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histone deacetylase T cells

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https://www.readbyqxmd.com/read/29163504/butyrate-conditions-human-dendritic-cells-to-prime-type-1-regulatory-t-cells-via-both-histone-deacetylase-inhibition-and-g-protein-coupled-receptor-109a-signaling
#1
Maria M M Kaisar, Leonard R Pelgrom, Alwin J van der Ham, Maria Yazdanbakhsh, Bart Everts
Recently, it has become clear that short-chain fatty acids (SCFAs), and in particular butyrate, have anti-inflammatory properties. Murine studies have shown that butyrate can promote regulatory T cells via the induction of tolerogenic dendritic cells (DCs). However, the effects of SCFAs on human DCs and how they affect their capacity to prime and polarize T-cell responses have not been addressed. Here, we report that butyrate suppresses LPS-induced maturation and metabolic reprogramming of human monocyte-derived DCs (moDCs) and conditions them to polarize naive CD4(+) T cells toward IL-10-producing type 1 regulatory T cells (Tr1)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29152082/panbinostat-decreases-cflip-and-enhances-killing-of-cancer-cells-by-immunotoxin-lmb-100-by-stimulating-the-extrinsic-apoptotic-pathway
#2
Xiu-Fen Liu, Qi Zhou, Raffit Hassan, Ira Pastan
LMB-100 (RG7787) is a recombinant immunotoxin, which kills mesothelin-expressing cancer cells and now being evaluated in phase 1 trials. To enhance the anti-tumor activity of LMB-100, we have searched for agents, already approved for cancer therapy, that can be combined with LMB-100 to increase its efficacy. Panbinostat is a pan-histone deacetylase inhibitor that is used to treat multiple myeloma. We incubated different types of cancer cells with panbinostat and LMB-100 and found that they interacted synergistically to cause cell death...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29150330/the-structural-requirements-of-histone-deacetylase-inhibitors-c4-modified-saha-analogs-display-dual-hdac6-hdac8-selectivity
#3
Ahmed T Negmeldin, Joseph R Knoff, Mary Kay H Pflum
Histone deacetylase (HDAC) enzymes govern the post-translational acetylation state of lysine residues on protein substrates, leading to regulatory changes in cell function. Due to their role in cancers, HDAC proteins have emerged as promising targets for cancer treatment. Four HDAC inhibitors have been approved as anti-cancer therapeutics, including SAHA (Suberoylanilide hydroxamic acid, Vorinostat, Zolinza). SAHA is a nonselective HDAC inhibitor that targets most of the eleven HDAC isoforms. The nonselectivity of SAHA might account for its clinical side effects, but certainly limits its use as a chemical tool to study cancer-related HDAC cell biology...
October 31, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29142617/acute-strenuous-exercise-induces-an-imbalance-on-histone-h4-acetylation-histone-deacetylase-2-and-increases-the-proinflammatory-profile-of-pbmc-of-obese-individuals
#4
Gilson P Dorneles, Maria Carolina R Boeira, Lucas L Schipper, Ivy R V Silva, Viviane R Elsner, Pedro Dal Lago, Alessandra Peres, Pedro R T Romão
This study evaluated the response of global histone H4 acetylation (H4ac), histone deacetylase 2 (HDAC2) activity, as well as the production of proinflammatory cytokines and monocyte phenotypes of lean and obese males after exercise. Ten lean and ten obese sedentary men were submitted to one session of strenuous exercise, and peripheral blood mononuclear cells (PBMC) were stimulated in vitro with lipopolysaccharide (LPS). Global H4ac levels, HDAC2 activity in PBMC, and IL-6, IL-8, and TNF-α production were analyzed...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29137331/hdac-inhibitors-enhance-the-immunotherapy-response-of-melanoma-cells
