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https://www.readbyqxmd.com/read/28646565/complete-molecular-remission-in-relapsed-and-refractory-acute-myeloid-leukaemia-with-mll-af9-treated-with-chidamide-based-chemotherapy
#1
Y Lun, J-J Yang, Y Wu
WHAT IS KNOWN AND OBJECTIVE: The mixed lineage leukaemia (MLL) gene translocations are found in approximately 10% of adults with acute myeloid leukaemia (AML) and are markers of poor prognosis. As the best reported response in relapsed and refractory MLL-rearranged AML is around 40%, reinduction treatment is very challenging for those patients. CASE DESCRIPTION: We report a case of relapsed and refractory AML with MLL-AF9, who did not respond to FLAG (fludarabine, cytarabine, granulocyte colony stimulating factor) regimen reinduction treatment, but achieved complete response and molecular remission after chidamide-based chemotherapy...
June 23, 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/28646552/targeting-histone-deacetylase-4-ubc9-impairs-dna-repair-for-radiosensitization-of-hepatocellular-carcinoma-cells
#2
Chiao-Ling Tsai, Wei-Lin Liu, Feng-Ming Hsu, Po-Sheng Yang, Ruoh-Fang Yen, Kai-Yuan Tzen, Ann-Lii Cheng, Pei-Jer Chen, Jason Chia-, Hsien Cheng
Several strategies to improve the efficacy of radiation therapy against hepatocellular carcinoma (HCC) have been investigated. One approach was to develop radiosensitizing compounds. Because histone deacetylase 4 (HDAC4) is highly expressed in liver cancer and known to regulate oncogenesis through chromatin structure remodeling and controlling protein access to DNA, we postulated that HDAC4 inhibition might enhance radiation's effect on HCC cells. HCC cell lines (Huh7 and PLC5) and an ectopic xenograft were pretreated with HDAC inhibitor or shRNA to knock down expression of HDAC4, and then irradiated (2...
June 23, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28646512/wmj-8-b-a-novel-hydroxamate-derivative-induces-mda-mb-231-breast-cancer-cell-death-via-shp-1-stat3-survivin-cascade
#3
Yu-Fan Chuang, Shiu-Wen Huang, Ya-Fen Hsu, Meng-Chieh Yu, George Ou, Wei-Jan Huang, Ming-Jen Hsu
BACKGROUND AND PURPOSE: Histone deacetylase (HDAC) inhibitors with broad-spectrum anti-tumor properties has been described and attracted lots of attention in the field of drug discovery. However, the underlying anti-tumor mechanisms of HDAC inhibitors remain incompletely understood. In this study, we aimed to characterize the underlying mechanisms of a novel hydroxamate-based HDAC inhibitor, WMJ-8-B, in inducing MDA-MB-231 breast cancer cell death. EXPERIMENTAL APPROACH: WMJ-8-B's effects on cell viability, cell cycle distribution, apoptosis, as well as signaling molecules modification and activation were analyzed by MTT assay, flowcytometric analysis, immunoblotting, reporter assay, ChIP analysis and siRNA strategy...
June 23, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28646124/nickel-ions-inhibit-histone-demethylase-jmjd1a-and-dna-repair-enzyme-abh2-by-replacing-the-ferrous-iron-in-the-catalytic-centers
#4
Haobin Chen, Nitai Charan Giri, Ronghe Zhang, Kenichi Yamane, Yi Zhang, Michael Maroney, Max Costa
No abstract text is available yet for this article.
June 23, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28645917/multivalent-binding-of-pwwp2a-to-h2a-z-regulates-mitosis-and-neural-crest-differentiation
#5
Sebastian Pünzeler, Stephanie Link, Gabriele Wagner, Eva C Keilhauer, Nina Kronbeck, Ramona Mm Spitzer, Susanne Leidescher, Yolanda Markaki, Edith Mentele, Catherine Regnard, Katrin Schneider, Daisuke Takahashi, Masayuki Kusakabe, Chiara Vardabasso, Lisa M Zink, Tobias Straub, Emily Bernstein, Masahiko Harata, Heinrich Leonhardt, Matthias Mann, Ralph Aw Rupp, Sandra B Hake
Replacement of canonical histones with specialized histone variants promotes altering of chromatin structure and function. The essential histone variant H2A.Z affects various DNA-based processes via poorly understood mechanisms. Here, we determine the comprehensive interactome of H2A.Z and identify PWWP2A as a novel H2A.Z-nucleosome binder. PWWP2A is a functionally uncharacterized, vertebrate-specific protein that binds very tightly to chromatin through a concerted multivalent binding mode. Two internal protein regions mediate H2A...
