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https://www.readbyqxmd.com/read/28918548/tumor-and-serum-dna-methylation-in-women-receiving-preoperative-chemotherapy-with-or-without-vorinostat-in-tbcrc008
#1
Roisin M Connolly, Mary Jo Fackler, Zhe Zhang, Xian C Zhou, Matthew P Goetz, Judy C Boughey, Bridget Walsh, John T Carpenter, Anna Maria Storniolo, Stanley P Watkins, Edward W Gabrielson, Vered Stearns, Saraswati Sukumar
BACKGROUND: Methylated gene markers have shown promise in predicting breast cancer outcomes and treatment response. We evaluated whether baseline and changes in tissue and serum methylation levels would predict pathological complete response (pCR) in patients with HER2-negative early breast cancer undergoing preoperative chemotherapy. METHODS: The TBCRC008 trial investigated pCR following 12 weeks of preoperative carboplatin and albumin-bound paclitaxel + vorinostat/placebo (n = 62)...
September 16, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28916365/sodium-phenylbutyrate-abrogates-african-swine-fever-virus-replication-by-disrupting-the-virus-induced-hypoacetylation-status-of-histone-h3k9-k14
#2
Gonçalo Frouco, Ferdinando B Freitas, Carlos Martins, Fernando Ferreira
African swine fever virus (ASFV) causes a highly lethal disease in swine for which neither a vaccine nor treatment are available. Recently, a new class of drugs that inhibit histone deacetylases enzymes (HDACs) has received an increasing interest as antiviral agents. Considering studies by others showing that valproic acid, an HDAC inhibitor (HDACi), blocks the replication of enveloped viruses and that ASFV regulates the epigenetic status of the host cell by promoting heterochromatinization and recruitment of class I HDACs to viral cytoplasmic factories, the antiviral activity of four HDACi against ASFV was evaluated in this study...
September 13, 2017: Virus Research
https://www.readbyqxmd.com/read/28915577/vorinostat-suppresses-hypoxia-signaling-by-modulating-nuclear-translocation-of-hypoxia-inducible-factor-1-alpha
#3
Chao Zhang, Chunzhang Yang, Michael J Feldman, Herui Wang, Ying Pang, Dominic M Maggio, Dongwang Zhu, Cody L Nesvick, Pauline Dmitriev, Petra Bullova, Prashant Chittiboina, Roscoe O Brady, Karel Pacak, Zhengping Zhuang
Histone deacetylase inhibitors (HDACis) are a potent class of tumor-suppressive agents traditionally believed to exert their effects through loosening tightly-wound chromatin resulting in de-inhibition of various tumor suppressive genes. Recent literature however has shown altered intratumoral hypoxia signaling with HDACi administration not attributable to changes in chromatin structure. We sought to determine the precise mechanism of HDACi-mediated hypoxia signaling attenuation using vorinostat (SAHA), an FDA-approved class I/IIb/IV HDACi...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28893609/supramolecular-cisplatin-vorinostat-nanodrug-for-overcoming-drug-resistance-in-cancer-synergistic-therapy
#4
Shuting Xu, Xinyuan Zhu, Wei Huang, Yongfeng Zhou, Deyue Yan
Cisplatin is a widely used anticancer drug in clinic. However, it may induce drug resistance after a course of treatment and it is difficult to accumulate at tumor site selectively, which result in clinic failure and side effects. We successfully bound cisplatin with vorinostat (a FDA-approved histone deacetylase inhibitor) to form a supramolecular conjugate, which can further self-assemble into nanoparticles. The nanodrug can retain in blood stream for a long time, accumulate in tumor site and hydrolyze to release the two drugs for synergistic therapy...
