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https://www.readbyqxmd.com/read/28101809/sequential-exposure-of-bortezomib-and-vorinostat-is-synergistic-in-multiple-myeloma-cells
#1
Charvi Nanavati, Donald E Mager
PURPOSE: To examine the combination of bortezomib and vorinostat in multiple myeloma cells (U266) and xenografts, and to assess the nature of their potential interactions with semi-mechanistic pharmacodynamic models and biomarkers. METHODS: U266 proliferation was examined for a range of bortezomib and vorinostat exposure times and concentrations (alone and in combination). A non-competitive interaction model was used with interaction parameters that reflect the nature of drug interactions after simultaneous and sequential exposures...
January 18, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28031458/normalization-of-hepatic-homeostasis-in-the-npc1nmf164-mouse-model-of-niemann-pick-type-c-disease-treated-with-the-histone-deacetylase-inhibitor-vorinostat
#2
Andrew B Munkacsi, Natalie Hammond, Remy T Schneider, Dinindu S Senanayake, Katsumi Higaki, Kirill Lagutin, Stephen J Bloor, Daniel S Ory, Robert A Maue, Fannie W Chen, Antonio Hernandez-Ono, Nicole Dahlson, Joyce J Repa, Henry N Ginsberg, Yiannis A Ioannou, Stephen L Sturley
Niemann-Pick type C (NP-C) disease is a fatal genetic lipidosis for which there is no FDA-approved therapy. Vorinostat, an FDA-approved inhibitor of histone deacetylases, ameliorates lysosomal lipid accumulation in cultured NP-C patient fibroblasts. To assess the therapeutic potential of histone deacetylase inhibition, we pursued these in vitro observations in two murine models of NP-C disease. Npc1nmf164 mice, which express a missense mutation in the NPC1 gene, were treated intraperitoneally, from weaning, with the maximum tolerated dose of Vorinostat (150 mg/kg, 5 days per week)...
December 28, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28019030/histone-deacetylase-inhibitors-suppress-abo-transcription-in-vitro-leading-to-reduced-expression-of-the-antigens
#3
Yoichiro Takahashi, Rieko Kubo, Rie Sano, Tamiko Nakajima, Keiko Takahashi, Momoko Kobayashi, Hiroshi Handa, Junichi Tsukada, Yoshihiko Kominato
BACKGROUND: The ABO system is of fundamental importance in the fields of transfusion and transplantation and has apparent associations with certain diseases, including cardiovascular disorders. ABO expression is reduced in the late phase of erythroid differentiation in vitro, whereas histone deacetylase inhibitors (HDACIs) are known to promote cell differentiation. Therefore, whether or not HDACIs could reduce the amount of ABO transcripts and A or B antigens is an intriguing issue. STUDY DESIGN AND METHODS: Quantitative polymerase chain reactions were carried out for the ABO transcripts in erythroid-lineage K562 and epithelial-lineage KATOIII cells after incubation with HDACIs, such as sodium butyrate, panobinostat, vorinostat, and sodium valproate...
December 26, 2016: Transfusion
https://www.readbyqxmd.com/read/27993720/synergistic-anticancer-activity-of-combined-histone-deacetylase-and-proteasomal-inhibitor-loaded-zein-nanoparticles-in-metastatic-prostate-cancers
#4
Raj Kumar Thapa, Hanh Thuy Nguyen, Jee-Heon Jeong, Beom Soo Shin, Sae Kwang Ku, Han-Gon Choi, Chul Soon Yong, Jong Oh Kim
The development of resistance and subsequent metastasis makes prostate cancer a leading cause of cancer-related death among men. Hence, nanoparticle-based combination chemotherapeutics could be a viable treatment strategy. We aimed to prepare vorinostat (Vor) and bortezomib (Bor) combination-loaded zein nanoparticles (ZNP, ZNP/VB) for treating metastatic prostate cancers. Our results revealed the successful preparation of ZNP/VB with a small particle size (~160nm) and polydispersity index (~0.20). Importantly, controlled and pH-dependent drug release profiles were observed...
