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https://www.readbyqxmd.com/read/29227276/alteration-in-the-cytokine-secretion-pattern-in-t-cells-of-patients-with-cystic-fibrosis-caused-by-dna-methyltransferase-inhibitor-5-azacitidine
#1
E Kvaratskhelia, N Dabrundashvili, M Gagua, E Maisuradze, M Kamkamidze, E Abzianidze
Cystic fibrosis (CF) is the autosomal-recessive disorder caused by mutation in the cystic fibrosis transmembrane conductance regulator gene (CFTR). The Airway inflammation plays a central role in the progression of CF disease. Cystic fibrosis characterized by the overproduction of the pro-inflammatory cytokines and reduced expression of anti-inflammatory cytokines. Although the mechanisms of abnormal cytokine expression is still poorly understood, altered epigenetic regulations in T cells might contribute. In the present study we examined the expression of IFN-γ and IL-10 by CF T cells prior to and following 5-azaC treatment...
November 2017: Georgian Medical News
https://www.readbyqxmd.com/read/29225771/methylation-mediated-gadd45%C3%AE-enhanced-the-chemosensitivity-of-hepatocellular-carcinoma-by-inhibiting-the-stemness-of-liver-cancer-cells
#2
Xiao-Juan Hou, Qiu-Dong Zhao, Ying-Ying Jing, Zhi-Peng Han, Xue Yang, Li-Xin Wei, Yu-Ting Zheng, Feng Xie, Bai-He Zhang
Background: Defects of the growth arrest DNA damage-inducible gene 45β (Gadd45β) play an important role in the progression of tumor and confer resistance to chemotherapy. However, the role of Gadd45β in the apoptosis of hepatocellular carcinoma is still not clear. Purpose of this study was to explore the effect of Gadd45β on the apoptosis of liver cancer cells, and the possible mechanism was examined. Result: In this study, we first confirmed the decreased expression of Gadd45β in human liver cancer tissues and human liver cancer cell lines, when compared to the peri-tumor liver tissue and normal liver cells...
2017: Cell & Bioscience
https://www.readbyqxmd.com/read/29222813/reln-signaling-modulates-glioblastoma-growth-and-substrate-dependent-migration
#3
Markus Schulze, Christ Violonchi, Stefan Swoboda, Tobias Welz, Eugen Kerkhoff, Sabine Hoja, Susanne Brüggemann, Johann Simbürger, Jörg Reinders, Markus J Riemenschneider
Glioblastoma (GBM) represents the most common and most malignant type of primary brain tumor and significantly contributes to cancer morbidity and mortality. Invasion into the healthy brain parenchyma is a major feature of glioblastoma aggressiveness. Reelin (RELN) is a large secreted extracellular matrix glycoprotein that regulates neuronal migration and positioning in the developing brain and sustains functionality in the adult brain. We here show that both RELN and its main downstream effector DAB1 are silenced in glioblastoma as compared to non-neoplastic tissue and mRNA expression is inversely correlated with malignancy grade...
December 8, 2017: Brain Pathology
https://www.readbyqxmd.com/read/29214328/5-azacytidine-treatment-and-tapbf-d-over-expression-increases-glutenin-accumulation-within-the-wheat-grain-by-hypomethylating-the-glu-1-promoters
#4
Jiantang Zhu, Linlin Fang, Jiaqi Yu, Ying Zhao, Fanguo Chen, Guangmin Xia
5-azaC treatment and TaPBF - D over-expression decrease C-methylation status of three Glu - 1 gene promoters, and aid in enhancing the expression of the Glu - 1 genes. The wheat glutenins exert a strong influence over dough elasticity, but the regulation of their encoding genes has not been firmly established. Following treatment with 5-azacytidine (5-azaC), both the weight and glutenin content of the developing and mature grains were significantly increased. The abundance of transcript produced by the Glu-1 genes (encoding high-molecular-weight glutenin subunits), as well as those encoding demethylases and transcriptional factors associated with prolamin synthesis was higher than in grain of non-treated plants...
