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Vorinostat

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https://www.readbyqxmd.com/read/29164054/effective-drug-delivery-in-diffuse-intrinsic-pontine-glioma-a-theoretical-model-to-identify-potential-candidates
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
https://www.readbyqxmd.com/read/29110173/combination-treatment-with-docetaxel-and-histone-deacetylase-inhibitors-downregulates-androgen-receptor-signaling-in-castration-resistant-prostate-cancer
#9
Sang Eun Park, Ha-Gyeong Kim, Dong Eun Kim, Yoo Jung Jung, Yunlim Kim, Seong-Yun Jeong, Eun Kyung Choi, Jung Jin Hwang, Choung-Soo Kim
Backgrounds Since most patients with castration-resistant prostate cancer (CRPC) develop resistance to its standard therapy docetaxel, many studies have attempted to identify novel combination treatment to meet the large clinical unmet need. In this study, we examined whether histone deacetylase inhibitors (HDACIs) enhanced the effect of docetaxel on AR signaling in CRPC cells harboring AR and its splice variants. Methods HDACIs (vorinostat and CG200745) were tested for their ability to enhance the effects of docetaxel on cell viability and inhibition of AR signaling in CRPC 22Rv1 and VCaP cells by using CellTiter-Glo™ Luminescent cell viability assay, synergy index analysis and Western blotting...
November 7, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/29108243/silencing-heme-oxygenase-1-increases-the-sensitivity-of-abc-dlbcl-cells-to-histone-deacetylase-inhibitor-in-vitro-and-in-vivo
#10
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 P27(Kip1) promoter...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29107335/analysis-of-chromatin-opening-in-heterochromatic-non-small-cell-lung-cancer-tumor-initiating-cells-in-relation-to-dna-damaging-antitumor-treatment
#11
Mina Eriksson, Petra Hååg, Beata Brzozowska, Magdalena Lipka, Halina Lisowska, Rolf Lewensohn, Andrzej Wojcik, Kristina Viktorsson, Lovisa Lundholm
PURPOSE: We previously reported that sphere-forming non-small cell lung cancer (NSCLC) tumor-initiating cells (TICs) have an altered activation of DNA damage response- and repair proteins and are refractory to DNA-damaging treatments. We analyzed whether chromatin organization plays a role in the observed refractoriness. METHODS AND MATERIALS: Bulk cells and TICs from the NSCLC H23 and H1299 cell lines were examined using cell viability, clonogenic survival, Western blot, short interfering RNA analysis, and micronucleus assay...
September 22, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/29102679/cutaneous-t-cell-lymphomas-focusing-on-novel-agents-in-relapsed-and-refractory-disease
#12
REVIEW
Lisa Argnani, Alessandro Broccoli, Pier Luigi Zinzani
Patients with relapsed or refractory cutaneous T-cell lymphoma (CTCL) display a dismal prognosis and their therapy represents an unmet medical need, as the best treatment strategy is yet to be determined. Exciting data on novel targeted agents are now emerging from recently concluded and ongoing clinical trials in patients with relapsed and refractory CTCL. Three FDA approved compounds are used as single agents including the oral retinoid bexarotene and histone deacetylase inhibitors romidepsin and vorinostat...
December 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29100385/histone-deacetylase-inhibitors-vorinostat-and-panobinostat-induce-g1-cell-cycle-arrest-and-apoptosis-in-multidrug-resistant-sarcoma-cell-lines
#13
Eva Bernhart, Nicole Stuendl, Heike Kaltenegger, Christian Windpassinger, Nicholas Donohue, Andreas Leithner, Birgit Lohberger
Synovial sarcoma and high grade chondrosarcoma are characterized by their lack of response to conventional cytotoxic chemotherapy, the tendency to develop lung metastases, and low survival rates. Research within the field prioritizes the development and expansion of new treatment options for dealing with unresectable or metastatic diseases. Numerous clinical trials using histone deacetylases inhibitors (HDACi) have shown specific efficacy as an active antitumor agent for treating a variety of solid tumors. However, as of yet the effect of different HDACi on synovial- and chondrosarcoma cells has not been investigated...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29093271/combined-inhibition-of-atypical-pkc-and-histone-deacetylase-1-is-cooperative-in-basal-cell-carcinoma-treatment
#14
Amar N Mirza, Micah A Fry, Nicole M Urman, Scott X Atwood, Jon Roffey, Gregory R Ott, Bin Chen, Alex Lee, Alexander S Brown, Sumaira Z Aasi, Tyler Hollmig, Mark A Ator, Bruce D Dorsey, Bruce R Ruggeri, Craig A Zificsak, Marina Sirota, Jean Y Tang, Atul Butte, Ervin Epstein, Kavita Y Sarin, Anthony E Oro
Advanced basal cell carcinomas (BCCs) circumvent Smoothened (SMO) inhibition by activating GLI transcription factors to sustain the high levels of Hedgehog (HH) signaling required for their survival. Unfortunately, there is a lack of efficacious therapies. We performed a gene expression-based drug repositioning screen in silico and identified the FDA-approved histone deacetylase (HDAC) inhibitor, vorinostat, as a top therapeutic candidate. We show that vorinostat only inhibits proliferation of BCC cells in vitro and BCC allografts in vivo at high dose, limiting its usefulness as a monotherapy...
