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Personalized epigenetics

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https://www.readbyqxmd.com/read/28441730/regulatory-mirnas-in-colorectal-carcinogenesis-and-metastasis
#1
REVIEW
Yongchen Guo, Yonghua Bao, Wancai Yang
Colorectal cancer is one of the most common malignancies and is the second-leading cause of cancer-related death world-wide, which is linked to genetic mutations, epigenetic alterations, and oncogenic signaling activation. MicroRNAs, one of the categories of epigenetics, have been demonstrated significant roles in carcinogenesis and progression through regulating of oncogenic signaling pathways, stem cells, epithelial-mesenchymal transition, and metastasis. This review summarizes the roles of microRNAs in the regulating of Wnt, Ras, TGF-β, and inflammatory signaling pathways, stemness, and epithelial-mesenchymal transition, for carcinogenesis and metastasis in colorectal cancer...
April 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28415743/survival-differences-of-cimp-subtypes-integrated-with-cna-information-in-human-breast-cancer
#2
Huihan Wang, Weili Yan, Shumei Zhang, Yue Gu, Yihan Wang, Yanjun Wei, Hongbo Liu, Fang Wang, Qiong Wu, Yan Zhang
CpG island methylator phenotype of breast cancer is associated with widespread aberrant methylation at specified CpG islands and distinct patient outcomes. However, the influence of copy number contributing to the prognosis of tumors with different CpG island methylator phenotypes is still unclear. We analyzed both genetic (copy number) and epigenetic alterations in 765 breast cancers from The Cancer Genome Atlas data portal and got a panel of 15 biomarkers for copy number and methylation status evaluation...
March 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28410846/initiative-for-molecular-profiling-and-advanced-cancer-therapy-and-challenges-in-the-implementation-of-precision-medicine
#3
Apostolia-Maria Tsimberidou
In the last decade, breakthroughs in technology have improved our understanding of genomic, transcriptional, proteomic, epigenetic aberrations and immune mechanisms in carcinogenesis. Genomics and model systems have enabled the validation of novel therapeutic strategies. Based on these developments, in 2007, we initiated the IMPACT (Initiative for Molecular Profiling and Advanced Cancer Therapy) study, the first personalized medicine program for patients with advanced cancer at The University of Texas MD Anderson Cancer Center...
February 10, 2017: Current Problems in Cancer
https://www.readbyqxmd.com/read/28397399/belinostat-exerts-anti-tumor-cytotoxicity-through-the-ubiquitin-proteasome-pathway-in-lung-squamous-cell-carcinoma
#4
Li Ren Kong, Tuan Zea Tan, Weijie Richard Ong, Chonglei Bi, Hung Huynh, Soo Chin Lee, Wee Joo Chng, Pieter Johan Adam Eichhorn, Boon Cher Goh
There have been advances in personalized therapy directed by molecular profiles in lung adenocarcinoma but not in lung squamous cell carcinoma (SCC). The lack of actionable driver oncogenes in SCC has restricted the use of small molecule inhibitors. Here, we show that SCC cell lines displayed differential sensitivities to belinostat, a pan-histone deacetylase (HDAC) inhibitor. Phosphoproteomic analysis of belinostat-treated SCC cells revealed significant downregulation of the MAPK pathway, along with induction of apoptosis...
April 11, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28395317/indoor-air-quality-in-photocopy-centers-nanoparticle-exposures-at-photocopy-workstations-and-the-need-for-exposure-controls
#5
John Martin, Philip Demokritou, Susan Woskie, Dhimiter Bello
Background: Photocopiers emit large amounts of nanoparticles (NP) and are a significant source of indoor air pollution. These emissions induce airway inflammation, irritation, and systemic oxidative stress in humans, lung injury and inflammation in animals, and cytotoxicity and epigenetic modifications in vitro. However, little is known regarding NP exposures at the workstation in the photocopy work environment, or the extent and use of emission controls. Objective: To survey the photocopy work environment with regards to emissions controls and to evaluate IAQ with emphasis on NP exposure at the operator's workstation...
