Read by QxMD icon Read


Jesse J McClure, Xiaoyang Li, C James Chou
Since the identification and cloning of human histone deacetylases (HDACs) and the rapid approval of vorinostat (Zolinza®) for the treatment of cutaneous T-cell lymphoma, the field of HDAC biology has met many initial successes. However, many challenges remain due to the complexity involved in the lysine posttranslational modifications, epigenetic transcription regulation, and nonepigenetic cellular signaling cascades. In this chapter, we will: review the discovery of the first HDAC inhibitor and present discussion regarding the future of next-generation HDAC inhibitors, give an overview of different classes of HDACs and their differences in lysine deacylation activity, discuss different classes of HDAC inhibitors and their HDAC isozyme preferences, and review HDAC inhibitors' preclinical studies, their clinical trials, their pharmacokinetic challenges, and future direction...
2018: Advances in Cancer Research
Miguel Fontecha-Barriuso, Diego Martin-Sanchez, Olga Ruiz-Andres, Jonay Poveda, Maria Dolores Sanchez-Niño, Lara Valiño-Rivas, Marta Ruiz-Ortega, Alberto Ortiz, Ana Belén Sanz
Epigenetics refers to heritable changes in gene expression patterns not caused by an altered nucleotide sequence, and includes non-coding RNAs and covalent modifications of DNA and histones. This review focuses on functional evidence for the involvement of DNA and histone epigenetic modifications in the pathogenesis of kidney disease and the potential therapeutic implications. There is evidence of activation of epigenetic regulatory mechanisms in acute kidney injury (AKI), chronic kidney disease (CKD) and the AKI-to-CKD transition of diverse aetiologies, including ischaemia-reperfusion injury, nephrotoxicity, ureteral obstruction, diabetes, glomerulonephritis and polycystic kidney disease...
March 9, 2018: Nephrology, Dialysis, Transplantation
Leilei Shi, Li Xu, Qinghua Guan, Xin Jin, Jiapei Yang, Xinyuan Zhu
Owing to the high spatial and temporal resolution of light, light related biotechnologies, for example, optogenetics, has wide ranging applications in neuroscience to control a subject's behavior. Applying light to control tumors' genetic behavior directly was still a challenge so far. Herein, we put forward a strategy of chemical optoepigenomics, in which epigenetic regulator (vorinostat) and paclitaxel (PTX) was conjugated onto a light-sensitive chemical molecule. The activity of vorinostat could be precisely controlled by the light, which could minimize the off-target effect...
March 7, 2018: Bioconjugate Chemistry
Xiangsheng Huang, Stefan Wiehr, Anna-Maria Wild, Patrick Voßberg, Wolfgang Hoffmann, Beate Grüner, Carsten Köhler, Peter T Soboslay
Cytostatic drugs used in cancer therapy were evaluated for their capacity to inhibit Echinococcus multilocularis metacestode growth and proliferation. Metacestode tissues were exposed in vitro to docetaxel, doxorubicin, navelbine, paclitaxel, and vorinostat for 1 week, then incubated in drug-free culture, and thereafter metacestodes were injected into the peritoneum of Meriones unguiculatus . Magnetic resonance imaging (MRI) and simultaneous positron emission tomography (PET) were applied to monitor in vivo growth of drug-exposed E...
February 6, 2018: Oncotarget
Yang-Ling Li, Ning-Yu Zhang, Xiu Hu, Jia-Ling Chen, Ming-Jun Rao, Lin-Wen Wu, Qing-Yu Li, Bo Zhang, Wei Yan, Chong Zhang
Hypoxia promotes HCC progression and therapy resistance, and there is no systemic treatment for HCC patients after sorafenib resistance. Thus, it is urgent to develop potential therapeutic regimens for HCC patients by targeting hypoxia signaling. In this study, we showed that evodiamine might be a potential therapeutic medicine for HCC by suppressing HIF-1α. In addition, evodiamine could sensitize the anti-HCC effect of vorinostat in HCC cells under hypoxia. Furthermore, evodiamine plus vorinostat accelerated the degradation of HIF-1α in HCC cells under hypoxia...
