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histone deacetylase T cells

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https://www.readbyqxmd.com/read/29327377/s%C3%A3-zary-syndrome-managed-with-histone-deacetylase-inhibitor-followed-by-anti-ccr4-monoclonal-antibody
#1
T Numata, T Nagatani, K Shirai, T Maeda, K Mae, M Nakasu, M Saito, T Usuda, R Tsuboi, Y Okubo
A 70-year-old man presented to our clinic with a 10-year history of recurrent pruritic erythema and plaques on his trunk and limbs. Based on the pathological findings and monoclonal rearrangement of the T-cell receptor (TCR)-Cβ1 gene, mycosis fungoides (T2N0M0B0 stage IB) was diagnosed. Despite combination therapy including histone deacetylase inhibitor (vorinostat), the symptoms slowly evolved into Sézary syndrome (SS; T4N1M0B2) over 4 years, with dense infiltrates due to atypical lymphocytes expressing CCR4 developing in the entire dermis...
January 12, 2018: Clinical and Experimental Dermatology
https://www.readbyqxmd.com/read/29305415/histone-modifier-gene-mutations-in-peripheral-t-cell-lymphoma-not-otherwise-specified
#2
Meng-Meng Ji, Yao-Hui Huang, Jin-Yan Huang, Zhao-Fu Wang, Di Fu, Han Liu, Feng Liu, Christophe Leboeuf, Li Wang, Jing Ye, Yi-Ming Lu, Anne Janin, Shu Cheng, Wei-Li Zhao
Due to heterogeneous morphological and immunophenotypic features, approximately 50% of peripheral T-cell lymphomas are unclassifiable and categorized as peripheral T-cell lymphomas, not otherwise specified, presenting aggressive disease course and poor clinical outcome. Identification of actionable biomarkers is urgently needed to develop better therapeutic strategies. Epigenetic alterations play a crucial role in tumor progression. Histone modifications, particularly methylation and acetylation, are generally involved in chromatin state regulation...
January 5, 2018: Haematologica
https://www.readbyqxmd.com/read/29302039/targeting-the-corest-complex-with-dual-histone-deacetylase-and-demethylase-inhibitors
#3
Jay H Kalin, Muzhou Wu, Andrea V Gomez, Yun Song, Jayanta Das, Dawn Hayward, Nkosi Adejola, Mingxuan Wu, Izabela Panova, Hye Jin Chung, Edward Kim, Holly J Roberts, Justin M Roberts, Polina Prusevich, Jeliazko R Jeliazkov, Shourya S Roy Burman, Louise Fairall, Charles Milano, Abdulkerim Eroglu, Charlotte M Proby, Albena T Dinkova-Kostova, Wayne W Hancock, Jeffrey J Gray, James E Bradner, Sergio Valente, Antonello Mai, Nicole M Anders, Michelle A Rudek, Yong Hu, Byungwoo Ryu, John W R Schwabe, Andrea Mattevi, Rhoda M Alani, Philip A Cole
Here we report corin, a synthetic hybrid agent derived from the class I HDAC inhibitor (entinostat) and an LSD1 inhibitor (tranylcypromine analog). Enzymologic analysis reveals that corin potently targets the CoREST complex and shows more sustained inhibition of CoREST complex HDAC activity compared with entinostat. Cell-based experiments demonstrate that corin exhibits a superior anti-proliferative profile against several melanoma lines and cutaneous squamous cell carcinoma lines compared to its parent monofunctional inhibitors but is less toxic to melanocytes and keratinocytes...
January 4, 2018: Nature Communications
https://www.readbyqxmd.com/read/29301535/inhibition-of-histone-deacetylase-activity-rescues-inflammatory-cystic-fibrosis-lung-disease-by-modulating-innate-and-adaptive-immune-responses
#4
Manish Bodas, Steven Mazur, Taehong Min, Neeraj Vij
BACKGROUND: Chronic lung disease resulting from dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR) and NFκB-mediated neutrophilic-inflammation forms the basis of CF-related mortality. Here we aimed to evaluate if HDAC inhibition controls Pseudomonas-aeruginosa-lipopolysaccharide (Pa-LPS) induced airway inflammation and CF-lung disease. METHODS: For in vitro experiments, HEK293-cells were transfected with IL-8 or NFκB-firefly luciferase, and SV40-renilla- luciferase reporter constructs or ΔF508-CFTR-pCEP, followed by treatment with suberoylanilide hydroxamic acid (SAHA), Trichostatin-A (TSA) and/or TNFα...
