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Personalized epigenetics

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https://www.readbyqxmd.com/read/28213088/personalized-medicine-genetic-risk-prediction-of-drug-response
#1
REVIEW
Ge Zhang, Daniel W Nebert
Pharmacogenomics (PGx), a substantial component of "personalized medicine", seeks to understand each individual's genetic composition to optimize drug therapy -- maximizing beneficial drug response, while minimizing adverse drug reactions (ADRs). Drug responses are highly variable because innumerable factors contribute to ultimate phenotypic outcomes. Recent genome-wide PGx studies have provided some insight into genetic basis of variability in drug response. These can be grouped into three categories. [a] Monogenic (Mendelian) traits include early examples mostly of inherited disorders, and some severe (idiosyncratic) ADRs typically influenced by single rare coding variants...
February 14, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28188297/alternative-splicing-in-the-cytochrome-p450-superfamily-expands-protein-diversity-to-augment-gene-function-and-redirect-human-drug-metabolism
#2
Andrew J Annalora, Craig B Marcus, Patrick L Iversen
The human genome encodes 57 cytochrome P450 (CYP) genes whose enzyme products metabolize hundreds of drugs, thousands of xenobiotics and unknown numbers of endogenous compounds including steroids, retinoids and icosinoids. Indeed, CYP genes are the first line of defense against daily environmental chemical challenges in a manner that parallels the immune system. Several databases, including PubMed, AceView, and Ensembl, were queried to establish a comprehensive analysis of the full human CYP transcriptome. This review describes a remarkable diversification of the 57 human CYP genes, which may be alternatively processed into nearly 1000 distinct mRNA transcripts to shape an individual's CYP proteome...
February 10, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28177878/whole-genome-sequencing-identifies-new-genetic-alterations-in-meningiomas
#3
Mei Tang, Heng Wei, Lu Han, Jiaojiao Deng, Yuelong Wang, Meijia Yang, Yani Tang, Gang Guo, Liangxue Zhou, Aiping Tong
The major known genetic contributor to meningioma formation was NF2, which is disrupted by mutation or loss in about 50% of tumors. Besides NF2, several recurrent driver mutations were recently uncovered through next-generation sequencing. Here, we performed whole-genome sequencing across 7 tumor-normal pairs to identify somatic genetic alterations in meningioma. As a result, Chromatin regulators, including multiple histone members, histone-modifying enzymes and several epigenetic regulators, are the major category among all of the identified copy number variants and single nucleotide variants...
February 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28176637/personalized-medicine-applied-to-forensic-sciences-new-advances-and-perspectives-for-a-tailored-forensic-approach
#4
Alessandro Santurro, Anna Maria Vullo, Marina Borro, Giovanna Gentile, Raffaele La Russa, Maurizio Simmaco, Paola Frati, Vittorio Fineschi
Personalized medicine (PM), included in P5 medicine (Personalized, Predictive, Preventive, Participative and Precision medicine) is an innovative approach to the patient, emerging from the need to tailor and to fit the profile of each individual. PM promises to dramatically impact also on forensic sciences and justice system in ways we are only beginning to understand. The application of omics (genomic, transcriptomics, epigenetics/imprintomics, proteomic and metabolomics) is ever more fundamental in the so called "molecular autopsy"...
February 7, 2017: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/28134926/dna-methylation-heterogeneity-defines-a-disease-spectrum-in-ewing-sarcoma
#5
Nathan C Sheffield, Gaelle Pierron, Johanna Klughammer, Paul Datlinger, Andreas Schönegger, Michael Schuster, Johanna Hadler, Didier Surdez, Delphine Guillemot, Eve Lapouble, Paul Freneaux, Jacqueline Champigneulle, Raymonde Bouvier, Diana Walder, Ingeborg M Ambros, Caroline Hutter, Eva Sorz, Ana T Amaral, Enrique de Álava, Katharina Schallmoser, Dirk Strunk, Beate Rinner, Bernadette Liegl-Atzwanger, Berthold Huppertz, Andreas Leithner, Gonzague de Pinieux, Philippe Terrier, Valérie Laurence, Jean Michon, Ruth Ladenstein, Wolfgang Holter, Reinhard Windhager, Uta Dirksen, Peter F Ambros, Olivier Delattre, Heinrich Kovar, Christoph Bock, Eleni M Tomazou
Developmental tumors in children and young adults carry few genetic alterations, yet they have diverse clinical presentation. Focusing on Ewing sarcoma, we sought to establish the prevalence and characteristics of epigenetic heterogeneity in genetically homogeneous cancers. We performed genome-scale DNA methylation sequencing for a large cohort of Ewing sarcoma tumors and analyzed epigenetic heterogeneity on three levels: between cancers, between tumors, and within tumors. We observed consistent DNA hypomethylation at enhancers regulated by the disease-defining EWS-FLI1 fusion protein, thus establishing epigenomic enhancer reprogramming as a ubiquitous and characteristic feature of Ewing sarcoma...
