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https://www.readbyqxmd.com/read/27913518/treatment-options-for-patients-with-myelodysplastic-syndromes-after-hypomethylating-agent-failure
#1
Hetty E Carraway
The treatment of patients with myelodysplastic syndromes (MDSs) has hinged primarily on supportive care (ie, blood transfusions, colony stimulating agents, iron chelation, etc.) and the US Food and Drug Administration-approved agents, including 5-azacytidine, deoxyazacytidine, and lenalidomide. For patients no longer benefitting from these agents, there is a paucity of effective therapies. The challenges at this time include our limited understanding of the mechanisms of resistance to these therapies and the variables employed to select next best therapies for patients based on: (1) their performance status and medical comorbidities; (2) the molecular feature(s) of their MDS; (3) the prior treatments they have received; and (4) the long-term goal(s)/possibilities for their future treatment (ie, transplant vs no transplant)...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27909741/the-role-of-epigenetic-modifiers-in-extended-cultures-of-functional-hepatocyte-like-cells-derived-from-human-neonatal-mesenchymal-stem-cells
#2
M Cipriano, J C Correia, S P Camões, N G Oliveira, P Cruz, H Cruz, M Castro, J L Ruas, J M Santos, J P Miranda
The development of predictive in vitro stem cell-derived hepatic models for toxicological drug screening is an increasingly important topic. Herein, umbilical cord tissue-derived mesenchymal stem cells (hnMSCs) underwent hepatic differentiation using an optimized three-step core protocol of 24 days that mimicked liver embryogenesis with further exposure to epigenetic markers, namely the histone deacetylase inhibitor trichostatin A (TSA), the cytidine analogue 5-azacytidine (5-AZA) and dimethyl sulfoxide (DMSO)...
December 1, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27889521/azacytidine-and-mir156-promote-rooting-in-adult-but-not-in-juvenile-arabidopsis-tissues
#3
Mehdi Massoumi, Frans A Krens, Richard G F Visser, Geert-Jan M De Klerk
Poor adventitious root (AR) formation is a major obstacle in micropropagation and conventional vegetative propagation of many crops. It is affected by many endogenous and exogenous factors. With respect to endogenous factors, the phase change from juvenile to adult has a major influence on AR formation and rooting is usually much reduced or even fully inhibited in adult tissues. It has been reported that the phase change is characterized by an increase in DNA-methylation and a decrease in the expression of microRNA156 (miR156)...
November 15, 2016: Journal of Plant Physiology
https://www.readbyqxmd.com/read/27877174/dna-methyltransferase-inhibitor-promotes-human-cd4-cd25-h-foxp3-regulatory-t-lymphocyte-induction-under-suboptimal-tcr-stimulation
#4
Chun-Hao Lu, Cheng-Jang Wu, Cheng-Chi Chan, Duc T Nguyen, Kuo-Ray Lin, Syh-Jae Lin, Li-Chen Chen, Jeffrey Jong-Yong Yen, Ming-Ling Kuo
The "master transcription factor" FOXP3 regulates the differentiation, homeostasis, and suppressor function of CD4(+) regulatory T (Treg) cells, which are critical in maintaining immune tolerance. Epigenetic regulation of FOXP3 expression has been demonstrated to be important to Treg cell development, but the induction of human Treg cells through epigenetic modification has not been clearly described. We report that the combination of the DNA methyltransferase inhibitor 5-azacytidine (5-Aza) and suboptimal T cell receptor (TCR) stimulation promoted CD4(+)CD25(h)FOXP3(+) T cell induction from human CD4(+)CD25(-) T cells...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27872192/the-chromatin-assembly-factor-complex-1-caf1-and-5-azacytidine-5-azac-affect-cell-motility-in-src-transformed-human-epithelial-cells
#5
Akinori Endo, Tony Ly, Raffaella Pippa, Dalila Bensaddek, Armel Nicolas, Angus I Lamond
Tumor invasion into surrounding stromal tissue is a hallmark of high-grade, metastatic cancers. Oncogenic transformation of human epithelial cells in culture can be triggered by activation of v-Src kinase, resulting in increased cell motility, invasiveness and tumorigenicity and provides a valuable model for studying how changes in gene expression cause cancer phenotypes. Here, we show that epithelial cells transformed by activated Src show increased levels of DNA methylation and that the methylation inhibitor, 5-AzaC, potently blocks the increased cell motility and invasiveness induced by Src activation...
