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histone deacetylase T cells

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https://www.readbyqxmd.com/read/28419965/chidamide-in-flt3-itd-positive-acute-myeloid-leukemia-and-the-synergistic-effect-in-combination-with-cytarabine
#1
Xia Li, Xiao Yan, Wenjian Guo, Xin Huang, Jiansong Huang, Mengxia Yu, Zhixin Ma, Yu Xu, ShuJuan Huang, Chenying Li, Yile Zhou, Jie Jin
Chidamide, a novel histone deacetylase inhibitor (HDACi), has been approved for treatment of T-cell lymphomas in multiple clinical trials. It has been demonstrated that chidamide can inhibit cell cycle, promote apoptosis and induce differentiation in leukemia cells, whereas its effect on acute myeloid leukemia (AML) patients with FLT3-ITD mutation has not been clarified. In this study, we found that chidamide specifically induced G0/G1 arrest and apoptosis in FLT3-ITD positive AML cells in a concentration and time-dependent manner...
April 15, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28414308/complex-regulation-of-lcor-signaling-in-breast-cancer-cells
#2
S Jalaguier, C Teyssier, T Nait Achour, A Lucas, S Bonnet, C Rodriguez, N Elarouci, M Lapierre, V Cavaillès
Ligand-dependent corepressor (LCoR) is a transcriptional repressor of ligand-activated estrogen receptors (ERs) and other transcription factors that acts both by recruiting histone deacetylases and C-terminal binding proteins. Here, we first studied LCOR gene expression in breast cancer cell lines and tissues. We detected two mRNAs variants, LCoR and LCoR2 (which encodes a truncated LCoR protein). Their expression was highly correlated and localized in discrete nuclear foci. LCoR and LCoR2 strongly repressed transcription, inhibited estrogen-induced target gene expression and decreased breast cancer cell proliferation...
April 17, 2017: Oncogene
https://www.readbyqxmd.com/read/28413671/paraneoplastic-limbic-encephalitis-in-a-patient-with-extensive-disease-small-cell-lung-cancer
#3
Sebastian Ochenduszko, Bartosz Wilk, Joanna Dabrowska, Izabela Herman-Sucharska, Anna Dubis, Miroslawa Puskulluoglu
Paraneoplastic limbic encephalitis (PLE) is a rare disorder infrequently accompanying malignancy, coexisting in ~50% of the cases with small-cell lung cancer (SCLC). The pathomechanism of PLE is considered to be immune-mediated, with production of specific anti-Hu antibodies and activation of T-cells directed against onconeural antigens present on both tumor cells and neurons. We herein report the case of a 50-year-old male patient who, prior to being diagnosed with SCLC, presented with typical symptoms of PLE (seizures, subacute cognitive dysfunction with severe memory impairment, anxiety and hallucinations)...
April 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28408401/synergistic-immunostimulatory-effects-and-therapeutic-benefit-of-combined-histone-deacetylase-and-bromodomain-inhibition-in-non-small-cell-lung-cancer
#4
Dennis Adeegbe, Yan Liu, Patrick H Lizotte, Yusuke Kamihara, Amir R Aref, Christina Almonte, Ruben Dries, Yuyang Li, Shengwu Liu, Xiaoen Wang, Tiquella Warner-Hatten, Jessica Castrillon, Guo-Cheng Yuan, Neermala Poudel-Neupane, Haikuo Zhang, Jennifer L Guerriero, Shiwei Han, Mark M Awad, David A Barbie, Jerome Ritz, Simon S Jones, Peter S Hammerman, James E Bradner, Steven N Quayle, Kwok-Kin Wong
Effective therapies for non-small cell lung cancer (NSCLC) remain challenging despite an increasingly comprehensive understanding of somatically altered oncogenic pathways. It is now clear that therapeutic agents with potential to impact the tumor immune microenvironment potentiate immune-orchestrated therapeutic benefit. Herein we evaluated the immunoregulatory properties of histone deacetylase (HDAC) and bromodomain inhibitors, two classes of drugs that modulate the epigenome, with a focus on key cell subsets that are engaged in an immune response...
April 13, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28394251/eed-orchestration-of-heart-maturation-through-interaction-with-hdacs-is-h3k27me3-independent
#5
Shanshan Ai, Yong Peng, Chen Li, Fei Gu, Xianhong Yu, Yanzhu Yue, Qing Ma, Jinghai Chen, Zhiqiang Lin, Pingzhu Zhou, Huafeng Xie, Terence W Prendiville, Wen Zheng, Yuli Liu, Stuart H Orkin, Da-Zhi Wang, Jia Yu, William T Pu, Aibin He
In proliferating cells, where most Polycomb repressive complex 2 (PRC2) studies have been performed, gene repression is associated with PRC2 trimethylation of H3K27 (H3K27me3). However, it is uncertain whether PRC2 writing of H3K27me3 is mechanistically required for gene silencing. Here, we studied PRC2 function in postnatal mouse cardiomyocytes, where the paucity of cell division obviates bulk H3K27me3 rewriting after each cell cycle. EED (embryonic ectoderm development) inactivation in the postnatal heart (Eed(CKO)) caused lethal dilated cardiomyopathy...
