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https://www.readbyqxmd.com/read/28202316/an-epigenetic-modifier-induces-production-of-10-s-verruculide-b-an-inhibitor-of-protein-tyrosine-phosphatases-by-phoma-sp-nov-lg0217-a-fungal-endophyte-of-parkinsonia-microphylla
#1
Juliana R Gubiani, E M Kithsiri Wijeratne, Taoda Shi, Angela R Araujo, A Elizabeth Arnold, Eli Chapman, A A Leslie Gunatilaka
Incorporation of the histone deacetylase (HDAC) inhibitor, suberoylanilide hydroxamic acid (SAHA), to a culture broth of the endophytic fungus Phoma sp. nov. LG0217 isolated from Parkinsonia microphylla changed its metabolite profile and resulted in the production of (10'S)-verruculide B (1), vermistatin (2) and dihydrovermistatin (3). When cultured in the absence of the epigenetic modifier, it produced a new metabolite, (S,Z)-5-(3',4'-dihydroxybutyldiene)-3-propylfuran-2(5H)-one (4) together with nafuredin (5)...
February 3, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28184324/comparison-of-anticancer-effects-of-carbamazepine-and-valproic-acid
#2
Ladan Akbarzadeh, Taraneh Moini Zanjani, Masoumeh Sabetkasaei
BACKGROUND: Valproic acid (VPA) and carbamazepine (CBZ), two widely used antiepileptic drugs, have recently been found to inhibit histone deacetylases (HDAC). HDAC inhibitors (HDACIs) have various effects on cancer cells. OBJECTIVES: The aim of this study was to compare the anticancer activity of these drugs on SW480 colon cancer cell lines. METHODS: In the present experimental study, implemented during 2014 - 2015 in Iran, after incubation of cells into 96-well plates with 5,500 cells/well, the tested drugs were added, and cytotoxic effects were assessed by MTT...
October 2016: Iranian Red Crescent Medical Journal
https://www.readbyqxmd.com/read/28177689/selective-inhibition-of-hdac2-by-magnesium-valproate-attenuates-cardiac-hypertrophy
#3
Suchi Raghunathan, Ramesh Goyal, Bhoomika Mayur Patel
The regulatory paradigm in cardiac hypertrophy involves alterations in gene expression that is mediated by chromatin remodeling. Various data suggest that class I and class II histone deacetylases (HDACs) play opposing roles in the regulation of hypertrophic pathways. To address this, we tested the effect of magnesium valproate (MgV), an HDAC inhibitor with 5 times more potency on Class I HDAC. Cardiac hypertrophy was induced by Partial abdominal aortic constriction in wistar rats, and at end of 6 weeks, we evaluated hypertrophic, hemodynamic and oxidative stress parameters, and mitochondrial DNA concentration...
December 8, 2016: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28167758/microrna-10a-is-crucial-for-endothelial-response-to-different-flow-patterns-via-interaction-of-retinoid-acid-receptors-and-histone-deacetylases
#4
Ding-Yu Lee, Ting-Er Lin, Chih-I Lee, Jing Zhou, Yi-Hsuan Huang, Pei-Ling Lee, Yu-Tsung Shih, Shu Chien, Jeng-Jiann Chiu
Histone deacetylases (HDACs) and microRNAs (miRs) have emerged as two important epigenetic factors in the regulation of vascular physiology. This study aimed to elucidate the relationship between HDACs and miRs in the hemodynamic modulation of endothelial cell (EC) dysfunction. We found that miR-10a has the lowest expression among all examined shear-responsive miRs in ECs under oscillatory shear stress (OS), and a relatively high expression under pulsatile shear stress (PS). PS and OS alter EC miR-10a expression to regulate the expression of its direct target GATA6 and downstream vascular cell adhesion molecule (VCAM)-1...
February 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28154524/p38-sp1-sp4-hdac4-bdnf-axis-is-a-novel-molecular-pathway-of-the-neurotoxic-effect-of-the-methylmercury
#5
Natascia Guida, Giusy Laudati, Luigi Mascolo, Valeria Valsecchi, Rossana Sirabella, Carmine Selleri, Gianfranco Di Renzo, Lorella M T Canzoniero, Luigi Formisano
The molecular pathways involved in methylmercury (MeHg)-induced neurotoxicity are not fully understood. Since pan-Histone deacetylases (HDACs) inhibition has been found to revert the neurodetrimental effect of MeHg, it appeared of interest to investigate whether the pattern of HDACs isoform protein expression is modified during MeHg-induced neurotoxicity and the transcriptional/transductional mechanisms involved. SH-SY5Y neuroblastoma cells treated with MeHg 1 μM for 12 and 24 h showed a significant increase of HDAC4 protein and gene expression, whereas the HDACs isoforms 1-3, 5, and 6 were unmodified...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28152480/securinine-enhances-smn2-exon-7-inclusion-in-spinal-muscular-atrophy-cells
#6
Yu-Chia Chen, Jan-Gowth Chang, Ting-Yuan Liu, Yuh-Jyh Jong, Wei-Lin Cheng, Chung-Yee Yuo
Spinal muscular atrophy (SMA) is an autosomal recessive disease characterized by the degeneration of motor neurons in the spinal cord, leading to muscular atrophy. SMA is caused by deletions or mutations in the survival motor neuron gene (SMN1) on chromosome 5q13. A second copy of the SMN gene (SMN2) also exists on chromosome 5, and both genes can produce functional protein. However, due to alternative splicing of the exon 7, the majority of SMN protein produced by SMN2 is truncated and unable to compensate for the loss of SMN1...