November 21, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27870873/herbivore-induced-dna-demethylation-changes-floral-signalling-and-attractiveness-to-pollinators-in-brassica-rapa
#6
Roman T Kellenberger, Philipp M Schlüter, Florian P Schiestl
Plants have to fine-tune their signals to optimise the trade-off between herbivore deterrence and pollinator attraction. An important mechanism in mediating plant-insect interactions is the regulation of gene expression via DNA methylation. However, the effect of herbivore-induced DNA methylation changes on pollinator-relevant plant signalling has not been systematically investigated. Here, we assessed the impact of foliar herbivory on DNA methylation and floral traits in the model crop plant Brassica rapa...
2016: PloS One
https://www.readbyqxmd.com/read/27868302/reduced-dna-methylation-of-sphingosine-1-phosphate-receptor-5-in-alveolar-macrophages-in-copd-a-potential-link-to-failed-efferocytosis
#7
Jameel Barnawi, Hubertus Jersmann, Rainer Haberberger, Sandra Hodge, Robyn Meech
BACKGROUND AND OBJECTIVE: We previously showed that alveolar macrophages from COPD patients are defective in their ability to phagocytose apoptotic cells ('efferocytosis') and that this defect is potentially linked to the sphingosine-1 phosphate (S1P) system, in particular the sphingosine-1 phosphate receptor 5 (S1PR5). In alveolar macrophages from COPD patients, S1PR5 mRNA expression levels increased and were correlated with both lung function and efferocytosis. However, it us unknown whether these changes are under epigenetic control via DNA methylation or whether DNA methylation directly modulates macrophage function...
November 20, 2016: Respirology: Official Journal of the Asian Pacific Society of Respirology
https://www.readbyqxmd.com/read/27863907/evidence-of-epigenetic-tags-in-cardiac-fibrosis
#8
REVIEW
Vincenzo Grimaldi, Maria Rosaria De Pascale, Alberto Zullo, Andrea Soricelli, Teresa Infante, Francesco Paolo Mancini, Claudio Napoli
In cardiac fibrosis, following an injury or a stress, non-functional fibrotic tissue substitutes normal myocardium, thus leading to progressive heart failure. Activated fibroblasts are principal determinants of cardiac fibrosis by producing excessive fibrotic extracellular matrix and causing hypertrophy of cardiomyocytes. Epigenetic changes, such as DNA methylation, histone modifications, and miRNAs have been involved in these mechanisms. Therefore, there is a strong interest in reverting such epigenetic transformations in order to arrest myocardial fibrotic degeneration...
November 15, 2016: Journal of Cardiology
https://www.readbyqxmd.com/read/27853634/dynamic-alterations-of-bone-marrow-cytokine-landscape-of-myelodysplastic-syndromes-patients-treated-with-5-azacytidine
#9
Alena Moudra, Sona Hubackova, Veronika Machalova, Marketa Vancurova, Jiri Bartek, Milan Reinis, Zdenek Hodny, Anna Jonasova
Myelodysplastic syndromes (MDS) represent a heterogeneous group of clonal stem cell disorders characterized by ineffective hematopoiesis frequently progressing into acute myeloid leukemia (AML), with emerging evidence implicating aberrant bone marrow (BM) microenvironment and inflammation-related changes. 5-azacytidine (5-AC) represents standard MDS treatment. Besides inhibiting DNA/RNA methylation, 5-AC has been shown to induce DNA damage and apoptosis in vitro. To provide insights into in vivo effects, we assessed the proinflammatory cytokines alterations during MDS progression, cytokine changes after 5-AC, and contribution of inflammatory comorbidities to the cytokine changes in MDS patients...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27852417/-influences-of-dna-methylation-upon-neuroglobin-sustained-expression-in-oxygen-glucose-deprivation-model
#10
L N Zhang, S B Hu, S Y Deng, C X Chen, L Wu, Q Y Peng, L Huang, Y H Ai
Objective: To investigate the influences of genomic DNA methylation upon neuroglobin sustained expression in oxygen- glucose deprivation model. Methods: With A549 cell strain as the research object, the control group were cultivated in the complete medium containing 10 μmol/L of 5-azacytidine for 4 days, and the control group was cultivated in the complete medium for 4 days.Then carried out oxygen glucose deprivation treatment for 4 h.Detecting neuroglobin expression, DNA methyltransferase expression, cell inhibition ratio and DNA methylation level at different time points...