December 18, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/27986747/histone-deacetylase-3-inhibition-overcomes-bim-deletion-polymorphism-mediated-osimertinib-resistance-in-egfr-mutant-lung-cancer
#5
Azusa Tanimoto, Shinji Takeuchi, Sachiko Arai, Koji Fukuda, Tadaaki Yamada, Xavier Roca, Sin Tiong Ong, Seiji Yano
PURPOSE: The BIM deletion polymorphism is associated with apoptosis resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib and erlotinib, in non-small cell lung cancer (NSCLC) harboring EGFR mutations. Here, we investigated whether the BIM deletion polymorphism contributes to resistance against osimertinib, a third-generation EGFR-TKI. In addition, we determined the efficacy of a histone deacetylase (HDAC) inhibitor, vorinostat, against this form of resistance and elucidated the underlying mechanism...
December 16, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27956831/a-facile-route-to-form-self-carried-redox-responsive-vorinostat-nanodrug-for-effective-solid-tumor-therapy
#6
Leiqiang Han, Tianqi Wang, Jingliang Wu, Xiaolan Yin, Hao Fang, Na Zhang
Small molecule-based nanodrugs with nanoparticles (NPs) that are mainly composed of small molecules, have been considered as a promising candidate for a next-generation nanodrug, owing to their unique properties. Vorinostat (SAHA) is a canonical US Food and Drug Administration-approved histone deacetylase (HDAC) inhibitor for the treatment of cutaneous T-cell lymphoma. However, the lack of efficacy against solid tumors hinders its progress in clinical use. Herein, a novel nanodrug of SAHA was developed based on disulfide-linked prodrug SAHA-S-S-VE...
2016: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/27935859/histone-deacetylase-inhibitors-inhibit-metastasis-by-restoring-a-tumor-suppressive-microrna-150-in-advanced-cutaneous-t-cell-lymphoma
#7
Fumito Abe, Akihiro Kitadate, Sho Ikeda, Junsuke Yamashita, Hiroki Nakanishi, Naoto Takahashi, Chikara Asaka, Kazuaki Teshima, Tomomitsu Miyagaki, Makoto Sugaya, Hiroyuki Tagawa
Tumor suppressive microRNA (miR)-150 inhibits metastasis by combining with the C-C chemokine receptor 6 (CCR6) "seed sequence" mRNA of the 3'-untranslated region (3'-UTR) in advanced cutaneous T-cell lymphoma (CTCL). Because the histone deacetylase inhibitor (HDACI) vorinostat showed excellent outcomes for treating advanced CTCL, HDACIs may reduce the metastasis of CTCL by targeting miR-150 and/ or CCR6. To examine whether these candidate molecules are essential HDACI targets in advanced CTCL, we used the My-La, HH, and HUT78 CTCL cell lines for functional analysis because we previously demonstrated that their xenografts in NOD/Shi-scid IL-2γnul mice (CTCL mice) induced multiple metastases...
December 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27925271/validation-of-an-lc-ms-ms-method-for-simultaneous-detection-of-four-hdac-inhibitors-belinostat-panobinostat-rocilinostat-and-vorinostat-in-mice-plasma-and-its-application-to-a-mice-pharmacokinetic-study
#8
Kalpesh Kumar Giri, Suresh P S, Syed Mohd Saim, Mohd Zainuddin, Ravi Kanth Bhamidipati, Purushottam Dewang, Mahanandeesha S Hallur, Sridharan Rajagopal, Sriram Rajagopal, Ramesh Mullangi
A sensitive and rapid LC-MS/MS method was developed and validated for the simultaneous quantitation of four HDAC inhibitors namely belinostat (BST), panobinostat (PST), rocilinostat (RST) and vorinostat (VST) in mice plasma as per regulatory guidelines. The analytes and internal standard were extracted from 50 μL mice plasma by protein precipitation, followed by chromatographic separation using an Atlantis C18 column with an isocratic mobile phase comprising 0.1% formic acid: acetonitrile (25:75,, v/v) at a flow rate of 0...