#5
Laurence Booth, Jane L Roberts, Andrew Poklepovic, John Kirkwood, Paul Dent
We focused on the ability of the pan-histone deacetylase (HDAC) inhibitors AR42 and sodium valproate to alter the immunogenicity of melanoma cells. Treatment of melanoma cells with HDAC inhibitors rapidly reduced the expression of multiple HDAC proteins as well as the levels of PD-L1, PD-L2 and ODC, and increased expression of MHCA. In a cell-specific fashion, melanoma isolates released the immunogenic protein HMGB1 into the extracellular environment. Very similar data were obtained in ovarian and H&NSCC PDX isolates, and in established tumor cell lines from the lung and kidney...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136005/a-17-molecule-set-as-a-predictor-of-complete-response-to-neoadjuvant-chemotherapy-with-docetaxel-cisplatin-and-5-fluorouracil-in-esophageal-cancer
#6
Hajime Fujishima, Shoichi Fumoto, Tomotaka Shibata, Kohei Nishiki, Yoshiyuki Tsukamoto, Tsuyoshi Etoh, Masatsugu Moriyama, Norio Shiraishi, Masafumi Inomata
BACKGROUND: Recently, neoadjuvant chemotherapy with docetaxel/cisplatin/5-fluorouracil (NAC-DCF) was identified as a novel strong regimen with a high rate of pathological complete response (pCR) in advanced esophageal cancer in Japan. Predicting pCR will contribute to the therapeutic strategy and the prevention of surgical invasion. However, a predictor of pCR after NAC-DCF has not yet been developed. The aim of this study was to identify a novel predictor of pCR in locally advanced esophageal cancer treated with NAC-DCF...
2017: PloS One
https://www.readbyqxmd.com/read/29129787/cd38-nad-axis-regulates-immunotherapeutic-anti-tumor-t-cell-response
#7
Shilpak Chatterjee, Anusara Daenthanasanmak, Paramita Chakraborty, Megan W Wyatt, Payal Dhar, Shanmugam Paneer Selvam, Jianing Fu, Jinyu Zhang, Hung Nguyen, Inhong Kang, Kyle Toth, Mazen Al-Homrani, Mahvash Husain, Gyda Beeson, Lauren Ball, Kristi Helke, Shahid Husain, Elizabeth Garrett-Mayer, Gary Hardiman, Meenal Mehrotra, Michael I Nishimura, Craig C Beeson, Melanie Gubbels Bupp, Jennifer Wu, Besim Ogretmen, Chrystal M Paulos, Jeffery Rathmell, Xue-Zhong Yu, Shikhar Mehrotra
Heightened effector function and prolonged persistence, the key attributes of Th1 and Th17 cells, respectively, are key features of potent anti-tumor T cells. Here, we established ex vivo culture conditions to generate hybrid Th1/17 cells, which persisted long-term in vivo while maintaining their effector function. Using transcriptomics and metabolic profiling approaches, we showed that the enhanced anti-tumor property of Th1/17 cells was dependent on the increased NAD(+)-dependent activity of the histone deacetylase Sirt1...
November 8, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/29126877/chidamide-a-histone-deacetylase-inhibitor-based-anticancer-drug-effectively-reactivates-latent-hiv-1-provirus
#8
Wenqian Yang, Zhiwu Sun, Chen Hua, Qian Wang, Wei Xu, Qiwen Deng, Yanbin Pan, Lu Lu, Shibo Jiang
Although combination antiretroviral therapy (cART) is highly effective in suppressing human immunodeficiency virus type 1 (HIV-1) replication, it fails to eradicate the virus from HIV-1-infected individuals because HIV-1 integrates into the resting CD4(+) T cells, establishing latently infected reservoirs. Histone deacetylation is a key element in regulating HIV-1 latent infection. Chidamide, a new anticancer drug, is a novel type of selective histone deacetylase inhibitor. Here we showed that chidamide effectively reactivated HIV-1 latent provirus in different latently infected cell lines in a dose- and time-dependent manner...