June 23, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28645871/aflatoxin-b1-induced-epigenetic-alterations-an-overview
#6
Yaqi Dai, Kunlun Huang, Boyang Zhang, Liye Zhu, Wentao Xu
Aflatoxin B1 (AFB1) is widely distributed in nature, especially in a variety of food commodities. It is confirmed to be the most toxic of all the aflatoxins. The toxicity of AFB1 has been well investigated, and it may result in severe health problems including carcinogenesis, mutagenesis, growth retardation, and immune suppression. Epigenetic modifications including DNA methylation, histone modifications and regulation of non-coding RNA play an important role in AFB1-induced disease and carcinogenesis. To better understand the evidence for AFB1-induced epigenetic alterations and the potential mechanisms of the toxicity of AFB1, we conducted a review of published studies of AFB1-induced epigenetic alterations...
June 20, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28645654/epigenome-dysregulation-in-cholangiocarcinoma
#7
REVIEW
Colm J O'Rourke, Patricia Munoz-Garrido, Esmeralda L Aguayo, Jesper B Andersen
Epigenomics is a fast-evolving field of research that has lately attracted considerable interest, mainly due to the reversibility of epigenetic marks. Clinically, among solid tumors, the field is still limited. In cholangiocarcinoma (CCA) it is well known that the epigenetic landscape is deregulated both during carcinogenesis and disease progression as a consequence of aberrant mechanisms leading to genome instability. In this article, we will briefly review the molecular alterations that have been described in the transformation of normal cholangiocytes into malignant derivatives, focusing on the role of non-coding RNA (ncRNA) interactions, DNA methylation, post-translational modifications (PTMs) of histones and chromatin remodeling complexes...
June 20, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28645561/boris-up-regulates-oct4-via-histone-methylation-to-promote-cancer-stem-cell-like-properties-in-human-liver-cancer-cells
#8
Qiuying Liu, Kefei Chen, Zhongjian Liu, Yuan Huang, Rongce Zhao, Ling Wei, Xiaoqin Yu, Jingyang He, Jun Liu, Jianguo Qi, Yang Qin, Bo Li
Accumulating evidence has revealed the importance of cancer stem cells (CSCs) in chemoresistance and recurrence. BORIS, a testes-specific CTCF paralog, has been shown to be associated with stemness traits of embryonic cancer cells and epithelial CSCs. We previously reported that BORIS is correlated with the expression of the CSC marker CD90 in hepatocellular carcinoma (HCC). These results encourage us to wonder whether BORIS exerts functions on CSC-like traits of human liver cancer cells. Here, we report that BORIS was enriched in HCC tissues...
June 20, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28644986/designing-novel-inhibitors-against-histone-acetyltransferase-hat-%C3%A2-gcn5-of-plasmodium-falciparum
#9
Amarjeet Kumar, Krishanu Bhowmick, Kunwar Somesh Vikramdeo, Neelima Mondal, Naidu Subbarao, Suman Kumar Dhar
During active proliferation phase of intra-erythrocytic cycle, the genome of P. falciparum is regulated epigenetically and evolutionary conserved parasite-specific histone proteins are extensively acetylated. The reversible process of lysine acetylation, causing transcriptional activation and its deacetylation, causing transcriptional repression is regulated by balanced activities of HATs and HDACs. They are also known to regulate antigenic variations and gametocytic conversion in P. falciparum. These histone modifying enzymes have been identified as potential targets for development of anitmalarials in literature...
June 10, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28644958/translating-cancer-epigenomics-into-the-clinic-focus-on-lung-cancer
#10
REVIEW
Josep Mari-Alexandre, Angel Diaz-Lagares, Maria Villalba, Oscar Juan, Ana B Crujeiras, Alfonso Calvo, Juan Sandoval
Epigenetic deregulation is increasingly being recognized as a hallmark of cancer. Recent studies have identified many new epigenetic biomarkers, some of which are being introduced into clinical practice for diagnosis, molecular classification, prognosis or prediction of response to therapies. O-6-methylguanine-DNA methyltransferase gene is the most clinically advanced epigenetic biomarker as it predicts the response to temozolomide and carmustine in gliomas. Therefore, epigenomics may represent a novel and promising tool for precision medicine, and in particular, the detection of epigenomic biomarkers in liquid biopsies will be of great interest for monitoring diseases in patients...
