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Epigenetics and cancer

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https://www.readbyqxmd.com/read/29457866/epigenetic-effects-of-metformin-from-molecular-mechanisms-to-clinical-implications
#1
REVIEW
S C Bridgeman, G C Ellison, P E Melton, P Newsholme, Cds Mamotte
There is a growing body of evidence that links epigenetic modifications to type 2 diabetes. Researchers have more recently investigated effects of commonly used medications, including those prescribed for diabetes, on epigenetic processes. This work reviews the influence of the widely used antidiabetic drug metformin on epigenomics, microRNA levels and subsequent gene expression and potential clinical implications. Metformin may influence the activity of numerous epigenetic modifying enzymes, mostly via modulating the activation of AMP-activated protein kinase (AMPK)...
February 19, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29456764/integrative-analysis-of-the-epigenetic-basis-of-muscle-invasive-urothelial-carcinoma
#2
Thomas Sanford, Maxwell V Meng, Reema Railkar, Piyush K Agarwal, Sima P Porten
Background: Elucidation of epigenetic alterations in bladder cancer will lead to further understanding of the biology of the disease and hopefully improved therapies. Our aim was to perform an integrative epigenetic analysis of invasive urothelial carcinoma of the bladder to identify the epigenetic abnormalities involved in the development and progression of this cancer. Methods: Pre-processed methylation data and RNA-seq data were downloaded from The Cancer Genome Atlas (TCGA) and processed using the R package TCGA-Assembler...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29456384/tea-polyphenols-and-prevention-of-epigenetic-aberrations-in-cancer
#3
REVIEW
Arundhati Bag, Niladri Bag
Tea polyphenols are secondary metabolites of tea plants and are well known for beneficial health effects. They can protect from a variety of illnesses including cancers. Tea polyphenols can prevent cancer by modulating epigenetic aberrations taking place in DNA methylation, histone modifications, and micro-RNAs. By altering these epimutations, they regulate chromatin dynamics and expression of genes those induce or suppress cancer formation. However, majority of the studies in existing literature are carried out for green tea polyphenols rather than black tea polyphenols despite the fact that black tea is the most commonly consumed form of tea (78%) followed by green tea (20%) and other forms of tea...
January 2018: Journal of Natural Science, Biology, and Medicine
https://www.readbyqxmd.com/read/29455658/receptor-tyrosine-kinases-rtks-in-breast-cancer-signaling-therapeutic-implications-and-challenges
#4
REVIEW
Ramesh Butti, Sumit Das, Vinoth Prasanna Gunasekaran, Amit Singh Yadav, Dhiraj Kumar, Gopal C Kundu
Breast cancer is a multifactorial disease and driven by aberrant regulation of cell signaling pathways due to the acquisition of genetic and epigenetic changes. An array of growth factors and their receptors is involved in cancer development and metastasis. Receptor Tyrosine Kinases (RTKs) constitute a class of receptors that play important role in cancer progression. RTKs are cell surface receptors with specialized structural and biological features which respond to environmental cues by initiating appropriate signaling cascades in tumor cells...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29455645/pyruvate-kinase-m2-fuels-multiple-aspects-of-cancer-cells-from-cellular-metabolism-transcriptional-regulation-to-extracellular-signaling
#5
REVIEW
Ming-Chuan Hsu, Wen-Chun Hung
Originally identified as a metabolic enzyme that catalyzes the transfer of a phosphate group from phosphoenolpyruvate (PEP) to ADP in the glycolytic pathway, pyruvate kinase M2-type (PKM2) has been shown to exhibit novel biological activities in the nucleus and outside the cells. Although cell-based studies reveal new non-canonical functions of PKM2 in gene transcription, epigenetic modulation and cell cycle progression, the importance of these non-canonical functions in PKM2-mediated tumorigenesis is still under debate because studies in genetically modified mice do not consistently echo the findings observed in cultured cancer cells...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29455003/combinatorial-strategy-of-epigenetic-and-hormonal-therapies-a-novel-promising-approach-for-treating-advanced-prostate-cancer
#6
Tarek K Motawi, Hebatallah A Darwish, Iman Diab, Maged W Helmy, Mohamed Noureldin
AIMS: Estrogens act as key factors in prostate biology, cellular proliferation and differentiation as well as cancer development and progression. The expression of estrogen receptor (ER)-β appears to be lost during prostate cancer progression through hypermethylation mechanism. Epigenetic drugs such as 5-aza-2'-deoxycytidine (5-AZAC) and Trichostatin A (TSA) showed efficacy in restoring ERβ expression in prostate cancer cells. This study was designed to explore the potential anti-carcinogenic effects resulting from re-expressing ERβ1 using 5-AZAC and/or TSA, followed by its stimulation with Diarylpropionitrile (DPN), a selective ERβ1 agonist, in prostate cancer cell line PC-3...
