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histone deacetylase T cells

Gianluigi Franci, Federica Sarno, Angela Nebbioso, Lucia Altucci
Epigenetic modifications are functionally involved in gene expression regulation. In particular, histone posttranslational modifications play a crucial role in functional chromatin organization. Several drugs able to inhibit or stimulate some families of proteins involved in epigenetic histone regulation have been found, a number of which are FDA-approved for the treatment of cutaneous T-cell lymphoma or are in phase I/II/III clinical trials for solid tumors. Although some protein families, such as histone deacetylases and their inhibitors, are well characterized, our understanding of histone lysine demethylases is still incomplete...
October 21, 2016: Epigenetics: Official Journal of the DNA Methylation Society
E Faghihloo, Y Araei, M Mohammadi, H Mirzaei, H R Mohammadi, T Mokhtari-Azad
Gastric cancer is among the leading causes of cancer-related death, and the symptoms are commonly characterized in advanced stages. Histone acetylation is among the most important epigenetic alterations occurring during cancer development. In addition, reduced E-cadherin expression is a major contributor in the process of tumor cell invasion and metastasis. Oxamflatin is a histone deacetylase inhibitor that has been suggested as a promising anti-tumor agent; yet its effect on the viability and invasion of gastric tumor cells is unclear...
October 21, 2016: Cancer Gene Therapy
P-H Liao, H-H Hsu, T-S Chen, M-C Chen, C-H Day, C-C Tu, Y-M Lin, F-J Tsai, W-W Kuo, C-Y Huang
Hepatocellular carcinoma (HCC) is the most common type of liver cancer. Despite the availability of several treatment strategies, resistance to chemotherapeutic agents, which limits the effectiveness of anticancer drugs, is a major problem in cancer therapy. In this study, we used a histone deacetylases inhibitor (HDACi) to establish drug-resistant HCC cells and further analyzed the molecular mechanisms underlying the development of resistance in HCC cells. Compared with the parental cells, HDACi-resistant cells showed high metastatic and pro-survival abilities...
October 17, 2016: Oncogene
Zachary T Rivers, Drew R Oostra, James S Westholder, Gregory M Vercellotti
BACKGROUND: Romidepsin is a novel histone deacetylase inhibitor that is approved for the treatment of cutaneous and peripheral T-cell lymphoma in patients who have had at least one prior therapy. Romidepsin is generally well tolerated, though it comes with a risk of cardiac toxicities. OBJECTIVE: We report a case of electrocardiogram changes in a 64-year-old male with enteropathy-associated T-cell lymphoma, type 2, treated with salvage romidepsin therapy who relapsed after non-myeloablative allogeneic sibling peripheral blood stem cell transplant...
October 5, 2016: Journal of Oncology Pharmacy Practice
P Larsson, I Alwis, B Niego, M Sashindranath, P Fogelstrand, M C L Wu, L Glise, M Magnusson, M Daglas, N Bergh, S P Jackson, R L Medcalf, S Jern
BACKGROUND: The endogenous fibrinolytic system has rarely been considered as a target to prevent thrombotic disease. Tissue plasminogen activator (t-PA) is potently increased by histone deacetylase (HDAC) inhibitors in endothelial cells in vitro, but whether this translates into increased vascular t-PA production and an enhanced fibrinolytic capacity in vivo is unknown. OBJECTIVES: The aim of this study was to determine if the HDAC inhibitor valproic acid (VPA) stimulates production of t-PA in the vasculature of mice, and further, if VPA pre-treatment affects fibrin deposition and clot formation after mechanical vessel injury...
October 5, 2016: Journal of Thrombosis and Haemostasis: JTH
M T Nuo, J L Yuan, W L Yang, X Y Gao, N He, H Liang, M Cang, D J Liu
Transgene silencing, which is common in transgenic plants and animals, limits the generation and application of genetically modified organisms, and is associated with the exogenous gene copy number, the methylation status of its promoters, and histone modification abnormalities. Here, we analyzed the expression of the exogenous gene DsRed and the methylation status of its cytomegalovirus (CMV) promoter in six healthy transgenic cashmere goats and transgenic nuclear donor cells. The CMV promoter exhibited high methylation levels (74...
