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histone deacetylase T cells

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https://www.readbyqxmd.com/read/29789603/vorinostat-and-quinacrine-have-synergistic-effects-in-t-cell-acute-lymphoblastic-leukemia-through-reactive-oxygen-species-increase-and-mitophagy-inhibition
#1
Bo Jing, Jin Jin, Rufang Xiang, Meng Liu, Li Yang, Yin Tong, Xinhua Xiao, Hu Lei, Wei Liu, Hanzhang Xu, Jiong Deng, Li Zhou, Yingli Wu
Despite recent progress in the treatment, the outcome of adult acute T-cell lymphoblastic leukemia (T-ALL) is poor. Development of novel approach to combat this disease is urgently required. Vorinostat, a pan-histone deacetylase (HDAC) inhibitor, exerts promising anticancer activity in a variety of solid and hematologic malignancies. However, the efficacy of vorinostat monotherapy is unsatisfactory. Here, we show that quinacrine (QC), an anti-malaria drug with potent autophagy inhibitory activity, could synergistically enhance vorinostat-induced cell death at a non-toxic concentration...
May 22, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29784816/encephalitis-is-mediated-by-rop18-of-toxoplasma-gondii-a-severe-pathogen-in-aids-patients
#2
Ran An, Yuewen Tang, Lijian Chen, Haijian Cai, De-Hua Lai, Kang Liu, Lijuan Wan, Linli Gong, Li Yu, Qingli Luo, Jilong Shen, Zhao-Rong Lun, Francisco J Ayala, Jian Du
The neurotropic parasite Toxoplasma gondii is a globally distributed parasitic protozoan among mammalian hosts, including humans. During the course of infection, the CNS is the most commonly damaged organ among invaded tissues. The polymorphic rhoptry protein 18 (ROP18) is a key serine (Ser)/threonine (Thr) kinase that phosphorylates host proteins to modulate acute virulence. However, the basis of neurotropism and the specific substrates through which ROP18 exerts neuropathogenesis remain unknown. Using mass spectrometry, we performed proteomic analysis of proteins that selectively bind to active ROP18 and identified RTN1-C, an endoplasmic reticulum (ER) protein that is preferentially expressed in the CNS...
May 21, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29778644/a-trichostatin-a-tsa-sp1-mediated-mechanism-for-the-regulation-of-sall2-tumor-suppressor-in-jurkat-t-cells
#3
Matías I Hepp, David Escobar, Carlos Farkas, Viviana Hermosilla, Claudia Álvarez, Roberto Amigo, José L Gutiérrez, Ariel F Castro, Roxana Pincheira
SALL2 is a transcription factor involved in development and disease. Deregulation of SALL2 has been associated with cancer, suggesting that it plays a role in the disease. However, how SALL2 is regulated and why is deregulated in cancer remain poorly understood. We previously showed that the p53 tumor suppressor represses SALL2 under acute genotoxic stress. Here, we investigated the effect of Histone Deacetylase Inhibitor (HDACi) Trichostatin A (TSA), and involvement of Sp1 on expression and function of SALL2 in Jurkat T cells...
May 17, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29776409/calcitriol-downregulates-fibroblast-growth-factor-receptor-1-through-histone-deacetylase-activation-in-hl-1-atrial-myocytes
#4
Ting-Wei Lee, Ting-I Lee, Yung-Kuo Lin, Yu-Hsun Kao, Yi-Jen Chen
BACKGROUND: Fibroblast growth factor (FGF)-2 plays a crucial role in the pathophysiology of cardiovascular diseases (CVDs). FGF-2 was reported to induce cardiac hypertrophy through activation of FGF receptor 1 (FGFR1). Multiple laboratory findings indicate that calcitriol may be a potential treatment for CVDs. In this study, we attempted to investigate whether calcitriol regulates FGFR1 expression to modulate the effects of FGF-2 signaling in cardiac myocytes and explored the potential regulatory mechanism...
