keyword
MENU ▼
Read by QxMD icon Read
search

Vorinostat

keyword
https://www.readbyqxmd.com/read/28637181/crosstalk-between-histone-modifications-indicates-that-inhibition-of-arginine-methyltransferase-carm1-activity-reverses-hiv-latency
#1
Zheng Zhang, Bryan C Nikolai, Leah A Gates, Sung Yun Jung, Edward B Siwak, Bin He, Andrew P Rice, Bert W O'Malley, Qin Feng
In eukaryotic cells, the gene expression status is strictly controlled by epigenetic modifications on chromatin. The repressive status of chromatin largely contributes to HIV latency. Studies have shown that modification of histone H3K27 acts as a key molecular switch for activation or suppression of many cellular genes. In this study, we found that K27-acetylated histone H3 specifically recruited Super Elongation Complex (SEC), the transcriptional elongation complex essential for HIV-1 long terminal repeat (LTR)-mediated and general cellular transcription...
June 20, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28623430/a-phase-i-ii-study-of-suberoylanilide-hydroxamic-acid-saha-in-combination-with-trastuzumab-herceptin-in-patients-with-advanced-metastatic-and-or-local-chest-wall-recurrent-her2-amplified-breast-cancer-a-trial-of-the-ecog-acrin-cancer-research-group-e1104
#2
Lori J Goldstein, Fengmin Zhao, Molin Wang, Ramona F Swaby, Joseph A Sparano, Neal J Meropol, Kapil N Bhalla, Christine M Pellegrino, R Katherine Alpaugh, Carla I Falkson, Paula Klein, George W Sledge
PURPOSE: Suberoylanilide hydroxamic acid (SAHA; vorinostat), a small molecule inhibitor of histone deacetylase, attenuates signaling pathways known to confer trastuzumab resistance. A combination of SAHA and trastuzumab may be a promising strategy to improve the efficacy of trastuzumab against breast cancer. In this Phase I/II study, we evaluated the toxicity and response rate after treatment with SAHA and trastuzumab in patients with HER2-overexpressing metastatic breast cancer with trastuzumab-resistant progressive disease...
June 16, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28612091/intracellular-vorinostat-accumulation-and-its-relationship-to-histone-deacetylase-activity-in-soft-tissue-sarcoma-patients
#3
Jürgen Burhenne, Lu Liu, Christoph E Heilig, Andreas D Meid, Margarete Leisen, Thomas Schmitt, Bernd Kasper, Walter E Haefeli, Gerd Mikus, Gerlinde Egerer
PURPOSE: In the regulation of chromatin-structure and histone function, histone deacetylases (HDACs) are key enzymes and thus modulators of epigenetic regulation and gene expression. Accesses of the HDAC inhibitor vorinostat to intracellular compartments are essential to exert epigenetic effects. METHODS: In ten sarcoma patients receiving oral Zolinza (400 mg qd) vorinostat concentrations in plasma and peripheral blood mononuclear cells (PBMCs) were quantified using validated LC/MS/MS assays to determine intracellular and extracellular pharmacokinetic data...
June 13, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28611287/vorinostat-suppresses-hypoxia-signaling-by-modulating-nuclear-translocation-of-hypoxia-inducible-factor-1-alpha
#4
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...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28601492/new-agents-in-multiple-myeloma-an%C3%A2-examination-of-safety-profiles
#5
REVIEW
Sara Bringhen, Edwin De Wit, Meletios-Athanassios Dimopoulos
Numerous treatments are available for relapsed and/or refractory multiple myeloma (MM), with safety profiles varying across drug classes and across agents within the same class. Thus, it is important to understand the toxicities of each antimyeloma agent when making treatment decisions. Neutropenia is commonly associated with lenalidomide and pomalidomide, and may be common with histone deacetylase (HDAC) inhibitors, but is relatively unusual with thalidomide, bortezomib, and carfilzomib. Infection was common in trials of lenalidomide and pomalidomide, and upper respiratory tract infection and pneumonia have been seen with carfilzomib...
May 10, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28589904/decitabine-vorinostat-combination-treatment-in-acute-myeloid-leukemia-activates-pathways-with-potential-for-novel-triple-therapy
#6
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...