January 4, 2018: Respiratory Research
https://www.readbyqxmd.com/read/29298886/class-1-selective-histone-deacetylase-inhibitors-enhance-hiv-latency-reversal-while-preserving-the-activity-of-hdac-isoforms-necessary-for-maximal-hiv-gene-expression
#5
Thomas D Zaikos, Mark M Painter, Nadia T Sebastian, Valeri H Terry, Kathleen L Collins
Combinations of drugs that affect distinct mechanisms of HIV latency aim to induce robust latency reversal leading to cytopathicity and elimination of the persistent HIV reservoir. Thus far, attempts have focused on combinations of PKC agonists and pan-histone deacetylase inhibitors (HDIs) despite the knowledge that HIV gene expression is regulated by class 1 histone deacetylases. We hypothesized that class 1-selective HDIs would promote more robust HIV latency reversal in combination with a PKC agonist than pan-HDIs because they preserve the activity of pro-viral factors regulated by non-class 1 histone deacetylases...
January 3, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29285209/combination-of-il-2-rapamycin-dna-methyltransferase-and-histone-deacetylase-inhibitors-for-the-expansion-of-human-regulatory-t-cells
#6
Makoto Miyara, Driss Chader, Aude Burlion, Jérémie Goldstein, Delphine Sterlin, Françoise Norol, Hélène Trebeden-Nègre, Laetitia Claër, Shimon Sakaguchi, Gilles Marodon, Zahir Amoura, Guy Gorochov
FOXP3+ regulatory T cell (Treg) based cellular therapies represent promising therapeutic options in autoimmunity, allergy, transplantation and prevention of Graft Versus Host (GVH) Disease. Among human FOXP3-expressing CD4+T cells, only the CD45RA+ naïve Treg (nTreg) subset is suitable for in vitro expansion. However, FoxP3 expression decays in cells using currently described culture protocols. Rapamycin alone was not able to prevent FOXP3 loss in nTregs cells, as only a half of them maintained FOXP3 expression after 14 days of culture...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29273397/pathological-histone-acetylation-in-parkinson-s-disease-neuroprotection-and-inhibition-of-microglial-activation-through-sirt-2-inhibition
#7
Ian F Harrison, Andrew D Smith, David T Dexter
Parkinson's disease (PD) is associated with degeneration of nigrostriatal neurons due to intracytoplasmic inclusions composed predominantly of a synaptic protein called α-synuclein. Accumulations of α-synuclein are thought to 'mask' acetylation sites on histone proteins, inhibiting the action of histone acetyltransferase (HAT) enzymes in their equilibrium with histone deacetylases (HDACs), thus deregulating the dynamic control of gene transcription. It is therefore hypothesised that the misbalance in the actions of HATs/HDACs in neurodegeneration can be rectified with the use of HDAC inhibitors, limiting the deregulation of transcription and aiding neuronal homeostasis and neuroprotection in disorders such as PD...
December 19, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/29251528/pendant-hdac-inhibitor-saha-derivatized-polymer-as-a-novel-prodrug-micellar-carrier-for-anticancer-drugs
#8
Jieni Xu, Jingjing Sun, Pengcheng Wang, Xiaochao Ma, Song Li
Suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor (HDACI) approved by FDA for the treatment of cutaneous T cell lymphoma, is a promising anticancer drug for various cancers with a unique mode of action. However, it demonstrates limited clinical benefits in solid tumors as a single drug. In order to achieve enhanced and synergistic co-delivery of SAHA and Doxorubicin (DOX), a cleavable SAHA-based prodrug polymer (POEG-b-PSAHA), consisting of hydrophilic poly(oligo(ethylene glycol) methacrylate) (POEG) blocks and hydrophobic SAHA segments, has been developed...
December 18, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/29240919/genome-wide-dose-dependent-inhibition-of-histone-deacetylases-studies-reveal-their-roles-in-enhancer-remodeling-and-suppression-of-oncogenic-super-enhancers
#9
Gilson J Sanchez, Phillip A Richmond, Eric N Bunker, Samuel S Karman, Joseph Azofeifa, Aaron T Garnett, Quanbin Xu, Graycen E Wheeler, Cathryn M Toomey, Qinghong Zhang, Robin D Dowell, Xuedong Liu
Histone deacetylase inhibitors (HDACIs) are known to alter gene expression by both up- and down-regulation of protein-coding genes in normal and cancer cells. However, the exact regulatory mechanisms of action remain uncharacterized. Here we investigated genome wide dose-dependent epigenetic and transcriptome changes in response to HDACI largazole in a transformed and a non-transformed cell line. Exposure to low nanomolar largazole concentrations (<GI50) predominantly resulted in upregulation of gene transcripts whereas higher largazole doses (≥GI50) triggered a general decrease in mRNA accumulation...