June 2, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28644902/sirt6-alters-adult-hippocampal-neurogenesis
#11
Eitan Okun, Daniel Marton, Daniel Cohen, Kathleen Griffioen, Yariv Kanfi, Tomer Illouz, Ravit Madar, Haim Y Cohen
Sirtuins are pleiotropic NAD+ dependent histone deacetylases involved in metabolism, DNA damage repair, inflammation and stress resistance. SIRT6, a member of the sirtuin family, regulates the process of normal aging and increases the lifespan of male mice over-expressing Sirt6 by 15%. Neurogenesis, the formation of new neurons within the hippocampus of adult mammals, involves several complex stages including stem cell proliferation, differentiation, migration and network integration. During aging, the number of newly generated neurons continuously declines, and this is correlated with a decline in neuronal plasticity and cognitive behavior...
2017: PloS One
https://www.readbyqxmd.com/read/28644763/methyltransferase-g9a-regulates-osteogenesis-via-twist-gene-repression
#12
N Higashihori, B Lehnertz, A Sampaio, T M Underhill, F Rossi, J M Richman
Here we investigate the role of epigenetic factors in controlling the timing of cranial neural crest cell differentiation. The gene coding for histone H3 lysine 9 methyltransferase G9A was conditionally deleted in neural crest cells with Wnt1-Cre. The majority of homozygous-null animals survived to birth but thereafter failed to thrive. Phenotypic analysis of postnatal animals revealed that the mutants displayed incomplete ossification and 20% shorter jaws as compared to their wild-type littermates. At E13...
June 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28644004/the-intricate-effects-of-alpha-amino-and-lysine-modifications-on-arginine-methylation-on-the-n-terminal-tail-of-histone-h4
#13
Melody D Fulton, Jing Zhang, Maomao He, Meng-Chiao Ho, Y George Zheng
Chemical modifications on the DNA and nucleosomal histones tightly control the gene transcription program in eukaryotic cells. The "histone code" hypothesis proposes that the frequency, combination, and location of post-translational modifications (PTMs) on the core histones compose a complex network of epigenetic regulation. Currently, there are at least 23 different types and over 450 histone PTMs discovered, and the PTMs on lysine and arginine residues account for a crucial part of the histone code. Although significant progress has been achieved in recent years, the molecular basis for the histone code is far from being fully understood...
June 23, 2017: Biochemistry
https://www.readbyqxmd.com/read/28643239/serum-histones-as-biomarkers-of-the-severity-of-heatstroke-in-dogs
#14
Yaron Bruchim, Isaac Ginsburg, Gilad Segev, Ahmad Mreisat, Yochai Avital, Itamar Aroch, Michal Horowitz
Heatstroke is associated with systemic inflammatory response syndrome, leading to multiple organ dysfunction and death. Currently, there is no specific treatment decreasing hyperthermia-induced inflammatory/hemostatic derangements. Emerging studies indicate that histones leaking from damaged cells into the extracellular space are toxic, pro-inflammatory, and pro-thrombotic. We therefore hypothesize that serum histones (sHs) are elevated during heatstroke and are associated with the severity of the disease. Sixteen dogs with heatstroke and seven healthy controls were included in the study...
June 22, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/28643114/synergistic-cardioprotective-effects-of-raav9-cyclina2-combined-with-fibrin-glue-in-rats-after-myocardial-infarction
#15
Wen Cao, Ya-Fei Chang, Ai-Chao Zhao, Bang-Dang Chen, Fen Liu, Yi-Tong Ma, Xiang Ma
The present study aimed to investigate the protective effects of rAAV9-CyclinA2 combined with fibrin glue (FG) in vivo in rats after myocardial infarction (MI). Ninety male Sprague-Dawley rats were randomized into 6 groups (15 in each group): sham, MI, rAAV9-green fluorescent protein (GFP) + MI, rAAV9-CyclinA2 + MI, FG + MI, and rAAV9-CyclinA2 + FG + MI. Packed virus (5 × 10(11)vg/ml) in 150 µl of normal saline or FG was injected into the infarcted myocardium at five locations in rAAV9-GFP + MI, rAAV9-CyclinA2 + MI, and rAAV9-CyclinA2 + FG + MI groups...
June 22, 2017: Journal of Molecular Histology
https://www.readbyqxmd.com/read/28642803/transcriptomic-profiles-of-aging-in-na%C3%A3-ve-and-memory-cd4-cells-from-mice
#16
Jackson Taylor, Lindsay Reynolds, Li Hou, Kurt Lohman, Wei Cui, Stephen Kritchevsky, Charles McCall, Yongmei Liu
BACKGROUND: CD4+ T cells can be broadly divided into naïve and memory subsets, each of which are differentially impaired by the aging process. It is unclear if and how these differences are reflected at the transcriptomic level. We performed microarray profiling on RNA derived from naïve (CD44(low)) and memory (CD44(high)) CD4+ T cells derived from young (2-3 month) and old (28 month) mice, in order to better understand the mechanisms of age-related functional alterations in both subsets...
