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Volker M Lauschke, Isabel Barragan, Magnus Ingelman-Sundberg
Pharmacological treatment and exposure to xenobiotics can cause substantial changes in epigenetic signatures. The majority of these epigenetic changes, caused by the compounds in question, occur downstream of transcriptional activation mechanisms, whereby the epigenetic alterations can create a transcriptional memory and stably modulate cell function. The increasing understanding of epigenetic mechanisms and their importance in disease has prompted the development of therapeutic interventions that target epigenetic modulatory mechanisms, particularly in oncology where inhibitors of epigenetic-modifying proteins (epidrugs) have been successfully used in treatment, mostly in combination with standard-of-care chemotherapy, provoking either direct cytotoxicity or inhibiting resistance to anticancer drugs...
October 13, 2017: Annual Review of Pharmacology and Toxicology
Babu Swathy, Moinak Banerjee
INTRODUCTION: Haloperidol has been extensively used in various psychiatric conditions. It has also been reported to induce severe side effects. We aimed to evaluate whether haloperidol can influence host methylome, and if so what are the possible mechanisms for it in neuronal cells. Impact on host methylome and miRNAs can have wide spread alterations in gene expression, which might possibly help in understanding how haloperidol may impact treatment response or induce side effects. METHODS: SK-N-SH, a neuroblasoma cell line was treated with haloperidol at 10μm concentration for 24 hours and global DNA methylation was evaluated...
2017: PloS One
Shih-Kai Chu, Hsin-Chou Yang
AIM: This is the first systematic study to examine the population differentiation effect of DNA methylation on the treatment response and drug absorption, distribution, metabolism and excretion in multiple tissue types and cancer types. MATERIALS & METHODS: We analyzed the whole methylome and transcriptome data of primary tumor tissues of four cancer types (breast, colon, head & neck and uterine corpus) and lymphoblastoid cell lines for African and European ancestry populations...
September 8, 2017: Epigenomics
Angela Lopomo, Fabio Coppedè
Our understanding of the epigenetic changes occurring in gastrointestinal cancers has gained tremendous advancements in recent years, and some epigenetic biomarkers are already translated into the clinics for cancer diagnostics. In parallel, pharmacoepigenetics and pharmacoepigenomics of solid tumors are relevant novel, but emerging and promising fields. Areas covered: A comprehensive review of the literature to summarize and update the emerging field of pharmacoepigenetics and pharmacoepigenomics of gastrointestinal cancers...
August 31, 2017: Expert Review of Gastroenterology & Hepatology
Nathalie K Zgheib
The pharmacogenetics (PGx) laboratory at the Department of Pharmacology and Toxicology at the American University of Beirut Faculty of Medicine was established in October 2007. Several projects on the genetic polymorphisms of drug metabolizing enzymes and transporters with treatment of noncommunicable diseases such as cardiac diseases and cancers are ongoing. We have been applying the 'candidate gene' PGx approach, and recently started using higher throughput analyses. The more recent research projects are geared towards performing more extensive genotyping and including bigger and more representative population samples such as by developing research registries and prospectively following up patients...
September 2017: Pharmacogenomics
Arron Munggela Foma, Saeed Aslani, Jafar Karami, Ahmadreza Jamshidi, Mahdi Mahmoudi
BACKGROUND: Recent researches in the field of genetics have extended our knowledge through the discovery of genetic factors associated with autoimmune diseases (AID). Genetics by itself, however, cannot elucidate all the uncertainties encountered in the etiopathology of AID. On the other hand, incomplete harmony in the prevalence of AID in identical twins suggests that non-genetic factors may play an important role in determining the disease susceptibility. Besides, epigenetics, which is defined by changes in gene expression without a corresponding change in the DNA sequences, has come in to provide new awareness in the disease etiopathology by bridging the genetic and epigenetic factors...
