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Azacytidine

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https://www.readbyqxmd.com/read/28644148/5-azacytidine-promotes-invadopodia-formation-and-tumor-metastasis-through-the-upregulation-of-pi3k-in-ovarian-cancer-cells
#1
Dan Cao, Dan Li, Yong Huang, Yu Ma, Binglan Zhang, Chengjian Zhao, Senyi Deng, Min Luo, Tao Yin, Yu-Quan Wei, Wei Wang
The high incidence of metastasis accounts for most of the lethality of ovarian cancer. Invadopodia are small, specialized types of machinery that degrade the extracellular matrix and are thus involved in the invasion and metastasis of cancer cells. The formation of invadopodia is regulated by both genetic and epigenetic factors. However, the ways by which methylation/demethylation regulates the dynamics of invadopodia in ovarian cancer are largely unknown. In this study, we found that the inhibition of methylation by 5-AZ (5-Azacytidine) increased the formation of invadopodia and enhanced degradation of the extracellular matrix in ovarian cancer cells...
June 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28638744/azacytidine-prevents-experimental-xenogeneic-graft-versus-host-disease-without-abrogating-graft-versus-leukemia-effects
#2
Grégory Ehx, Gilles Fransolet, Laurence de Leval, Stéphanie D'Hondt, Sophie Lucas, Muriel Hannon, Loïc Delens, Sophie Dubois, Pierre Drion, Yves Beguin, Stéphanie Humblet-Baron, Frédéric Baron
The demethylating agent 5-azacytidine (AZA) has proven its efficacy in the treatment of myelodysplastic syndrome and acute myeloid leukemia. In addition, AZA can demethylate FOXP3 intron 1 (FOXP3i1) leading to the generation of regulatory T cells (Treg). Here, we investigated the impact of AZA on xenogeneic graft-vs.-host disease (xGVHD) and graft-vs.-leukemia effects in a humanized murine model of transplantation (human PBMCs-infused NSG mice), and described the impact of the drug on human T cells in vivo...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28615266/antitumor-effects-of-epidrug-ifnalpha%C3%A2-combination-driven-by-modulated-gene-signatures-in-both-colorectal-cancer-and-dendritic-cells
#3
Alessandra Fragale, Giulia Romagnoli, Valerio Licursi, Maria Buoncervello, Giorgia Del Vecchio, Caterina Giuliani, Stefania Parlato, Celeste Leone, Marta De Angelis, Irene Canini, Elena Toschi, Filippo Belardelli, Rodolfo Negri, Imerio Capone, Carlo Presutti, Lucia Gabriele
Colorectal cancer (CRC) results from progressive accumulation of genetic and epigenetic alterations. IFN signaling defects play an important role in the carcinogenesis process, in which the inability of IFN transcription regulatory factors (IRFs) to access regulatory sequences in IFN-stimulated genes (ISGs) in tumors and in immune cells may be pivotal. We reported that low-dose combination of two FDA-approved epidrugs, azacytidine (A) and romidepsin (R), with IFNa2 (ARI) hampers the aggressiveness of both CRC metastatic and stem cells in vivo and triggers immunogenic cell death signals that stimulate dendritic cell (DC) function...
June 14, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28607150/wnt3a-induces-the-expression-of-acetylcholinesterase-during-osteoblast-differentiation-via-the-runx2-transcription-factor
#4
Miranda L Xu, Cathy W C Bi, Etta Y L Liu, Tina T X Dong, Karl W K Tsim
Acetylcholinesterase (AChE) hydrolyzes acetylcholine to terminate cholinergic transmission in neurons. Apart from this AChE activity, emerging evidence suggests that AChE could also function in other, nonneuronal cells. For instance, in bone, AChE exists as a proline-rich membrane anchor (PRiMA)-linked globular form in osteoblasts, in which it is proposed to play a noncholinergic role in differentiation. However, this hypothesis is untested. Here, we found that in cultured rat osteoblasts, AChE expression was increased in parallel with osteoblastic differentiation...
June 12, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28601197/a-comparative-study-to-evaluate-myogenic-differentiation-potential-of-human-chorion-versus-umbilical-cord-blood-derived-mesenchymal-stem-cells
#5
Nikoo Bana, Davood Sanooghi, Mansoureh Soleimani, Nasim Hayati Roodbari, Sepideh Alavi Moghaddam, Mohammad Taghi Joghataei, Forough Azam Sayahpour, Faezeh Faghihi
OBJECTIVE: Musculodegenerative diseases threaten the life of many patients in the world. Since drug administration is not efficient in regeneration of damaged tissues, stem cell therapy is considered as a good strategy to restore the lost cells. Since the efficiency of myogenic differentiation potential of human Chorion- derived Mesenchymal Stem Cells (C-MSCs) has not been addressed so far; we set out to evaluate myogenic differentiation property of these cells in comparison with Umbilical Cord Blood- derived Mesenchymal Stem Cells (UCB-MSCs) in the presence of 5-azacytidine...