April 10, 2017: ELife
https://www.readbyqxmd.com/read/28382171/hdac6-regulates-il-17-expression-in-t-lymphocytes-implications-for-hdac6-targeted-therapies
#6
Bing Yan, Yang Liu, Hong Bai, Miao Chen, Songbo Xie, Dengwen Li, Min Liu, Jun Zhou
The pro-inflammatory cytokine interleukin 17 (IL-17) is critically involved in immunity and inflammation. T-helper 17 and γδ T cells are the predominant sources of IL-17 in the immune system. However, the mechanisms by which the expression of IL-17 is regulated in T cells remain elusive. Here, we demonstrate that loss of histone deacetylase 6 (HDAC6) in mice does not affect the generation of CD4(+) or CD8(+) T cells, but stimulates the development of IL-17-producing γδ T cells. Our data further show that HDAC6 deficiency increases the production of IL-17 by Vγ4(+) γδ T cells in the spleen and lymph nodes...
2017: Theranostics
https://www.readbyqxmd.com/read/28378227/epigenetic-approach-for-angiostatic-therapy-promising-combinations-for-cancer-treatment
#7
REVIEW
Robert H Berndsen, U Kulsoom Abdul, Andrea Weiss, Marloes Zoetemelk, Marije T Te Winkel, Paul J Dyson, Arjan W Griffioen, Patrycja Nowak-Sliwinska
Cancer cells are often dependent on epigenetic pathways for their survival. Consequently, drugs that target the epigenome, rather than the underlying DNA sequence, are currently attracting considerable attention. In recent years, the first epigenetic drugs have been approved for cancer chemotherapy, mainly for hematological applications. Limitations in single-drug efficacies have thus far limited their application in the treatment of solid tumors. Nevertheless, promising activity for these compounds has been suggested when combined with other, distinctly targeted agents...
April 4, 2017: Angiogenesis
https://www.readbyqxmd.com/read/28375564/effects-of-histone-deacetylase-inhibitors-on-regenerative-cell-responses-in-human-dental-pulp-cells
#8
Z Luo, Z Wang, X He, N Liu, B Liu, L Sun, J Wang, F Ma, H Duncan, W He, P Cooper
AIM: To investigate the growth, migratory and adhesive effects of Trichostatin A (TSA) and Valproic acid (VPA), two HDACis, on hDPSCs. METHODOLOGY: To verify that TSA or VPA functions as an HDAC inhibitor, the expressions of histone H3 and H4 were examined using Western blotting analysis. hDPSC growth and metabolic activity was evaluated by MTT viability analysis at different time-points and by cell count experiments. The expression of cell cycle regulatory and the apoptosis associated proteins were examined by Western blot analysis...
April 4, 2017: International Endodontic Journal
https://www.readbyqxmd.com/read/28369619/histone-deacetylase-class-i-inhibition-promotes-epithelial-gene-expression-in-pancreatic-cancer-cells-in-a-brd4-and-myc-dependent-manner
#9
Vivek Kumar Mishra, Florian Wegwitz, Robyn Laura Kosinsky, Madhobi Sen, Roland Baumgartner, Tanja Wulff, Jens T Siveke, Hans-Ulrich Schildhaus, Zeynab Najafova, Vijayalakshmi Kari, Hella Kohlhof, Elisabeth Hessmann, Steven A Johnsen
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with a particularly dismal prognosis. Histone deacetylases (HDAC) are epigenetic modulators whose activity is frequently deregulated in various cancers including PDAC. In particular, class-I HDACs (HDAC 1, 2, 3 and 8) have been shown to play an important role in PDAC. In this study, we investigated the effects of the class I-specific HDAC inhibitor (HDACi) 4SC-202 in multiple PDAC cell lines in promoting tumor cell differentiation. We show that 4SC-202 negatively affects TGFβ signaling and inhibits TGFβ-induced epithelial-to-mesenchymal transition (EMT)...