February 15, 2018: Life Sciences
https://www.readbyqxmd.com/read/29454856/nucleosidic-dna-demethylating-epigenetic-drugs-a-comprehensive-review-from-discovery-to-clinic
#7
REVIEW
Khushboo Agrawal, Viswanath Das, Pankhuri Vyas, Marián Hajdúch
DNA methylation plays a pivotal role in the etiology of cancer by mediating epigenetic silencing of cancer-related genes. Since the relationship between aberrant DNA methylation and cancer has been understood, there has been an explosion of research at developing anti-cancer therapies that work by inhibiting DNA methylation. From the discovery of first DNA hypomethylating drugs in the 1980s to recently discovered second generation pro-drugs, exceedingly large number of studies have been published that describe the DNA hypomethylation-based anti-neoplastic action of these drugs in various stages of the pre-clinical investigation and advanced stages of clinical development...
February 15, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29453919/genetic-and-epigenetic-differences-of-benign-and-malignant-pheochromocytomas-and-paragangliomas-ppgls
#8
Fatemeh Khatami, Mahsa Mohammadamoli, Seyed Mohammad Tavangar
Pheochromocytomas and paragangliomas (PPGLs) are tumors arising from the adrenal medulla and sympathetic/parasympathetic paraganglia, respectively. According to Th e Cancer Genome Atlas (TCGA), approximately 40% of PPGLs are due to germ line mutations in one of 16 susceptibility genes, and a further 30% are due to somatic alterations in at least seven main genes (VHL, EPAS1, CSDE1, MAX, HRAS, NF1, RET, and possibly KIF1B). Th e diagnosis of malignant PPGL was straight forward in most cases as it was defined as presence of PPGL in non-chromaffin tissues...
January 1, 2018: Endocrine Regulations
https://www.readbyqxmd.com/read/29453678/differential-expression-of-the-tweak-receptor-fn14-in-idh1-wild-type-and-mutant-gliomas
#9
David S Hersh, Sen Peng, Jimena G Dancy, Rebeca Galisteo, Jennifer M Eschbacher, Rudy J Castellani, Jonathan E Heath, Teklu Legesse, Anthony J Kim, Graeme F Woodworth, Nhan L Tran, Jeffrey A Winkles
The TNF receptor superfamily member Fn14 is overexpressed by many solid tumor types, including glioblastoma (GBM), the most common and lethal form of adult brain cancer. GBM is notable for a highly infiltrative growth pattern and several groups have reported that high Fn14 expression levels can increase tumor cell invasiveness. We reported previously that the mesenchymal and proneural GBM transcriptomic subtypes expressed the highest and lowest levels of Fn14 mRNA, respectively. Given the recent histopathological re-classification of human gliomas by the World Health Organization based on isocitrate dehydrogenase 1 (IDH1) gene mutation status, we extended this work by comparing Fn14 gene expression in IDH1 wild-type (WT) and mutant (R132H) gliomas and in cell lines engineered to overexpress the IDH1 R132H enzyme...
February 16, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29453320/methylation-of-the-hoxa10-promoter-directs-mir-196b-5p-dependent-cell-proliferation-and-invasion-of-gastric-cancer-cells
#10
Linlin Shao, Zheng Chen, Dunfa Peng, Mohammed Soutto, Shoumin Zhu, Andreia Bates, Shutian Zhang, Wael El-Rifai
The cross-talk between epigenetics and miRNA expression plays an important role in human tumorigenesis. Herein, we investigated the regulation and role of miR-196b-5p in gastric cancer. Using quantitative real-time RT-PCR, we demonstrate that miR-196b-5p is significantly overexpressed in human gastric cancer tissues (P<0.01). In addition, we also found that HOXA10, the host gene for miR-196b-5p, is overexpressed and positively correlated with miR-196b-5p expression levels (P<0.001). Quantitative pyrosequencing methylation analysis of HOXA10 promoter, demonstrated significantly lower levels of promoter DNA methylation of HOXA10 in gastric cancer samples, as compared to normal gastric mucosa samples (non-tumor control)...