December 6, 2017: TAG. Theoretical and Applied Genetics. Theoretische und Angewandte Genetik
https://www.readbyqxmd.com/read/29208426/5-azacytidine-engages-an-ire1%C3%AE-egfr-erk1-2-signaling-pathway-that-stabilizes-the-ldl-receptor-mrna
#5
Nourhen Mnasri, Maya Mamarbachi, Bruce G Allen, Gaétan Mayer
Hepatic low-density lipoprotein receptor (LDLR) is the primary conduit for the clearance of plasma LDL-cholesterol and increasing its expression represents a central goal for treating cardiovascular disease. However, LDLR mRNA is unstable and undergoes rapid turnover mainly due to the three AU-rich elements (ARE) in its proximal 3'-untranslated region (3'-UTR). Herein, our data revealed that 5-azacytidine (5-AzaC), an antimetabolite used in the treatment of myelodysplastic syndrome, stabilizes the LDLR mRNA through a previously unrecognized signaling pathway resulting in a strong increase of its protein level in human hepatocytes in culture...
December 2, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29203668/epigenetic-therapy-activates-type-i-interferon-signaling-in-murine-ovarian-cancer-to-reduce-immunosuppression-and-tumor-burden
#6
Meredith L Stone, Katherine B Chiappinelli, Huili Li, Lauren M Murphy, Meghan E Travers, Michael J Topper, Dimitrios Mathios, Michael Lim, Ie-Ming Shih, Tian-Li Wang, Chien-Fu Hung, Vipul Bhargava, Karla R Wiehagen, Glenn S Cowley, Kurtis E Bachman, Reiner Strick, Pamela L Strissel, Stephen B Baylin, Cynthia A Zahnow
Ovarian cancer is the most lethal of all gynecological cancers, and there is an urgent unmet need to develop new therapies. Epithelial ovarian cancer (EOC) is characterized by an immune suppressive microenvironment, and response of ovarian cancers to immune therapies has thus far been disappointing. We now find, in a mouse model of EOC, that clinically relevant doses of DNA methyltransferase and histone deacetylase inhibitors (DNMTi and HDACi, respectively) reduce the immune suppressive microenvironment through type I IFN signaling and improve response to immune checkpoint therapy...
December 4, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29190771/synergistic-role-of-5-azacytidine-and-ascorbic-acid-in-directing-cardiosphere-derived-cells-to-cardiomyocytes-in-vitro-by-downregulating-wnt-signaling-pathway-via-phosphorylation-of-%C3%AE-catenin
#7
Reddy Sailaja Mundre, Pavani Koka, Prakash Dhanaraj, Nitin Khatri, Sanjana Vig, Yamini Chandramohan, Anuradha Dhanasekaran
BACKGROUND: Cardiosphere derived cells (CDCs) represent a valuable source in stem cell based therapy for cardiovascular diseases, yet poor differentiation rate hinders the transplantation efficiency. The aim of this study is to check the ability of 5-Azacytidine (Aza) alone and in combination with ascorbic acid (Aza+AA) in delineating CDCs to cardiomyogenesis and the underlying Wnt signaling mechanism in induced differentiation. METHODS: CDCs were treated with Aza and Aza+AA for a period of 14 days to examine the expression of cardiac specific markers and Wnt downstream regulators by immunofluorescence, real time PCR and western blot...
2017: PloS One
https://www.readbyqxmd.com/read/29181164/recent-findings-on-epigenetic-gene-abnormalities-involved-in-uterine-cancer
#8
Megumi Yanokura, Kouji Banno, Yusuke Kobayashi, Hiroyuki Nomura, Shigenori Hayashi, Eiichiro Tominaga, Daisuke Aoki
Selective aberrant genetic effects that do not depend on abnormal DNA sequences are referred to as epigenetic abnormalities and are involved in carcinogenesis. In uterine cancer, various genes involved in apoptosis, cell cycle, DNA repair, cell proliferation and cell adhesion are abnormally methylated, resulting in gene silencing. Reversal of such epigenetic abnormalities in cancer cells is a potential strategy for cancer therapy, and studies on epigenetic abnormalities and treatment methods in uterine cancer are in progress...
