the couples wanting to conceive. In 30 - 40% of the cases the aetiology of male infertility remains unknown and is called idiopathic male infertility. When assisted reproductive technologies are used to obtain pregnancy, an adequate (epi)genetic diagnosis of male infertility is of major importance to evaluate if a genetic abnormality will be transmitted to the offspring. In addition, there is need for better diagnostic seminal biomarkers to assess the success rates of these assisted reproductive technologies...
December 27, 2017: Reproductive Biomedicine Online
https://www.readbyqxmd.com/read/29332326/carcinogenic-potential-of-antitumor-therapies-is-the-risk-predictable
#6
Ivanka Nenova, Janet Grudeva-Popova
The growing number of successfully cured cancer patients has created a new field in oncogenesis. The life expectancy of such patients has increased, however this favorable event may create enough time for epigenetic events to occur which can cause a new carcinognic event, i.e. a secondary malignancy. The terms in use are second primary malignancies as well as therapy-related neoplasms in case the treatment of the first neoplasm is a direct cause. Second primary malignancies can be hematological neoplasms or solid tumors, with solid tumors having higher frequency...
November 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29330943/epigenetic-markers-in-circulating-cell-free-dna-as-prognostic-markers-for-survival-of-castration-resistant-prostate-cancer-patients
#7
Rianne J Hendriks, Siebren Dijkstra, Frank P Smit, Johan Vandersmissen, Hendrik Van de Voorde, Peter F A Mulders, Inge M van Oort, Wim Van Criekinge, Jack A Schalken
BACKGROUND: Noninvasive biomarkers to guide personalized treatment for castration-resistant prostate cancer (CRPC) are needed. In this study, we analyzed hypermethylation patterns of two genes (GSTP1 and APC) in plasma cell-free DNA (cfDNA) of CRPC patients. The aim of this study was to analyze the cfDNA concentrations and levels of the epigenetic markers and to assess the value of these biomarkers for prognosis. METHODS: In this prospective study, patients were included before starting new treatment after developing CRPC...
January 12, 2018: Prostate
https://www.readbyqxmd.com/read/29330282/population-dependent-intron-retention-and-dna-methylation-in-breast-cancer
#8
Dongwook Kim, Manu Shivakumar, Seonggyun Han, Michael S Sinclair, Youngji Lee, Yonglan Zheng, Olufunmilayo I Olopade, Dokyoon Kim, Younghee Lee
Regulation of gene expression by DNA methylation in gene promoter regions is well-studied; however, the effects of methylation in the gene body (exons and introns) on gene expression are comparatively understudied. Recently, hyper-methylation has been implicated in the inclusion of alternatively spliced exons; moreover, exon recognition can be enhanced by recruiting the methyl-CpG-binding protein (MeCP2) to hyper-methylated sites. This study examines if methylation status of an intron is correlated with how frequently the intron is retained during splicing using DNA methylation and RNA sequencing (RNA-seq) data from breast cancer tissue specimens in The Cancer Genome Atlas (TCGA)...
January 12, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29330202/high-risk-tp53-mutations-are-associated-with-extra-nodal-extension-ene-in-oral-cavity-squamous-cell-carcinoma-oscc
#9
Vlad C Sandulache, Chieko Michikawa, Pranav Kataria, Frederico O Gleber-Netto, Diana Bell, Sanchit Trivedi, Xiayu Rao, Jing Wang, Mei Zhao, Samar A Jasser, Jeffrey N Myers, Curtis R Pickering
PURPOSE:   Development of extra-nodal extension (ENE) has been associated with poor survival in patients with oral cavity squamous cell carcinoma (OSCC). Here we sought to confirm the role of ENE as a poor prognostic factor, and identify genomic and epigenetic markers of ENE in order to develop a predictive model and improve treatment selection. EXPERIMENTAL DESIGN: An institutional cohort (University of Texas MD Anderson Cancer Center) was utilized to confirm the impact of ENE on clinical outcomes and evaluate the genomic signature of primary and ENE containing tissue...
January 12, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29327808/the-rocky-road-to-personalized-medicine-in-acute-myeloid-leukaemia
#10
REVIEW
Bryan Brinda, Irum Khan, Brian Parkin, Heiko Konig
Acute myeloid leukaemia (AML) is a malignant disorder of the myeloid blood lineage characterized by impaired differentiation and increased proliferation of hematopoietic precursor cells. Recent technological advances have led to an improved understanding of AML biology but also uncovered the enormous cytogenetic and molecular heterogeneity of the disease. Despite this heterogeneity, AML is mostly managed by a 'one-size-fits-all' approach consisting of intensive, highly toxic induction and consolidation chemotherapy...