December 12, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29238349/the-roles-of-glycodelin-in-cancer-development-and-progression
#10
REVIEW
Juan Cui, Yanguo Liu, Xiuwen Wang
Glycodelin is a kind of glycoprotein expressed in secretory endometrium, pregnancy deciduas, and amniotic fluid originally, which is vital for the maintenance of normal human reproductive activities. Recent researches have reported that glycodelin is specifically expressed in various malignancies, including female-specific cancers such as endometrial cancer, ovarian cancer and breast cancer, and non-gender specific cancers including lung cancer, and colon cancer, and glycodelin expression correlates with the diagnosis and prognosis of cancer patients...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29223388/transplantation-in-the-treatment-of-primary-cutaneous-aggressive-epidermotropic-cytotoxic-cd8-positive-t-cell-lymphoma
#11
Benoit M Cyrenne, Juliet Fraser Gibson, Antonio Subtil, Michael Girardi, Iris Isufi, Stuart Seropian, Francine Foss
BACKGROUND: Primary cutaneous aggressive epidermotropic cytotoxic CD8 positive T-cell lymphoma (CD8+ PCAETL) is a rare subtype of peripheral T-cell lymphoma with poor outcomes and without a standardized treatment strategy. Allogeneic hematopoietic stem cell transplantation (HSCT) has been suggested as a potential curative therapy. PATIENTS AND METHODS: We conducted a retrospective case series. We identified 8 patients with the diagnosis of CD8+ PCAETL, 4 of whom also underwent allogeneic HSCT...
December 6, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29223096/discovery-of-aliphatic-chain-hydroxamates-containing-indole-derivatives-with-potent-class-i-histone-deacetylase-inhibitory-activities
#12
Shi-Wei Chao, Liang-Chieh Chen, Chia-Chun Yu, Chang-Yi Liu, Tony Eight Lin, Jih-Hwa Guh, Chen-Yu Wang, Chun-Yung Chen, Kai-Cheng Hsu, Wei-Jan Huang
Histone deacetylase (HDAC) is a validated drug target for various diseases. This study combined indole recognition cap with SAHA, an FDA-approved HDAC inhibitor used to treat cutaneous T-cell lymphoma (CTCL). The structure activity relationship of the resulting compounds that inhibited HDAC was disclosed as well. Some compounds exhibited much stronger inhibitory activities than SAHA. We identified two meta-series compounds 6j and 6k with a two-carbon linker had IC50 values of 3.9 and 4.5 nM for HDAC1, respectively...
December 5, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29222071/hdac11-is-a-regulator-of-diverse-immune-functions
#13
REVIEW
Cansu Yanginlar, Colin Logie
Histone deacetylases deacetylate histone and non-histone protein targets. Aberrant HDAC expression and function have been observed in several diseases, which makes these enzymes attractive treatment targets. Here, we summarize recent literature that addresses the roles of HDAC11 on the regulation of different immune cells including neutrophils, myeloid derived suppressor cells and T-cells. HDAC11 was initially identified as a negative regulator of the well-known anti-inflammatory cytokine IL-10. Hence, antagonizing HDAC11 activity may have anti-tumor potential, whereas activating HDAC11 may be useful to treat chronic inflammation or autoimmunity...
December 5, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29213086/3d-microniches-reveal-the-importance-of-cell-size-and-shape
#14
Min Bao, Jing Xie, Aigars Piruska, Wilhelm T S Huck
Geometrical cues have been shown to alter gene expression and differentiation on 2D substrates. However, little is known about how geometrical cues affect cell function in 3D. One major reason for this lack of understanding is rooted in the difficulties of controlling cell geometry in a complex 3D setting and for long periods of culture. Here, we present a robust method to control cell volume and shape of individual human mesenchymal stem cells (hMSCs) inside 3D microniches with a range of different geometries (e...
December 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/29205773/treponema-denticola-increases-mmp-2-expression-and-activation-in-the-periodontium-via-reversible-dna-and-histone-modifications
#15
Islam M Ateia, Pimchanok Sutthiboonyapan, Pachiyappan Kamarajan, Taocong Jin, Valentina Godovikova, Yvonne L Kapila, J Christopher Fenno
Host-derived matrix metalloproteinases (MMPs) and bacterial proteases mediate destruction of extracellular matrices and supporting alveolar bone in periodontitis. The Treponema denticola dentilisin protease induces MMP-2 expression and activation in periodontal ligament (PDL) cells, and dentilisin-mediated activation of pro-MMP-2 is required for cellular fibronectin degradation. Here we report that T. denticola regulates MMP-2 expression through epigenetic modifications in the periodontium. PDL cells were treated with epigenetic enzyme inhibitors before or after T...