November 8, 2017: Microbes and Infection
https://www.readbyqxmd.com/read/29124315/the-class-i-iv-hdac-inhibitor-mocetinostat-increases-tumor-antigen-presentation-decreases-immune-suppressive-cell-types-and-augments-checkpoint-inhibitor-therapy
#9
David Briere, Niranjan Sudhakar, David M Woods, Jill Hallin, Lars D Engstrom, Ruth Aranda, Harrah Chiang, Andressa L Sodré, Peter Olson, Jeffrey S Weber, James G Christensen
Checkpoint inhibitor therapy has led to major treatment advances for several cancers including non-small cell lung cancer (NSCLC). Despite this, a significant percentage of patients do not respond or develop resistance. Potential mechanisms of resistance include lack of expression of programmed death ligand 1 (PD-L1), decreased capacity to present tumor antigens, and the presence of an immunosuppressive tumor microenvironment. Mocetinostat is a spectrum-selective inhibitor of class I/IV histone deacetylases (HDACs), a family of proteins implicated in epigenetic silencing of immune regulatory genes in tumor and immune cells...
November 9, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29113816/hdac2-suppresses-il17a-mediated-airway-remodeling-in-human-and-experimental-modeling-of-copd
#10
Tianwen Lai, Baoping Tian, Chao Cao, Yue Hu, Jiesen Zhou, Yong Wang, Yanping Wu, Zhouyang Li, Xuchen Xu, Min Zhang, Feng Xu, Yuan Cao, Min Chen, Dong Wu, Bin Wu, Chen Dong, Wen Li, Songmin Ying, Zhihua Chen, Huahao Shen
BACKGROUND: Airway remodeling is a central feature of chronic obstructive pulmonary disease (COPD), but the mechanisms underlying its development have not been fully elucidated. OBJECTIVE: To determine whether histone deacetylase (HDAC) 2 protects against cigarette smoke (CS)-induced airway remodeling through IL17A-dependent mechanisms. METHODS: Sputum samples and lung tissues were obtained from control subjects and patients with COPD. The relationships between HDAC2, IL17A, and airway remodeling were investigated...
November 4, 2017: Chest
https://www.readbyqxmd.com/read/29102679/cutaneous-t-cell-lymphomas-focusing-on-novel-agents-in-relapsed-and-refractory-disease
#11
REVIEW
Lisa Argnani, Alessandro Broccoli, Pier Luigi Zinzani
Patients with relapsed or refractory cutaneous T-cell lymphoma (CTCL) display a dismal prognosis and their therapy represents an unmet medical need, as the best treatment strategy is yet to be determined. Exciting data on novel targeted agents are now emerging from recently concluded and ongoing clinical trials in patients with relapsed and refractory CTCL. Three FDA approved compounds are used as single agents including the oral retinoid bexarotene and histone deacetylase inhibitors romidepsin and vorinostat...
December 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29057046/synthesis-and-pharmacological-evaluation-of-selective-histone-deacetylase-6-inhibitors-in-melanoma-models
#12
Maurício T Tavares, Sida Shen, Tessa Knox, Melissa Hadley, Zsófia Kutil, Cyril Bařinka, Alejandro Villagra, Alan P Kozikowski
Only a handful of therapies offer significant improvement in the overall survival in cases of melanoma, a cancer whose incidence has continued to rise in the past 30 years. In our effort to identify potent and isoform-selective histone deacetylase (HDAC) inhibitors as a therapeutic approach to melanoma, a series of new HDAC6 inhibitors based on the nexturastat A scaffold were prepared. The new analogues 4d, 4e, and 7b bearing added hydrophilic substituents, so as to establish additional hydrogen bonding on the rim of the HDAC6 catalytic pocket, exhibit improved potency against HDAC6 and retain selectivity over HDAC1...