August 29, 2016: Genetics and Molecular Research: GMR
Hana Čipčić Paljetak, Linda Tomašković, Mario Matijašić, Mirjana Bukvić, Andrea Fajdetić, Donatella Verbanac, Mihaela Perića
5-LOX - 5-lipoxygenase; ACT - artemisinin-based combination therapies; ADME - absorption, distribution, metabolism and excretion; BAL - broncho alveolar lavage; CABP - community acquired bacterial pneumonia; cAMP - cyclic adenosine monophosphate; CAP - community-acquired pneumonia; CF - cystic fibrosis, BOS bronchiolitis obliterans syndrome; cGMP - cyclic guanosine monophosphate; COPD - chronic obstructive pulmonary disease; COX - cyclooxygenase; DPB - diffuse panbronchiolitis; HDACs - histone deacetylases; IBD - inflammatory bowel disease; IL-1p - interleukin 1p; IL-6 - interleukin 6; MIC - minimal inhibitory concentrations; MLSB - macrolide, lincosamide, streptogramin B; NSAIDs - non-steroidal anti-inflammatory drugs; OVA - ovalbumin; PDE4 - phosphodiesterase 4; PMA - phorbol 12-myristate 13-acetate; RA - rheumatoid arthritis; RTI - respiratory tract infections; SAHA - suberoylanilide hydroxamic acid; SAR - structure-activity-relationship; Th1 - type 1 helper T-cell; TNBS - trinitrobenzene sulfonic acid; TNF-α - tumour necrosis factor α; UN - United Nations, WHO - World Health Organisation...
September 27, 2016: Current Topics in Medicinal Chemistry
A E Witt, C-W Lee, T I Lee, D J Azzam, B Wang, C Caslini, F Petrocca, J Grosso, M Jones, E B Cohick, A B Gropper, C Wahlestedt, A L Richardson, R Shiekhattar, R A Young, T A Ince
Tumours are comprised of a highly heterogeneous population of cells, of which only a small subset of stem-like cells possess the ability to regenerate tumours in vivo. These cancer stem cells (CSCs) represent a significant clinical challenge as they are resistant to conventional cancer therapies and play essential roles in metastasis and tumour relapse. Despite this realization and great interest in CSCs, it has been difficult to develop CSC-targeted treatments due to our limited understanding of CSC biology...
October 3, 2016: Oncogene
Raffaele Simeoli, Giuseppina Mattace Raso, Claudio Pirozzi, Adriano Lama, Anna Santoro, Roberto Russo, Trinidad Montero-Melendez, Roberto Berni Canani, Antonio Calignano, Mauro Perretti, Rosaria Meli
BACKGROUND AND PURPOSE: Butyrate has shown benefits in inflammatory bowel diseases (IBD). However, its oral administration is infrequent due to rancid smell and unpleasant taste. The efficacy of a more palatable butyrate-releasing derivative, N-(1-carbamoyl-2-phenylethyl) butyramide (FBA), was evaluated in a mouse model of colitis induced by dextran sodium sulphate (DSS). EXPERIMENTAL APPROACH: Male 10-week-old BALB/c mice received DSS (2.5%) in drinking water (for 5d) followed by DSS-free water for 7d (DSS group)...
September 29, 2016: British Journal of Pharmacology
Shaorong Zhao, Wei Liu, Yinghui Li, Pengjiang Liu, Shufang Li, Daolei Dou, Yue Wang, Rongcun Yang, Rong Xiang, Feifei Liu
The molecular defects which lead to multistep incidences of human T-cell leukemia have yet to be identified. The DNA-binding protein Helios (known as IKZF2), a member of the Ikaros family of Krüppel-like zinc-finger proteins, functions pivotally in T-cell differentiation and activation. In this study, we identify three novel short Helios splice variants which are T-cell leukemic specific, and demonstrate their dominant-negative function. We then test the cellular localization of distinct Helios isoforms, as well as their capability to form heterodimer with Ikaros, and the association with complexes comprising histone deacetylase (HDAC)...