December 7, 2016: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/27921344/uhplc-ms-based-hdac-assay-applied-to-bio-guided-microfractionation-of-fungal-extracts
#9
Vincent Zwick, Pierre-Marie Allard, Lucie Ory, Claudia A Simões-Pires, Laurence Marcourt, Katia Gindro, Jean-Luc Wolfender, Muriel Cuendet
INTRODUCTION: Histone deacetylases (HDAC) are considered as promising targets for cancer treatment. Today, four HDAC inhibitors, vorinostat, romidepsin, belinostat, and panobinostat, have been approved by the Food and Drug Administration (FDA) for cancer treatment, while others are in clinical trials. Among them, several are naturally occurring fungal metabolites. OBJECTIVE: To develop and optimise an enzyme assay for bio-guided identification of HDAC inhibitors in fungal strains...
December 5, 2016: Phytochemical Analysis: PCA
https://www.readbyqxmd.com/read/27916918/subchronic-toxicities-of-hz1006-a-hydroxamate-based-histone-deacetylase-inhibitor-in-beagle-dogs-and-sprague-dawley-rats
#10
Xiaofang Zhang, Xiaodong Zhang, Bojun Yuan, Lijun Ren, Tianbao Zhang, Guocai Lu
Histone deacetylase inhibitors (HDACIs), such as vorinostat and panobinostat, have been shown to have active effects on many hematologic malignancies, including multiple myeloma and cutaneous T-cell lymphoma. Hydroxamate-based (Hb) HDACIs have very good toxicity profiles and are currently being tested in phases I and II clinical trials with promising results in selected neoplasms, such as bladder carcinoma. One of the Hb-HDACIs, HZ1006, has been demonstrated to be a promising drug for clinical use. The aim of our study was to determine the possible target of toxicity and to identify a non-toxic dose of HZ1006 for clinical use...
November 30, 2016: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/27910927/novel-chemoimmunotherapeutic-strategy-for-hepatocellular-carcinoma-based-on-a-genome-wide-association-study
#11
Kaku Goto, Dorcas A Annan, Tomoko Morita, Wenwen Li, Ryosuke Muroyama, Yasuo Matsubara, Sayaka Ito, Ryo Nakagawa, Yasushi Tanoue, Masahisa Jinushi, Naoya Kato
Pharmacotherapeutic options are limited for hepatocellular carcinoma (HCC). Recently, we identified the anti-tumor ligand MHC class I polypeptide-related sequence A (MICA) gene as a susceptibility gene for hepatitis C virus-induced HCC in a genome-wide association study (GWAS). To prove the concept of HCC immunotherapy based on the results of a GWAS, in the present study, we searched for drugs that could restore MICA expression. A screen of the FDA-approved drug library identified the anti-cancer agent vorinostat as the strongest hit, suggesting histone deacetylase inhibitors (HDACis) as potent candidates...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27899892/age-dependent-hepatic-udp-glucuronosyltransferase-gene-expression-and-activity-in-children
#12
Elizabeth Neumann, Huma Mehboob, Jacqueline Ramírez, Snezana Mirkov, Min Zhang, Wanqing Liu
UDP-glucuronosyltransferases (UGTs) are important phase II drug metabolism enzymes. The aim of this study was to explore the relationship between age and changes in mRNA expression and activity of major human hepatic UGTs, as well as to understand the potential regulatory mechanism underlying this relationship. Using previously generated data, we investigated age-dependent mRNA expression levels of 11 hepatic UGTs (UGT1A1, UGT1A3, UGT1A4, UGT1A5, UGT1A6, UGT1A9, UGT2B4, UGT2B7, UGT2B10, UGT2B15, and UGT2B17) and 16 transcription factors (AHR, AR, CAR, ESR2, FXR, GCCR, HNF1a, HNF3a, HNF3b, HNF4a, PPARA, PPARG, PPARGC, PXR, SP1, and STAT3) in liver tissue of donors (n = 38) ranging from 0 to 25 years of age...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27884140/phase-ii-clinical-study-of-valproic-acid-plus-cisplatin-and-cetuximab-in-recurrent-and-or-metastatic-squamous-cell-carcinoma-of-head-and-neck-v-chance-trial
#13
