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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/29313067/combinatorial-effects-of-histone-deacetylase-inhibitors-hdaci-vorinostat-and-entinostat-and-adaphostin-are-characterized-by-distinct-redox-alterations
#2
Nilsa Rivera-Del Valle, Tiewei Cheng, Mary E Irwin, Hayley Donnella, Melissa M Singh, Joya Chandra
PURPOSE: Amongst the epigenetically targeted therapies, targeting of the histone deacetylases (HDACs) has yielded numerous drugs for clinical use in hematological malignancies, but none as yet for acute lymphocytic leukemia (ALL). Single agent activity of HDAC inhibitors (HDACi) has been elusive in ALL, and has prompted study of combinatorial strategies. Because several HDACi raise levels of intracellular oxidative stress, we evaluated combinations of two structurally distinct HDACi with the redox active compound adaphostin in ALL...
January 8, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29300993/the-existing-drug-vorinostat-as-a-new-lead-against-cryptosporidiosis-by-targeting-the-parasite-histone-deacetylases
#3
Fengguang Guo, Haili Zhang, Nina N McNair, Jan R Mead, Guan Zhu
Background: Cryptosporidiosis affects all human populations, but can be much more severe or life-threatening in children and individuals with weak or weakened immune systems. However, current options to treat cryptosporidiosis are limited. Methods: An in vitro phenotypic screening assay was employed to screen 1,200 existing drugs for their anti-cryptosporidial activity, and to determine the inhibitory kinetics of top hits. Selected top hits were further evaluated in mice...
January 2, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29298770/mogamulizumab-tops-standard-of-care-for-ctcl
#4
(no author information available yet)
In the large international phase III MAVORIC trial, patients with previously treated cutaneous T-cell lymphoma who received the anti-CCR4 monoclonal antibody mogamulizumab experienced significantly longer progression-free survival and higher response rates, as well as better quality of life, than those who received vorinostat, a standard therapy.
January 3, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29239146/vorinostat-enhances-the-anticancer-effect-of-oxaliplatin-on-hepatocellular-carcinoma-cells
#5
Bo Liao, Yingying Zhang, Quan Sun, Ping Jiang
Oxaliplatin-based systemic chemotherapy has been proposed to have efficacy in hepatocellular carcinoma (HCC). We investigated the combination of vorinostat and oxaliplatin for possible synergism in HCC cells. SMMC7721, BEL7402, and HepG2 cells were treated with vorinostat and oxaliplatin. Cytotoxicity assay, tumorigenicity assay in vitro, cell cycle analysis, apoptosis analysis, western blot analysis, animal model study, immunohistochemistry, and quantitative PCR were performed. We found that vorinostat and oxaliplatin inhibited the proliferation of SMMC7721, BEL7402, and HepG2 cells...
December 13, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/29223029/design-synthesis-and-evaluation-of-novel-n-hydroxybenzamides-n-hydroxypropenamides-incorporating-quinazolin-4-3h-ones-as-histone-deacetylase-inhibitors-and-antitumor-agents
#6
Doan Thanh Hieu, Duong Tien Anh, Nguyen Minh Tuan, Pham-The Hai, Le-Thi-Thu Huong, Jisung Kim, Jong Soon Kang, Tran Khac Vu, Phan Thi Phuong Dung, Sang-Bae Han, Nguyen-Hai Nam, Nguyen-Dang Hoa
In our search for novel small molecules targeting histone deacetylases, we have designed and synthesized several series of novel N-hydroxybenzamides/N-hydroxypropenamides incorporating quinazolin-4(3H)-ones (4a-h, 8a-d, 10a-d). Biological evaluation showed that these hydroxamic acids were generally cytotoxic against three human cancer cell lines (SW620, colon; PC-3, prostate; NCI-H23, lung cancer). It was found that the N-hydroxypropenamides (10a-d) were the most potent, both in term of HDAC inhibition and cytotoxicity...