January 1, 2017: Annals of Work Exposures and Health
https://www.readbyqxmd.com/read/28388695/regulation-of-drug-metabolism-and-toxicity-by-multiple-factors-of-genetics-epigenetics-lncrnas-gut-microbiota-and-diseases-a-meeting-report-of-the-21-st-international-symposium-on-microsomes-and-drug-oxidations-mdo
#6
Ai-Ming Yu, Magnus Ingelman-Sundberg, Nathan J Cherrington, Lauren M Aleksunes, Ulrich M Zanger, Wen Xie, Hyunyoung Jeong, Edward M Morgan, Peter J Turnbaugh, Curtis D Klaassen, Aadra P Bhatt, Matthew R Redinbo, Pengying Hao, David J Waxman, Li Wang, Xiao-Bo Zhong
Variations in drug metabolism may alter drug efficacy and cause toxicity; better understanding of the mechanisms and risks shall help to practice precision medicine. At the 21(st) International Symposium on Microsomes and Drug Oxidations held in Davis, California, USA, in October 2-6, 2016, a number of speakers reported some new findings and ongoing studies on the regulation mechanisms behind variable drug metabolism and toxicity, and discussed potential implications to personalized medications. A considerably insightful overview was provided on genetic and epigenetic regulation of gene expression involved in drug absorption, distribution, metabolism, and excretion (ADME) and drug response...
March 2017: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/28378229/advances-in-the-development-of-molecularly-targeted-agents-in-non-small-cell-lung-cancer
#7
Saoirse O Dolly, Dearbhaile C Collins, Raghav Sundar, Sanjay Popat, Timothy A Yap
Non-small-cell lung cancer (NSCLC) remains a significant global health challenge and the leading cause of cancer-related mortality. The traditional 'one-size-fits-all' treatment approach has now evolved into one that involves personalized strategies based on histological and molecular subtypes. The molecular era has revolutionized the treatment of patients harboring epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK) and ROS1 gene aberrations. In the appropriately selected population, anti-tumor agents against these molecular targets can significantly improve progression-free survival...
April 4, 2017: Drugs
https://www.readbyqxmd.com/read/28377395/integrated-approach-of-nutritional-and-molecular-epidemiology-mineralogical-and-chemical-pollutant-characterisation-the-protocol-of-a-cross-sectional-study-in-women
#8
Martina Barchitta, Annalisa Quattrocchi, Andrea Maugeri, Germana Barone, Paolo Mazzoleni, Alfio Catalfo, Guido De Guidi, Maria Iemmolo, Nunzio Crimi, Antonella Agodi
INTRODUCTION: Environmentally-related health and disease are the result of the exposome, the totality of a person's environmental exposures, from all sources and routes, across their lifespan. Epigenetic phenomena, including DNA methylation, can be potentially modified by environmental and lifestyle factors, and result in environmental reprogramming of the genome for exposed individuals and for future generations of offspring. OBJECTIVE: The objective of the project is to evaluate the risk of DNA hypomethylation due to air pollution, Mediterranean diet adherence, folate intake, and demographic and socioeconomic factors, in healthy women living in the metropolitan area of Catania, Italy...
April 4, 2017: BMJ Open
https://www.readbyqxmd.com/read/28367231/molecular-subtyping-of-pancreatic-cancer-translating-genomics-and-transcriptomics-into-the-clinic
#9
REVIEW
Yongxing Du, Bangbo Zhao, Ziwen Liu, Xiaoxia Ren, Wenjing Zhao, Zongze Li, Lei You, Yupei Zhao
Pancreatic cancer remains one of the most lethal malignancies, and insights into both personalized diagnosis and intervention of this disease are urgently needed. The rapid development of sequencing technologies has enabled the successive completion of a series of genetic and epigenetic sequencing studies of pancreatic cancer. The mutational landscape of pancreatic cancer is generally portrayed in terms of somatic mutations, structural variations, epigenetic alterations and the core signaling pathways. In recent years, four significant molecular subtype classifications of pancreatic cancer have been proposed based on the expression of transcription factors and downstream targets or the distribution of structural rearrangements...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28359242/small-molecule-inhibitors-of-epigenetic-mutations-as-compelling-drug-targets-for-myelodysplastic-syndromes
#10
Bani Bandana Ganguly
BACKGROUND: Involvement of mutations in epigenetic mechanism in development of heterogeneous MDS and its evolution to AML has been understood with at least one mutation and median of 2-3 mutations of the landscapes of driver mutations in ~40 genes described >90% MDS patients. Exclusivity and cooperating effects of mutations have directed therapeutic implementation with hypomethylating agents and identified a number of first-in-class small molecules as inhibitors of mutational expression...