May 18, 2018: Journal of Biomedical Science
https://www.readbyqxmd.com/read/29774040/-oligocellula1-high-expression-of-osmotically-responsive-genes15-promotes-cell-proliferation-with-histone-deacetylase9-and-powerdress-during-leaf-development-in-arabidopsis-thaliana
#5
Marina Suzuki, Nanae Shinozuka, Tomohiro Hirakata, Miyuki T Nakata, Taku Demura, Hirokazu Tsukaya, Gorou Horiguchi
Organ size regulation is dependent on the precise spatial and temporal regulation of cell proliferation and cell expansion. A number of transcription factors have been identified that play a key role in the determination of aerial lateral organ size, but their functional relationship to various chromatin modifiers has not been well understood. To understand how leaf size is regulated, we previously isolated the oligocellula1 ( oli1 ) mutant of Arabidopsis thaliana that develops smaller first leaves than the wild type (WT) mainly due to a reduction in the cell number...
2018: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29769011/evolving-strategies-for-the-treatment-of-t-cell-lymphoma-a-systematic-review-and-recent-patents
#6
Kamel Laribi, Mustapha Alani, Catherine Truong, Alix Baugier de Materre
OBJECTIVE: Mature T-cell lymphomas are a heterogeneous group of T-cell malignancies with a poor outcome. The discovery of new molecular biomarkers has led to the emergence of new drugs in recent years that target various signaling pathways. METHOD: We examined all pertinent published patents through 2015 that analyzed novel methods for the diagnosis and treatment of T cell lymphoma, as well as related published and unpublished studies. Selection criteria were established before data collection...
May 16, 2018: Recent Patents on Anti-cancer Drug Discovery
https://www.readbyqxmd.com/read/29750914/pro-and-anti-inflammatory-effects-of-short-chain-fatty-acids-on-immune-and-endothelial-cells
#7
Meng Li, Betty C A M van Esch, Gerry T M Wagenaar, Johan Garssen, Gert Folkerts, Paul A J Henricks
In the gastro-intestinal tract, short chain fatty acids (SCFAs) have protective effects on epithelial cells. However, their effects on inflammatory cytokine production by endothelial and immune cells and the recruitment of immune cells and their trans-migration across the endothelial layer remain controversial. Both cell types are associated with the initiation and development of inflammatory diseases, such as atherosclerosis and sepsis. SCFAs modulate immune and inflammatory responses via activation of free fatty acid (FFA) receptors type 2 and 3 (FFA2 and FFA3 receptors), G protein-coupled receptor 109A (GPR109A) and inhibition of histone deacetylases (HDACs)...
May 8, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29733973/design-and-development-of-microemulsion-systems-of-a-new-antineoplaston-a10-analog-for-enhanced-intravenous-antitumor-activity-in-vitro-characterization-molecular-docking-125-i-radiolabeling-and-in-vivo-biodistribution-studies
#8
Mohamed H Aboumanei, Aly A Abdelbary, Ismail T Ibrahim, Mina I Tadros, Mohamed T El-Kolaly
A10, (3-phenylacetylamino-2,6-piperidinedione), is a natural peptide with broad antineoplastic activity. Recently, in vitro antitumor effect of a new A10 analog [3-(4-methoxybenzoylamino)-2,6-piperidinedione] (MPD) has been verified. However, poor aqueous solubility represents an obstacle towards intravenous formulation of MPD and impedes successful in vivo antitumor activity. To surmount such limitation, MPD microemulsion (MPDME) was developed. A 31 22 full factorial design using Design-Expert® software was adopted to study the influence of different parameters and select the optimum formulation (MPDME1)...