December 5, 2017: Bioorganic Chemistry
https://www.readbyqxmd.com/read/29212973/-refractory-cd20-positive-peripheral-t-cell-lymphoma-showing-loss-of-cd20-expression-after-rituximab-therapy-and-gain-of-cd20-expression-after-administration-of-vorinostat-and-gemcitabine
#7
Kazuaki Teshima, Hideaki Ohyagi, Masaaki Kume, Satsuki Takahashi, Masahiro Saito, Naoto Takahashi
A 79-year-old male patient presented with systemic lymphadenopathy. A lymph node biopsy revealed effacement of the normal nodal architecture with diffuse proliferation of medium-sized atypical lymphoid cells. Southern blot analyses demonstrated rearrangement of the T-cell receptor gene but not the immunoglobulin heavy chain gene. He was diagnosed with CD20-positive peripheral T-cell lymphoma (PTCL), NOS. Although he achieved partial remission after six cycles of R-CHOP, he relapse occurred after 2 months. CD20-negative conversion was confirmed in the lymph node, which was positive for CCR4, and the skin at the time of relapse...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/29212250/histone-deacetylase-inhibitors-reduce-differentiating-osteoblast-mediated-protection-of-acute-myeloid-leukemia-cells-from-cytarabine
#8
Rosalie M Sterner, Kimberly N Kremer, Aref Al-Kali, Mrinal M Patnaik, Naseema Gangat, Mark R Litzow, Scott H Kaufmann, Jennifer J Westendorf, Andre J van Wijnen, Karen E Hedin
The bone marrow microenvironment protects acute myeloid leukemia (AML) cells during chemotherapy and is a major factor in relapse. Here, we examined which type(s) of bone marrow cells are responsible for the relapse of AML following treatment with cytarabine (Ara-C), and we identified a means to inhibit this protection. To determine the protective cell type(s), AML cells were treated with Ara-C, and AML cell survival in the presence or absence of osteoblast lineage cells was assessed. Cultured AML cells and patient bone marrow isolates were each significantly protected from Ara-C-induced apoptosis by co-culture with differentiating osteoblasts...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29212192/vorinostat-and-metformin-sensitize-egfr-tki-resistant-nsclc-cells-via-bim-dependent-apoptosis-induction
#9
Hengyi Chen, Yubo Wang, Caiyu Lin, Conghua Lu, Rui Han, Lin Jiao, Li Li, Yong He
There is a close relationship between low expression of BIM and resistance to epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). Vorinostat is a pan-histone deacetylase inhibitor (HDACi) that augments BIM expression in various types of tumor cells, however, this effect is attenuated by the high expression of anti-apoptotic proteins in EGFR-TKI resistant non-small cell lung cancer (NSCLC) cells. Vorinostat in combination with metformin - a compound that can inhibit anti-apoptotic proteins expression, might cooperate to activate apoptotic signaling and overcome EGFR-TKI resistance...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29209628/inhibitors-of-histone-deacetylases-are-weak-activators-of-the-fmr1-gene-in-fragile-x-syndrome-cell-lines
#10
Alexander A Dolskiy, Vladimir O Pustylnyak, Andrey A Yarushkin, Natalya A Lemskaya, Dmitry V Yudkin
Fragile X syndrome is the most common cause of inherited intellectual disability in humans. It is a result of CGG repeat expansion in the 5' untranslated region (5' UTR) of the FMR1 gene. This gene encodes the FMRP protein that is involved in neuronal development. Repeat expansion leads to heterochromatinization of the promoter, gene silencing, and the subsequent absence of FMRP. To date, there is no specific therapy for the syndrome. All treatments in clinic practice provide symptomatic therapy. The development of drug therapy for Fragile X syndrome treatment is connected with the search for inhibitors of enzymes that are responsible for heterochromatinization...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29191808/suberanilohydroxamic-acid-as-a-pharmacological-kruppel-like-factor-2-activator-that-represses-vascular-inflammation-and-atherosclerosis
#11
Yanni Xu, Suowen Xu, Peng Liu, Marina Koroleva, Shuya Zhang, Shuyi Si, Zheng Gen Jin
BACKGROUND: Kruppel-like factor 2 (KLF2) is an important zinc-finger transcription factor that maintains endothelial homeostasis by its anti-inflammatory, -thrombotic, -oxidative, and -proliferative effects in endothelial cells. In light of the potent vasoprotective effects of KLF2, modulating KLF2 expression or function could give rise to new therapeutic strategies to treat cardiovascular diseases. METHODS AND RESULTS: High-throughput drug screening based on KLF2 promoter luciferase reporter assay was performed to screen KLF2 activators...