September 8, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28881658/decitabine-vorinostat-combination-treatment-in-acute-myeloid-leukemia-activates-pathways-with-potential-for-novel-triple-therapy
#5
Christine S Young, Kathryn M Clarke, Laura M Kettyle, Alexander Thompson, Ken I Mills
Despite advancements in cancer therapeutics, acute myeloid leukemia patients over 60 years old have a 5-year survival rate of less than 8%. In an attempt to improve this, epigenetic modifying agents have been combined as therapies in clinical studies. In particular combinations with Decitabine and Vorinostat have had varying degrees of efficacy. This study therefore aimed to understand the underlying molecular mechanisms of these agents to identify potential rational epi-sensitized combinations. Combined Decitabine-Vorinostat treatment synergistically decreased cell proliferation, induced apoptosis, enhanced acetylation of histones and further decreased DNMT1 protein with HL-60 cells showing a greater sensitivity to the combined treatment than OCI-AML3...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28874382/evaluation-of-the-innate-immune-modulator-acitretin-as-a-strategy-to-clear-the-hiv-reservoir
#6
Edurne Garcia-Vidal, Marc Castellví, Maria Pujantell, Roger Badia, Antoni Jou, Lucia Gomez, Teresa Puig, Bonaventura Clotet, Ester Ballana, Eva Riveira-Muñoz, José A Esté
The persistence of HIV despite suppressive antiretroviral therapy is a major roadblock to HIV eradication. Current strategies focused on inducing the expression of latent HIV fail to clear the persistent reservoir, prompting the development of new approaches for killing HIV+ cells. Recently, acitretin has been proposed as a pharmacological innate cellular-defense network enhancer that led to virus reactivation and preferential death of infected cells. We have evaluated the capacity of acitretin to reactivate and/or facilitate immune-mediated clearance of HIV+ cells...
September 5, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28860561/short-chain-fatty-acids-enhance-aryl-hydrocarbon-ah-responsiveness-in-mouse-colonocytes-and-caco-2-human-colon-cancer-cells
#7
Un-Ho Jin, Yating Cheng, Hyejin Park, Laurie A Davidson, Evelyn S Callaway, Robert S Chapkin, Arul Jayaraman, Andrew Asante, Clinton Allred, Evelyn A Weaver, Stephen Safe
Aryl hydrocarbon receptor (AhR) ligands are important for gastrointestinal health and play a role in gut inflammation and the induction of T regulatory cells, and the short chain fatty acids (SCFAs) butyrate, propionate and acetate also induce similar protective responses. Initial studies with butyrate demonstrated that this compound significantly increased expression of Ah-responsive genes such as Cyp1a1/CYP1A1 in YAMC mouse colonocytes and Caco-2 human colon cancer cell lines. Butyrate synergistically enhanced AhR ligand-induced Cyp1a1/CYP1A1 in these cells with comparable enhancement being observed for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and also microbiota-derived AhR ligands tryptamine, indole and 1,4-dihydroxy-2-naphthoic acid (DHNA)...
August 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28860124/quantitative-analysis-of-the-proteome-response-to-the-histone-deacetylase-inhibitor-hdaci-vorinostat-in-niemann-pick-type-c1-disease
#8
Kanagaraj Subramanian, Navin Rauniyar, Mathieu Lavalleé-Adam, John R Yates, William E Balch
Niemann-Pick type C (NPC) disease is an inherited, progressive neurodegenerative disorder principally caused by mutations in the NPC1 gene. NPC disease is characterized by the accumulation of unesterified cholesterol in the late endosomes (LE) and lysosomes (LE) (LE/Ly). Vorinostat, a histone deacetylase inhibitor (HDACi), restores cholesterol homeostasis in fibroblasts derived from NPC patients; however, the exact mechanism by which Vorinostat restores cholesterol level is not known yet. In this study, we performed comparative proteomic profiling of the response of NPC1I1061T fibroblasts to Vorinostat...