May 4, 2018: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29733868/investigation-of-belinostat-induced-genomic-instability-by-molecular-cytogenetic-analysis-and-pathway-focused-gene-expression-profiling
#9
S M Attia, M A Al-Hamamah, M R Alotaibi, G I Harisa, M M Attia, S F Ahmad, M A Ansari, A Nadeem, S A Bakheet
Histone deacetylases (HDACs), which regulate transcription and specific functions such as tumor suppression by p53, are frequently altered in tumors and have a contentious role in carcinogenesis. HDAC inhibitors, which have a long history of use in psychiatry and neurology, have recently been tested as possible treatments for tumors. Belinostat received regulatory approval in the USA on July 3, 2014, for use against peripheral T-cell lymphoma. However, the unavailability of information on belinostat genotoxicity in normal cells and the molecular mechanisms involved in the genetic instability after exposure to belinostat encouraged us to conduct this study...
May 4, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29719411/forodesine-in-the-treatment-of-relapsed-refractory-peripheral-t-cell-lymphoma-an-evidence-based-review
#10
REVIEW
Shinichi Makita, Akiko Miyagi Maeshima, Dai Maruyama, Koji Izutsu, Kensei Tobinai
T-cell lymphoma is a rare hematologic malignancy with an incidence rate between 10% and 20% of that of non-Hodgkin lymphomas. Patients with peripheral T-cell lymphoma (PTCL) generally have a poor prognosis when treated with cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP)/CHOP-like chemotherapy; once relapse occurs, it is mostly regarded as an incurable disease. To overcome the chemorefractoriness of PTCL, several novel agents have been developed. Since the first approval of pralatrexate, a dihydrofolate reductase inhibitor, for relapsed/refractory PTCL by the US Food and Drug Administration, several new agents, such as romidepsin (histone deacetylase inhibitor), brentuximab vedotin (antibody-drug conjugate targeting CD30), chidamide (histone deacetylase inhibitor), and mogamulizumab (anti-CC chemokine receptor 4 monoclonal antibody), have been approved as a therapeutic option for relapsed/refractory PTCL in several countries, including the US, Europe, China, and Japan...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29716651/overexpressed-hdac8-in-cervical-cancer-cells-shows-functional-redundancy-of-tubulin-deacetylation-with-hdac6
#11
G R Vanaja, Hemalatha Golaconda Ramulu, Arunasree M Kalle
BACKGROUND: Histone deacetylases (HDACs) are involved in epigenetic gene regulation via deacetylation of acetylated lysine residues of both histone and non-histone proteins. Among the 18 HDACs identified in humans, HDAC8, a class I HDAC, is best understood structurally and enzymatically. However, its precise subcellular location, function in normal cellular physiology, its protein partners and substrates still remain elusive. METHODS: The subcellular localization of HDAC8 was studied using immunofluorescence and confocal imaging...
May 2, 2018: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/29706951/transcriptional-modulation-of-human-endogenous-retroviruses-in-primary-cd4-t-cells-following-vorinostat-treatment
#12
Cory H White, Nadejda Beliakova-Bethell, Steven M Lada, Michael S Breen, Tara P Hurst, Celsa A Spina, Douglas D Richman, John Frater, Gkikas Magiorkinis, Christopher H Woelk
The greatest obstacle to a cure for HIV is the provirus that integrates into the genome of the infected cell and persists despite antiretroviral therapy. A "shock and kill" approach has been proposed as a strategy for an HIV cure whereby drugs and compounds referred to as latency-reversing agents (LRAs) are used to "shock" the silent provirus into active replication to permit "killing" by virus-induced pathology or immune recognition. The LRA most utilized to date in clinical trials has been the histone deacetylase (HDAC) inhibitor-vorinostat...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29704439/histone-deacetylase-inhibitor-chidamide-promotes-reactivation-of-latent-hiv-by-introducing-histone-acetylation
#13
Qiyuan Kuai, Xiaofan Lu, Zhixin Qiao, Rui Wang, Yanbing Wang, Sanxian Ye, Min He, Yu Wang, Tong Zhang, Hao Wu, Suping Ren, Qun Yu
Highly active antiretroviral therapy (HAART) can reduce the HIV viral load in the plasma to undetectable levels. However, due to the presence of latent HIV reservoirs, it is difficult to completely eradicate HIV in infected patients. Our objective was to assess the potency of chidamide, a novel histone deacetylase inhibitor (HDACi) recently approved for cancer treatment by the China Food and Drug Administration (CFDA), to reactivate latent HIV-1 via histone acetylation. Viral reactivities of chidamide were accessed in two latent HIV pseudotype virus cell reporter systems (J-Lat Tat-GFP Clone A72 and TZM-bl), a latently infected full-length HIV virus cell system (U1/HIV), and resting CD4+ T cells from nine HIV-infected patients under HAART with undetectable viral load...