January 30, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28124158/pathogenesis-of-gastric-cancer-genetics-and-molecular-classification
#6
Ceu Figueiredo, M Constanza Camargo, Marina Leite, Ezequiel M Fuentes-Pananá, Charles S Rabkin, José C Machado
Gastric cancer is the fifth most incident and the third most common cause of cancer-related death in the world. Infection with Helicobacter pylori is the major risk factor for this disease. Gastric cancer is the final outcome of a cascade of events that takes decades to occur and results from the accumulation of multiple genetic and epigenetic alterations. These changes are crucial for tumor cells to expedite and sustain the array of pathways involved in the cancer development, such as cell cycle, DNA repair, metabolism, cell-to-cell and cell-to-matrix interactions, apoptosis, angiogenesis, and immune surveillance...
2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28122798/pituitary-acromegaly-not-one-disease
#7
Sylvia L Asa, Walter Kucharczyk, Shereen Ezzat
Acromegaly has traditionally been regarded as a monomorphous disorder resulting from a benign pituitary adenoma. Increasing evidence, however, is highlighting that this disorder is associated with a spectrum of morphologically distinct pituitary tumors with variable clinical, biochemical and radiologic features and differing therapeutic outcomes that are attributed to different genetic and epigenetic changes. These data underscore the need for developing a more refined clinicopathological risk stratification system and implementing personalized targeted therapeutic approaches...
January 25, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28118933/integrative-medicine-breaking-down-silos-of-knowledge-and-practice-an-epigenetic-approach
#8
Bruce S McEwen
The future of medicine is discussed in the context of epigenetic influences during the entire life course and the lived experiences of each person, avoiding as much as possible the "medicalization" of the individual and taking a more humanistic view. The reciprocal communication between brain and body via the neuroendocrine, autonomic, metabolic and immune systems and the plasticity of brain architecture provide the basis for devising better "top down" interventions that engage the whole person in working towards his or her welfare...
January 11, 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28116311/genetic-and-epigenetic-regulation-of-aortic-aneurysms
#9
REVIEW
Ha Won Kim, Brian K Stansfield
Aneurysms are characterized by structural deterioration of the vascular wall leading to progressive dilatation and, potentially, rupture of the aorta. While aortic aneurysms often remain clinically silent, the morbidity and mortality associated with aneurysm expansion and rupture are considerable. Over 13,000 deaths annually in the United States are attributable to aortic aneurysm rupture with less than 1 in 3 persons with aortic aneurysm rupture surviving to surgical intervention. Environmental and epidemiologic risk factors including smoking, male gender, hypertension, older age, dyslipidemia, atherosclerosis, and family history are highly associated with abdominal aortic aneurysms, while heritable genetic mutations are commonly associated with aneurysms of the thoracic aorta...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28114969/integrated-analysis-of-hematopoietic-differentiation-outcomes-and-molecular-characterization-reveals-unbiased-differentiation-capacity-and-minor-transcriptional-memory-in-hpc-hsc-ipscs
#10
Shuai Gao, Xinfeng Hou, Yonghua Jiang, Zijian Xu, Tao Cai, Jiajie Chen, Gang Chang
BACKGROUND: Transcription factor-mediated reprogramming can reset the epigenetics of somatic cells into a pluripotency compatible state. Recent studies show that induced pluripotent stem cells (iPSCs) always inherit starting cell-specific characteristics, called epigenetic memory, which may be advantageous, as directed differentiation into specific cell types is still challenging; however, it also may be unpredictable when uncontrollable differentiation occurs. In consideration of biosafety in disease modeling and personalized medicine, the availability of high-quality iPSCs which lack a biased differentiation capacity and somatic memory could be indispensable...