November 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/29181143/myeloid-neoplasms-with-isolated-isochromosome-17q-a-yet-to-be-defined-entity
#9
Eleftheria Lamprianidou, Chryssoula Kordella, Menelaos Papoutselis, Zoi Bezyrgiannidou, Evangelia Nakou, Spyros Papamichos, Emmanouil Spanoudakis, Andreas Giannopoulos, Katerina Zoi, Ioannis Kotsianidis
Myeloid neoplasms with isolated isochromosome 17q [MN i(17q)] has been described as a distinct entity with poor prognosis. However, literature reports show a considerable clinical and molecular heterogeneity. We describe a 58-year-old male patient who was diagnosed as refractory anemia with multilineage dysplasia and ringed sideroblasts with isolated i(17q). Though he initially responded well to erythropoietin, he gradually progressed to an aggressive form of MDS/MPN refractory to azacytidine and died 29 months after the first diagnosis...
2017: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/29181058/value-of-cnrip1-promoter-methylation-in-colorectal-cancer-screening-and-prognosis-assessment-and-its-influence-on-the-activity-of-cancer-cells
#10
Ting Zhang, Ge Cui, Yun-Liang Yao, Qi-Chun Wang, Hong-Guang Gu, Xi-Ning Li, Hui Zhang, Wen-Ming Feng, Qi-Lin Shi, Weiwei Cui
Introduction: The aim of the study was to investigate the effect of CNRIP1 promoter methylation on the proliferative, invasive and migration potential of colorectal cancer cells, including its potential use for the early detection and prognostic assessment of colorectal cancer. Material and methods: Quantitative methylation-specific PCR (qMSP) was used to detect the methylation status of the CNRIP1 promoter region in peripheral blood samples drawn from patients with colorectal adenocarcinoma, benign colorectal adenoma, and matched healthy controls...
October 2017: Archives of Medical Science: AMS
https://www.readbyqxmd.com/read/29179634/azacytidine-in-combination-with-tyrosine-kinase-inhibitors-induced-durable-responses-in-patients-with-advanced-phase-chronic-myelogenous-leukemia
#11
Mathilde Ruggiu, Florence Oberkampf, David Ghez, Pascale Cony-Makhoul, Florence Beckeriche, Isabelle Cano, Anne L Taksin, Omar Benbrahim, Stéphanie Ghez, Hassan Farhat, Sophie Rigaudeau, Noémie de Gunzburg, Diane Lara, Christine Terre, Victoria Raggueneau, Isabel Garcia, Marc Spentchian, Stéphane De Botton, Philippe Rousselot
Although the tyrosine kinase inhibitor (TKI) era has brought great improvement in outcome in chronic myelogenous leukemia (CML), prognosis of accelerated phase or myeloid blast crisis patients or of de novo Philadelphia chromosome-positive acute myeloid leukemia remains poor. We conducted a retrospective study on patients with advanced phase disease treated with a TKI and azacytidine. Sixteen patients were eligible. Median age was 64.9 years, the median number of previous therapies was 2.5 lines, and median follow-up was 23...
November 28, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29179587/in-vitro-differentiation-of-progenitor-cells-isolated-from-juvenile-pig-hearts-expression-of-relevant-gene-and-protein-markers
#12
Simon Limbrecht Mogensen, Martin Krøyer Rasmussen, Niels Oksbjerg, Jette Feveile Young, Jens Rolighed Larsen
OBJECTIVES: Heart failure is a significant cause of mortality worldwide, and most current therapies treat only its symptoms. The results of cardiac stem cell research suggest a promising treatment option for heart failure, but there is currently an unmet demand for better research models. We have therefore, for the first time, isolated, expanded and differentiated progenitor cells obtained from juvenile pig hearts to use as a platform for cardiac stem cell research. DESIGN: Progenitor cells were isolated from the left ventricles of porcine hearts using collagenase enzymatic digestion and Percoll®-gradient centrifugation...
November 27, 2017: Scandinavian Cardiovascular Journal: SCJ
https://www.readbyqxmd.com/read/29167115/epigenetic-modulation-of-intestinal-na-h-exchanger-3-expression
#13
Anoop Kumar, Pooja Malhotra, Hayley P Coffing, Shubha Priyamvada, Arivarasu Natarajan Anbazhagan, Harish R Krishnan, Ravinder K Gill, Waddah A Alrefai, David P Gavin, Subhash C Pandey, Pradeep K Dudeja, Seema Saksena
Na(+)/H(+) exchanger-3 (NHE3) is crucial for intestinal Na+ absorption and its reduction has been implicated in infectious and Inflammatory Bowel Diseases (IBD)-associated diarrhea. Epigenetic mechanisms such as DNA methylation are involved in the pathophysiology of IBD. Whether changes in DNA methylation are involved in modulating intestinal NHE3 gene expression is not known. Caco-2 and HUTU-80 cells were used as models of human intestinal epithelial cells (IECs). Normal C57/BL6, wild type or GADD45b KO mice were used as in vivo models...