March 27, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28359186/impact-of-lactational-exposure-to-polychlorinated-biphenyl-causes-epigenetic-modification-and-impairs-sertoli-cells-functional-regulators-in-f1-progeny
#10
E Sugantha Priya, T Sathish Kumar, P Raja Singh, S Balakrishnan, J Arunakaran
Polychlorinated biphenyl (PCB) is an endocrine-disrupting chemical. Sertoli cells (SCs) provide physical and nutritional support for developing germ cells. Dysfunction in SCs has adverse effects on spermatogenesis. Previously, we found that the lactational exposure of PCBs (1, 2, and 5 mg/kg birth weight/day, orally from postnatal days 1 to 20) decreased the follicle-stimulating hormone receptor (FSHR) and androgen receptor (AR) expression in SCs of F1 progeny. Transcription factors initiate and regulate the transcription of genes...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28343758/synergistic-expression-of-histone-deacetylase-9-and-matrix-metalloproteinase-12-in-m4-macrophages-in-advanced-carotid-plaques
#11
N K J Oksala, I Seppälä, R Rahikainen, K-M Mäkelä, E Raitoharju, T Illig, N Klopp, I Kholova, R Laaksonen, P J Karhunen, V P Hytönen, T Lehtimäki
OBJECTIVE/BACKGROUND: Expression patterns and association with cell specific gene expression signatures of the epigenetic regulator histone deacetylase 9 (HDAC9) and matrix metalloproteinase 12 (MMP12) in human plaque are not known. METHODS: This was a prospective cohort study. Genome wide expression analysis was performed in carotid, femoral, aortic plaques (n = 68) and left internal thoracic (LITA) controls (n = 28) and plaque histological severity assessed...
March 23, 2017: European Journal of Vascular and Endovascular Surgery
https://www.readbyqxmd.com/read/28342734/integration-of-microbiome-and-epigenome-to-decipher-the-pathogenesis-of-autoimmune-diseases
#12
REVIEW
Beidi Chen, Luxi Sun, Xuan Zhang
The interaction between genetic predisposition and environmental factors are of great significance in the pathogenesis and development of autoimmune diseases (AIDs). The human mucosa is the most frequent site that interacts with the exterior environment, and commensal microbiota at the gut and other human mucosal cavities play a crucial role in the regulation of immune system. Growing evidence has shown that the compositional and functional changes of mucosal microbiota are closely related to AIDs. Gut dysbiosis not only influence the expression level of Toll-like receptors (TLRs) of antigen presenting cells, but also contribute to Th17/Treg imbalance...
March 23, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28337317/structural-requirements-of-hdac-inhibitors-saha-analogues-modified-at-the-c2-position-display-hdac6-8-selectivity
#13
Ahmed T Negmeldin, Geetha Padige, Anton V Bieliauskas, Mary Kay H Pflum
Histone deacetylase (HDAC) proteins are epigenetic regulators that deacetylate protein substrates, leading to subsequent changes in cell function. HDAC proteins are implicated in cancers, and several HDAC inhibitors have been approved by the FDA as anticancer drugs, including SAHA (suberoylanilide hydroxamic acid; Vorinostat and Zolinza). Unfortunately, SAHA inhibits most HDAC isoforms, which limits its use as a pharmacological tool and may lead to side effects in the clinic. In this work SAHA analogues substituted at the C2 position were synthesized and screened for HDAC isoform selectivity in vitro and in cells...
March 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28336124/ultraviolet-b-inhibition-of-dnmt1-activity-via-ahr-activation-dependent-sirt1-suppression-in-cd4-t-cells-from-systemic-lupus-erythematosus-patients
#14
Zhouwei Wu, Xingyu Mei, Zuolin Ying, Yue Sun, Jun Song, Weimin Shi
BACKGROUND: Previous studies have reported that ultraviolet B (UVB) inhibits DNA methyltransferase1 (DNMT1) activity in CD4+ T cells from systemic lupus erythematosus (SLE) patients. Silent mating type information regulation 2 homolog 1 (SIRT1) is a type of Class III histone deacetylases (HDACs), and has been reported to play roles in the pathogenesis of different autoimmune diseases and can modulate DNMT1 activity. Moreover, aryl hydrocarbon receptor (AhR) has been reported to link UVB with SLE...
March 10, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28322226/highly-effective-combination-of-lsd1-kdm1a-antagonist-and-pan-histone-deacetylase-inhibitor-against-human-aml-cells
#15
W Fiskus, S Sharma, B Shah, B P Portier, S G T Devaraj, K Liu, S P Iyer, D Bearss, K N Bhalla
No abstract text is available yet for this article.