August 31, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28840938/loss-of-hdac3-in-osteoprogenitors-increases-bone-expression-of-osteoprotegerin-improving-systemic-insulin-sensitivity
#9
Meghan E McGee-Lawrence, Jessica L Pierce, Kanglun Yu, Natasha R Culpepper, Elizabeth W Bradley, Jennifer J Westendorf
Type 2 diabetes is an emerging global health epidemic. Foundations for new therapies are arising from understanding interactions between body systems. Bone-derived factors that reduce RANKL (receptor activator of NF-kappa B ligand) signaling in the liver may prevent insulin resistance and the onset of type 2 diabetes. Here we demonstrate that deletion of the epigenetic regulator, Hdac3, in Osx1-expressing osteoprogenitors prevents insulin resistance induced by high fat diet by increasing serum and skeletal gene expression levels of osteoprotegerin (Opg), a natural inhibitor of RANKL signaling...
August 25, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28838999/animacroxam-a-novel-dual-mode-compound-targeting-histone-deacetylases-and-cytoskeletal-integrity-of-testicular-germ-cell-cancer-cells
#10
Gustav Steinemann, Alexandra Dittmer, Weronika Kuzyniak, Björn Hoffmann, Mark Schrader, Rainer Schobert, Bernhard Biersack, Bianca Nitzsche, Michael Hoepfner
Novel approaches for the medical treatment of advanced solid tumors including testicular germ cell tumors (TGCT) are desperately needed. Especially, TGCT patients not responding to cisplatin-based therapy need therapeutic alternatives, as there is no effective medical treatment available for this particular subgroup. Here, we studied the suitability of the novel dual mode compound animacroxam for TGCT treatment. Animacroxam consists of a HDAC-inhibitory hydroxamate moiety coupled to a 4,5-diarylimidazole with inherent cytoskeleton disrupting potency...
August 24, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28835903/flow-cytometric-analysis-of-drug-induced-hiv-1-transcriptional-activity-in-a2-and-a72-j-lat-cell-lines
#11
Daniela Boehm, Melanie Ott
The main obstacle to eradicating HIV-1 from patients is post-integration latency (Finzi et al., 1999). Antiretroviral treatments target only actively replicating virus, while latent infections that have low or no transcriptional activity remain untreated (Sedaghat et al., 2007). A combination of antiretroviral treatments with latency-purging strategies may accelerate the depletion of latent reservoirs and lead to a cure (Geeraert et al., 2008). Current strategies to reactivate HIV-1 from latency include use of prostratin, a non-tumor-promoting phorbol ester (Williams et al...
May 20, 2017: Bio-protocol
https://www.readbyqxmd.com/read/28826913/vorinostat-and-simvastatin-have-synergistic-effects-on-triple-negative-breast-cancer-cells-via-abrogating-rab7-prenylation
#12
Xinhui Kou, Yonghua Yang, Xiaoxiao Jiang, Huijuan Liu, Fanghui Sun, Xuan Wang, Longkai Liu, Hongrui Liu, Zhaohu Lin, Lan Jiang
Since the lack of targeted treatment, triple-negative breast cancer (TNBC) has poor outcomes. Histone deacetylase inhibitors (HDACi) blocking the activity of specific HDACs have emerged as cancer therapeutic agents. However, the therapeutic efficiency is still not satisfactory for patients with solid tumor. We thus performed screening for the synergistic agents of Vorinostat (SAHA). The resulting candidate Simvastatin was obtained. The efficacy and mechanism of combination have been studied in TNBC cells. The synergism of SAHA and Simvastatin was evaluated by IC50 of proliferation and combination index (CI)...
August 19, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28816142/vorinostat-and-concurrent-stereotactic-radiosurgery-for-non-small-cell-lung-cancer-brain-metastases-a-phase-1-dose-escalation-trial
#13
MULTICENTER STUDY
Clara Y H Choi, Heather A Wakelee, Joel W Neal, Mary C Pinder-Schenck, Hsiang-Hsuan Michael Yu, Steven D Chang, John R Adler, Leslie A Modlin, Griffith R Harsh, Scott G Soltys
PURPOSE: To determine the maximum tolerated dose (MTD) of vorinostat, a histone deacetylase inhibitor, given concurrently with stereotactic radiosurgery (SRS) to treat non-small cell lung cancer (NSCLC) brain metastases. Secondary objectives were to determine toxicity, local failure, distant intracranial failure, and overall survival rates. MATERIALS AND METHODS: In this multicenter study, patients with 1 to 4 NSCLC brain metastases, each ≤2 cm, were enrolled in a phase 1, 3 + 3 dose escalation trial...