Francesco Caponigro, Elena Di Gennaro, Franco Ionna, Francesco Longo, Corrado Aversa, Ettore Pavone, Maria Grazia Maglione, Massimiliano Di Marzo, Paolo Muto, Ernesta Cavalcanti, Antonella Petrillo, Fabio Sandomenico, Piera Maiolino, Roberta D'Aniello, Gerardo Botti, Rossella De Cecio, Nunzia Simona Losito, Stefania Scala, Annamaria Trotta, Andrea Ilaria Zotti, Francesca Bruzzese, Antonio Daponte, Ester Calogero, Massimo Montano, Monica Pontone, Gianfranco De Feo, Francesco Perri, Alfredo Budillon
BACKGROUND: Recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN) has a poor prognosis and the combination of cisplatin and cetuximab, with or without 5-fluorouracil, is the gold standard treatment in this stage. Thus, the concomitant use of novel compounds represents a critical strategy to improve treatment results. Histone deacetylase inhibitors (HDACi) enhance the activity of several anticancer drugs including cisplatin and anti-Epidermal Growth Factor Receptor (anti-EGFR) compounds...
November 25, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27877053/synergistic-activity-of-vorinostat-combined-with-gefitinib-but-not-with-sorafenib-in-mutant-kras-human-non-small-cell-lung-cancers-and-hepatocarcinoma
#14
Victor Jeannot, Benoit Busser, Laetitia Vanwonterghem, Sophie Michallet, Sana Ferroudj, Murat Cokol, Jean-Luc Coll, Mehmet Ozturk, Amandine Hurbin
Development of drug resistance limits the efficacy of targeted therapies. Alternative approaches using different combinations of therapeutic agents to inhibit several pathways could be a more effective strategy for treating cancer. The effects of the approved epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (gefitinib) or a multi-targeted kinase inhibitor (sorafenib) in combination with a histone deacetylase inhibitor (vorinostat) on cell proliferation, cell cycle distribution, apoptosis, and signaling pathway activation in human lung adenocarcinoma and hepatocarcinoma cells with wild-type EGFR and mutant KRAS were investigated...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27870832/position-effects-influence-hiv-latency-reversal
#15
Heng-Chang Chen, Javier P Martinez, Eduard Zorita, Andreas Meyerhans, Guillaume J Filion
The main obstacle to curing HIV is the presence of latent proviruses in the bodies of infected patients. The partial success of reactivation therapies suggests that the genomic context of integrated proviruses can interfere with treatment. Here we developed a method called Barcoded HIV ensembles (B-HIVE) to map the chromosomal locations of thousands of individual proviruses while tracking their transcriptional activities in an infected cell population. B-HIVE revealed that, in Jurkat cells, the expression of HIV is strongest close to endogenous enhancers...
November 21, 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27859001/a-phase-iib-trial-of-vorinostat-in-combination-with-lenalidomide-and-dexamethasone-in-patients-with-multiple-myeloma-refractory-to-previous-lenalidomide-containing-regimens
#16
Larysa Sanchez, David H Vesole, Joshua R Richter, Noa Biran, Elizabeth Bilotti, Laura McBride, Palka Anand, Kristin Ivanovski, David S Siegel
Clinical trials of vorinostat, a Class I/II histone deacetylase inhibitor, in combination with proteasome inhibitors and immunomodulatory agents have shown activity in relapsed/refractory multiple myeloma. This phase IIb, open-label, single-institution study evaluated the efficacy of vorinostat in combination with lenalidomide and dexamethasone in lenalidomide-refractory patients. Patients were considered lenalidomide-refractory if they had no clinical response (<minimal response) on a previous lenalidomide-containing regimen (lenalidomide non-responsive) or if they had progressive disease on or within 60 days of discontinuing a previous lenalidomide-containing regimen (lenalidomide relapsed/refractory)...