April 28, 2018: Journal of Medical Virology
https://www.readbyqxmd.com/read/29676460/resistance-to-proteasome-inhibitors-and-other-targeted-therapies-in-myeloma
#14
REVIEW
Craig T Wallington-Beddoe, Magdalena Sobieraj-Teague, Bryone J Kuss, Stuart M Pitson
The number of novel therapies for the treatment of myeloma is rapidly increasing, as are the clinical trials evaluating them in combination with other novel and established therapies. Proteasome inhibitors, immunomodulatory agents and monoclonal antibodies are the most well known and studied classes of novel agents targeting myeloma, with histone deacetylase inhibitors, nuclear export inhibitors and several other approaches also being actively investigated. However, in parallel with the development and clinical use of these novel myeloma therapies is the emergence of novel mechanisms of resistance, many of which remain elusive, particularly for more recently developed agents...
April 20, 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29675169/bioorthogonal-pro-metabolites-for-profiling-short-chain-fatty-acylation
#15
Wilson R Sinclair, Jonathan H Shrimp, Thomas T Zengeya, Rhushikesh A Kulkarni, Julie M Garlick, Hans Luecke, Andrew J Worth, Ian A Blair, Nathaniel W Snyder, Jordan L Meier
Short chain fatty acids (SCFAs) play a central role in health and disease. One function of these signaling molecules is to serve as precursors for short chain fatty acylation, a class of metabolically-derived posttranslational modifications (PTMs) that are established by lysine acetyltransferases (KATs) and lysine deacetylases (KDACs). Via this mechanism, short chain fatty acylation serves as an integrated reporter of metabolism as well as KAT and KDAC activity, and has the potential to illuminate the role of these processes in disease...
February 7, 2018: Chemical Science
https://www.readbyqxmd.com/read/29670210/phase-i-trial-of-histone-deacetylase-inhibitor-panobinostat-in-addition-to-glucocorticoids-for-primary-therapy-of-acute-graft-versus-host-disease
#16
Lia Perez, Hugo Fernandez, Pedro Horna, Marcie Riches, Frederick Locke, Teresa Field, John Powers, Eva Sahakian, Alejandro Villagra, Asmita Mishra, Brian Betts, Mohamed Kharfan-Dabaja, Francisca Beato, Leonel Ochoa-Bayona, Joseph Pidala, Claudio Anasetti
Glucocorticoids for primary therapy of acute GVHD have limited responses. A phase I/II trial tested 4 weeks of deacetylase inhibitor panobinostat started within 48 h of glucocorticoids (1 mg/kg/day prednisone or equivalent) as primary treatment for patients with either classic acute GVHD (n = 16) or acute GVHD overlapping with chronic (n = 6). Four patients received 2.5 mg/m2 IV three times a week (TIW). Subsequent to discontinuation of IV panobinostat, patients received oral doses (PO). Two patients treated with 10 mg TIW (PO level 1) had progressive GVHD, after which patients were treated with 5 mg TIW (PO level -1; n = 16); 31/41 adverse events were possibly related, including thrombocytopenia (n = 13), leukopenia (n = 7), hypercholesterolemia (n = 3), hypertriglyceridemia (n = 5), anemia (n = 1), fatigue (n = 1), and hepatobiliary disorder (n = 1)...