December 2017: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
Babu Swathy, Moinak Banerjee
The diatheses of gene and environment interaction in schizophrenia (SCZ) are becoming increasingly evident. Genetic and epigenetic backgrounds are being considered in stratifying and addressing phenotypic variation and drug response in SCZ. But how much of these epigenetic alterations are the primary contributing factor, toward disease pathogenesis and drug response, needs further clarity. Evidence indicates that antipsychotic drugs can also alter the epigenetic homeostasis thereby inducing pharmacoepigenomic effects...
May 2017: Epigenomics
Babu Swathy, Koramannil R Saradalekshmi, Indu V Nair, Chandrasekharan Nair, Moinak Banerjee
AIM: It is imperative to differentiate the role of host epigenetics from pharmacoepigenetics in resolving therapeutic response. Therefore, the objective was to identify how antipsychotic drugs influence epigenetic response on pharmacogenes. MATERIALS & METHODS: The study design was based on in vitro evaluation of pharmacoepigenetic response of haloperidol, clozapine and olanzapine. Post antipsychotic treatment, the alterations in expression of ABCB1, CYP1A2 and CYP3A4 were monitored, and followed up by promoter methylation and their target miRNA expression studies...
April 21, 2017: Epigenomics
Manikandan Palrasu, Siddavaram Nagini
The cytochrome P450 (CYP) enzymes are membrane-bound hemoproteins that play a pivotal role in the detoxification of xenobiotics, cellular metabolism and homeostasis. Induction or inhibition of CYP enzymes is a major mechanism that underlies drug-drug interactions. CYP enzymes can be transcriptionally activated by various xenobiotics and endogenous substrates through receptor-dependent mechanisms. CYP enzyme inhibition is a principal mechanism for metabolism-based drug-drug interactions. Many chemotherapeutic drugs can cause drug interactions due to their ability to either inhibit or induce the CYP enzyme system...
January 25, 2017: Current Drug Targets
Aleksandra Majchrzak-Celińska, Wanda Baer-Dubowska
Epigenetics is a rapidly growing field describing heritable alterations in gene expression that do not involve DNA sequence variations. Advances in epigenetics and epigenomics have influenced pharmacology, leading to the development of a new specialty, pharmacoepigenetics, the study of the epigenetic basis for the individual variation in drug response. Areas covered: We present an overview of the major epigenetic mechanisms and their effects on the expression of drug metabolizing enzymes and drug transporters, as well as the epigenetic status of drug protein targets affecting therapy response...
April 2017: Expert Opinion on Drug Metabolism & Toxicology
Claudia Knothe, Bruno G Oertel, Alfred Ultsch, Mattias Kettner, Peter Harald Schmidt, Cora Wunder, Stefan W Toennes, Gerd Geisslinger, Jörn Lötsch
AIM: Exposure to opioids has been associated with epigenetic effects. Studies in rodents suggested a role of varying degrees of DNA methylation in the differential regulation of μ-opioid receptor expression across the brain. METHODS: In a translational investigation, using tissue acquired postmortem from 21 brain regions of former opiate addicts, representing a human cohort with chronic opioid exposure, μ-opioid receptor expression was analyzed at the level of DNA methylation, mRNA and protein...
December 2016: Epigenomics
Rihab Nasr, Fatima Sleiman, Zeinab Awada, Natalie K Zgheib
The focus of this manuscript is on DNA methylation and miRNA regulation of drug-metabolizing enzymes and drug transporters involved in the disposition of drugs commonly used in breast cancer. We start with a review of the available scant literature and follow with an in silico analysis of the CpG islands and miRNA binding sites of genes of interest. We make the case that there is room for further research to include more genes and miRNAs despite the extensive sharing of miRNA targets by candidate genes of interest...