2017: Immunity & Ageing: I & A
https://www.readbyqxmd.com/read/28642769/histone-acetylation-modifications-affect-tissue-dependent-expression-of-poplar-homologs-of-c4-photosynthetic-enzyme-genes
#17
Yuan Li, Xiu-Mei Dong, Feng Jin, Zhuo Shen, Qing Chao, Bai-Chen Wang
Histone modifications play important roles in regulating the expression of C4 photosynthetic genes. Given that all enzymes required for the C4 photosynthesis pathway are present in C3 plants, it has been hypothesized that this expression regulatory mechanism has been conserved. However, the relationship between histone modification and the expression of homologs of C4 photosynthetic enzyme genes has not been well determined in C3 plants. In the present study, we cloned nine hybrid poplar (Populus simonii × Populus nigra) homologs of maize (Zea mays) C4 photosynthetic enzyme genes, carbonic anhydrase (CA), pyruvate orthophosphate dikinase (PPDK), phosphoenolpyruvate carboxykinase (PCK), and phosphoenolpyruvate carboxylase (PEPC), and investigated the correlation between the expression levels of these genes and the levels of promoter histone acetylation modifications in four vegetative tissues...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28642444/upregulation-of-cd11b-and-cd86-through-lsd1-inhibition-promotes-myeloid-differentiation-and-suppresses-cell-proliferation-in-human-monocytic-leukemia-cells
#18
Jianwu Fang, Haiyan Ying, Ting Mao, Yanjia Fang, Yuan Lu, He Wang, Irene Zang, Zhaofu Wang, Ying Lin, Mengxi Zhao, Xiao Luo, Zongyao Wang, Yan Zhang, Chao Zhang, Wei Xiao, Yan Wang, Wei Tan, Zhui Chen, Chris Lu, Peter Atadja, En Li, Kehao Zhao, Jianfeng Liu, Justin Gu
LSD1 (Lysine Specific Demethylase1)/KDM1A (Lysine Demethylase 1A), a flavin adenine dinucleotide (FAD)-dependent histone H3K4/K9 demethylase, sustains oncogenic potential of leukemia stem cells in primary human leukemia cells. However, the pro-differentiation and anti-proliferation effects of LSD1 inhibition in acute myeloid leukemia (AML) are not yet fully understood. Here, we report that small hairpin RNA (shRNA) mediated LSD1 inhibition causes a remarkable transcriptional activation of myeloid lineage marker genes (CD11b/ITGAM and CD86), reduction of cell proliferation and decrease of clonogenic ability of human AML cells...
June 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28642327/declining-histone-acetyltransferase-gcn5-represses-bmsc-mediated-angiogenesis-during-osteoporosis
#19
Huan Jing, Li Liao, Xiaoxia Su, Yi Shuai, Xinjing Zhang, Zhihong Deng, Yan Jin
Angiogenesis is disrupted in age-related and postmenopausal osteoporosis. However, the mechanisms of the disorder remain elusive. We confirmed in this study that, in accordance with the decrease of H-type vessels, the proangiogenic potential of bone marrow-derived mesenchymal stem cells (BMSCs) declined during osteoporosis. Screening of the histone acetyltransferase family revealed that GCN5 decreased in BMSCs derived from osteoporotic femur. Further analysis identified that GCN5 plays important roles in regulating the proangiogenic potential of BMSCs...
June 22, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28641467/green-tea-polyphenol-egcg-causes-anti-cancerous-epigenetic-modulations-in-acute-promyelocytic-leukemia-cells
#20
Veronika Borutinskaitė, Aida Virkšaitė, Giedrė Gudelytė, Rūta Navakauskienė
Green tea (Camellia sinensis) catechin epigallocatechin-3-gallate (EGCG) has been shown to possess diverse anti-cancerous properties. We demonstrated EGCG ability to inhibit acute promyelocytic leukemia (APL) cell proliferation and cause apoptosis. In addition, quantitative real-time polymerase chain reaction (RT-qPCR) analysis revealed elevated expression of genes associated with cell cycle arrest and differentiation (p27, PCAF, C/EBPα, and C/EBPɛ). Furthermore, EGCG caused anti-cancerous epigenetic changes: downregulation of epigenetic modifiers DNMT1, HDAC1, HDAC2, and G9a was observed by RT-qPCR analysis...
June 22, 2017: Leukemia & Lymphoma
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