March 30, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28358303/a-novel-bio-psychosocial-behavioral-treatment-model-in-schizophrenia
#11
REVIEW
Yong-Ku Kim, Joonho Choi, Seon-Cheol Park
Despite the substantial burden of illness in schizophrenia, there has been a discrepancy between the beneficial effects of an increased use of antipsychotic medications and achieving limited recovery or remission. Because the focus of the most common antipsychotic medications is on dopamine, which is associated with positive symptoms, there is an unmet need for patients with negative symptoms. Since cognitive and negative symptoms rather than positive symptoms are more closely associated with psychosocial impairments in patients with schizophrenia, the non-dopaminergic systems including glutamate and γ-aminobutyric acid (GABA) of the prefrontal cortex should be of concern as well...
March 30, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28357066/association-of-two-synonymous-splicing-associated-cpg-single-nucleotide-polymorphisms-in-calpain-10-and-solute-carrier-family-2-member-2-with-type-2-diabetes
#12
Maria Karambataki, Andigoni Malousi, Georgios Tzimagiorgis, Constantinos Haitoglou, Aikaterini Fragou, Elisavet Georgiou, Foteini Papadopoulou, Gerasimos E Krassas, Sofia Kouidou
Coding synonymous single nucleotide polymorphisms (SNPs) have attracted little attention until recently. However, such SNPs located in epigenetic, CpG sites modifying exonic splicing enhancers (ESEs) can be informative with regards to the recently verified association of intragenic methylation and splicing. The present study describes the association of type 2 diabetes (T2D) with the exonic, synonymous, epigenetic SNPs, rs3749166 in calpain 10 (CAPN10) glucose transporter (GLUT4) translocator and rs5404 in solute carrier family 2, member 2 (SLC2A2), also termed GLUT2, which, according to prior bioinformatic analysis, strongly modify the splicing potential of glucose transport-associated genes...
February 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28334277/in-bone-metastasis-mir-34a-5p-absence-inversely-correlates-with-met-expression-while-met-oncogene-is-unaffected-by-mir-34a-5p-in-non-metastatic-and-metastatic-breast-carcinomas
#13
Paola Maroni, Rossella Puglisi, Gianfranco Mattia, Alessandra Carè, Emanuela Matteucci, Paola Bendinelli, Maria Alfonsina Desiderio
The highlight of the molecular basis and therapeutic targets of the bone-metastatic process requires the identification of biomarkers of metastasis colonization. Here, we studied miR-34a-5p expression, and Met-receptor expression and localization in bone metastases from ductal breast carcinomas, and in ductal carcinomas without history of metastasis (20 cases). miR-34a-5p was elevated in non-metastatic breast carcinoma, intermediate in the adjacent tissue and practically absent in bone metastases, opposite to pair-matched carcinoma...
March 16, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28302680/genomic-and-epigenomic-heterogeneity-of-hepatocellular-carcinoma
#14
De-Chen Lin, Anand Mayakonda, Huy Q Dinh, Pinbo Huang, Lehang Lin, Xiaoping Liu, Ling-Wen Ding, Jie Wang, Benjamin Berman, Erwei Song, Dong Yin, H Phillip Koeffler
Understanding the intratumoral heterogeneity of hepatocellular carcinoma (HCC) is instructive for developing personalized therapy and identifying molecular biomarkers. Here we applied whole-exome sequencing to 69 samples from 11 patients to resolve the genetic architecture of subclonal diversification. Spatial genomic diversity was found in all 11 HCC cases, with 29% of driver mutations being heterogeneous, including TERT, ARID1A, NOTCH2, and STAG2. Similar with other cancer types, TP53 mutations were always shared between all tumor regions i...