April 18, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29664401/histone-deacetylase-7-mediates-tissue-specific-autoimmunity-via-control-of-innate-effector-function-in-invariant-natural-killer-t-cells
#17
Herbert G Kasler, Intelly S Lee, Hyung W Lim, Eric Verdin
We report that Histone Deacetylase 7 (HDAC7) controls the thymic effector programming of Natural Killer T (NKT) cells, and that interference with this function contributes to tissue-specific autoimmunity. Gain of HDAC7 function in thymocytes blocks both negative selection and NKT development, and diverts Vα14/Jα18 TCR transgenic thymocytes into a Tconv-like lineage. Conversely, HDAC7 deletion promotes thymocyte apoptosis and causes expansion of innate-effector cells. Investigating the mechanisms involved, we found that HDAC7 binds PLZF and modulates PLZF-dependent transcription...
April 17, 2018: ELife
https://www.readbyqxmd.com/read/29643474/histone-deacetylase-6-controls-notch3-trafficking-and-degradation-in-t-cell-acute-lymphoblastic-leukemia-cells
#18
Marica Pinazza, Margherita Ghisi, Sonia Minuzzo, Valentina Agnusdei, Gianluca Fossati, Vincenzo Ciminale, Laura Pezzè, Yari Ciribilli, Giorgia Pilotto, Carolina Venturoli, Alberto Amadori, Stefano Indraccolo
Several studies have revealed that endosomal sorting controls the steady-state levels of Notch at the cell surface in normal cells and prevents its inappropriate activation in the absence of ligands. However, whether this highly dynamic physiologic process can be exploited to counteract dysregulated Notch signaling in cancer cells remains unknown. T-ALL is a malignancy characterized by aberrant Notch signaling, sustained by activating mutations in Notch1 as well as overexpression of Notch3, a Notch paralog physiologically subjected to lysosome-dependent degradation in human cancer cells...
April 12, 2018: Oncogene
https://www.readbyqxmd.com/read/29603600/histone-protein-deacetylase-inhibitor-therapy-for-enhancement-of-foxp3-t-regulatory-cell-function-post-transplantation
#19
L Wang, U H Beier, T Akimova, S Dahiya, R Han, A Samanta, M H Levine, W W Hancock
T-regulatory (Treg) cells are like other cells present throughout the body in being subject to biochemical modifications in response to extracellular signals. An important component of these responses involves changes in post-translational modifications (PTMs) of histones and many non-histone proteins, including phosphorylation/dephosphorylation, ubiquitination/deubiquitination and acetylation/deacetylation. Foxp3, the key transcription factor of Tregs, is constantly being rapidly turned over, and a number of these PTMs determine its level of expression and activity...
March 30, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/29593659/how-to-control-htlv-1-associated-diseases-preventing-de-novo-cellular-infection-using-antiviral-therapy
#20
Amandine Pasquier, Sandrine Alais, Loic Roux, Maria-Isabel Thoulouze, Karine Alvarez, Chloé Journo, Hélène Dutartre, Renaud Mahieux
Five to ten million individuals are infected by Human T-cell Leukemia Virus type 1 (HTLV-1). HTLV-1 is transmitted through prolonged breast-feeding, by sexual contacts and by transmission of infected T lymphocytes through blood transfusion. One to ten percent of infected carriers will develop a severe HTLV-1-associated disease: Adult-T-cell leukemia/lymphoma (ATLL), or a neurological disorder named Tropical Spastic Paraparesis/HTLV-1 Associated Myelopathy (TSP/HAM). In vivo , HTLV-1 is mostly detected in CD4+ T-cells, and to a lesser extent in CD8+ T cells and dendritic cells...
2018: Frontiers in Microbiology
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