May 11, 2017: Tissue & Cell
https://www.readbyqxmd.com/read/28586038/mir-1247-5p-functions-as-a-tumor-suppressor-in-human-hepatocellular-carcinoma-by-targeting-wnt3
#6
Yuankui Chu, Weining Fan, Wenwei Guo, Yixin Zhang, Lixin Wang, Le Guo, Xiangguo Duan, Jun Wei, Guangxian Xu
Increasing evidence suggests that aberrant expression of certain microRNAs (miRNAs) may participate in the genesis and progression of tumors. Several studies have indicated that miR-1247-5p plays different roles in various types of cancer cells. The effects of miR-1247-5p on human hepatocellular carcinoma (HCC) cells are elusive. In the present study, we investigated the effects of miR-1247-5p on the progression of HCC. The transcript of miR-1247-5p was markedly downregulated in clinical samples of patients with HCC and HCC cell lines, and ectopic overexpression of miR‑1247-5p markedly inhibited the proliferation and invasion of HepG2 cells, induced cell apoptosis in vitro, and suppressed the growth of transplanted tumors in vivo...
June 6, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28575160/dynamic-changes-in-methylome-and-transcriptome-patterns-in-response-to-methyltransferase-inhibitor-5-azacytidine-treatment-in-citrus
#7
Jidi Xu, Xia Wang, Hongbo Cao, Haidan Xu, Qiang Xu, Xiuxin Deng
DNA methylation is known to play an important role in various developmental processes in plants. However, there is a general lack of understanding about the possible functions of DNA methylation in fruit trees. Using callus as a model, methylome, transcriptome and metabolite changes were assessed after treatment with the DNA methyltransferase inhibitor 5-azacytidine (5azaC). Genome-wide methylome analysis revealed the demethylation of a diverse of genes, including many genes encoding transcription factors (TFs), genes involved in biological processes, and the up-regulation of a wide range of transposable elements (TEs)...
June 1, 2017: DNA Research: An International Journal for Rapid Publication of Reports on Genes and Genomes
https://www.readbyqxmd.com/read/28543390/the-effect-of-ebv-on-wif1-nlk-and-apc-gene-methylation-and-expression-in-gastric-carcinoma-and-nasopharyngeal-cancer
#8
Zhenzhen Zhao, Wen Liu, Jincheng Liu, Jiayi Wang, Bing Luo
Epstein-Barr virus (EBV) is an important DNA tumor virus that is associated with approximately 10% of gastric carcinomas and 99% of nasopharyngeal cancers. DNA methylation and microRNAs (miRNAs) are the most studied epigenetic mechanisms that can prompt disease susceptibility. This study aimed to detect the effect of EBV on Wnt inhibitory factor 1 (WIF1), Nemo-like kinase (NLK), and adenomatous polyposis coli (APC) gene methylation and expression in gastric carcinoma and nasopharyngeal cancer. METHODS: The WIF1, NLK, and APC gene mRNA expression levels were measured by real-time quantitative RT-PCR in four EBV-positive cell lines and four EBV-negative cell lines...
May 23, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28542496/zinc-blocks-sos-induced-antibiotic-resistance-via-inhibition-of-reca-in-escherichia-coli
#9
Bryan E Bunnell, Jillian F Escobar, Kirsten L Bair, Mark D Sutton, John K Crane
Zinc inhibits the virulence of diarrheagenic E. coli by inducing the envelope stress response and inhibiting the SOS response. The SOS response is triggered by damage to bacterial DNA. In Shiga-toxigenic E. coli, the SOS response strongly induces the production of Shiga toxins (Stx) and of the bacteriophages that encode the Stx genes. In E. coli, induction of the SOS response is accompanied by a higher mutation rate, called the mutator response, caused by a shift to error-prone DNA polymerases when DNA damage is too severe to be repaired by canonical DNA polymerases...