February 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28292312/comprehensive-discovery-of-subsample-gene-expression-components-by-information-explanation-therapeutic-implications-in-cancer
#15
Shirley Pepke, Greg Ver Steeg
BACKGROUND: De novo inference of clinically relevant gene function relationships from tumor RNA-seq remains a challenging task. Current methods typically either partition patient samples into a few subtypes or rely upon analysis of pairwise gene correlations that will miss some groups in noisy data. Leveraging higher dimensional information can be expected to increase the power to discern targetable pathways, but this is commonly thought to be an intractable computational problem. METHODS: In this work we adapt a recently developed machine learning algorithm for sensitive detection of complex gene relationships...
March 15, 2017: BMC Medical Genomics
https://www.readbyqxmd.com/read/28273839/parkinson-s-disease-from-pathogenesis-to-pharmacogenomics
#16
REVIEW
Ramón Cacabelos
Parkinson's disease (PD) is the second most important age-related neurodegenerative disorder in developed societies, after Alzheimer's disease, with a prevalence ranging from 41 per 100,000 in the fourth decade of life to over 1900 per 100,000 in people over 80 years of age. As a movement disorder, the PD phenotype is characterized by rigidity, resting tremor, and bradykinesia. Parkinson's disease -related neurodegeneration is likely to occur several decades before the onset of the motor symptoms. Potential risk factors include environmental toxins, drugs, pesticides, brain microtrauma, focal cerebrovascular damage, and genomic defects...
March 4, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28254385/dna-methylation-based-forensic-age-prediction-using-artificial-neural-networks-and-next-generation-sequencing
#17
Athina Vidaki, David Ballard, Anastasia Aliferi, Thomas H Miller, Leon P Barron, Denise Syndercombe Court
The ability to estimate the age of the donor from recovered biological material at a crime scene can be of substantial value in forensic investigations. Aging can be complex and is associated with various molecular modifications in cells that accumulate over a person's lifetime including epigenetic patterns. The aim of this study was to use age-specific DNA methylation patterns to generate an accurate model for the prediction of chronological age using data from whole blood. In total, 45 age-associated CpG sites were selected based on their reported age coefficients in a previous extensive study and investigated using publicly available methylation data obtained from 1156 whole blood samples (aged 2-90 years) analysed with Illumina's genome-wide methylation platforms (27K/450K)...
May 2017: Forensic Science International. Genetics
https://www.readbyqxmd.com/read/28248239/personalized-proteomics-the-future-of-precision-medicine
#18
REVIEW
Trevor T Duarte, Charles T Spencer
Medical diagnostics and treatment has advanced from a one size fits all science to treatment of the patient as a unique individual. Currently, this is limited solely to genetic analysis. However, epigenetic, transcriptional, proteomic, posttranslational modifications, metabolic, and environmental factors influence a patient's response to disease and treatment. As more analytical and diagnostic techniques are incorporated into medical practice, the personalized medicine initiative transitions to precision medicine giving a holistic view of the patient's condition...
October 1, 2016: Proteomes
https://www.readbyqxmd.com/read/28240173/personalized-medicine-of-alcohol-addiction-pharmacogenomics-and-beyond
#19
Vangelis George Manolopoulos, Georgia Ragia
Alcohol addiction or alcoholism is the most severe form of problem drinking. A variety of treatment methods for alcoholism are currently available that combine medications, behavioral treatment and peer support. The drugs that are currently approved by the U.S. Food and Drug Administration (FDA) for treatment of alcohol dependence are disulfiram, naltrexone and acamprosate. For many patients, however, these treatments are not effective. Evidence from a number of different studies suggests that different factors, both psychosocial and economic, as well as genetic variation, are significant contributors to interindividual variation both of clinical presentation of alcohol problems and response to a given treatment...
February 23, 2017: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/28220199/-novel-pharmaceutical-treatment-approaches-for-gastric-cancer
#20
F Lordick
This review article delineates novel approaches for the pharmaceutical treatment of gastric cancer. A newly developed molecular classification of gastric cancer based on histology, genetic, epigenetic and proteomic characteristics has evolved. It provides a road map for development of new drugs and combinations as well as for patient stratification in clinical research and it is expected to be introduced into clinical practice in the near future. Anti-HER2 targeted treatment is a validated strategy for treatment of metastatic gastric cancer and is now also being studied in the perioperative setting to increase response rates and ultimately survival in patients undergoing curative surgery; however, the resistance mechanisms of HER2-targeted treatment are poorly understood and optimal patient selection remains challenging...
February 20, 2017: Der Pathologe
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