November 18, 2016: British Journal of Haematology
https://www.readbyqxmd.com/read/27843649/procaine-induces-epigenetic-changes-in-hct116-colon-cancer-cells
#17
Hussein Sabit, Mariam B Samy, Osama A M Said, Mokhtar M El-Zawahri
Colon cancer is the third most commonly diagnosed cancer in the world, and it is the major cause of morbidity and mortality throughout the world. The present study aimed at treating colon cancer cell line (HCT116) with different chemotherapeutic drug/drug combinations (procaine, vorinostat "SAHA," sodium phenylbutyrate, erlotinib, and carboplatin). Two different final concentrations were applied: 3 μM and 5 μM. Trypan blue test was performed to assess the viability of the cell before and after being treated with the drugs...
2016: Genetics Research International
https://www.readbyqxmd.com/read/27821078/vorinostat-enhances-the-cisplatin-mediated-anticancer-effects-in-small-cell-lung-cancer-cells
#18
Chun-Hao Pan, Ying-Fang Chang, Ming-Shuo Lee, B-Chen Wen, Jen-Chung Ko, Sheng-Kai Liang, Mei-Chih Liang
BACKGROUND: Vorinostat, a histone deacetylase (HDAC) inhibitor, is a promising agent for cancer therapy. Combining vorinostat with cisplatin may relax the chromatin structure and facilitate the accessibility of cisplatin, thus enhancing its cytotoxicity. Studies have not yet investigated the effects of the combination of vorinostat and cisplatin on small cell lung cancer (SCLC). METHODS: We first assessed the efficacy of vorinostat with etoposide/cisplatin (EP; triple combination) and then investigated the effects of cotreatment with vorinostat and cisplatin on H209 and H146 SCLC cell lines...
November 7, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27819724/histone-h3k9-acetylation-influences-growth-characteristics-of-goat-adipose-derived-stem-cells-in-vitro
#19
X Wang, F X Zhang, Z M Wang, Q Wang, H F Wang, Y Ren, D P Tai, H Liang, D J Liu
Adipose-derived stem cells (ADSCs) show nearly unlimited potential in medical and animal science. Currently, understanding of the biological mechanisms regulating ADSC growth in vitro remains very limited. Histone acetylation, an epigenetic modification, plays a key role in maintaining stem cell properties. To further study its effect on ADSC growth characteristics in vitro, we treated goat ADSCs with the histone deacetylase inhibitors trichostatin A (TSA) and vorinostat (SAHA). This inhibited SIRT1 expression and increased histone H3K9 acetylation, leading to decreased cell viability, cell cycle arrest, and apoptosis...
November 3, 2016: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/27813438/targeting-histone-deacetylases-in-t-cell-lymphoma
#20
Alison J Moskowitz, Steven M Horwitz
Histone deacetylase inhibitors (HDACi) are epigenetic modifiers with single-agent activity in patients with cutaneous and peripheral T-cell lymphoma (CTCL, PTCL). The mechanisms for this preferential activity remain unclear, and although some would term this as 'class effect,' there are differences in efficacy and safety, likely a result of the varying chemical structures/classes, histone and non-histone targets, potencies, and clinical dosing for each. Three HDACi have single-agent approval in relapsed/refractory TCL in the United States: romidepsin in CTCL and PTCL, vorinostat in CTCL, and belinostat in PTCL...
November 4, 2016: Leukemia & Lymphoma
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