2017: PloS One
https://www.readbyqxmd.com/read/28529454/characterization-of-cytosine-methylation-and-the-dna-methyltransferases-of-toxoplasma-gondii
#10
Haixia Wei, Shichen Jiang, Longfei Chen, Cheng He, Shuizhen Wu, Hongjuan Peng
DNA methylation is a key epigenetic modification which confers phenotypic plasticity and adaptation. Cyst-forming strains of Toxoplasma gondii undergo tachyzoite to bradyzoite conversion after initial acute infection of a host, and the reverse conversion may occur in immune-suppressed hosts. The formation of m(5)C is catalyzed by DNA methyltransferase (DNMT). We identified two functional DNA methyltransferases, TgDNMTa and TgDNMTb, in T. gondii that may mediate DNA methylation. The recombinant proteins showed intrinsic methyltransferase activity; both have higher transcription levels in bradyzoites than that in tachyzoites...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28527889/enhanced-cardiomyogenic-induction-of-mouse-pluripotent-cells-by-cyclic-mechanical-stretch
#11
Akankshya Shradhanjali, Brandon D Riehl, Jeong Soon Lee, Ligyeom Ha, Jung Yul Lim
The cardiac milieu is mechanically active with spontaneous contraction beginning from early development and persistent through maturation and homeostasis, suggesting that mechanical loading may provide a biomimetic myocardial developmental signal. In this study, we tested the role of cyclic mechanical stretch loading in the cardiomyogenesis of pluripotent murine embryonic (P19) stem cells. A Flexcell tension system was utilized to apply equiaxial stretch (12% strain, 1.25 Hz frequency) to P19 cell-derived embryoid bodies (EBs)...
May 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28514852/separated-immobilization-of-incompatible-enzymes-on-polymer-substrate-via-visible-light-induced-living-photografting-polymerization
#12
Xing Zhu, Bin He, Changwen Zhao, Yuhong Ma, Wantai Yang
The use of the mixed catalytic system with several enzymes can provide multiple benefits in terms of the cost, simplification of a multistep reaction, and effectiveness of complex chemical reactions. Although study of different enzyme coimmobilization systems has attracted increasing attention in recent years, separately immobilizing enzymes which can not coexist on one support is still one of the great challenges. In this paper, a simple and effective strategy was introduced to separately encapsulate incompatible trypsin and transglutaminase (TGase) into different poly(ethylene glycol) (PEG) network layer grafted on low-density polyethylene (LDPE) film via visible light induced living photografting polymerization...
June 6, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28512793/5-azacytidine-mediated-hmsc-behavior-on-electrospun-scaffolds-for-skeletal-muscle-regeneration
#13
Ines Fasolino, Vincenzo Guarino, Valentina Cirillo, Luigi Ambrosio
Incomplete regeneration after trauma or muscular dysfunction is a common problem in muscle replacement therapies. Recent approaches in tissue engineering allow for the replication of skeletal muscle structure and function in vitro and in vivo by molecular therapies and implantable scaffolds which properly address muscle cells toward myotube differentiation and maturation. Here, we investigate the in vitro response of human mesenchymal stem cells (hMSC) on electrospun fibers made of polycaprolactone (PCL) in the presence of 5-azacytidine (5-AZA) to evaluate how fibrous network may influence the therapeutic effect of drug during in vitro myogenesis...
May 16, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28511071/effects-of-%C3%AE-radiation-on-cell-growth-cell-cycle-and-promoter-methylation-of-22-cell-cycle-genes-in-the-1321ni-astrocytoma-cell-line
#14
Yaman Alghamian, Ghalia Abou Alchamat, Hossam Murad, Ammar Madania
PURPOSE: DNA damage caused by radiation initiates biological responses affecting cell fate. DNA methylation regulates gene expression and modulates DNA damage pathways. Alterations in the methylation profiles of cell cycle regulating genes may control cell response to radiation. In this study we investigated the effect of ionizing radiation on the methylation levels of 22 cell cycle regulating genes in correlation with gene expression in 1321NI astrocytoma cell line. METHODS: 1321NI cells were irradiated with 2, 5 or 10Gy doses then analyzed after 24, 48 and 72h for cell viability using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliu bromide) assay...
May 13, 2017: Advances in Medical Sciences
https://www.readbyqxmd.com/read/28510781/5-azacytidine-mediated-reactivation-of-silenced-transgenes-in-potato-solanum-tuberosum-at-the-whole-plant-level
#15
Dimitrij Tyč, Eva Nocarová, Lenka Sikorová, Lukáš Fischer
Transient 5-azacytidine treatment of leaf explants from potato plants with transcriptionally silenced transgenes allows de novo regeneration of plants with restored transgene expression at the whole plant level. Transgenes introduced into plant genomes frequently become silenced either at the transcriptional or the posttranscriptional level. Transcriptional silencing is usually associated with DNA methylation in the promoter region. Treatments with inhibitors of maintenance DNA methylation were previously shown to allow reactivation of transcriptionally silenced transgenes in single cells or tissues, but not at the whole plant level...