March 2, 2018: Biochemical and Biophysical Research Communications
Ju Hwan Cho, Filiz Oezkan, Michael Koenig, Gregory A Otterson, James Gordon Herman, Kai He
Lung cancer is the leading cause of cancer-related death in the United States and worldwide. Novel therapeutic developments are critically necessary to improve outcomes for this disease. Aberrant epigenetic change plays an important role in lung cancer development and progression. Therefore, drugs targeting the epigenome are being investigated in the treatment of lung cancer. Monotherapy of epigenetic therapeutics such as DNA methyltransferase inhibitors (DNMTi) and histone deacetylase inhibitors (HDACi) have so far not shown any apparent benefit while one of the clinical trials with the combinations of DNMTi and HDACi showed a small positive signal for treating lung cancer...
December 2017: Current Pharmacology Reports
Martin Rao, Davide Valentini, Alimuddin Zumla, Markus Maeurer
BACKGROUND: New tuberculosis (TB) drug treatment regimens are urgently needed. We evaluated the potential of the histone deacetylase inhibitors (HDIs) valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA) to enhance the effects of first-line TB drugs against intracellular Mycobacterium tuberculosis (M. tb). METHODS: M. tb H37Rv cultures were exposed to VPA or SAHA over six days, in the presence or absence of isoniazid (INH) and rifampicin (RIF). The efficacy of VPA and SAHA against intracellular M...
March 1, 2018: International Journal of Infectious Diseases: IJID
Jinyu Yang, Gaoliang Cheng, Qihao Xu, Shenglin Luan, Shuxiang Wang, Dan Liu, Linxiang Zhao
In recent years, inhibition of HDAC6 became a promising therapeutic strategy for the treatment of cancer and HDAC6 inhibitors were considered to be potent anti-cancer agents. In this work, celecoxib showed moderate degree of HDAC6 inhibition activity and selectivity in preliminary enzyme inhibition activity assay. A series of hydroxamic acid derivatives bearing phenylpyrazol moiety were designed and synthesized as HDAC6 inhibitors. Most compounds showed potent HDAC6 inhibition activity. 11i was the most selective compound against HDAC6 with IC50 values of 0...
August 19, 2017: Bioorganic & Medicinal Chemistry
Md Suhail Alam, Bruce Cooper, Joseph D Farris, Kasturi Haldar
Histone deacetylase (HDAC) inhibitors are of significant interest as drugs. However, their use to treat neurological disorders has raised concern because HDACs are required for brain function. We have previously shown that a triple combination formulation (TCF) of the pan HDACi vorinostat (Vo), 2-hydroxypropyl-beta-cyclodextrin (HPBCD) and polyethylene glycol (PEG) 400 improves pharmacokinetic exposure and entry of Vo into the brain. TCF treatment significantly delayed both neurodegeneration and death in the Npc1nmf164 murine model of Niemann-Pick Type C (NPC) disease...
March 1, 2018: Scientific Reports
Andrea Milelli, Chiara Marchetti, Eleonora Turrini, Elena Catanzaro, Roberta Mazzone, Daniela Tomaselli, Carmela Fimognari, Vincenzo Tumiatti, Anna Minarini
Epigenetic modulators Histone deacetylases (HDACs) and Lysine demethylase (LSD1) are validated targets for anticancer therapy. Both HDAC1/2 and LSD1 are found in association with the repressor protein CoREST in a transcriptional co-repressor complex, which is responsible for gene silencing. Combined modulation of both targets results in a synergistic antiproliferative activity. In the present investigation, we report about the design and synthesis of a series of polyamine-based HDACs-LSD1 dual binding inhibitors obtained by coupling Vorinostat and Tranylcypromine...
February 17, 2018: Bioorganic & Medicinal Chemistry Letters
Shuai Ye, Matthew A Lawlor, Adrian Rivera-Reyes, Shaun Egolf, Susan Chor, Koreana Pak, Gabrielle E Ciotti, Avery C Lee, Gloria Marino, Jennifer Shah, David Niedzwicki, Kristy Weber, Paul M C Park, Md Zahidul Alam, Alison Grazioli, Malay Haldar, Mousheng Xu, Jennifer A Perry, Jun Qi, T S Karin Eisinger-Mathason
To date, no consistent oncogenic driver mutations have been identified in most adult soft tissue sarcomas; these tumors are thus generally insensitive to existing targeted therapies. Here we investigated alternate mechanisms underlying sarcomagenesis to identify potential therapeutic interventions. Undifferentiated pleomorphic sarcoma (UPS) is an aggressive tumor frequently found in skeletal muscle where deregulation of the Hippo pathway and aberrant stabilization of its transcriptional effector yes-associated protein 1 (YAP1) increases proliferation and tumorigenesis...