October 12, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29050320/epigenetic-regulation-of-interleukin-8-expression-by-class-i-hdac-and-cbp-in-ovarian-cancer-cells
#13
Himavanth R Gatla, Yue Zou, Mohammad M Uddin, Ivana Vancurova
Although inhibitors of epigenetic regulators have been effective in the treatment of cutaneous T cell lymphoma (CTCL) and other hematopoietic malignancies, they have been less effective in solid tumors, including ovarian cancer (OC). We have previously shown that inhibition of histone deacetylase (HDAC) activity induces expression of the pro-inflammatory and pro-angiogenic chemokine interleukin-8 (CXCL8, IL-8) in OC cells, resulting in their increased survival and proliferation. Here, we show that in addition to ovarian cancer SKOV3, OVCAR3, and CAOV3 cells, HDAC inhibition induces the CXCL8 expression in HeLa cells, but not in CTCL Hut-78 cells...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29030662/oral-histone-deacetylase-inhibitor-synergises-with-t-cell-targeted-immunotherapy-to-preserve-beta-cell-metabolic-function-and-induce-stable-remission-of-new-onset-autoimmune-diabetes-in-nod-mice
#14
Alix Besançon, Tania Goncalves, Fabrice Valette, Mattias S Dahllöf, Thomas Mandrup-Poulsen, Lucienne Chatenoud, Sylvaine You
AIM/HYPOTHESIS: Combination therapy targeting the major actors involved in the immune-mediated destruction of pancreatic beta cells appears to be an indispensable approach to treat type 1 diabetes effectively. We hypothesised that the combination of an orally active pan-histone deacetylase inhibitor (HDACi: givinostat) with subtherapeutic doses of CD3 antibodies may provide ideal synergy to treat ongoing autoimmunity. METHODS: NOD mice transgenic for the human CD3ε (also known as CD3E) chain (NOD-huCD3ε) were treated for recent-onset diabetes with oral givinostat, subtherapeutic doses of humanised CD3 antibodies (otelixizumab, 50 μg/day, 5 days, i...
October 13, 2017: Diabetologia
https://www.readbyqxmd.com/read/29025909/histone-deacetylase-inhibitors-downregulate-ccr4-expression-and-decrease-mogamulizumab-efficacy-in-ccr4-positive-mature-t-cell-lymphomas
#15
Akihiro Kitadate, Sho Ikeda, Fumito Abe, Naoto Takahashi, Norio Shimizu, Kosei Matsue, Hiroyuki Tagawa
HDAC inhibitors are promising agents for various T-cell lymphomas, including cutaneous T-cell lymphoma, peripheral T-cell lymphoma, and adult T-cell lymphoma/leukemia. CCR4 is an important therapeutic target molecule because mogamulizumab, an anti-CCR4 antibody, has shown promising efficacy against various T-cell lymphomas. In this study, we examined the in vitro synergistic effects of mogamulizumab and HDAC inhibitors against various T-cell lymphomas. First, we examined the expression of CCR4 mRNA and surface CCR4 in various T-cell lymphoma cell lines and found it was downregulated upon treatment with vorinostat, a pan-HDAC inhibitor...
October 12, 2017: Haematologica
https://www.readbyqxmd.com/read/29023392/disposition-metabolism-and-histone-deacetylase-and-acetyltransferase-inhibition-activity-of-tetrahydrocurcumin-and-other-curcuminoids
#16
Júlia T Novaes, Ryan Lillico, Casey L Sayre, Kalyanam Nagabushnam, Muhammed Majeed, Yufei Chen, Emmanuel A Ho, Ana Luísa de P Oliveira, Stephanie E Martinez, Samaa Alrushaid, Neal M Davies, Ted M Lakowski
Tetrahydrocurcumin (THC), curcumin and calebin-A are curcuminoids found in turmeric (Curcuma longa). Curcuminoids have been established to have a variety of pharmacological activities and are used as natural health supplements. The purpose of this study was to identify the metabolism, excretion, antioxidant, anti-inflammatory and anticancer properties of these curcuminoids and to determine disposition of THC in rats after oral administration. We developed a UHPLC-MS/MS assay for THC in rat serum and urine. THC shows multiple redistribution phases with corresponding increases in urinary excretion rate...
