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histone deacetylase T cells

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https://www.readbyqxmd.com/read/28933264/from-a-better-understanding-of-the-mechanisms-of-action-of-histone-deacetylases-inhibitors-to-the-progress-of-the-treatment-of-malignant-lymphomas-and-plasma-cell-myeloma
#1
Romeo-Gabriel Mihăilă
BACKGROUND: Notable progress has been made in chemo- and immunotherapy of B-cell lymphomas, but less in the treatment of T-cell lymphomas. OBJECTIVE: Histone deacetylases inhibitors are a potentially useful therapeutic mean, as an epigenetic dysregulation is present in lymphomas, and especially in T-cell types. We aimed to study the progress made in this area. METHOD: A minireview was achieved using the articles published in PubMed in the last two years and the new patents made in this field...
September 19, 2017: Recent Patents on Anti-cancer Drug Discovery
https://www.readbyqxmd.com/read/28932644/romidepsin-alone-or-in-combination-with-anti-cd20-chimeric-antigen-receptor-expanded-natural-killer-cells-targeting-burkitt-lymphoma-in-vitro-and-in-immunodeficient-mice
#2
Yaya Chu, Ashlin Yahr, Brian Huang, Janet Ayello, Matthew Barth, Mitchell S Cairo
Facilitating the development of alternative targeted therapeutic strategies is urgently required to improve outcome or circumvent chemotherapy resistance in children, adolescents, and adults with recurrent/refractory de novo mature B-cell (CD20) non-Hodgkin lymphoma, including Burkitt lymphoma (BL). Romidepsin, a histone deacetylase inhibitor (HDACi), has been used to treat cutaneous T-cell lymphoma. We have demonstrated the significant anti-tumor effect of anti-CD20 chimeric antigen receptor (CAR) modified expanded peripheral blood natural killer (exPBNK) against rituximab-sensitive and -resistant BL...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28928414/disruption-to-schizophrenia-associated-gene-fez1-in-the-hippocampus-of-hdac11-knockout-mice
#3
Dale T Bryant, Christian Landles, Aikaterini S Papadopoulou, Agnesska C Benjamin, Joshua K Duckworth, Thomas Rosahl, Caroline L Benn, Gillian P Bates
Histone Deacetylase 11 (HDAC11) is highly expressed in the central nervous system where it has been reported to have roles in neural differentiation. In contrast with previous studies showing nuclear and cytoplasmic localisation, we observed synaptic enrichment of HDAC11. Knockout mouse models for HDACs 1-9 have been important for guiding the development of isoform specific HDAC inhibitors as effective therapeutics. Given the close relationship between HDAC11 and neural cells in vitro, we examined neural tissue in a previously uncharacterised Hdac11 knockout mouse (Hdac11 (KO/KO))...
September 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28900183/a-brain-derived-neurotrophic-factor-mimetic-is-sufficient-to-restore-cone-photoreceptor-visual-function-in-an-inherited-blindness-model
#4
Conor Daly, Lisa Shine, Theresa Heffernan, Sudhakar Deeti, Alison L Reynolds, John J O'Connor, Eugène T Dillon, David J Duffy, Walter Kolch, Gerard Cagney, Breandán N Kennedy
Controversially, histone deacetylase inhibitors (HDACi) are in clinical trial for the treatment of inherited retinal degeneration. Utilizing the zebrafish dye (ucd6) model, we determined if treatment with HDACi can rescue cone photoreceptor-mediated visual function. dye exhibit defective visual behaviour and retinal morphology including ciliary marginal zone (CMZ) cell death and decreased photoreceptor outer segment (OS) length, as well as gross morphological defects including hypopigmentation and pericardial oedema...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28894447/the-microbial-metabolite-butyrate-induces-expression-of-th1-associated-factors-in-cd4-t-cells
#5
Meike Kespohl, Niyati Vachharajani, Maik Luu, Hani Harb, Sabine Pautz, Svenja Wolff, Nina Sillner, Alesia Walker, Philippe Schmitt-Kopplin, Thomas Boettger, Harald Renz, Stefan Offermanns, Ulrich Steinhoff, Alexander Visekruna
Short-chain fatty acids (SCFAs), which are generated by the bacterial fermentation of dietary fibers, promote expansion of regulatory T cells (Tregs). Potential therapeutic value of SCFAs has been recently highlighted in the experimental models of T cell-mediated autoimmunity and allergic inflammation. These studies suggest that physiological intestinal concentrations of SCFAs within the millimolar range are crucial for dampening inflammation-mediated processes. Here, we describe opposing effects of SCFAs on T cell-mediated immune responses...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28884410/an-7-a-butyric-acid-prodrug-sensitizes-cutaneous-t-cell-lymphoma-cell-lines-to-doxorubicin-via-inhibition-of-dna-double-strand-breaks-repair
#6
Lilach Moyal, Neta Goldfeiz, Batia Gorovitz, Ada Rephaeli, Efrat Tal, Nataly Tarasenko, Abraham Nudelman, Yael Ziv, Emmilia Hodak
We previously found that the novel histone deacetylase inhibitor (HDACI) butyroyloxymethyl diethylphosphate (AN-7) had greater selectivity against cutaneous T-cell lymphoma (CTCL) than SAHA. AN-7 synergizes with doxorubicin (Dox), an anthracycline antibiotic that induces DNA breaks. This study aimed to elucidate the mechanism underlying the effect of AN-7 on Dox-induced double-strand DNA breaks (DSBs) in CTCL, MyLa and Hut78 cell lines. The following markers/assays were employed: comet assay; western blot of γH2AX and p-KAP1; immunofluorescence of γH2AX nuclear foci; Western blot of repair protein; quantification of DSBs-repair through homologous recombination...