May 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28566628/histone-deacetylase-inhibitors-sensitize-murine-b16f10-melanoma-cells-to-carbon-ion-irradiation-by-inducing-g1-phase-arrest
#7
Katsuyo Saito, Tomoo Funayama, Yuichiro Yokota, Takashi Murakami, Yasuhiko Kobayashi
Epigenetic processes, in addition to genetic abnormalities, play a critical role in refractory malignant diseases and cause the unresponsiveness to various chemotherapeutic regimens and radiotherapy. Herein we demonstrate that histone deacetylase inhibitors (HDACis) can be used to sensitize malignant melanoma B16F10 cells to carbon ion irradiation. The cells were first treated with HDACis (romidepsin [FK228, depsipeptide], trichostatin A [TSA], valproic acid [VPA], and suberanilohydroxamic acid [SAHA, vorinostat]) and were then exposed to two types of radiation (carbon ions and gamma-rays)...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28562519/epigenetic-combination-therapy-for-children-with-secondary-myelodysplastic-syndrome-mds-acute-myeloid-leukemia-aml-and-concurrent-solid-tumor-relapse
#8
Chana L Glasser, Alice Lee, Don Eslin, Lianna Marks, Shakeel Modak, Julia L Glade Bender
Secondary myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) is a rare but devastating complication of solid tumor treatment involving high-dose topoisomerase II inhibitor and alkylator chemotherapy. For relapsed or elderly MDS and AML patients ineligible for hematopoietic stem cell transplantation, epigenetic therapies, including DNA methyltransferase inhibitors and histone deacetylase inhibitors, have been utilized as palliative therapy, offering a well-tolerated approach to disease stabilization, prolonged survival, and quality of life...
May 29, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28560392/the-blueberry-component-pterostilbene-has-potent-anti-myeloma-activity-in-bortezomib-resistant-cells
#9
Gege Chen, Zhijian Xu, Gaomei Chang, Jun Hou, Liangning Hu, Yiwen Zhang, Dandan Yu, Bo Li, Shuaikang Chang, Yongsheng Xie, Yong Zhang, Rong Wei, Huiqun Wu, Wenqin Xiao, Xi Sun, Yi Tao, Lu Gao, Bojie Dai, Jumei Shi, Weiliang Zhu
Multiple myeloma (MM) is an incurable hematologic malignancy because of its drug resistance. Pterostilbene (Pter) is found mainly in blueberries and grapes. The effects of Pter and its exact pharmacologic mechanisms on chemoresistant myeloma are not known. Herein, we investigated the anti-myeloma activity of Pter in bortezomib-resistant cell line H929R and explored the related mechanism of action for the first time. We found that Pter inhibited proliferation of H929R cells and promoted apoptosis of the cells through a caspase-dependent pathway, loss of mitochondrial membrane potential, and activation of Akt and p38 mitogen-activated protein kinase (MAPK) signaling pathways...
May 30, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28537899/nras-mutations-in-cutaneous-t-cell-lymphoma-ctcl-sensitize-tumors-towards-treatment-with-the-multikinase-inhibitor-sorafenib
#10
Michael K Kießling, Jan P Nicolay, Tabea Schlör, Claus-Detlev Klemke, Dorothee Süss, Peter H Krammer, Karsten Gülow
Therapy of cutaneous T cell lymphoma (CTCL) is complicated by a distinct resistance of the malignant T cells towards apoptosis that can be caused by NRAS mutations in late-stage patients. These mutations correlate with decreased overall survival, but sensitize the respective CTCL cells towards MEK-inhibition-induced apoptosis which represents a promising novel therapeutic target in CTCL. Here, we show that the multi-kinase inhibitor Sorafenib induces apoptosis in NRAS-mutated CTCL cells. CTCL cell lines and to a minor extent primary T cells from Sézary patients without NRAS mutations are also affected by Sorafenib-induced apoptosis suggesting a sensitizing role of NRAS mutations for Sorafenib-induced apoptosis...
May 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537897/mek-inhibitors-cobimetinib-and-trametinib-regressed-a-gemcitabine-resistant-pancreatic-cancer-patient-derived-orthotopic-xenograft-pdox
#11
Kei Kawaguchi, Kentaro Igarashi, Takashi Murakami, Tasuku Kiyuna, Thinzar M Lwin, Ho Kyoung Hwang, Jonathan C Delong, Bryan M Clary, Michael Bouvet, Michiaki Unno, Robert M Hoffman
A pancreatic ductal adenocarcinoma (PDAC), obtained from a patient, was grown orthotopically in the pancreatic tail of nude mice to establish a patient-derived orthotopic (PDOX) model. Seven weeks after implantation, PDOX nude mice were divided into the following groups: untreated control (n = 7); gemcitabine (100 mg/kg, i.p., once a week for 2 weeks, n = 7); cobimetinib (5 mg/kg, p.o., 14 consecutive days, n = 7); trametinib (0.3 mg/kg, p.o., 14 consecutive days, n = 7); trabectedin (0.15 mg/kg, i.v., once a week for 2 weeks, n = 7); temozolomide (25 mg/kg, p...