October 25, 2016: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/27852227/long-lasting-reduction-in-clonogenic-potential-of-colorectal-cancer-cells-by-sequential-treatments-with-5-azanucleosides-and-topoisomerase-inhibitors
#11
Alicja Pawlak, Ewa Ziolo, Anna Fiedorowicz, Klaudyna Fidyt, Leon Strzadala, Wojciech Kalas
BACKGROUND: The currently approved therapies fail in a substantial number of colorectal cancer (CRC) patients due to the molecular heterogeneity of CRC, hence new efficient drug combinations are urgently needed. Emerging data indicate that 5-azanucleosides are able to sensitize cancer cells to the standard chemotherapeutic agents and contribute to overcoming intrinsic or acquired chemoresistance. METHODS: CRC cells with different genetic backgrounds (HCT116, DLD-1, HT-29) were sequentially treated with 5-azanucleosides and topoisomerase inhibitors...
November 16, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27835920/-acute-myeloid-leukemia
#12
Jan Braess
Acute myeloid leukemia (AML) has been genetically characterized extensively and can now be subdivided into 9 to 11 pathogenetically different subtypes according to their profile of driver mutations. In clinical practice karyotyping and molecular analysis of NPM1, cEBPa and FLT3-ITD are required for treatment stratification and potentially genotype specific treatment. Some markers such as NPM1 not only offer prognostic information but can also serve as markers of minimal residual disease and thus have the potential to guide therapy in the future...
November 2016: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/27818666/comparative-analysis-of-dna-methyltransferase-gene-family-in-fungi-a-focus-on-basidiomycota
#13
Ruirui Huang, Qiangqiang Ding, Yanan Xiang, Tingting Gu, Yi Li
DNA methylation plays a crucial role in the regulation of gene expression in eukaryotes. Mushrooms belonging to the phylum Basidiomycota are highly valued for both nutritional and pharmaceutical uses. A growing number of studies have demonstrated the significance of DNA methylation in the development of plants and animals. However, our understanding of DNA methylation in mushrooms is limited. In this study, we identified and conducted comprehensive analyses on DNA methyltransferases (DNMtases) in representative species from Basidiomycota and Ascomycota, and obtained new insights into their classification and characterization in fungi...
2016: Frontiers in Plant Science
https://www.readbyqxmd.com/read/27813551/rehmannia-glutinosa-oligosaccharide-induces-differentiation-of-bone-marrow-mesenchymal-stem-cells-into-cardiomyocyte-like-cells
#14
X H Wang, H W Du, X H Guo, S W Wang, R B Zhou, Y Li, Z B Li, Y S Zhao, Q L Zhu
The aim of this study was to observe the effect of Rehmannia glutinosa oligosaccharide (RGO) on differentiation of bone marrow mesenchymal stem cells (MSCs) into cardiomyocyte-like cells . Rat MSCs were isolated, treated, and grouped as follows: RGO treatment group, 5-azacytidine (5-aza) treatment group, RGO + 5-aza treatment group, and control group. Following a four-week induction period, cardiac troponin I (cTnI) levels in MSCs were quantified by chemiluminescence, and the levels of myocardial enzymes creatine kinase (CK) and creatine kinase isoenzyme-MB (CK-MB) were measured using a dry chemistry analyzer...
October 17, 2016: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/27809774/quantitative-trait-variation-is-revealed-in-a-novel-hypomethylated-population-of-woodland-strawberry-fragaria-vesca
#15
Jihua Xu, Karen K Tanino, Kyla N Horner, Stephen J Robinson
BACKGROUND: Phenotypic variation is determined by a combination of genotype, environment and their interactions. The realization that allelic diversity can be both genetic and epigenetic allows the environmental component to be further separated. Partitioning phenotypic variation observed among inbred lines with an altered epigenome can allow the epigenetic component controlling quantitative traits to be estimated. To assess the contribution of epialleles on phenotypic variation and determine the fidelity with which epialleles are inherited, we have developed a novel hypomethylated population of strawberry (2n = 2x = 14) using 5-azacytidine from which individuals with altered phenotypes can be identified, selected and characterized...
