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https://www.readbyqxmd.com/read/27921344/uhplc-ms-based-hdac-assay-applied-to-bio-guided-microfractionation-of-fungal-extracts
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/27812279/discovering-outliers-of-potential-drug-toxicities-using-a-large-scale-data-driven-approach
#13
Jake Luo, Ron A Cisler
We systematically compared the adverse effects of cancer drugs to detect event outliers across different clinical trials using a data-driven approach. Because many cancer drugs are toxic to patients, better understanding of adverse events of cancer drugs is critical for developing therapies that could minimize the toxic effects. However, due to the large variabilities of adverse events across different cancer drugs, methods to efficiently compare adverse effects across different cancer drugs are lacking. To address this challenge, we present an exploration study that integrates multiple adverse event reports from clinical trials in order to systematically compare adverse events across different cancer drugs...
2016: Cancer Informatics
https://www.readbyqxmd.com/read/27798860/histone-deacetylase-inhibitors-a-novel-therapeutic-weapon-against-medullary-thyroid-cancer
#14
REVIEW
Christos Damaskos, Serena Valsami, Eleftherios Spartalis, Efstathios A Antoniou, Periklis Tomos, Stefanos Karamaroudis, Theofano Zoumpou, Vasilios Pergialiotis, Konstantinos Stergios, Constantinos Michaelides, Konstantinos Kontzoglou, Despina Perrea, Nikolaos Nikiteas, Dimitrios Dimitroulis
BACKGROUND/AIM: Medullary thyroid cancer (MTC) is highly malignant, metastatic and recurrent, remaining generally incurable, and responsible for approximately 14% of all thyroid carcinoma-related deaths. MTC can metastasize to lymph nodes, trachea and distant organs, such as brain, lungs, liver and bones. MTC cells are resistant to chemotherapy and traditional external therapies are not showing definite clinical benefits. Scientists are trying to understand the molecular background of carcinogenesis and histone deacetylase (HDAC) seems to play a potential role to gene transcription...
October 2016: Anticancer Research
https://www.readbyqxmd.com/read/27797970/molecular-pathways-maintaining-mapk-inhibitor-sensitivity-by-targeting-nonmutational-tolerance
#15
Michael P Smith, Claudia Wellbrock
Targeting hyperactive MAPK signaling has proven to be an effective treatment for a variety of different cancers. Responses to the BRAF inhibitors vemurafenib and dabrafenib and the MEK inhibitors trametinib and cobimetinib are, however, transient, and complete remission is rarely observed; rather, outgrowth of resistant clones within progressed tumors appears inevitable. These resistant tumors display great heterogeneity, which poses a major challenge to any salvage therapy. Recent focus has, therefore, been on the early dynamics of inhibitor response during tumor regression...
October 19, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27795561/a-clinical-trial-for-patients-with-acute-myeloid-leukemia-or-myelodysplastic-syndromes-not-eligible-for-standard-clinical-trials
#16
G Montalban-Bravo, X Huang, E Jabbour, G Borthakur, C D DiNardo, N Pemmaraju, J Cortes, S Verstovsek, T Kadia, N Daver, W Wierda, Y Alvarado, M Konopleva, F Ravandi, Z Estrov, N Jain, A Alfonso, M Brandt, T Sneed, H-C Chen, H Yang, C Bueso-Ramos, S Pierce, E Estey, Z Bohannan, H M Kantarjian, G Garcia-Manero
Most clinical trials exclude patients with poor performance or comorbidities. To study whether patients with these characteristics can be treated within a clinical trial, we conducted a study for patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) with poor performance, organ dysfunction or comorbidities. Primary endpoint was 60-day survival. Study included stopping rules for survival and response. Treatment consisted on a combination of azacitidine and vorinostat. Thirty patients (16 with MDS, 14 with AML) were enrolled...
October 31, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27792246/inhibition-of-histone-deacetylases-in-melanoma-a-perspective-from-bench-to-bedside
#17
REVIEW
Eva Hornig, Markus V Heppt, Saskia A Graf, Thomas Ruzicka, Carola Berking
Histone deacetylases (HDACs) are critically involved in epigenetic gene regulation through alterations of the chromatin status of DNA. Aberrant expression, dysregulation of their enzymatic activity or imbalances between HDACs and histone acetyltransferases are likely involved in the development and progression of cancer. Pharmacologic inhibition of HDACs shows potent antitumor activity in a panel of malignancies such as colon or gastric cancer and multiple myeloma. In this review, we summarize the current knowledge of HDACs in melanoma and evaluate the application of HDAC inhibition from an experimental and clinical perspective...
November 2016: Experimental Dermatology
https://www.readbyqxmd.com/read/27786474/efficient-palladium-triggered-release-of-vorinostat-from-a-bioorthogonal-precursor
#18
Belén Rubio-Ruiz, Jason T Weiss, Asier Unciti-Broceta
Bioorthogonal uncaging strategies have recently emerged as an experimental therapeutic approach to control drug release. Herein we report a novel masking strategy that enables to modulate the metal chelating properties of hydroxamic acid groups by bioorthogonal chemistry using Pd-functionalized resins. This novel approach allowed to devise an inactive precursor of the histone deacetylase inhibitor vorinostat that was efficiently uncaged by heterogeneous Pd catalysis in cell culture models of glioma and lung cancer...
October 27, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27769558/vorinostat-in-combination-with-lenalidomide-and-dexamethasone-in-lenalidomide-refractory-multiple-myeloma
#19
Elizabeth Bilotti, David H Vesole, Laura McBride, Linda Schmidt, Zhijie Gao, Madiha Gilani, Ann McNeill, Urszula Bednarz, Joshua Richter, Anthony Mato, Thorsten Graef, David S Siegel
BACKGROUND: This is a retrospective chart review to evaluate the efficacy of the addition of vorinostat to lenalidomide and dexamethasone in patients with multiple myeloma relapsed/refractory to lenalidomide and dexamethasone. METHODS: Charts from 26 consecutive patients able to obtain commercial vorinostat were analyzed for response and safety data. RESULTS: The overall response rate was 31%, and the clinical beneficial rate was 50%. The median duration of response was 3 months, and the median overall survival was 28...
October 2016: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/27769267/activation-of-hiv-1-expression-in-latently-infected-cd4-t-cells-by-the-small-molecule-pkc412
#20
Zhujun Ao, Rong Zhu, Xiaoli Tan, Lisa Liu, Liyu Chen, Shuiping Liu, XiaoJian Yao
BACKGROUND: HIV-1 latency is a major obstacle for HIV-1 eradication. Extensive efforts are being directed toward the reactivation of latent HIV reservoirs with the aim of eliminating latently infected cells via the host immune system and/or virus-mediated cell lysis. RESULTS: We screened over 1,500 small molecules and kinase inhibitors and found that a small molecule, PKC412 (midostaurin, a broad-spectrum kinase inhibitor), can stimulate viral transcription and expression from the HIV-1 latently infected ACH2 cell line and primary resting CD4+ T cells...
October 21, 2016: Virology Journal
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