November 30, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29191068/an-exploratory-cost-effectiveness-analysis-of-systemic-treatments-for-cutaneous-t-cell-lymphoma
#12
Larisa Geskin, Daniel C Malone
PURPOSE: To conduct an exploratory cost-effectiveness analysis of systemic treatment options for more advanced cutaneous T-cell lymphoma (CTCL). METHODS: A cost-effectiveness model compared systemic bexarotene, denileukin diftitox, interferon-α, methotrexate, pralatrexate, romidepsin, vorinostat, and extracorporeal photopheresis (ECP) treatment of CTCL. Treatment effectiveness data were extracted from published studies and/or US product labeling. Overall response, the primary effectiveness measure, was defined as the proportion of patients achieving complete or partial response...
December 18, 2017: Journal of Dermatological Treatment
https://www.readbyqxmd.com/read/29164054/effective-drug-delivery-in-diffuse-intrinsic-pontine-glioma-a-theoretical-model-to-identify-potential-candidates
#13
Fatma E El-Khouly, Dannis G van Vuurden, Thom Stroink, Esther Hulleman, Gertjan J L Kaspers, N Harry Hendrikse, Sophie E M Veldhuijzen van Zanten
Despite decades of clinical trials for diffuse intrinsic pontine glioma (DIPG), patient survival does not exceed 10% at two years post-diagnosis. Lack of benefit from systemic chemotherapy may be attributed to an intact bloodbrain barrier (BBB). We aim to develop a theoretical model including relevant physicochemical properties in order to review whether applied chemotherapeutics are suitable for passive diffusion through an intact BBB or whether local administration via convection-enhanced delivery (CED) may increase their therapeutic potential...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/29162825/outcomes-of-patients-with-sarcoma-enrolled-in-clinical-trials-of-pazopanib-combined-with-histone-deacetylase-mtor-her2-or-mek-inhibitors
#14
Vikas Dembla, Roman Groisberg, Ken Hess, Siqing Fu, Jennifer Wheler, David S Hong, Filip Janku, Ralph Zinner, Sarina Anne Piha-Paul, Vinod Ravi, Robert S Benjamin, Shreyaskumar Patel, Neeta Somaiah, Cynthia E Herzog, Daniel D Karp, Jason Roszik, Funda Meric-Bernstam, Vivek Subbiah
Pazopanib is US FDA approved for the treatment of advanced soft tissue sarcomas. All patients with this disease ultimately develop resistance to therapy. Mechanisms of resistance include activation of the mTOR, histone deacetylase (HDAC), MAPK, and ERBB4 pathways. We hypothesized that combining pazopanib with other targeted agents inhibiting these pathways would increase response rates. We retrospectively evaluated the safety and efficacy of pazopanib plus vorinostat, everolimus, lapatinib or trastuzumab, and MEK inhibitor in patients with advanced sarcoma...
November 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29160717/reprogramming-tumor-associated-macrophages-to-reverse-egfr-t790m-resistance-by-dual-targeting-codelivery-of-gefitinib-vorinostat
#15
Huige Peng, Binfan Chen, Wei Huang, Yubo Tang, Yifan Jiang, Wenyuan Zhang, Yongzhuo Huang
Gefitinib is a first-line therapy in the EGFR-mutated nonsmall cell lung cancer (NSCLC). However, the development of drug resistance is almost unavoidable, thus leading to an unsustainable regimen. EGFR(T790M) mutation is the major cause responsible for the molecular-targeting therapy failure in NSCLC. Although the recently approved osimertinib is effective for the EGFR(T790M)-positive NSCLC, the osimertinib-resistant EGFR mutation is rapidly developed, too. In this study, we proposed a tumor-associated macrophage (TAM) reprogramming strategy for overcoming the EGFR(T790M)-associated drug resistance via a dual-targeting codelivery system of gefitinib/vorinostat that acted on both TAM with overexpression of mannose receptors and the HER-2 positive NSCLC cells...