February 28, 2018: Cancer Research
Claudio Festuccia, Andrea Mancini, Alessandro Colapietro, Giovanni Luca Gravina, Flora Vitale, Francesco Marampon, Simona Delle Monache, Simona Pompili, Loredana Cristiano, Antonella Vetuschi, Vincenzo Tombolini, Yi Chen, Thomas Mehrling
BACKGROUND: The use of alkylating agents such as temozolomide in association with radiotherapy (RT) is the therapeutic standard of glioblastoma (GBM). This regimen modestly prolongs overall survival, also if, in light of the still dismal prognosis, further improvements are desperately needed, especially in the patients with O6-methylguanine-DNA-methyltransferase (MGMT) unmethylated tumors, in which the benefit of standard treatment is less. Tinostamustine (EDO-S101) is a first-in-class alkylating deacetylase inhibitor (AK-DACi) molecule that fuses the DNA damaging effect of bendamustine with the fully functional pan-histone deacetylase (HDAC) inhibitor, vorinostat, in a completely new chemical entity...
February 27, 2018: Journal of Hematology & Oncology
Hengyu Zhou, Ying Cai, Dina Liu, Menghui Li, Yu Sha, Wenlu Zhang, Kai Wang, Jianping Gong, Ni Tang, Ailong Huang, Jie Xia
OBJECTIVES: Histone deacetylases (HDACs) are commonly dysregulated in cancer and represent promising therapeutic targets. However, global HDAC inhibitors have shown limited efficacy in the treatment of solid tumours, including hepatocellular carcinoma (HCC). In this study, we investigated the therapeutic effect of selectively inhibiting HDAC1 and 2 in HCC. METHODS: HDAC1 inhibitor Tacedinaline (CI994), HDAC2 inhibitor Santacruzamate A (CAY10683), HDAC1/2 common inhibitor Romidepsin (FK228) and global HDAC inhibitor Vorinostat (SAHA) were used to treat HCC cells...
February 27, 2018: Cell Proliferation
Anssi Lipponen, Assam El-Osta, Antony Kaspi, Mark Ziemann, Ishant Khurana, Harikrishnan Kn, Vicente Navarro-Ferrandis, Noora Puhakka, Jussi Paananen, Asla Pitkänen
Traumatic brain injury (TBI) induces a wide variety of cellular and molecular changes that can continue for days to weeks to months, leading to functional impairments. Currently, there are no pharmacotherapies in clinical use that favorably modify the post-TBI outcome, due in part to limited understanding of the mechanisms of TBI-induced pathologies. Our system biology analysis tested the hypothesis that chronic transcriptomics changes induced by TBI are controlled by altered DNA-methylation in gene promoter areas or by transcription factors...
February 27, 2018: Acta Neuropathologica Communications
Victor Jeannot, Cony Gauche, Silvia Mazzaferro, Morgane Couvet, Laetitia Vanwonterghem, Maxime Henry, Chloé Didier, Julien Vollaire, Véronique Josserand, Jean-Luc Coll, Christophe Schatz, Sébastien Lecommandoux, Amandine Hurbin
Combinations of therapeutic agents could synergistically enhance the response of lung cancer cells. Co-delivery systems capable of transporting chemotherapeutics with different physicochemical properties and with the simultaneous release of drugs remain elusive. Here, we assess the ability of nanoparticles of 30-nm diameter obtained from the self-assembly of hyaluronan-based copolymer targeting CD44 receptors to encapsulate both gefitinib and vorinostat for effective combinational lung cancer treatment. Drug loading was performed by nanoprecipitation...