October 12, 2017: Pharmaceutics
https://www.readbyqxmd.com/read/29021396/quiescence-promotes-latent-hiv-infection-and-resistance-to-reactivation-from-latency-with-histone-deacetylase-inhibitors
#17
Mark M Painter, Thomas D Zaikos, Kathleen L Collins
Human immunodeficiency virus type-1 (HIV-1) establishes transcriptionally silent latent infections in many cell types, including resting memory T cells and hematopoietic stem and progenitor cells (HSPCs), which allow the virus to persist in infected individuals despite antiretroviral therapy. Developing in vitro models of HIV-1 latency that recapitulate the characteristics of latently-infected cells in vivo is crucial to identifying and developing effective latency-reversing therapies. HSPCs exist in a quiescent state in vivo, and quiescence is correlated with latent infections in T cells...
October 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28972015/synergy-of-bcl2-and-histone-deacetylase-inhibition-against-leukemic-cells-from-cutaneous-t-cell-lymphoma-patients
#18
Benoit M Cyrenne, Julia Lewis, Jason Weed, Kacie Carlson, Fatima N Mirza, Francine Foss, Michael Girardi
The presence and degree of peripheral blood involvement in patients with cutaneous T-cell lymphoma (CTCL) portend a worse clinical outcome. Available systemic therapies for CTCL may variably decrease tumor burden and improve quality of life, but offer limited effects on survival; thus, novel approaches to the treatment of advanced stages of this non-Hodgkin lymphoma are clearly warranted. Mutational analyses of CTCL patient peripheral blood malignant cell samples suggested the anti-apoptotic mediator BCL2 as a potential therapeutic target...
October 2, 2017: Blood
https://www.readbyqxmd.com/read/28968979/mir-122-socs1-jak2-axis-regulates-allergic-inflammation-and-allergic-inflammation-promoted-cellular-interactions
#19
Kyeonga Noh, Misun Kim, Youngmi Kim, Hanearl Kim, Hyuna Kim, Jaehwan Byun, Yeongseo Park, Hansoo Lee, Yun Sil Lee, Jongseon Choe, Young Myeong Kim, Dooil Jeoung
The regulatory role of suppressor of cytokine signaling 1 (SOCS1) in inflammation has been reported. However, its role in allergic inflammation has not been previously reported. SOCS1 mediated in vitro and in vivo allergic inflammation. Histone deacetylase-3 (HDAC3), a mediator of allergic inflammation, interacted with SOCS1, and miR-384 inhibitor, a positive regulator of HDAC3, induced features of allergic inflammation in an SOCS1-dependent manner. miRNA array analysis showed that the expression of miR-122 was decreased by antigen-stimulation...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28964722/a-t-cell-specific-deletion-of-hdac1-protects-against-experimental-autoimmune-encephalomyelitis
#20
Lisa Göschl, Teresa Preglej, Patricia Hamminger, Michael Bonelli, Liisa Andersen, Nicole Boucheron, Alexandra F Gülich, Lena Müller, Victoria Saferding, Ilgiz A Mufazalov, Kiyoshi Hirahara, Christian Seiser, Patrick Matthias, Thomas Penz, Michael Schuster, Christoph Bock, Ari Waisman, Günter Steiner, Wilfried Ellmeier
Multiple sclerosis (MS) is a human neurodegenerative disease characterized by the invasion of autoreactive T cells from the periphery into the CNS. Application of pan-histone deacetylase inhibitors (HDACi) ameliorates experimental autoimmune encephalomyelitis (EAE), an animal model for MS, suggesting that HDACi might be a potential therapeutic strategy for MS. However, the function of individual HDAC members in the pathogenesis of EAE is not known. In this study we report that mice with a T cell-specific deletion of HDAC1 (using the Cd4-Cre deleter strain; HDAC1-cKO) were completely resistant to EAE despite the ability of HDAC1cKO CD4(+) T cells to differentiate into Th17 cells...
September 27, 2017: Journal of Autoimmunity
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