September 1, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28814661/hdac-inhibition-induces-hiv-1-protein-and-enables-immune-based-clearance-following-latency-reversal
#14
Guoxin Wu, Michael Swanson, Aarthi Talla, Donald Graham, Julie Strizki, Daniel Gorman, Richard Jo Barnard, Wade Blair, Ole S Søgaard, Martin Tolstrup, Lars Østergaard, Thomas A Rasmussen, Rafick-Pierre Sekaly, Nancie M Archin, David M Margolis, Daria J Hazuda, Bonnie J Howell
Promising therapeutic approaches for eradicating HIV include transcriptional activation of provirus from latently infected cells using latency-reversing agents (LRAs) and immune-mediated clearance to purge reservoirs. Accurate detection of cells capable of producing viral antigens and virions, and the measurement of clearance of infected cells, is essential to assessing therapeutic efficacy. Here, we apply enhanced methodology extending the sensitivity limits for the rapid detection of subfemtomolar HIV gag p24 capsid protein in CD4+ T cells from ART-suppressed HIV+ individuals, and we show viral protein induction following treatment with LRAs...
August 17, 2017: JCI Insight
https://www.readbyqxmd.com/read/28812060/reolysin-and-histone-deacetylase-inhibition-in-the-treatment-of-head-and-neck-squamous-cell-carcinoma
#15
Alena C Jaime-Ramirez, Jun-Ge Yu, Enrico Caserta, Ji Young Yoo, Jianying Zhang, Tae Jin Lee, Craig Hofmeister, John H Lee, Bhavna Kumar, Quintin Pan, Pawan Kumar, Robert Baiocchi, Theodoros Teknos, Flavia Pichiorri, Balveen Kaur, Matthew Old
Oncolytic viruses (OVs) are emerging as powerful anti-cancer agents and are currently being tested for their safety and efficacy in patients. Reovirus (Reolysin), a naturally occurring non-pathogenic, double-stranded RNA virus, has natural oncolytic activity and is being tested in phase I-III clinical trials in a variety of tumor types. With its recent US Food and Drug Administration (FDA) orphan drug designation for several tumor types, Reolysin is a potential therapeutic agent for various cancers, including head and neck squamous cell carcinomas (HNSCCs), which have a 5-year survival of ∼55%...
June 16, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/28803740/vorinostat-renders-the-replication-competent-latent-reservoir-of-human-immunodeficiency-virus-hiv-vulnerable-to-clearance-by-cd8-t-cells
#16
Julia A Sung, Katherine Sholtis, Jennifer Kirchherr, Joann D Kuruc, Cynthia L Gay, Jeffrey L Nordstrom, Catherine M Bollard, Nancie M Archin, David M Margolis
Latently human immunodeficiency virus (HIV)-infected cells are transcriptionally quiescent and invisible to clearance by the immune system. To demonstrate that the latency reversing agent vorinostat (VOR) induces a window of vulnerability in the latent HIV reservoir, defined as the triggering of viral antigen production sufficient in quantity and duration to allow for recognition and clearance of persisting infection, we developed a latency clearance assay (LCA). The LCA is a quantitative viral outgrowth assay (QVOA) that includes the addition of immune effectors capable of clearing cells expressing viral antigen...