May 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28535287/a-flow-cytometry-based-screen-identifies-mbnl1-modulators-that-rescue-splicing-defects-in-myotonic-dystrophy-type-i
#12
Fan Zhang, Nicole E Bodycombe, Keith M Haskell, Yumei L Sun, Eric T Wang, Carl A Morris, Lyn H Jones, Lauren D Wood, Mathew T Pletcher
Myotonic Dystrophy Type 1 (DM1) is a rare genetic disease caused by expansion of CTG trinucleotide repeats ((CTG)exp) in the 3' untranslated region of the DMPK gene. The repeat transcripts sequester the RNA binding protein Muscleblind-like protein 1 (MBNL1) and hamper its normal function in pre-mRNA splicing. Overexpressing exogenous MBNL1 in the DM1 mouse model has been shown to rescue the splicing defects and reverse myotonia. Although a viable therapeutic strategy, pharmacological modulators of MBNL1 expression have not been identified...
May 23, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28530797/unexpected-biotransformation-of-the-hdac-inhibitor-vorinostat-yields-aniline-containing-fungal-metabolites
#13
Donovon A Adpressa, Kayla J Stalheim, Philip Jerome Proteau, Sandra Loesgen
The diversity of genetically encoded small molecules produced by filamentous fungi remains largely unexplored, which makes these fungi an attractive source for the discovery of new compounds. However, accessing their full chemical repertoire under common laboratory culture conditions is a challenge. Epigenetic manipulation of gene expression has become a well-established tool for overcoming this obstacle. Here we report that perturbation of the endophytic ascomycete Chalara sp. 6661, producer of the isofusidienol class of antibiotics, with the HDAC inhibitor vorinostat resulted in the production of four new modified xanthones...
May 22, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28486043/randomized-phase-ii-study-of-azacitidine-alone-or-in-combination-with-lenalidomide-or-with-vorinostat-in-higher-risk-myelodysplastic-syndromes-and-chronic-myelomonocytic-leukemia-north-american-intergroup-study-swog-s1117
#14
Mikkael A Sekeres, Megan Othus, Alan F List, Olatoyosi Odenike, Richard M Stone, Steven D Gore, Mark R Litzow, Rena Buckstein, Min Fang, Diane Roulston, Clara D Bloomfield, Anna Moseley, Aziz Nazha, Yanming Zhang, Mario R Velasco, Rakesh Gaur, Ehab Atallah, Eyal C Attar, Elina K Cook, Alyssa H Cull, Michael J Rauh, Frederick R Appelbaum, Harry P Erba
Purpose Azacitidine is standard, first-line therapy in higher-risk myelodysplastic syndromes (MDS). Whether azacitidine-based combinations with lenalidomide or vorinostat produce superior overall response rates (ORRs) to azacitidine is not known. Patients and Methods North American Intergroup Study S1117 is a phase II/III trial that randomly assigned patients with higher-risk MDS and chronic myelomonocytic leukemia (CMML) 1:1:1 to azacitidine (75 mg/m(2)/day on days 1 to 7 of a 28-day cycle); azacitidine plus lenalidomide (10 mg/day on days 1 to 21); or azacitidine plus vorinostat (300 mg twice daily on days 3 to 9)...
May 9, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28454309/targeting-cd146-in-combination-with-vorinostat-for-the-treatment-of-ovarian-cancer-cells
#15
Xiaoli Ma, Jiandong Wang, Jia Liu, Qingqing Mo, Xiyun Yan, Ding Ma, Hua Duan
Drug resistance is the predominant cause of mortality in late-stage patients with ovarian cancer. Histone deacetylase inhibitors (HDACis) have emerged as a novel type of second line drug with high specificity for tumor cells, including ovarian cancer cells. However, HDACis usually exhibit relatively low potencies when used as a single agent. The majority of current clinical trials are combination strategies. These strategies are more empirical than mechanism-based applications. Previously, it was reported that the adhesion molecule cluster of differentiation 146 (CD146) is significantly induced in HDACi-treated tumor cells...