February 20, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Lillianne H Wright, Daniel J Herr, Symone S Brown, Harinath Kasiganesan, Donald R Menick
Myocardial infarctions (MIs) cause the loss of myocytes due to lack of sufficient oxygenation and latent revascularization. Although the administration of histone deacetylase (HDAC) inhibitors reduces the size of infarctions and improves cardiac physiology in small-animal models of MI injury, the cellular targets of the HDACs, which the drugs inhibit, are largely unspecified. Here, we show that WNT-inducible secreted protein-1 (Wisp-1), a matricellular protein that promotes angiogenesis in cancers as well as cell survival in isolated cardiac myocytes and neurons, is a target of HDACs...
February 22, 2018: JCI Insight
Hamid Sayar, Yan Liu, Rui Gao, Mohammad Abu Zaid, Larry D Cripe, Jill Weisenbach, Katie J Sargent, Mehdi Nassiri, Lang Li, Heiko Konig, Attaya Suvannasankha, Feng Pan, Rajasubramaniam Shanmugam, Chirayu Goswami, Reuben Kapur, Mingjiang Xu, H Scott Boswell
Co-occurrence of Flt3ITD and TET2 mutations provoke an animal model of AML by epigenetic repression of Wnt pathway antagonists, including RUNX3, and by hyperexpression of ID1, encoding Wnt agonist. These affect HOXA over-expression and treatment resistance. A comparable epigenetic phenotype was identified among adult AML patients needing novel intervention. We chose combinations of targeted agents acting on distinct effectors, at the levels of both signal transduction and chromatin remodeling, in relapsed/refractory AML's, including Flt3ITD+ve, described with a signature of repressed tumor suppressor genes, involving Wnt antagonist RUNX3 , occurring along with ID1 and HOXA over-expressions...
January 19, 2018: Oncotarget
Guochun Jiang, Don Nguyen, Nancie M Archin, Steven A Yukl, Gema Méndez-Lagares, Yuyang Tang, Maher M Elsheikh, George R Thompson, Dennis J Hartigan-O'Connor, David M Margolis, Joseph K Wong, Satya Dandekar
Eradication of HIV-1 (HIV) is hindered by stable viral reservoirs. Viral latency is epigenetically regulated. While the effects of histone acetylation and methylation at the HIV long-terminal repeat (LTR) have been described, our knowledge of the proviral epigenetic landscape is incomplete. We report that a previously unrecognized epigenetic modification of the HIV LTR, histone crotonylation, is a regulator of HIV latency. Reactivation of latent HIV was achieved following the induction of histone crotonylation through increased expression of the crotonyl-CoA-producing enzyme acyl-CoA synthetase short-chain family member 2 (ACSS2)...
February 19, 2018: Journal of Clinical Investigation
Athira Kv, Rajaram Mohanrao Madhana, Indu Chandran Js, Mangala Lahkar, Swapnil Sinha, V G M Naidu
Major depressive disorder (MDD) is a multifactorial neuropsychiatric disorder. Chronic administration of corticosterone (CORT) to rodents is used to mimic the stress associated dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, a well-established feature found in depressive patients. Recently, preclinical studies have demonstrated the antidepressant potential of histone deacetylase (HDAC) inhibitors. So, we examined the antidepressant potential of vorinostat (VOR), a HDAC inhibitor against CORT injections in male mice...
February 13, 2018: Behavioural Brain Research
Juan C Ramos, Joseph A Sparano, Michelle A Rudek, Page C Moore, Ethel Cesarman, Erin G Reid, David Henry, Lee Ratner, David Aboulafia, Jeanette Y Lee, Richard F Ambinder, Ronald Mitsuyasu, Ariela Noy
INTRODUCTION: Vorinostat (VOR), a histone deacetylase inhibitor, enhances the anti-tumor effects of rituximab (R) and cytotoxic chemotherapy, induces viral lytic expression and cell killing in Epstein-Barr virus-positive (EBV+) or human herpesvirus-8-positive (HHV-8+) tumors, and reactivates latent human immunodeficiency virus (HIV) for possible eradication by combination antiretroviral therapy (cART). PATIENTS AND METHODS: We performed a phase I trial of VOR given with R-based infusional EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin hydrochloride) (n = 12) and cART in aggressive HIV-associated B-cell non-Hodgkin lymphoma (NHL) in order to identify safe dosing and schedule...
February 2, 2018: Clinical Lymphoma, Myeloma & Leukemia
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"