September 8, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28878027/death-by-hdac%C3%A2-inhibition-in-synovial-sarcoma-cells
#7
Aimée N Laporte, Neal M Poulin, Jared J Barrott, Xiu Qing Wang, Alireza Lorzadeh, Ryan Vander Werff, Kevin B Jones, T Michael Underhill, Torsten O Nielsen
Conventional cytotoxic therapies for synovial sarcoma provide limited benefit, and no drugs specifically targeting the causative SS18-SSX fusion oncoprotein are currently available. Histone deacetylase (HDAC) inhibition has been shown in previous studies to disrupt the synovial sarcoma oncoprotein complex, resulting in apoptosis. To understand the molecular effects of HDAC inhibition, RNA-Seq transcriptome analysis was undertaken in six human synovial sarcoma cell lines. HDAC inhibition induced pathways of cell cycle arrest, neuronal differentiation and response to oxygen-containing species, effects also observed in other cancers treated with this class of drugs...
September 6, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28872191/cutaneous-t-cell-lymphoma-2017-update-on-diagnosis-risk-stratification-and-management
#8
Ryan A Wilcox
DISEASE OVERVIEW: Cutaneous T-cell lymphomas are a heterogenous group of T-cell lymphoproliferative disorders involving the skin, the majority of which may be classified as Mycosis Fungoides (MF) or Sézary Syndrome (SS). DIAGNOSIS: The diagnosis of MF or SS requires the integration of clinical and histopathologic data. RISK-ADAPTED THERAPY: TNMB (tumor, node, metastasis, blood) staging remains the most important prognostic factor in MF/SS and forms the basis for a "risk-adapted," multi-disciplinary approach to treatment...
October 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28860561/short-chain-fatty-acids-enhance-aryl-hydrocarbon-ah-responsiveness-in-mouse-colonocytes-and-caco-2-human-colon-cancer-cells
#9
Un-Ho Jin, Yating Cheng, Hyejin Park, Laurie A Davidson, Evelyn S Callaway, Robert S Chapkin, Arul Jayaraman, Andrew Asante, Clinton Allred, Evelyn A Weaver, Stephen Safe
Aryl hydrocarbon receptor (AhR) ligands are important for gastrointestinal health and play a role in gut inflammation and the induction of T regulatory cells, and the short chain fatty acids (SCFAs) butyrate, propionate and acetate also induce similar protective responses. Initial studies with butyrate demonstrated that this compound significantly increased expression of Ah-responsive genes such as Cyp1a1/CYP1A1 in YAMC mouse colonocytes and Caco-2 human colon cancer cell lines. Butyrate synergistically enhanced AhR ligand-induced Cyp1a1/CYP1A1 in these cells with comparable enhancement being observed for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and also microbiota-derived AhR ligands tryptamine, indole and 1,4-dihydroxy-2-naphthoic acid (DHNA)...
August 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28853310/responses-to-romidepsin-in-patients-with-cutaneous-t-cell-lymphoma-and-prior-treatment-with-systemic-chemotherapy
#10
Madeleine Duvic, Susan E Bates, Richard Piekarz, Robin Eisch, Youn H Kim, Adam Lerner, Tadeusz Robak, Alexey Samtsov, Jürgen C Becker, William McCulloch, Joel Waksman, Sean Whittaker
Cutaneous T-cell lymphomas (CTCL) are a group of non-Hodgkin lymphomas that typically present in the skin but can progress to systemic involvement. The optimal treatment for patients who relapse from or are refractory to systemic chemotherapy remains unclear. Romidepsin is a potent, class-I selective histone deacetylase inhibitor approved for the treatment of patients with CTCL who have had ≥1 prior systemic therapy. Here, we present a subanalysis of two phase-2 trials (NCT00106431, NCT00007345) of romidepsin in patients with CTCL who had prior treatment with systemic chemotherapy...