November 4, 2016: BMC Plant Biology
https://www.readbyqxmd.com/read/27806562/purification-and-characterization-of-principle-antimutagenic-bioactive-as-ethoxy-substituted-phylloquinone-from-spinach-spinacea-oleracea-l-based-on-evaluation-in-models-including-human-lymphoblast-tk-cells
#16
Sanjeev Kumar, Suchandra Chatterjee, Jyoti Tripathi, Satyendra Gautam
During in vitro analysis, spinach (Spinacea oleracea L.) leaves extracts displayed varying antimutagenicity when analyzed in models including human lymphoblast (TK+/-) cell line (thymidine kinase gene mutation assay) and Escherichia coli MG1655 (rifampicin resistance assay) against chemical (ethyl methanesulfonate and 5-azacytidine) induced mutagenicity. Highest antimutagenicity was displayed by the quinone extract. The principle bioactive compound exhibited fluorescence in TLC at 366 nm (termed C4) resolved at Rf:0...
November 2, 2016: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/27779661/notch1-is-associated-with-the-differentiation-of-human-bone-marrow%C3%A2-derived-mesenchymal-stem-cells-to-cardiomyocytes
#17
Zipu Yu, Yu Zou, Jingya Fan, Chengchen Li, Liang Ma
Notch signaling is involved in the early process of differentiation to determine the fate of stem cells. However, the precise role of Notch in human bone marrow‑derived mesenchymal stem cells (hBMSCs) remains unclear. The present study aimed to investigate the involvement of Notch signalling during the course of hBMSC differentiation into cardiomyocytes using hBMSCs, with multilineage differentiation ability, isolated and purified from human bone marrow. Flow cytometric analysis revealed that CD29, CD44 and CD90 were highly expressed on the surface of cells in their fifth passage, whereas detection of CD34, CD45, CD54 and HLA‑DR was negative...
October 19, 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27766220/enhanced-in-vitro-anti-tumor-activity-of-5-azacytidine-by-entrapment-into-solid-lipid-nanoparticles
#18
Farhad Jahanfar, Akbar Hasani, Dariush Shanebandi, Mohammad Rahmati, Hamed Hamishehkar
Purpose: In this study the effectiveness of encapsulating of 5-azacytidine into the lipid nanoparticles was investigated and in vitro effect of encapsulated 5-azacytidine studied on MCF-7 cell lines Methods: 5-azacytidine -loaded solid lipid nanoparticles were produced by double emulsification (w/o/w) method by using stearic acid as lipid matrix, soy lecithin and poloxamer 407 as surfactant and co-surfactant respectively. Particle size, zeta potential, surface morphology, entrapment efficiency and kinetic of drug release were studied...
September 2016: Advanced Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/27745548/enzyme-driven-chemo-and-radiation-therapy-with-12-pyrimidine-nucleoside-analogs-not-yet-in-the-clinic
#19
Sheldon Greer, Tieran Han, Cristina Dieguez, Nicola McLean, Rafael Saer, Isildinha Reis, Joe Levi, Victor E Marquez
Enzymatic activity from tumor and adjacent normal tissue of 200 patients involving deoxycytidine kinase (dCK), uridine/cytidine kinase (U/CK), cytidine deaminase (CD) and deoxycytidylate deaminase (dCMPD) was quantified. . Patients with brain (17), colon (24), and breast (30) tumors, 53, 67, and 73%, respectively, had an elevated T/N value (Specific Activity of tumor/ Specific Activity of normal tissue) involving dCK and dCMPD suggesting chemo therapy with 5-fluorodeoxycytidine (5-FdC) alone or in combination with thymidine plus deoxytetrahydrouridine, or with the radiosensitizer, 5-chlorodeoxycytidine (5-CldC) plus tetrahydrouridine (H4U)...
October 13, 2016: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/27706651/promoter-methylation-and-histone-modifications-affect-the-expression-of-the-exogenous-dsred-gene-in-transgenic-goats
#20
M T Nuo, J L Yuan, W L Yang, X Y Gao, N He, H Liang, M Cang, D J Liu
Transgene silencing, which is common in transgenic plants and animals, limits the generation and application of genetically modified organisms, and is associated with the exogenous gene copy number, the methylation status of its promoters, and histone modification abnormalities. Here, we analyzed the expression of the exogenous gene DsRed and the methylation status of its cytomegalovirus (CMV) promoter in six healthy transgenic cashmere goats and transgenic nuclear donor cells. The CMV promoter exhibited high methylation levels (74...
August 29, 2016: Genetics and Molecular Research: GMR
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