March 2017: Oncology Letters
https://www.readbyqxmd.com/read/28425177/design-and-synthesis-of-c3-substituted-%C3%AE-carboline-based-histone-deacetylase-inhibitors-with-potent-antitumor-activities
#16
Yong Ling, Jiao Feng, Lin Luo, Jing Guo, Yanfu Peng, Tingting Wang, Xiang Ge, Qibing Xu, Xinyang Wang, Hong Dai, Yanan Zhang
A series of hydroxamic acid histone deacetylase (HDAC) inhibitors in which the β-carboline motif has been incorporated were designed and synthesized. The effect of substitution at the C3 amide on HDAC inhibition and antiproliferative activities was investigated. Most of these compounds were found to display significant HDAC inhibitory effects and good antiproliferative activity, with IC50 values in the low-micromolar range. In particular, the HDAC inhibition IC50 value of N-(2-(dimethylamino)ethyl)-N-(4-(hydroxylcarbamoyl)benzyl)-1-(4-methoxyphenyl)-9H-pyrido[3,4-b]indole-3-carboxamide (9 h) is five-fold lower than that of suberoylanilide hydroxamic acid (SAHA, vorinostat)...
April 20, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28415633/a-phase-2-study-of-vorinostat-in-locally-advanced-recurrent-or-metastatic-adenoid-cystic-carcinoma
#17
Priscila H Goncalves, Lance K Heilbrun, Michael T Barrett, Shivaani Kummar, Aaron R Hansen, Lillian L Siu, Richard L Piekarz, Ammar W Sukari, Joseph Chao, Mary Jo Pilat, Daryn W Smith, Lindsay Casetta, Scott A Boerner, Alice Chen, Elizabeth Lenkiewicz, Smriti Malasi, Patricia M LoRusso
PURPOSE: Vorinostat is a histone deacetylase inhibitor (HDACi). Based on a confirmed partial response (PR) in an adenoid cystic carcinoma (ACC) patient treated with vorinostat in a prior phase 1 trial, we initiated this phase 2 trial. METHODS: Vorinostat was administered orally 400 mg daily, 28 day cycles. The primary objective was to evaluate response rate (RR). Exploratory studies included whole exome sequencing (WES) of selected patients. RESULTS: Thirty patients were enrolled...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28398261/novel-proteasome-inhibitors-and-histone-deacetylase-inhibitors-progress-in-myeloma-therapeutics
#18
REVIEW
Saurabh Chhabra
The unfolded protein response is responsible for the detection of misfolded proteins and the coordination of their disposal and is necessary to maintain the cellular homoeostasis. Multiple myeloma cells secrete large amounts of immunoglobulins, proteins that need to be correctly folded by the chaperone system. If this process fails, the misfolded proteins have to be eliminated by the two main garbage-disposal systems of the cell: proteasome and aggresome. The blockade of either of these systems will result in accumulation of immunoglobulins and other toxic proteins in the cytoplasm and cell death...
April 11, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28371677/design-synthesis-and-biological-evaluation-of-quinoline-derivatives-as-hdac-class-i-inhibitors
#19
Chen Chen, Xuben Hou, Guohua Wang, Wenyan Pan, Xinying Yang, Yingkai Zhang, Hao Fang
Inhibition of histone deacetylase (HDAC) has been regarded as a potential therapeutic approach for treatment of multiple diseases including cancer. Based on pharmacophore model of HDAC inhibitors, a series of quinoline-based N-hydroxycinnamamides and N-hydroxybenzamides were designed and synthesized as potent HDAC inhibitors. All target compounds were evaluated for their in vitro HDAC inhibitory activities and anti-proliferative activities and the best compound 4a surpass Vorinostat in both enzymatic inhibitory activity and cellular anti-proliferative activity...
March 28, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28352654/net-silencing-by-let-7i-in-postural-tachycardia-syndrome
#20
Abdul Waheed Khan, Mark Ziemann, Susan J Corcoran, Harikrishnan K N, Jun Okabe, Haloom Rafehi, Scott S Maxwell, Murray D Esler, Assam El-Osta
While strongly implicated in postural tachycardia syndrome (POTS), considerable controversy exists regarding norepinephrine transporter (NET) loss of function. POTS is characterized by the clinical symptoms of orthostatic intolerance, lightheadedness, tachycardia, and syncope or near syncope with upright posture. Abnormal sympathetic nervous system activity is typical, of a type which suggests dysfunction of the NET, with evidence that the gene responsible is under tight epigenetic control. Using RNA of isolated chromatin combined with massive parallel sequencing (RICh-seq) we show that let-7i miRNA suppresses NET by methyl-CpG-binding protein 2 (MeCP2)...
March 23, 2017: JCI Insight
keyword
keyword
66763
1
2
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"