January 23, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28102490/genome-engineering-of-stem-cell-organoids-for-disease-modeling
#11
REVIEW
Yingmin Sun, Qiurong Ding
Precision medicine emerges as a new approach that takes into account individual variability. Successful realization of precision medicine requires disease models that are able to incorporate personalized disease information and recapitulate disease development processes at the molecular, cellular and organ levels. With recent development in stem cell field, a variety of tissue organoids can be derived from patient specific pluripotent stem cells and adult stem cells. In combination with the state-of-the-art genome editing tools, organoids can be further engineered to mimic disease-relevant genetic and epigenetic status of a patient...
January 19, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28098061/prostate-cancer-immunotherapy-particularly-in-combination-with-androgen-deprivation-or-radiation-treatment-customized-pharmacogenomic-approaches-to-overcome-immunotherapy-cancer-resistance
#12
REVIEW
C Alberti
Conventional therapeutic approaches for advanced prostate cancer - such as androgen deprivation, chemotherapy, radiation - come up often against lack of effectiveness because of possible arising of correlative cancer cell resistance and/or inadequate anti-tumor immune conditions. Whence the timeliness of resorting to immune-based treatment strategies including either therapeutic vaccination-based active immunotherapy or anti-tumor monoclonal antibody-mediated passive immunotherapy. Particularly attractive, as for research studies and clinical applications, results to be the cytotoxic T-lymphocyte check point blockade by the use of anti-CTLA-4 and PD-1 monoclonal antibodies, particularly when combined with androgen deprivation therapy or radiation...
September 2017: Il Giornale di Chirurgia
https://www.readbyqxmd.com/read/28076791/mll-af4-spreading-identifies-binding-sites-that-are-distinct-from-super-enhancers-and-that-govern-sensitivity-to-dot1l-inhibition-in-leukemia
#13
Jon Kerry, Laura Godfrey, Emmanouela Repapi, Marta Tapia, Neil P Blackledge, Helen Ma, Erica Ballabio, Sorcha O'Byrne, Frida Ponthan, Olaf Heidenreich, Anindita Roy, Irene Roberts, Marina Konopleva, Robert J Klose, Huimin Geng, Thomas A Milne
Understanding the underlying molecular mechanisms of defined cancers is crucial for effective personalized therapies. Translocations of the mixed-lineage leukemia (MLL) gene produce fusion proteins such as MLL-AF4 that disrupt epigenetic pathways and cause poor-prognosis leukemias. Here, we find that at a subset of gene targets, MLL-AF4 binding spreads into the gene body and is associated with the spreading of Menin binding, increased transcription, increased H3K79 methylation (H3K79me2/3), a disruption of normal H3K36me3 patterns, and unmethylated CpG regions in the gene body...
January 10, 2017: Cell Reports
https://www.readbyqxmd.com/read/28076319/impact-of-nutrition-on-pollutant-toxicity-an-update-with-new-insights-into-epigenetic-regulation
#14
Jessie B Hoffman, Michael C Petriello, Bernhard Hennig
Exposure to environmental pollutants is a global health problem and is associated with the development of many chronic diseases, including cardiovascular disease, diabetes and metabolic syndrome. There is a growing body of evidence that nutrition can both positively and negatively modulate the toxic effects of pollutant exposure. Diets high in proinflammatory fats, such as linoleic acid, can exacerbate pollutant toxicity, whereas diets rich in bioactive and anti-inflammatory food components, including omega-3 fatty acids and polyphenols, can attenuate toxicant-associated inflammation...
January 11, 2017: Reviews on Environmental Health
https://www.readbyqxmd.com/read/28072632/asc-methylation-and-interleukin-1%C3%AE-are-associated-with-aerobic-capacity-in-heart-failure
#15
Brittany Butts, Javed Butler, Sandra B Dunbar, Elizabeth Corwin, Rebecca A Gary
BACKGROUND: Aerobic capacity, as measured by peak oxygen uptake (V[Combining Dot Above]O2), is one of the most powerful predictors of prognosis in heart failure (HF). Inflammation is a key factor contributing to alterations in aerobic capacity, and interleukin (IL)-1 cytokines are implicated in this process. The adaptor protein ASC is necessary for inflammasome activation of IL-1β and IL-18. ASC expression is controlled through epigenetic modification; lower ASC methylation is associated with worse outcomes in HF...