March 21, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28317157/design-and-synthesis-of-novel-anti-plasmodial-histone-deacetylase-inhibitors-containing-an-alkoxyamide-connecting-unit
#16
Leandro A Alves Avelar, Jana Held, Jessica A Engel, Parichat Sureechatchaiyan, Finn K Hansen, Alexandra Hamacher, Matthias U Kassack, Benjamin Mordmüller, Katherine T Andrews, Thomas Kurz
Despite recent declines in mortality, malaria remains an important global health problem. New therapies are needed, including new drugs with novel modes of action compared to existing agents. Among new potential therapeutic targets for malaria, inhibition of parasitic histone deacetylases (HDACs) is a promising approach. Homology modeling of PfHDAC1, a known target of some anti-plasmodial HDAC inhibitors, revealed a unique threonine residue at the rim of the active site in close proximity to the location of the cap group of vorinostat-type HDAC inhibitors...
March 20, 2017: Archiv der Pharmazie
https://www.readbyqxmd.com/read/28306192/histone-deacetylase-activity-mediates-acquired-resistance-towards-structurally-diverse-hsp90-inhibitors
#17
Ryan C Chai, Jessica L Vieusseux, Benjamin J Lang, Chau H Nguyen, Michelle M Kouspou, Kara L Britt, John T Price
Heat Shock Protein 90 (HSP90) regulates multiple signaling pathways critical for tumor growth. As such, HSP90 inhibitors have been shown to act as effective anticancer agents in preclinical studies but, for a number of reasons, the same effect has not been observed in the clinical trials to date. One potential reason for this may the presence of de novo or acquired resistance within the tumors. To investigate mechanisms of resistance, we generated resistant cell lines through gradual dose escalation of the HSP90 inhibitor 17-AAG...
March 17, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28288848/bcl11b-mediated-epigenetic-repression-is-a-crucial-target-for-histone-deacetylase-inhibitors-in-cutaneous-t-cell-lymphoma
#18
Wenjing Fu, Shengguo Yi, Lei Qiu, Jingru Sun, Ping Tu, Yang Wang
The treatment options for advanced cutaneous T-cell lymphoma (CTCL) are limited due to its unclear pathogenesis. HDAC inhibitors (HDACi) are recently developed therapeutics approved for refractory CTCL. However, the response rate is relatively low and unpredictable. Previously, we discovered that BCL11B, a key T-cell development regulator, was aberrantly overexpressed in mycosis fungoides (MF), the most common CTCL, as compared with benign inflammatory skin. In the current study, we identified positive correlation between BCL11B expression and the sensitivity to HDACi in CTCL lines...
March 10, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28273064/class-iia-hdac-inhibition-reduces-breast-tumours-and-metastases-through-anti-tumour-macrophages
#19
Jennifer L Guerriero, Alaba Sotayo, Holly E Ponichtera, Jessica A Castrillon, Alexandra L Pourzia, Sara Schad, Shawn F Johnson, Ruben D Carrasco, Suzan Lazo, Roderick T Bronson, Scott P Davis, Mercedes Lobera, Michael A Nolan, Anthony Letai
Although the main focus of immuno-oncology has been manipulating the adaptive immune system, harnessing both the innate and adaptive arms of the immune system might produce superior tumour reduction and elimination. Tumour-associated macrophages often have net pro-tumour effects, but their embedded location and their untapped potential provide impetus to discover strategies to turn them against tumours. Strategies that deplete (anti-CSF-1 antibodies and CSF-1R inhibition) or stimulate (agonistic anti-CD40 or inhibitory anti-CD47 antibodies) tumour-associated macrophages have had some success...
March 8, 2017: Nature
https://www.readbyqxmd.com/read/28270022/a-phase-1-trial-of-the-hdac-inhibitor-ar-42-in-patients-with-multiple-myeloma-and-t-and-b-cell-lymphomas
#20
Douglas W Sborov, Alessandro Canella, Erinn M Hade, Xiaokui Mo, Soun Khountham, Jiang Wang, Wenjun Ni, Ming Poi, Christopher Coss, Zhongfa Liu, Mitch A Phelps, Amir Mortazavi, Leslie Andritsos, Robert A Baiocchi, Beth A Christian, Don M Benson, Joseph Flynn, Pierluigi Porcu, John C Byrd, Flavia Pichiorri, Craig C Hofmeister
Histone deacetylase inhibitors (HDACi) have proven activity in hematologic malignancies, and their FDA approval in multiple myeloma (MM) and T-cell lymphoma highlights the need for further development of this drug class. We investigated AR-42, an oral pan-HDACi, in a first-in-man phase 1 dose escalation clinical trial. Overall, treatment was well tolerated, no DLTs were evident, and the MTD was defined as 40 mg dosed three times weekly for three weeks of a 28-day cycle. One patient each with MM and mantle cell lymphoma demonstrated disease control for 19 and 27 months (ongoing), respectively...
March 7, 2017: Leukemia & Lymphoma
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