February 16, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29452350/extra-virgin-olive-oil-contains-a-metabolo-epigenetic-inhibitor-of-cancer-stem-cells
#11
Bruna Corominas-Faja, Elisabet Cuyàs, Jesús Lozano-Sánchez, Sílvia Cufí, Sara Verdura, Salvador Fernández-Arroyo, Isabel Borrás-Linares, Begoña Martin-Castillo, Ángel G Martin, Ruth Lupu, Alfons Nonell-Canals, Melchor Sanchez-Martinez, Vicente Micol, Jorge Joven, Antonio Segura-Carretero, Javier A Menendez
Targeting tumor-initiating, drug-resistant populations of cancer stem cells (CSC) with phytochemicals is a novel paradigm for cancer prevention and treatment. We herein employed a phenotypic drug discovery approach coupled to mechanism-of-action profiling and target deconvolution to identify phenolic components of extra virgin olive oil (EVOO) capable of suppressing the functional traits of CSC in breast cancer (BC). In vitro screening revealed that the secoiridoid decarboxymethyl oleuropein aglycone (DOA) could selectively target sub-populations of epithelial-like, aldehyde dehydrogenase (ALDH)-positive and mesenchymal-like, CD44+CD24-/low CSC...
February 14, 2018: Carcinogenesis
https://www.readbyqxmd.com/read/29449933/a-simplified-characterization-of-s-adenosyl-l-methionine-consuming-enzymes-with-1-step-ez-mtase-a-universal-and-straightforward-coupled-assay-for-in-vitro-and-in-vivo-setting
#12
Emmanuel S Burgos, Ryan O Walters, Derek M Huffman, David Shechter
Methyltransferases use S -adenosyl-l-methionine (SAM) to deposit methyl marks. Many of these epigenetic 'writers' are associated with gene regulation. As cancer etiology is highly correlated with misregulated methylation patterns, methyltransferases are emerging therapeutic targets. Successful assignment of methyltransferases' roles within intricate biological networks relies on (1) the access to enzyme mechanistic insights and (2) the efficient screening of chemical probes against these targets. To characterize methyltransferases in vitro and in vivo , we report a highly-sensitive one-step deaminase-linked continuous assay where the S -adenosyl-l-homocysteine (SAH) enzyme-product is rapidly and quantitatively catabolized to S -inosyl-l-homocysteine (SIH)...
September 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/29449053/genetic-and-epigenetic-alterations-in-the-tumour-tumour-margins-and-normal-buccal-mucosa-of-patients-with-oral-cancer
#13
N Eljabo, N Nikolic, J Carkic, D Jelovac, M Lazarevic, N Tanic, J Milasin
Despite adequate surgical resection, oral squamous cell carcinoma (OSCC) shows a high rate of recurrence and metastasis, which could be explained by the presence of molecular alterations in seemingly normal tumour margins and the entire oral mucosa. The aims of this study were (1) to assess the presence of gene amplification (c-Myc and HER2) and promoter methylation (p14 and p16) in the tumours, tumour margins, and unaffected oral mucosa of 40 OSCC patients, and (2) to evaluate the possibility of using these alterations as prognostic markers...
February 12, 2018: International Journal of Oral and Maxillofacial Surgery
https://www.readbyqxmd.com/read/29445424/promoter-methylation-of-dna-damage-repair-ddr-genes-in-human-tumor-entities-rbbp8-ctip-is-almost-exclusively-methylated-in-bladder-cancer
#14
Jolein Mijnes, Jürgen Veeck, Nadine T Gaisa, Eduard Burghardt, Tim C de Ruijter, Sonja Gostek, Edgar Dahl, David Pfister, Sebastian C Schmid, Ruth Knüchel, Michael Rose
Background: Genome-wide studies identified pan-cancer genes and shared biological networks affected by epigenetic dysregulation among diverse tumor entities. Here, we systematically screened for hypermethylation of DNA damage repair (DDR) genes in a comprehensive candidate-approach and exemplarily identify and validate candidate DDR genes as targets of epigenetic inactivation unique to bladder cancer (BLCA), which may serve as non-invasive biomarkers. Methods: Genome-wide DNA methylation datasets (2755 CpG probes of n = 7819 tumor and n = 659 normal samples) of the TCGA network covering 32 tumor entities were analyzed in silico for 177 DDR genes...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29445380/the-role-of-indoleamine-2-3-dioxygenase-in-cancer-development-diagnostics-and-therapy
#15
REVIEW
Lilla Hornyák, Nikoletta Dobos, Gábor Koncz, Zsolt Karányi, Dénes Páll, Zoltán Szabó, Gábor Halmos, Lóránt Székvölgyi
Tumors are composed of abnormally transformed cell types and tissues that differ from normal tissues in their genetic and epigenetic makeup, metabolism, and immunology. Molecular compounds that modulate the immune response against neoplasms offer promising new strategies to combat cancer. Inhibitors targeting the indoleamine-2,3-dioxygenase 1 enzyme (IDO1) represent one of the most potent therapeutic opportunities to inhibit tumor growth. Herein, we assess the biochemical role of IDO1 in tumor metabolism and immune surveillance, and review current diagnostic and therapeutic approaches that are intended to increase the effectiveness of immunotherapies against highly aggressive and difficult-to-treat IDO-expressing cancers...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29445084/the-carnitine-system-and-cancer-metabolic-plasticity
#16
REVIEW
Melone Mariarosa Anna Beatrice, Valentino Anna, Margarucci Sabrina, Galderisi Umberto, Giordano Antonio, Peluso Gianfranco
Metabolic flexibility describes the ability of cells to respond or adapt its metabolism to support and enable rapid proliferation, continuous growth, and survival in hostile conditions. This dynamic character of the cellular metabolic network appears enhanced in cancer cells, in order to increase the adaptive phenotype and to maintain both viability and uncontrolled proliferation. Cancer cells can reprogram their metabolism to satisfy the energy as well as the biosynthetic intermediate request and to preserve their integrity from the harsh and hypoxic environment...