December 4, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/29203668/epigenetic-therapy-activates-type-i-interferon-signaling-in-murine-ovarian-cancer-to-reduce-immunosuppression-and-tumor-burden
#16
Meredith L Stone, Katherine B Chiappinelli, Huili Li, Lauren M Murphy, Meghan E Travers, Michael J Topper, Dimitrios Mathios, Michael Lim, Ie-Ming Shih, Tian-Li Wang, Chien-Fu Hung, Vipul Bhargava, Karla R Wiehagen, Glenn S Cowley, Kurtis E Bachman, Reiner Strick, Pamela L Strissel, Stephen B Baylin, Cynthia A Zahnow
Ovarian cancer is the most lethal of all gynecological cancers, and there is an urgent unmet need to develop new therapies. Epithelial ovarian cancer (EOC) is characterized by an immune suppressive microenvironment, and response of ovarian cancers to immune therapies has thus far been disappointing. We now find, in a mouse model of EOC, that clinically relevant doses of DNA methyltransferase and histone deacetylase inhibitors (DNMTi and HDACi, respectively) reduce the immune suppressive microenvironment through type I IFN signaling and improve response to immune checkpoint therapy...
December 4, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29201907/developmental-testicular-expression-cloning-and-characterization-of-rat-hdac6-in-silico
#17
Pratibha Verma, Omshree Shetty, Sweta Parab, Karen Menezes, Priyanka Parte
We had previously reported presence of histone deacetylase 6 (HDAC6) in sperm and demonstrated its tubulin deacetylase activity and role in sperm motility in rat. In the present study we report its abundant expression in testis, epididymis, accessory sex organs, brain, and adrenal. In the testis, HDAC6 transcript and protein were observed throughout development. We therefore cloned the gene from rat testis using primers for hdac6 (accession number XM_228753.8) in order to determine the role of acetylation/deacetylation in spermatogenesis...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29197589/sirt6-expression-and-oxidative-dna-damage-in-individuals-with-prediabetes-and-type-2-diabetes-mellitus
#18
Z Caliskan, T Mutlu, M Guven, M Tuncdemir, M Niyazioğlu, Y Hacioglu, Y Dincer
Sirtuins (SIRTs) is a family of NAD+ dependent histone deacetylases. SIRT6 takes play in glucose homeostasis, genomic stability and DNA repair. Although increased oxidative DNA damage and decreased DNA repair activity were determined in diabetes mellitus, the possible relation between level of oxidative DNA damage and SIRT6 expression has not been investigated so far. We determined SIRT6 expression and urinary 8-hydroxy deoxyguanosine (8-OHdG) levels, marker of oxidative DNA damage, in cases with prediabetes (PreDM) and type 2 diabetes mellitus (T2DM)...
November 29, 2017: Gene
https://www.readbyqxmd.com/read/29195073/epigenetic-therapy-ties-myc-depletion-to-reversing-immune-evasion-and-treating-lung-cancer
#19
Michael J Topper, Michelle Vaz, Katherine B Chiappinelli, Christina E DeStefano Shields, Noushin Niknafs, Ray-Whay Chiu Yen, Alyssa Wenzel, Jessica Hicks, Matthew Ballew, Meredith Stone, Phuoc T Tran, Cynthia A Zahnow, Matthew D Hellmann, Valsamo Anagnostou, Pamela L Strissel, Reiner Strick, Victor E Velculescu, Stephen B Baylin
Combining DNA-demethylating agents (DNA methyltransferase inhibitors [DNMTis]) with histone deacetylase inhibitors (HDACis) holds promise for enhancing cancer immune therapy. Herein, pharmacologic and isoform specificity of HDACis are investigated to guide their addition to a DNMTi, thus devising a new, low-dose, sequential regimen that imparts a robust anti-tumor effect for non-small-cell lung cancer (NSCLC). Using in-vitro-treated NSCLC cell lines, we elucidate an interferon α/β-based transcriptional program with accompanying upregulation of antigen presentation machinery, mediated in part through double-stranded RNA (dsRNA) induction...
November 30, 2017: Cell
https://www.readbyqxmd.com/read/29194108/epigenetics-of-inflammatory-arthritis
#20
Deepa Hammaker, Gary S Firestein
PURPOSE OF REVIEW: Aberrant epigenetic changes in DNA methylation, histone marks, and noncoding RNA expression regulate the pathogenesis of many rheumatic diseases. The present article will review the recent advances in the epigenetic profile of inflammatory arthritis and discuss diagnostic biomarkers and potential therapeutic targets. RECENT FINDINGS: Methylation signatures of fibroblast-like synoviocytes not only distinguish rheumatoid arthritis (RA) and osteoarthritis (OA), but also early RAs from late RAs or juvenile idiopathic arthritis...
November 30, 2017: Current Opinion in Rheumatology
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