January 9, 2017: Medicine and Science in Sports and Exercise
https://www.readbyqxmd.com/read/28067828/pharmacogenetic-foundations-of-therapeutic-efficacy-and-adverse-events-of-statins
#16
REVIEW
Elena Arrigoni, Marzia Del Re, Leonardo Fidilio, Stefano Fogli, Romano Danesi, Antonello Di Paolo
BACKGROUND: In the era of precision medicine, more attention is paid to the search for predictive markers of treatment efficacy and tolerability. Statins are one of the classes of drugs that could benefit from this approach because of their wide use and their incidence of adverse events. METHODS: Literature from PubMed databases and bibliography from retrieved publications have been analyzed according to terms such as statins, pharmacogenetics, epigenetics, toxicity and drug-drug interaction, among others...
January 6, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28044047/parental-obesity-and-early-childhood-development
#17
Edwina H Yeung, Rajeshwari Sundaram, Akhgar Ghassabian, Yunlong Xie, Germaine Buck Louis
BACKGROUND: Previous studies identified associations between maternal obesity and childhood neurodevelopment, but few examined paternal obesity despite potentially distinct genetic/epigenetic effects related to developmental programming. METHODS: Upstate KIDS (2008-2010) recruited mothers from New York State (excluding New York City) at ∼4 months postpartum. Parents completed the Ages and Stages Questionnaire (ASQ) when their children were 4, 8, 12, 18, 24, 30, and 36 months of age corrected for gestation...
February 2017: Pediatrics
https://www.readbyqxmd.com/read/28040600/predictive-and-prognostic-biomarkers-in-colorectal-cancer-a-systematic-review-of-recent-advances-and-challenges
#18
REVIEW
Vishal Das, Jatin Kalita, Mintu Pal
BACKGROUND: Colorectal cancer (CRC) is one of the leading cause of cancer deaths worldwide. Since CRC is largely asymptomatic until alarm features develop to advanced stages, the implementation of the screening programme is very much essential to reduce cancer incidence and mortality rates. CRC occurs predominantly from accumulation of genetic and epigenetic changes in colon epithelial cells, which later gets transformed into adenocarcinomas. SCOPE OF REVIEW: The current challenges of screening paradigm and diagnostic ranges are from semi-invasive methods like colonoscopy to non-invasive stool-based test, have resulted in over-diagnosis and over-treatment of CRC...
December 29, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28036257/epigenetic-therapy-in-urologic-cancers-an-update-on-clinical-trials
#19
REVIEW
Inês Faleiro, Ricardo Leão, Alexandra Binnie, Ramon Andrade de Mello, Ana-Teresa Maia, Pedro Castelo-Branco
Epigenetic dysregulation is one of many factors that contribute to cancer development and progression. Numerous epigenetic alterations have been identified in urologic cancers including histone modifications, DNA methylation changes, and microRNA expression. Since these changes are reversible, efforts are being made to develop epigenetic drugs that restore the normal epigenetic patterns of cells, and many clinical trials are already underway to test their clinical potential. In this review we analyze multiple clinical trials (n=51) that test the efficacy of these drugs in patients with urologic cancers...
December 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/28034764/the-concept-of-the-personal-vitamin-d-response-index
#20
REVIEW
Carsten Carlberg, Afrozul Haq
Humans are able to synthesize vitamin D3 in their skin when exposed to UV-B, but seasonal variations, textile coverage and predominant indoor activities often make supplementation with the compound necessary. There is some dispute on the desired vitamin D status, measured via the serum concentration of the most stable vitamin D3 metabolite, 25-hydroxyvitamin D3, and the respective recommended daily supplementation. A possible answer may be provided by the concept of the personal vitamin D response index describing the efficiency of the molecular response to supplementation with vitamin D...
December 26, 2016: Journal of Steroid Biochemistry and Molecular Biology
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