November 21, 2017: Nano Letters
https://www.readbyqxmd.com/read/29150330/the-structural-requirements-of-histone-deacetylase-inhibitors-c4-modified-saha-analogs-display-dual-hdac6-hdac8-selectivity
#16
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/29136884/electrooxidation-and-amperometric-determination-of-vorinostat-on-hierarchical-leaf-like-gold-nanolayers
#17
R Dehdari Vais, K Karimian, H Heli
Hierarchical leaf-like gold nanolayers were electrodeposited using choline chloride as a shape directing agent and characterized using field emission scanning electron microscopy. The electrooxidation behavior of vorinostat was then studied on the nanolayers and the kinetic parameters of the electrodic process were obtained by voltammetric measurements in a phosphate buffer solution at pH 7.40. Vorinostat was electrooxidized on the nanolayers' surface at a lower potential and with a higher rate, compared to a polycrystalline smooth gold surface, through an irreversible process...
February 1, 2018: Talanta
https://www.readbyqxmd.com/read/29135083/comparison-of-the-anticancer-properties-of-a-novel-valproic-acid-prodrug-to-leading-histone-deacetylase-inhibitors
#18
Nataly Tarasenko, Hanna Chekroun-Setti, Abraham Nudelman, Ada Rephaeli
The HDAC inhibitory activity of valproic acid (VPA) has led to on-going evaluation of it as an anticancer agent. The histone deacetylase (HDAC) inhibitor AN446, a prodrug of VPA, releases the acid upon metabolic degradation. AN446 is >60 fold more potent than VPA in killing cancer cells in vitro. Herein, we compare the activities of AN446, as an anticancer agent, to those of representative types from each of the four major classes of HDAC inhibitors (HDACIs): vorinostat, romidepsin, entinostat and VPA. AN446 exhibited the greatest selectivity and HDAC inhibitory activity against cancer cells...
November 14, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29133513/phase-ii-study-of-bevacizumab-and-vorinostat-for-patients-with-recurrent-world-health-organization-grade-4-malignant-glioma
#19
Ashley Ghiaseddin, David Reardon, Woody Massey, Alex Mannerino, Eric S Lipp, James E Herndon, Frances McSherry, Annick Desjardins, Dina Randazzo, Henry S Friedman, Katherine B Peters
LESSONS LEARNED: Combination regimen with bevacizumab (BEV) and vorinostat is well tolerated in patients with recurrent glioblastoma.Treatment of recurrent glioblastoma remains challenging as this study and others attempt to improve progression-free survival and overall survival with BEV-containing regimens. BACKGROUND: Recurrent glioblastoma (GBM; World Health Organization grade 4) continues to have a very poor prognosis. Bevacizumab (BEV) has been shown to improve progression-free survival (PFS) in recurrent GBM and is approved by the U...
November 13, 2017: Oncologist
https://www.readbyqxmd.com/read/29114207/histone-deacetylase-inhibitors-are-protective-in-acute-but-not-in-chronic-models-of-ototoxicity
#20
Chao-Hui Yang, Zhiqi Liu, Deanna Dong, Jochen Schacht, Dev Arya, Su-Hua Sha
Previous studies have reported that modification of histones alters aminoglycoside-induced hair cell death and hearing loss. In this study, we investigated three FDA-approved histone deacetylase (HDAC) inhibitors (vorinostat/SAHA, belinostat, and panobinostat) as protectants against aminoglycoside-induced ototoxicity in murine cochlear explants and in vivo in both guinea pigs and CBA/J mice. Individually, all three HDAC inhibitors reduced gentamicin (GM)-induced hair cell loss in a dose-dependent fashion in explants...
2017: Frontiers in Cellular Neuroscience
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