May 16, 2017: Plant Cell Reports
https://www.readbyqxmd.com/read/28510608/the-biomphalaria-glabrata-dna-methylation-machinery-displays-spatial-tissue-expression-is-differentially-active-in-distinct-snail-populations-and-is-modulated-by-interactions-with-schistosoma-mansoni
#16
Kathrin K Geyer, Umar H Niazi, David Duval, Céline Cosseau, Chad Tomlinson, Iain W Chalmers, Martin T Swain, David J Cutress, Utibe Bickham-Wright, Sabrina E Munshi, Christoph Grunau, Timothy P Yoshino, Karl F Hoffmann
BACKGROUND: The debilitating human disease schistosomiasis is caused by infection with schistosome parasites that maintain a complex lifecycle alternating between definitive (human) and intermediate (snail) hosts. While much is known about how the definitive host responds to schistosome infection, there is comparably less information available describing the snail's response to infection. METHODOLOGY/PRINCIPLE FINDINGS: Here, using information recently revealed by sequencing of the Biomphalaria glabrata intermediate host genome, we provide evidence that the predicted core snail DNA methylation machinery components are associated with both intra-species reproduction processes and inter-species interactions...
May 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28498806/epigenetic-modifiers-upregulate-mhc-ii-and-impede-ovarian-cancer-tumor-growth
#17
Taylor B Turner, Selene Meza-Perez, Angelina Londoño, Ashwini Katre, Jacelyn E Peabody, Haller J Smith, Andres Forero, Lyse A Norian, J Michael Straughn, Donald J Buchsbaum, Troy D Randall, Rebecca C Arend
Expression of MHC class II pathway proteins in ovarian cancer correlates with prolonged survival. Murine and human ovarian cancer cells were treated with epigenetic modulators - histone deacetylase inhibitors and a DNA methyltransferase inhibitor. mRNA and protein expression of the MHC II pathway were evaluated by qPCR and flow cytometry. Treatment with entinostat and azacytidine of ID8 cells in vitro increased mRNA levels of Cd74, Ciita, and H2-Aa, H2-Eb1. MHC II and CD74 protein expression were increased after treatment with either agent...
April 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28491035/proteomic-analysis-reveals-autophagy-as-pro-survival-pathway-elicited-by-long-term-exposure-with-5-azacitidine-in-high-risk-myelodysplasia
#18
Alessandra Romano, Cesarina Giallongo, Piera La Cava, Nunziatina L Parrinello, Antonella Chiechi, Calogero Vetro, Daniele Tibullo, Francesco Di Raimondo, Lance A Liotta, Virginia Espina, Giuseppe A Palumbo
Azacytidine (5-AZA) is the standard first-choice treatment for high-risk myelodysplasia (MDS) patients. However, the clinical outcome for those patients who interrupt treatment or whose disease failed to respond is very poor. In order to identify the cellular pathways that are modified by long-term exposure to 5-AZA, we evaluated key proteins associated with the autophagy pathway by reverse-phase microarray (RPPA). Comparing bone marrow mononucleated cells (BMMCs) obtained from 20 newly-diagnosed patients and after four 5-AZA cycles we found an increased autophagy signaling...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28490812/hdac3-regulates-dnmt1-expression-in-multiple-myeloma-therapeutic-implications
#19
T Harada, H Ohguchi, Y Grondin, S Kikuchi, M Sagawa, Y-T Tai, R Mazitschek, T Hideshima, K C Anderson
Epigenetic signaling pathways are implicated in tumorigenesis and therefore histone deacetylases (HDACs) represent novel therapeutic targets for cancers including multiple myeloma (MM). Although non-selective HDAC inhibitors show anti-MM activities, unfavorable side effects limit their clinical efficacy. Isoform- and/or class-selective HDAC inhibition offers the possibility to maintain clinical activity while avoiding adverse events attendant to broad non-selective HDAC inhibition. We have previously reported that HDAC3 inhibition, either by genetic knockdown or selective inhibitor BG45, abrogates MM cell proliferation...
May 11, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28486212/anti-oxidative-and-anti-inflammatory-benefits-of-the-ribonucleoside-analogue-5-azacitidine-in-mice-with-acetaminophen-induced-toxic-hepatitis
#20
Changming Yang, Jun Yi, Xianqiong Gong, Pu Ge, Jie Dai, Ling Lin, Yu Xing, Li Zhang
Toxic hepatitis induced by overdose of acetaminophen (APAP) is one of the major life-threatening problems, oxidative stress and inflammatory injury are the essential underlying mechanisms. 5-Azacytidine (5-AZA) is a ribonucleoside analogue which has been approved for the treatment of patients with acute myeloid leukemia and myelodyplastic syndrome, but recent studies also found that 5-AZA might have anti-oxidative and anti-inflammatory benefits in non-tumor disorders. In the present study, the potential effects of 5-AZA on APAP-induced toxic hepatitis were investigated in a mouse model in vivo...
July 2017: International Immunopharmacology
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