August 30, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28842659/hiv-1-envelope-glycoprotein-stimulates-viral-transcription-and-increases-the-infectivity-of-the-progeny-virus-through-the-manipulation-of-cellular-machinery
#11
Xiaozhuo Ran, Zhujun Ao, Adriana Trajtman, Wayne Xu, Gary Kobinger, Yoav Keynan, Xiaojian Yao
During HIV infection, large amounts of progeny viral particles, including infectious virus and a large proportion of defective viral particles, are produced. Despite of the critical role of the infectious viruses in infection and pathogenesis in vivo, whether and how those defective viral particles, especially the virus-associated envelope glycoprotein (vEnv), would impact viral infection remains elusive. In this study, we investigated the effect of vEnv on HIV-infected T cells and demonstrated that the vEnv was able to stimulate HIV transcription in HIV-infected cells, including peripheral blood mononuclear cells (PBMCs) isolated from HIV patients...
August 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28836127/relaxed-chromatin-induced-by-histone-deacetylase-inhibitors-improves-the-oligonucleotide-directed-gene-editing-in-plant-cells
#12
Hilda Tiricz, Bettina Nagy, Györgyi Ferenc, Katalin Török, István Nagy, Dénes Dudits, Ferhan Ayaydin
Improving efficiency of oligonucleotide-directed mutagenesis (ODM) is a prerequisite for wide application of this gene-editing approach in plant science and breeding. Here we have tested histone deacetylase inhibitor treatments for induction of relaxed chromatin and for increasing the efficiency of ODM in cultured maize cells. For phenotypic assay we produced transgenic maize cell lines expressing the non-functional Green Fluorescent Protein (mGFP) gene carrying a TAG stop codon. These transgenic cells were bombarded with corrective oligonucleotide as editing reagent to recover GFP expression...
August 23, 2017: Journal of Plant Research
https://www.readbyqxmd.com/read/28832971/class-i-hdac-inhibition-improves-pancreatitis-outcome-by-limiting-leukocyte-recruitment-and-acinar-to-ductal-metaplasia
#13
Marta Bombardo, Enrica Saponara, Ermanno Malagola, Rong Chen, Gitta M Seleznik, Cecile Haumaitre, Evans Quilichini, Anja Zabel, Theresia Reding, Rolf Graf, Sabrina Sonda
BACKGROUND AND PURPOSE: Pancreatitis is a common inflammation of the pancreas with rising incidence in many countries. Despite improvements in diagnostic techniques, the disease is associated with high risk of severe morbidity and mortality and there is an urgent need for new therapeutic interventions. In this study we evaluated whether histone deacetylases (HDACs), key epigenetic regulators of gene transcription, are involved in the development of the disease. EXPERIMENTAL APPROACH: We analyzed HDAC regulation during cerulein-induced acute, chronic and autoimmune pancreatitis using different transgenic mouse models...
August 17, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28819166/histone-protein-deacetylase-11-targeting-promotes-foxp3-treg-function
#14
Jianbing Huang, Liqing Wang, Satinder Dahiya, Ulf H Beier, Rongxiang Han, Arabinda Samanta, Joel Bergman, Eduardo M Sotomayor, Edward Seto, Alan P Kozikowski, Wayne W Hancock
Current interest in Foxp3+ T-regulatory (Treg) cells as therapeutic targets in transplantation is largely focused on their harvesting pre-transplant, expansion and infusion post-transplantation. An alternate strategy of pharmacologic modulation of Treg function using histone/protein deacetylase inhibitors (HDACi) may allow more titratable and longer-term dosing. However, the effects of broadly acting HDACi vary, such that HDAC isoform-selective targeting is likely required. We report data from mice with constitutive or conditional deletion of HDAC11 within Foxp3+ Treg cells, and their use, along with small molecule HDAC11 inhibitors, in allograft models...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28814661/hdac-inhibition-induces-hiv-1-protein-and-enables-immune-based-clearance-following-latency-reversal
#15
Guoxin Wu, Michael Swanson, Aarthi Talla, Donald Graham, Julie Strizki, Daniel Gorman, Richard Jo Barnard, Wade Blair, Ole S Søgaard, Martin Tolstrup, Lars Østergaard, Thomas A Rasmussen, Rafick-Pierre Sekaly, Nancie M Archin, David M Margolis, Daria J Hazuda, Bonnie J Howell
Promising therapeutic approaches for eradicating HIV include transcriptional activation of provirus from latently infected cells using latency-reversing agents (LRAs) and immune-mediated clearance to purge reservoirs. Accurate detection of cells capable of producing viral antigens and virions, and the measurement of clearance of infected cells, is essential to assessing therapeutic efficacy. Here, we apply enhanced methodology extending the sensitivity limits for the rapid detection of subfemtomolar HIV gag p24 capsid protein in CD4+ T cells from ART-suppressed HIV+ individuals, and we show viral protein induction following treatment with LRAs...