November 2, 2017: JCI Insight
https://www.readbyqxmd.com/read/29089762/vorinostat-eluting-poly-dl-lactide-co-glycolide-nanofiber-coated-stent-for-inhibition-of-cholangiocarcinoma-cells
#15
Tae Won Kwak, Hye Lim Lee, Yeon Hui Song, Chan Kim, Jungsoo Kim, Sol-Ji Seo, Young-Il Jeong, Dae Hwan Kang
PURPOSE: The aim of this study was to fabricate a vorinostat (Zolinza™)-eluting nanofiber membrane-coated gastrointestinal (GI) stent and to study its antitumor activity against cholangiocarcinoma (CCA) cells in vitro and in vivo. METHODS: Vorinostat and poly(DL-lactide-co-glycolide) dissolved in an organic solvent was sprayed onto a GI stent to make a nanofiber-coated stent using an electro-spinning machine. Intact vorinostat and vorinostat released from nanofibers was used to assess anticancer activity in vitro against various CCA cells...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/29081676/possible-involvement-of-ros-generation-in-vorinostat-pretreatment-induced-enhancement-of-the-antibacterial-activity-of-ciprofloxacin
#16
Majed M Masadeh, Karem H Alzoubi, Sayer I Al-Azzam, Ahlam M Al-Buhairan
The mechanism underlying ciprofloxacin action involves interference with transcription and replication of bacterial DNA and, thus, the induction of double-strand breaks in DNA. It also involves elevated oxidative stress, which might contribute to bacterial cell death. Vorinostat was shown to induce oxidative DNA damage. The current work investigated a possible interactive effect of vorinostat on ciprofloxacin-induced cytotoxicity against a number of reference bacteria. Standard bacterial strains were Escherichia coli ATCC 35218, Staphylococcus aureus ATCC29213, Pseudomonas aeruginosa ATCC 9027, Staphylococcus epidermidis ATCC 12228, Acinetobacter baumannii ATCC 17978, Proteus mirabilis ATCC 12459, Klebsiella pneumoniae ATCC 13883, methicillin-resistant Staphylococcus aureus (MRSA) (ATCC 43300), and Streptococcus pneumoniae (ATCC 25923)...
2017: Clinical Pharmacology: Advances and Applications
https://www.readbyqxmd.com/read/29045072/cell-signaling-model-connects-vorinostat-pharmacokinetics-and-tumor-growth-response-in-multiple-myeloma-xenografts
#17
Charvi Nanavati, Donna Ruszaj, Donald E Mager
Multiple myeloma is a fatal hematological malignancy with high rates of drug resistance and relapse. Vorinostat, a histone deacetylase inhibitor, has shown promise in enhancing efficacy when combined with current myeloma therapies. In this study, temporal changes of critical proteins and cell proliferation were measured in myeloma cells exposed to vorinostat. A model linking biomarker dynamics to cell proliferation was developed that captured vorinostat effects on signal transduction and cell viability. The model structure and parameters were fixed to describe tumor dynamics in vivo, and tumor-specific growth and death rate parameters were estimated...
October 17, 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/29025909/histone-deacetylase-inhibitors-downregulate-ccr4-expression-and-decrease-mogamulizumab-efficacy-in-ccr4-positive-mature-t-cell-lymphomas
#18
Akihiro Kitadate, Sho Ikeda, Fumito Abe, Naoto Takahashi, Norio Shimizu, Kosei Matsue, Hiroyuki Tagawa
HDAC inhibitors are promising agents for various T-cell lymphomas, including cutaneous T-cell lymphoma, peripheral T-cell lymphoma, and adult T-cell lymphoma/leukemia. CCR4 is an important therapeutic target molecule because mogamulizumab, an anti-CCR4 antibody, has shown promising efficacy against various T-cell lymphomas. In this study, we examined the in vitro synergistic effects of mogamulizumab and HDAC inhibitors against various T-cell lymphomas. First, we examined the expression of CCR4 mRNA and surface CCR4 in various T-cell lymphoma cell lines and found it was downregulated upon treatment with vorinostat, a pan-HDAC inhibitor...
October 12, 2017: Haematologica
https://www.readbyqxmd.com/read/29025718/vorinostat-is-victorious-in-gvhd-prevention
#19
Shernan G Holtan, Daniel J Weisdorf
No abstract text is available yet for this article.
October 12, 2017: Blood
https://www.readbyqxmd.com/read/29024573/targeting-mta1-hif-1%C3%AE-signaling-by-pterostilbene-in-combination-with-histone-deacetylase-inhibitor-attenuates-prostate-cancer-progression
#20
Nasir A Butt, Avinash Kumar, Swati Dhar, Agnes M Rimando, Israh Akhtar, John C Hancock, Janice M Lage, Charles R Pound, Jack R Lewin, Christian R Gomez, Anait S Levenson
The metastasis-associated protein 1(MTA1)/histone deacetylase (HDAC) unit is a cancer progression-related epigenetic regulator, which is overexpressed in hormone-refractory and metastatic prostate cancer (PCa). In our previous studies, we found a significantly increased MTA1 expression in a prostate-specific Pten-null mouse model. We also demonstrated that stilbenes, namely resveratrol and pterostilbene (Pter), affect MTA1/HDAC signaling, including deacetylation of tumor suppressors p53 and PTEN. In this study, we examined whether inhibition of MTA1/HDAC using combination of Pter and a clinically approved HDAC inhibitor, SAHA (suberoylanilide hydroxamic acid, vorinostat), which also downregulates MTA1, could block prostate tumor progression in vivo...
November 2017: Cancer Medicine
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