November 22, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29158523/treatment-of-myocardial-infarction-with-gene-modified-mesenchymal-stem-cells-in-a-small-molecular-hydrogel
#14
Zhiye Wu, Guoqin Chen, Jianwu Zhang, Yongquan Hua, Jinliang Li, Bei Liu, Anqing Huang, Hekai Li, Minsheng Chen, Caiwen Ou
The effect of transplanted rat mesenchymal stem cells (MSCs) can be reduced by extracellular microenvironment in myocardial infarction (MI). We tested a novel small-molecular hydrogel (SMH) on whether it could provide a scaffold for hepatocyte growth factor (HGF)-modified MSCs and alleviate ventricular remodeling while preserving cardiac function after MI. Overexpression of HGF in MSCs increased Bcl-2 and reduced Bax and caspase-3 levels in response to hypoxia in vitro. Immunocytochemistry demonstrated that cardiac troponin (cTnT), desmin and connexin 43 expression were significantly enhanced in the 5-azacytidine (5-aza) with SMH group compared with the 5-aza only group in vitro and in vivo...
November 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29157092/single-agent-and-synergistic-combinatorial-efficacy-of-first-in-class-small-molecule-imipridone-onc201-in-hematological-malignancies
#15
Varun V Prabhu, Mala K Talekar, Amriti R Lulla, C Leah B Kline, Lanlan Zhou, Junior Hall, A Pieter J Van den Heuvel, David T Dicker, Jawad Babar, Stephan A Grupp, Mathew J Garnett, Ultan McDermott, Cyril H Benes, Jeffrey J Pu, David F Claxton, Nadia Khan, Wolfgang Oster, Joshua E Allen, Wafik S El-Deiry
ONC201, founding member of the imipridone class of small molecules, is currently being evaluated in advancer cancer clinical trials. We explored single agent and combinatorial efficacy of ONC201 in preclinical models of hematological malignancies. ONC201 demonstrated (GI50 1-8 µM) dose- and time-dependent efficacy in acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML), chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), Burkitt's lymphoma, anaplastic large cell lymphoma (ALCL), cutaneous T-cell lymphoma (CTCL), Hodgkin's lymphoma (nodular sclerosis) and multiple myeloma (MM) cell lines including cells resistant to standard of care (dexamethasone in MM) and primary samples...
November 20, 2017: Cell Cycle
https://www.readbyqxmd.com/read/29146735/reduced-dnmt3a-increases-gdf5-expression-with-suppressed-satellite-cell-differentiation-and-impaired-skeletal-muscle-regeneration
#16
Yukino Hatazawa, Yusuke Ono, Yuma Hirose, Sayaka Kanai, Nobuharu L Fujii, Shuichi Machida, Ichizo Nishino, Takahiko Shimizu, Masaki Okano, Yasutomi Kamei, Yoshihiro Ogawa
DNA methylation is an epigenetic mechanism regulating gene expression. In this study, we observed that DNA methyltransferase 3a (Dnmt3a) expression is decreased after muscle atrophy. We made skeletal muscle-specific Dnmt3a knockout mice (Dnmt3a-KO mice). The regeneration capacity after muscle injury was markedly decreased in Dnmt3a-KO mice. Diminished mRNA and protein expression of Dnmt3a were observed in skeletal muscles as well as in satellite cells, which are important for muscle regeneration, in Dnmt3a-KO mice...