2016: PloS One
Xianping Lu, Zhiqiang Ning, Zhibin Li, Haixiang Cao, Xinhao Wang
Peripheral T-cell lymphoma (PTCL) is a set of rare and highly heterogeneous group of mature T- and NK-cell neoplasms associated with poor outcomes and lack of standard and effective therapies. The total number of newly diagnosed cases of PTCL yearly in China is estimated about 50,000. Chidamide (CS055) is a novel and orally active benzamide class of histone deacetylase (HDAC) inhibitor that selectively inhibits activity of HDAC1, 2, 3 and 10, the enzymes that are involved and play an important role in tumor initiation and development in both tumor cells and their surrounding micro-environment...
August 2016: Intractable & Rare Diseases Research
Natascia Guida, Giusy Laudati, Luigi Mascolo, Ornella Cuomo, Serenella Anzilotti, Rossana Sirabella, Marianna Santopaolo, Mario Galgani, Paolo Montuori, Gianfranco Di Renzo, Lorella M T Canzoniero, Luigi Formisano
Ethylmercury thiosalicylate (thimerosal) is an organic mercury-based compound commonly used as an antimicrobial preservative that has been found to be neurotoxic. In contrast, histone deacetylases (HDACs) inhibition has been found to be neuroprotective against several environmental contaminants, such as polychlorinated biphenyls, di-2-ethylhexyl phthalate, and methylmercury. The aim of this study was to investigate the effect of HDAC inhibition on thimerosal-induced neurotoxicity in neuroblastoma cells and cortical neurons...
September 22, 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
Claudius Irlé, Jonathan Weintraub
Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of aggressive non-Hodgkin lymphomas. Angioimmunoblastic T-cell lymphoma (AITL) is a common subtype of PTCL, and patients with AITL typically have a poor prognosis with limited treatment options. Clinical studies have demonstrated the activity of romidepsin, a structurally unique, potent, bicyclic class 1 selective histone deacetylase inhibitor, in patients with relapsed or refractory AITL. In the case presented herein, we describe a patient treated with single-agent romidepsin at first diagnosis of AITL, resulting in complete remission for over 2 years and leading to the use of maintenance dosing...
2016: Case Reports in Hematology
Jens Heyn, Benjamin Luchting, Ludwig C Hinske, Max Hübner, Shahnaz C Azad, Simone Kreth
BACKGROUND: Accumulating evidence indicates that neuropathic pain is a neuro-immune disorder with enhanced activation of the immune system. Recent data provided proof that neuropathic pain patients exhibit increased numbers of immunosuppressive regulatory T cells (Tregs), which may represent an endogenous attempt to limit inflammation and to reduce pain levels. We here investigate the molecular mechanisms underlying these alterations. METHODS: Our experimental approach includes functional analyses of primary human T cells, 3'-UTR reporter assays, and expression analyses of neuropathic pain patients' samples...
2016: Journal of Neuroinflammation
Sy-Jye Leu, Yi-Yuan Yang, Hsing-Cheng Liu, Chieh-Yu Cheng, Yu-Chen Wu, Ming-Chyi Huang, Yuen-Lun Lee, Chi-Ching Chen, Winston W Shen, Ko-Jiunn Liu
Valproic acid (VPA), with inhibition activity mainly towards histone deacetylase (HDAC) and Glycogen Synthase Kinase (GSK)-3, and lithium, with inhibition activity mainly toward GSK-3, are both prescribed in clinical as mood-stabilizers and anticonvulsants for the control of bipolar disorder. This study aims to compare the immuno-modulation activities of VPA and lithium, especially on the differentiation and functions of dendritic cells (DC). Our data show that treatment with VPA or lithium effectively alleviated the severity of collagen-induced arthritis triggered by LPS in mice...