August 17, 2017: JCI Insight
https://www.readbyqxmd.com/read/28812434/-pemetrexed-sildenafil-via-autophagy-dependent-hdac-down-regulation-enhances-the-immunotherapy-response-of-nsclc-cells
#16
Laurence Booth, Jane L Roberts, Andrew Poklepovic, Paul Dent
Pemetrexed is an approved therapeutic in NSCLC and ovarian cancer. Our studies focused on the ability of [pemetrexed + sildenafil] exposure to alter the immunogenicity of lung and ovarian cancer cells. Treatment of lung and ovarian cancer cells with [pemetrexed + sildenafil] in vitro rapidly reduced the expression of PD-L1, PD-L2 and ornithine decarboxylase (ODC), and increased the expression of Class I MHCA. In a cell-specific fashion, some cells also released the immunogenic nuclear protein HMGB1 into the extracellular environment...
August 16, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28812327/design-and-synthesis-of-terephthalic-acid-based-histone-deacetylase-inhibitors-with-dual-stage-anti-plasmodium-activity
#17
Katharina Stenzel, Ming Jang Chua, Sandra Duffy, Yevgeniya Antonova-Koch, Stephan Meister, Alexandra Hamacher, Matthias U Kassack, Elizabeth Winzeler, Vicky M Avery, Thomas Kurz, Katherine T Andrews, Finn K Hansen
In this work we aimed to develop parasite-selective histone deacetylase inhibitors (HDAC) inhibitors with activity against the disease-causing asexual blood stages of Plasmodium as well as causal prophylactic and/or transmission blocking properties. We report the design, synthesis, and biological testing of a series of 13 terephthalic acid-based HDAC inhibitors. All compounds showed low cytotoxicity against human embryonic kidney (HEK293) cells (IC50 : 8->51 μm), with 11 also having sub-micromolar in vitro activity against drug-sensitive (3D7) and multidrug-resistant (Dd2) asexual blood-stage P...
August 15, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28809557/in-silico-and-in-vitro-interactions-between-short-chain-fatty-acids-and-human-histone-deacetylases
#18
Rou Hui Ho, James Chun Yip Chan, Hao Fan, Dorinda Yan Qin Kioh, Bee Wah Lee, Eric Chun Yong Chan
Short chain fatty acids (SCFAs) are postulated to modulate the immune development of neonates via epigenetic regulations such as histone deacetylase (HDAC) inhibition. In the context of atopic diseases, the inhibition of HDAC maintains T-cell homeostasis and induces naïve T-cell differentiation into adaptive Treg, which regulates the production of anti-inflammatory cytokines and suppression of Th2 immune responses. We investigated the structure-inhibition relationships of SCFAs with class I HDAC3 and class IIa HDAC7 using in silico docking simulation and the in vitro human recombinant HDAC inhibition assay...
September 12, 2017: Biochemistry
https://www.readbyqxmd.com/read/28799436/immunotherapy-based-approaches-in-myelofibrosis
#19
Lucia Masarova, Srdan Verstovsek, Hagop Kantarjian, Naval Daver
Aberrant regulation of the immune system with up-regulation of pro-inflammatory cytokines contributes to disease pathophysiology in myelofibrosis (MF). Therapeutic options for MF associated anemia, thrombocytopenia, and bone marrow fibrosis remain limited. Areas covered: This review focuses on immune based therapies in MF, including immunomodulatory imide drugs (IMiDs), interferons, monoclonal antibodies and targeted agents (SL-401), and checkpoint inhibitors. Published literature was reviewed using available databases (PubMed, Cochrane, Scopus) and web pages (clinicaltrials...
August 22, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28782836/histone-deacetylase-3-deletion-in-mesenchymal-progenitor-cells-hinders-long-bone-development
#20
Marina Feigenson, Lomeli Carpio Shull, Earnest L Taylor, Emily T Camilleri, Scott M Riester, Andre J van Wijnen, Elizabeth W Bradley, Jennifer J Westendorf
Long bone formation is a complex process that requires precise transcriptional control of gene expression programs in mesenchymal progenitor cells. Histone deacetylases (Hdacs) coordinate chromatin structure and gene expression by enzymatically removing acetyl groups from histones and other proteins. Hdac inhibitors are used clinically to manage mood disorders, cancers, and other conditions but are teratogenic to the developing skeleton and increase fracture risk in adults. In this study, the functions of Hdac3, one of the enzymes blocked by current Hdac inhibitor therapies, in skeletal mesenchymal progenitor cells were determined...
August 7, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
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