September 2016: Pharmacogenomics
Stephen J Anderson, Kristina M Feye, Garrett R Schmidt-McCormack, Emir Malovic, Gregory S A Mlynarczyk, Patricia Izbicki, Larissa F Arnold, Matthew A Jefferson, Bierlein M de la Rosa, Rita F Wehrman, K C Luna, Hilary Z Hu, Naveen C Kondru, Michael D Kleinhenz, Joe S Smith, Sireesha Manne, Marson R Putra, Shivani Choudhary, Nyzil Massey, Diou Luo, Carrie A Berg, Sreemoyee Acharya, Shaunik Sharma, Sri Harsha Kanuri, Jennifer K Lange, Steve A Carlson
This review synthesizes examples of pharmacological agents who have off-target effects of an epigenetic nature. We expand upon the paradigm of epigenetics to include "quasi-epigenetic" mechanisms. Quasi-epigenetics includes mechanisms of drugs acting upstream of epigenetic machinery or may themselves impact transcription factor regulation on a more global scale. We explore these avenues with four examples of conventional pharmaceuticals and their unintended, but not necessarily adverse, biological effects. The quasi-epigenetic drugs identified in this review include the use of beta-lactam antibiotics to alter glutamate receptor activity and the action of cyclosporine on multiple transcription factors...
May 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Lorenzo Fornaro, Caterina Vivaldi, Chiara Caparello, Gianna Musettini, Editta Baldini, Gianluca Masi, Alfredo Falcone
Epigenetic mechanisms are involved in gastrointestinal (GI) cancer pathogenesis. Insights into the molecular basis of GI carcinogenesis led to the identification of different epigenetic pathways and signatures that may play a role as therapeutic targets in metastatic colorectal cancer (mCRC) and non-colorectal GI tumors. Among these alterations, O6-methylguanine DNA methyltransferase (MGMT) gene promoter methylation is the most investigated biomarker and seems to be an early and frequent event, at least in CRC...
2016: Frontiers in Bioscience (Elite Edition)
G Mátis, A Kulcsár, J Petrilla, K Hermándy-Berencz, Zs Neogrády
The expression of hepatic drug-metabolizing cytochrome P450 (CYP) enzymes may be affected by several nutrition-derived compounds, such as by the commonly applied feed additive butyrate, possibly leading to feed-drug interactions. The aim of this study was to provide some evidence if butyrate can alter the activity of hepatic CYPs in chickens exposed to CYP-inducing xenobiotics, monitoring for the first time the possibility of such interaction. Ross 308 chickens in the grower phase were treated with daily intracoelomal phenobarbital (PB) injection (80 mg/kg BW), applied as a non-specific CYP-inducer, simultaneously with two different doses of intra-ingluvial sodium butyrate boluses (0...
August 2016: Journal of Animal Physiology and Animal Nutrition
Mei-Mei Li, Balasubrahmanyam Addepalli, Mei-Juan Tu, Qiu-Xia Chen, Wei-Peng Wang, Patrick A Limbach, Janine M LaSalle, Su Zeng, Min Huang, Ai-Ming Yu
In contrast to the growing interests in studying noncoding RNAs (ncRNAs) such as microRNA (miRNA or miR) pharmacoepigenetics, there is a lack of efficient means to cost effectively produce large quantities of natural miRNA agents. Our recent efforts led to a successful production of chimeric pre-miR-27b in bacteria using a transfer RNA (tRNA)-based recombinant RNA technology, but at very low expression levels. Herein, we present a high-yield expression of chimeric pre-miR-1291 in common Escherichia coli strains using the same tRNA scaffold...
July 2015: Drug Metabolism and Disposition: the Biological Fate of Chemicals
M Ouni, M P Belot, A L Castell, D Fradin, P Bougnères
Short children using growth hormone (GH) to accelerate their growth respond to this treatment with a variable efficacy. The causes of this individual variability are multifactorial and could involve epigenetics. Quantifying the impact of epigenetic variation on response to treatments is an emerging challenge. Here we show that methylation of a cluster of CGs located within the P2 promoter of the insulin-like growth factor 1 (IGF1) gene, notably CG-137, is inversely closely correlated with the response of growth and circulating IGF1 to GH administration...
February 2016: Pharmacogenomics Journal
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