January 12, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29318979/role-of-epigenetics-and-oxidative-stress-in-gliomagenesis
#11
Edgar Rangel-Lopez, Yesennia Sanchez-Perez, Ernesto Soto-Reyes, Claudia Maria Garcia-Cuellar, Bernardo Cacho-Diaz, Abel Santamaria
Malignant gliomas constitute more than 49% of all central nervous system (CNS) tumors and exhibit very poor prognosis. Two main events involved with the progression of gliomas are the deregulation of genes by genetic events and cellular damage elicited by the formation of reactive oxygen species (ROS). In gliomas, epigenetic abnormalities implicated in the deregulation of DNA methylation, nucleosome rearrangement, and acetylation of histones have been depicted. The overproduction of ROS has been implicated in the promotion of these modifications...
January 10, 2018: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/29304146/from-early-stress-to-12-month-development-in-very-preterm-infants-preliminary-findings-on-epigenetic-mechanisms-and-brain-growth
#12
Monica Fumagalli, Livio Provenzi, Pietro De Carli, Francesca Dessimone, Ida Sirgiovanni, Roberto Giorda, Claudia Cinnante, Letizia Squarcina, Uberto Pozzoli, Fabio Triulzi, Paolo Brambilla, Renato Borgatti, Fabio Mosca, Rosario Montirosso
Very preterm (VPT) infants admitted to Neonatal Intensive Care Unit (NICU) are at risk for altered brain growth and less-than-optimal socio-emotional development. Recent research suggests that early NICU-related stress contributes to socio-emotional impairments in VPT infants at 3 months through epigenetic regulation (i.e., DNA methylation) of the serotonin transporter gene (SLC6A4). In the present longitudinal study we assessed: (a) the effects of NICU-related stress and SLC6A4 methylation variations from birth to discharge on brain development at term equivalent age (TEA); (b) the association between brain volume at TEA and socio-emotional development (i...
2018: PloS One
https://www.readbyqxmd.com/read/29291160/a-dual-biomarker-detection-platform-for-quantitating-circulating-tumor-dna-ctdna
#13
Chunyan Cai, Zhenzhong Guo, Yiping Cao, Weiying Zhang, Yong Chen
Circulating tumor DNA (ctDNA), which includes DNA mutations, epigenetic alterations and other forms of tumor-specific abnormalities, is a promising "real-time" biomarker for noninvasive cancer assessment. Tumor DNA is of great value in the process of cancer treatment, including diagnostic and prognostic information before, during treatment and at progression. Here we introduce a peptide nucleic acids probe-gold nanoparticles (PNA-AuNPs) and lead phosphate apoferritin (LPA)-based dual biomarker detection platform, which could be used in a DNA biosensor to quantify ctDNA by detection of tumor-specific mutations and methylation of PIK3CA gene...
2018: Nanotheranostics
https://www.readbyqxmd.com/read/29276780/the-role-of-epigenomics-in-personalized-medicine
#14
Mohamad M Kronfol, Mikhail G Dozmorov, Rong Huang, Patricia W Slattum, Joseph L McClay
Introduction: Epigenetics is the study of reversible modifications to chromatin and their extensive and profound effects on gene regulation. To date, the role of epigenetics in personalized medicine has been under-explored. Therefore, this review aims to highlight the vast potential that epigenetics holds. Areas covered: We first review the cell-specific nature of epigenetic states and how these can vary with developmental stage and in response to environmental factors...
2017: Expert Review of Precision Medicine and Drug Development
https://www.readbyqxmd.com/read/29275244/environmental-arsenic-exposure-from-genetic-susceptibility-to-pathogenesis
#15
REVIEW
Brenda C Minatel, Adam P Sage, Christine Anderson, Roland Hubaux, Erin A Marshall, Wan L Lam, Victor D Martinez
More than 200 million people in 70 countries are exposed to arsenic through drinking water. Chronic exposure to this metalloid has been associated with the onset of many diseases, including cancer. Epidemiological evidence supports its carcinogenic potential, however, detailed molecular mechanisms remain to be elucidated. Despite the global magnitude of this problem, not all individuals face the same risk. Susceptibility to the toxic effects of arsenic is influenced by alterations in genes involved in arsenic metabolism, as well as biological factors, such as age, gender and nutrition...