November 16, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29134664/a-phase-ii-trial-of-ruxolitinib-in-combination-with-azacytidine-in-myelodysplastic-syndrome-myeloproliferative-neoplasms
#17
Rita Assi, Hagop M Kantarjian, Guillermo Garcia-Manero, Jorge E Cortes, Naveen Pemmaraju, Xuemei Wang, Graciela Nogueras-Gonzalez, Elias Jabbour, Prithviraj Bose, Tapan Kadia, Courtney D Dinardo, Keyur Patel, Carlos Bueso-Ramos, Lingsha Zhou, Sherry Pierce, Romany Gergis, Carla Tuttle, Gautam Borthakur, Zeev Estrov, Rajyalakshmi Luthra, Juliana Hidalgo-Lopez, Srdan Verstovsek, Naval Daver
Ruxolitinib and azacytidine target distinct disease manifestations of myelodysplastic syndrome/myeloproliferative neoplasms (MDS/MPNs). Patients with MDS/MPNs initially received ruxolitinib BID (doses based on platelets count), continuously in 28-day cycles for the first 3 cycles. Azacytidine 25 mg/m(2) (Day 1-5) intravenously or subcutaneously was recommended to be added to each cycle starting cycle 4 and could be increased to 75 mg/m(2) (Days 1-5) for disease control. Azacytidine could be started earlier than cycle 4 and/or at higher dose in patients with rapidly proliferative disease or with elevated blasts...
November 14, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/29130642/dual-inhibition-of-dnmts-and-ezh2-can-overcome-both-intrinsic-and-acquired-resistance-of-myeloma-cells-to-imids-in-a-cereblon-independent-manner
#18
Konstantinos Dimopoulos, Alexandra Søgaard Helbo, Helga Fibiger Munch-Petersen, Lene Sjö, Jesper Christensen, Lasse Sommer Kristensen, Fazila Asmar, Emil Hermansen, Casey O'Connel, Peter Gimsing, Gangning Liang, Kirsten Grønbaek
Thalidomide and its derivatives, lenalidomide and pomalidomide (also known as IMiDs), have significantly changed the treatment landscape of multiple myeloma, and the recent discovery of cereblon (CRBN) as their direct biological target has led to a deeper understanding of their complex mechanism of action. In an effort to comprehend the precise mechanisms behind the development of IMiD resistance and examine whether it is potentially reversible, we established lenalidomide- (-LR) and pomalidomide-resistant (-PR) human myeloma cell lines from two IMiD-sensitive cell lines, OPM2 and NCI-H929, by continuous culture in the presence of lenalidomide or pomalidomide for 4-6 months, until acquirement of stable resistance...
November 11, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/29129488/dna-hypomethylating-agents-as-epigenetic-therapy-before-and-after-allogeneic-hematopoietic-stem-cell-transplantation-in-myelodysplastic-syndromes-and-juvenile-myelomonocytic-leukemia
#19
REVIEW
Christian Flotho, Sebastian Sommer, Michael Lübbert
Myelodysplastic syndrome (MDS) is a clonal bone marrow disorder, typically of older adults, which is characterized by ineffective hematopoiesis, peripheral blood cytopenias and risk of progression to acute myeloid leukemia. Juvenile myelomonocytic leukemia (JMML) is an aggressive myeloproliferative neoplasm occurring in young children. The common denominator of these malignant myeloid disorders is the limited benefit of conventional chemotherapy and a particular responsiveness to epigenetic therapy with the DNA-hypomethylating agents 5-azacytidine (azacitidine) or decitabine...
November 9, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29067487/epigenetic-modifications-of-the-zfp-znf423-gene-control-murine-adipogenic-commitment-and-are-dysregulated-in-human-hypertrophic-obesity
#20
Michele Longo, Gregory A Raciti, Federica Zatterale, Luca Parrillo, Antonella Desiderio, Rosa Spinelli, Ann Hammarstedt, Shahram Hedjazifar, Jenny M Hoffmann, Cecilia Nigro, Paola Mirra, Francesca Fiory, Pietro Formisano, Claudia Miele, Ulf Smith, Francesco Beguinot
AIMS/HYPOTHESIS: Subcutaneous adipocyte hypertrophy is associated with insulin resistance and increased risk of type 2 diabetes, and predicts its future development independent of obesity. In humans, subcutaneous adipose tissue hypertrophy is a consequence of impaired adipocyte precursor cell recruitment into the adipogenic pathway rather than a lack of precursor cells. The zinc finger transcription factor known as zinc finger protein (ZFP) 423 has been identified as a major determinant of pre-adipocyte commitment and maintained white adipose cell function...
October 24, 2017: Diabetologia
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