September 17, 2016: Journal of Cellular Physiology
Francine Foss, Madeleine Duvic, Adam Lerner, Joel Waksman, Sean Whittaker
BACKGROUND: Tumor stage and folliculotropic mycosis fungoides are uncommon subtypes of cutaneous T-cell lymphoma (CTCL) with an aggressive disease course. Romidepsin is a histone deacetylase inhibitor approved by the US Food and Drug Administration for patients with CTCL who have received ≥ 1 previous systemic therapy. In the present study, we examined the efficacy and safety of romidepsin in patients from the pivotal, single-arm, open-label, phase II study of relapsed or refractory CTCL with cutaneous tumors and/or folliculotropic disease involvement...
August 10, 2016: Clinical Lymphoma, Myeloma & Leukemia
Sunil A Reddy
Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of rare non-Hodgkin lymphomas that arise in the skin. In advanced stages, CTCL becomes systemic and is associated with poor prognosis. Diagnosis of CTCL and treatment of early-stage disease with topical therapies often occurs under the care of a dermatologist. Community oncologists see few patients with CTCL due to direct referrals from dermatologists to academic or lymphoma specialty centers. However, some patients will continue to be managed in a community setting...
October 2016: Critical Reviews in Oncology/hematology
Marie Saghaeian Jazi, Saeed Mohammadi, Yaghoub Yazdani, Sima Sedighi, Ali Memarian, Mehrdad Aghaei
OBJECTIVES: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignant tumor. Administration of chemical compounds influencing apoptosis and T cell development has been discussed as promising novel therapeutic strategies. Valproic acid (VPA) as a recently emerged anti-neoplastic histone deacetylase (HDAC) inhibitor and pioglitazone (PGZ) as a high-affinity peroxisome proliferator-activated receptor-gamma (PPARγ) agonist have been shown to induce apoptosis and cell cycle arrest in different studies...
July 2016: Iranian Journal of Basic Medical Sciences
Julian C Bahr, Robert W Robey, Victoria Luchenko, Agnes Basseville, Arup R Chakraborty, Hanna Kozlowski, Gary T Pauly, Paresma Patel, Joel P Schneider, Michael M Gottesman, Susan E Bates
We previously demonstrated activation of the mitogen-activated protein kinase (MAPK) pathway in a series of romidepsin-selected T-cell lymphoma cell lines as a mechanism of resistance to the histone deacetylase inhibitor (HDI), romidepsin. As Ras mutation leads to activation of both the MAPK and the phosphoinositide 3-kinase (PI3K) pathway, we examined whether combining romidepsin with small molecule pathway inhibitors would lead to increased apoptosis in cancers harboring Ras mutations. We treated 18 Ras mutant or wild-type cell lines with romidepsin in the presence of a MEK inhibitor (PD-0325901) and/or an AKT inhibitor (MK-2206) and examined apoptosis by flow cytometry...
September 13, 2016: Oncotarget
Benjamin B Policicchio, Cuiling Xu, Egidio Brocca-Cofano, Kevin D Raehtz, Tianyu He, Dongzhu Ma, Hui Li, Ranjit Sivanandham, George S Haret-Richter, Tammy Dunsmore, Anita Trichel, John W Mellors, Beatrice H Hahn, George M Shaw, Ruy M Ribeiro, Ivona Pandrea, Cristian Apetrei
Viruses that persist despite seemingly effective antiretroviral treatment (ART) and can reinitiate infection if treatment is stopped preclude definitive treatment of HIV-1 infected individuals, requiring lifelong ART. Among strategies proposed for targeting these viral reservoirs, the premise of the "shock and kill" strategy is to induce expression of latent proviruses [for example with histone deacetylase inhibitors (HDACis)] resulting in elimination of the affected cells through viral cytolysis or immune clearance mechanisms...
September 2016: PLoS Pathogens
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