December 21, 2017: Environment International
https://www.readbyqxmd.com/read/29274998/dna-methylation-of-apba3-and-mcf2-in-borderline-personality-disorder-potential-biomarkers-for-response-to-psychotherapy
#16
Nora Knoblich, Friederike Gundel, Christof Brückmann, Julia Becker-Sadzio, Christian Frischholz, Vanessa Nieratschker
Borderline personality disorder (BPD) is a severe and complex mental disease associated with high suicidal tendencies and hospitalization rates. Accumulating evidence suggests that epigenetic mechanisms are implicated in the etiology of BPD. A recent epigenome-wide study identified several novel genes which are epigenetically dysregulated in BPD. Those genes include APBA3 and MCF2. Psychotherapy such as Dialectical Behavior Therapy (DBT), an established treatment for BPD, provides an excellent setting to investigate environmental influences on epigenetic mechanisms in order to identify biomarkers for disease status and therapy success...
December 20, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29251357/epigenetic-and-transcriptional-variability-shape-phenotypic-plasticity
#17
REVIEW
Simone Ecker, Vera Pancaldi, Alfonso Valencia, Stephan Beck, Dirk S Paul
Epigenetic and transcriptional variability contribute to the vast diversity of cellular and organismal phenotypes and are key in human health and disease. In this review, we describe different types, sources, and determinants of epigenetic and transcriptional variability, enabling cells and organisms to adapt and evolve to a changing environment. We highlight the latest research and hypotheses on how chromatin structure and the epigenome influence gene expression variability. Further, we provide an overview of challenges in the analysis of biological variability...
December 18, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/29248854/spatial-bio-accumulation-of-pharmaceuticals-illicit-drugs-plasticisers-perfluorinated-compounds-and-metabolites-in-river-sediment-aquatic-plants-and-benthic-organisms
#18
John L Wilkinson, Peter S Hooda, Julian Swinden, James Barker, Stephen Barton
Organic contaminants such as pharmaceuticals, personal care products (PPCPs) and other emerging contaminants (ECs) are known to persist in the aquatic environment and many are indicated as endocrine, epigenetic, or other toxicants. Typically, the study of PPCPs/ECs in the aquatic environment is limited to their occurrence dissolved in river water. In this study, accumulation and spatial distribution of thirteen PPCPs/ECs were assessed in aquatic sediment (n = 23), periphyton (biofilm, n = 8), plants Callitriche sp...
December 14, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/29245896/metabolomic-mapping-of-cancer-stem-cells-for-reducing-and-exploiting-tumor-heterogeneity
#19
Elisabet Cuyàs, Sara Verdura, Salvador Fernández-Arroyo, Joaquim Bosch-Barrera, Begoña Martin-Castillo, Jorge Joven, Javier A Menendez
Personalized cancer medicine based on the analysis of tumors en masse is limited by tumor heterogeneity, which has become a major obstacle to effective cancer treatment. Cancer stem cells (CSC) are emerging as key drivers of inter- and intratumoral heterogeneity. CSC have unique metabolic dependencies that are required not only for specific bioenergetic/biosynthetic demands but also for sustaining their operational epigenetic traits, i.e. self-renewal, tumor-initiation, and plasticity. Given that the metabolome is the final downstream product of all the -omic layers and, therefore, most representative of the biological phenotype, we here propose that a novel approach to better understand the complexity of tumor heterogeneity is by mapping and cataloging small numbers of CSC metabolomic phenotypes...
November 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/29230297/from-genetics-and-epigenetics-to-the-future-of-precision-treatment-for-obesity
#20
REVIEW
Xulong Sun, Pengzhou Li, Xiangwu Yang, Weizheng Li, Xianjie Qiu, Shaihong Zhu
Obesity has become a major global health problem, epitomized by excess accumulation of body fat resulting from an imbalance between energy intake and expenditure. The treatments for obesity range from modified nutrition and additional physical activity, to drugs or surgery. But the curative effect of each method seems to vary between individuals. With progress in the genetics and epigenetics of obesity, personalization of the clinical management of obesity may be at our doorstep. This review presents an overview of our current understanding of the genetics and epigenetics of obesity and how these findings influence responses to treatments...
November 2017: Gastroenterology Report
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