July 29, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28799948/anticancer-drugs-and-the-regulation-of-hedgehog-genes-gli1-and-ptch1-a-comparative-study-in-nonmelanoma-skin-cancer-cell-lines
#17
Uffe H Olesen, Sophie Bojesen, Julie Gehl, Merete Haedersdal
Nonmelanoma skin cancer is the most common cancer in humans, comprising mainly basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). BCC proliferation is highly dependent on the Hedgehog signaling pathway. We aimed to investigate a panel of anticancer drugs with known activity against skin cancer for their therapeutic potential in localized, enhanced topical treatment of SCC and BCC. Cytotoxicity profiles for vismodegib, 5-fluorouracil (5-FU), methotrexate (MTX), cisplatin, bleomycin, and vorinostat were established in terms of half maximal inhibitory concentration values in a panel of immortalized keratinocytes (HaCaT), BCC (UWBCC1 and BCC77015), and SCC (A431 and SCC25) cell lines...
August 9, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28790110/replication-stress-leading-to-apoptosis-within-the-s-phase-contributes-to-synergism-between-vorinostat-and-azd1775-in-hnscc-harboring-high-risk-tp53-mutation
#18
Noriaki Tanaka, Ameeta A Patel, Lin Tang, Natalie L Silver, Antje Lindemann, Hideaki Takahashi, Roman Jaksik, Xiayu Rao, Nene N Kalu, Tseng-Cheng Chen, Jiping Wang, Mitchell J Frederick, Faye M Johnson, Frederico Gleber-Netto, Siqing Fu, Marek Kimmel, Jing Wang, Walter N Hittelman, Curtis R Pickering, Jeffrey N Myers, Abdullah A Osman
PURPOSE: The cure rate for patients with advanced head and neck squamous cell carcinoma (HNSCC) remains poor due to resistance to standard therapy primarily consisting of chemoradiation. Since mutation of TP53 in HNSCC occurs in 60-80% of non-HPV associated cases and is in turn associated with resistance to these treatments, more effective therapies are needed. In this study, we evaluated the efficacy of a regimen combining vorinostat and AZD1775 in HNSCC cells with a variety of p53 mutations...
August 8, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28780424/the-cholesterol-transport-inhibitor-u18666a-inhibits-type-i-feline-coronavirus-infection
#19
Tomomi Takano, Misaki Endoh, Hiroaki Fukatsu, Haruko Sakurada, Tomoyoshi Doki, Tsutomu Hohdatsu
Feline infectious peritonitis (FIP) is a feline coronavirus (FCoV)-induced fatal disease in wild and domestic cats. FCoV exists in two serotypes. Type I FCoV is the dominant serotype worldwide. Therefore, it is necessary to develop antiviral drugs against type I FCoV infection. We previously reported that type I FCoV is closely associated with cholesterol throughout the viral life cycle. In this study, we investigated whether U18666A, the cholesterol synthesis and transport inhibitor, shows antiviral effects against type I FCoV...
August 3, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28775232/silencing-heme-oxygenase-1-increases-the-sensitivity-of-abc-dlbcl-cells-to-histone-deacetylase-inhibitor-in-vitro-and-in-vivo
#20
Zhen Zhou, Qin Fang, Dan Ma, Nana Zhe, Mei Ren, Bingqing Cheng, Peifan Li, Ping Liu, Xiaojing Lin, Sishi Tang, Xiuying Hu, Yudan Liao, Yaming Zhang, Tingting Lu, Jishi Wang
Heme oxygenase-1 (HO-1) can promote tumor growth and reinforce the resistance of diffuse large B-cell lymphoma (DLBCL) cells to chemotherapeutic drug vincristine. We herein found that HO-1 protein expression was higher in high-risk DLBCL patients than in low-risk ones. Silencing HO-1 gene expression resisted vorinostat-induced apoptosis and arrested cell cycle in the G0/G1 phase of LY-10 cells. Western blot, co-immunoprecipitation and chromatin immunoprecipitation assays confirmed that the possible mechanisms may be increased cleaved caspase-3 protein expression, decreased phospho-histone deacetylase 3 protein expression, and activated histone acetylation of P27Kip1 promoter...
July 28, 2017: Oncotarget
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