February 14, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29444131/chromatin-immunoprecipitation-improvements-for-the-processing-of-small-frozen-pieces-of-adipose-tissue
#17
Daniel Castellano-Castillo, Pierre-Damien Denechaud, Isabel Moreno-Indias, Francisco Tinahones, Lluis Fajas, María Isabel Queipo-Ortuño, Fernando Cardona
Chromatin immunoprecipitation (ChIP) has gained importance to identify links between the genome and the proteome. Adipose tissue has emerged as an active tissue, which secretes a wide range of molecules that have been related to metabolic and obesity-related disorders, such as diabetes, cardiovascular failure, metabolic syndrome, or cancer. In turn, epigenetics has raised the importance in discerning the possible relationship between metabolic disorders, lifestyle and environment. However, ChIP application in human adipose tissue is limited by several factors, such as sample size, frozen sample availability, high lipid content and cellular composition of the tissue...
2018: PloS One
https://www.readbyqxmd.com/read/29443889/alteration-of-epigenetic-regulation-by-long-noncoding-rnas-in-cancer
#18
REVIEW
Mariangela Morlando, Alessandro Fatica
Long noncoding RNAs (lncRNAs) are important regulators of the epigenetic status of the human genome. Besides their participation to normal physiology, lncRNA expression and function have been already associated to many diseases, including cancer. By interacting with epigenetic regulators and by controlling chromatin topology, their misregulation may result in an aberrant regulation of gene expression that may contribute to tumorigenesis. Here, we review the functional role and mechanisms of action of lncRNAs implicated in the aberrant epigenetic regulation that has characterized cancer development and progression...
February 14, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29443391/human-papillomavirus-genome-integration-in-squamous-carcinogenesis-what-have-next-generation-sequencing-studies-taught-us
#19
REVIEW
Ian J Groves, Nicholas Coleman
Human papillomavirus (HPV) infection is associated with ~5% of all human cancers, including a range of squamous cell carcinomas (SCCs). Persistent infection by high-risk HPVs (HRHPVs) is associated with the integration of virus genomes (which are usually stably maintained as extrachromosomal episomes) into host chromosomes. Although HRHPV integration rates differ across human sites of infection, this process appears to be an integral event in HPV-associated neoplastic progression, leading to deregulation of virus oncogene expression, host gene expression modulation and further genomic instability...
February 14, 2018: Journal of Pathology
https://www.readbyqxmd.com/read/29441069/interleukin-6-and-interferon-%C3%AE-signaling-via-jak1-stat-differentially-regulate-oncolytic-versus-cytoprotective-antiviral-states
#20
Oded Danziger, Tal Pupko, Eran Bacharach, Marcelo Ehrlich
Malignancy-induced alterations to cytokine signaling in tumor cells differentially regulate their interactions with the immune system and oncolytic viruses. The abundance of inflammatory cytokines in the tumor microenvironment suggests that such signaling plays key roles in tumor development and therapy efficacy. The JAK-STAT axis transduces signals of interleukin-6 (IL-6) and interferons (IFNs), mediates antiviral responses, and is frequently altered in prostate cancer (PCa) cells. However, how activation of JAK-STAT signaling with different cytokines regulates interactions between oncolytic viruses and PCa cells is not known...
2018: Frontiers in Immunology
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