January 30, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28146421/the-hdac-inhibitor-ar42-interacts-with-pazopanib-to-kill-trametinib-dabrafenib-resistant-melanoma-cells-in-vitro-and-in-vivo
#7
Laurence Booth, Jane L Roberts, Cindy Sander, John Lee, John M Kirkwood, Andrew Poklepovic, Paul Dent
Studies focused on the killing of activated B-RAF melanoma cells by the histone deacetylase (HDAC) inhibitor AR42. Compared to other tumor cell lines, PDX melanoma isolates were significantly more sensitive to AR42-induced killing. AR42 and the multi-kinase inhibitor pazopanib interacted to activate: an eIF2α-Beclin1 pathway causing autophagosome formation; an eIF2α-DR4/DR5/CD95 pathway; and an eIF2α-dependent reduction in the expression of c-FLIP-s, MCL-1 and BCL-XL. AR42 did not alter basal chaperone activity but increased the ability of pazopanib to inhibit HSP90, HSP70 and GRP78...
January 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28138828/phase-i-ii-study-of-docetaxel-combined-with-resminostat-an-oral-hydroxamic-acid-hdac-inhibitor-for-advanced-non-small-cell-lung-cancer-in-patients-previously-treated-with-platinum-based-chemotherapy
#8
Yuichi Tambo, Yukio Hosomi, Hiroshi Sakai, Naoyuki Nogami, Shinji Atagi, Yasutsuna Sasaki, Terufumi Kato, Toshiaki Takahashi, Takashi Seto, Makoto Maemondo, Hiroshi Nokihara, Ryo Koyama, Kazuhiko Nakagawa, Tomoya Kawaguchi, Yuta Okamura, Osamu Nakamura, Makoto Nishio, Tomohide Tamura
Objectives To determine the recommended dose and efficacy/safety of docetaxel combined with resminostat (DR) in non-small cell lung cancer (NSCLC) patients with previous platinum-based chemotherapy. Materials and Methods A multicenter, open-label, phase I/II study was performed in Japanese patients with stage IIIB/IV or recurrent NSCLC and prior platinum-based chemotherapy. The recommended phase II dose was determined using a standard 3 + 3 dose design in phase I part. Resminostat was escalated from 400 to 600 mg/day and docetaxel fixed at 75 mg/m(2)...
January 30, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28138695/involvement-of-retinoblastoma-associated-protein%C3%A2-48-during-photodynamic-therapy-of-cervical-cancer-cells
#9
Shuxia Wu, Lijun Wang, Xingye Ren, Yulu Pan, Yan Peng, Xiaoyan Zou, Cuige Shi, Youzhong Zhang
5-Aminolevulinic acid-mediated photodynamic therapy (ALA‑PDT) is an effective treatment option for cervical intraepithelial neoplasia, the precancerous lesion of cervical cancer, and early cervical cancer, particularly for young or nulliparous women who want to remain fertile. A previous report described the involvement of histone deacetylases (HDAC) during ALA‑PDT mediated apoptosis in the cerebral cortex of a mouse model. Retinoblastoma‑associated protein 48 (RbAp48), a highly abundant component of HDACs, is a critical mediator that controls the transforming activity of human papillomavirus 16 in cervical cancer cells...
January 26, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28132875/the-impact-of-cruciferous-vegetable-isothiocyanates-on-histone-acetylation-and-histone-phosphorylation-in-bladder-cancer
#10
Besma Abbaoui, Kelly H Telu, Christopher R Lucas, Jennifer M Thomas-Ahner, Steven J Schwartz, Steven K Clinton, Michael A Freitas, Amir Mortazavi
: Cruciferous vegetable intake is associated with reduced risk of bladder cancer, yet mechanisms remain unclear. Cruciferous vegetable isothiocyanates (ITCs), namely sulforaphane (SFN) and erucin (ECN), significantly inhibit histone deacetylase (HDAC) activity in human bladder cancer cells representing superficial to invasive biology (59-83% inhibition with 20μM, 48h treatment), and in bladder cancer xenografts (59±3% ECN inhibition). Individual HDACs inhibited by SFN and ECN include HDACs 1, 2, 4 and 6...
March 6, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28129654/time-dependent-modulation-of-tumor-radiosensitivity-by-a-pan-hdac-inhibitor-abexinostat
#11
Sofia Rivera, Céline Leteur, Frédérique Mégnin, Frédéric Law, Isabelle Martins, Ioana Kloos, Stéphane Depil, Nazanine Modjtahedi, Jean Luc Perfettini, Christophe Hennequin, Eric Deutsch
Despite prominent role of radiotherapy in lung cancer management, there is an urgent need for strategies increasing therapeutic efficacy. Reversible epigenetic changes are promising targets for combination strategies using HDAC inhibitors (HDACi).Here we evaluated on two NSCLC cell lines, the antitumor effect of abexinostat, a novel pan HDACi combined with irradiation in vitro in normoxia and hypoxia, by clonogenic assays, demonstrating that abexinostat enhances radiosensitivity in a time dependent way with mean SER10 between 1...
January 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28123935/deletion-of-histone-deacetylase-3-in-adult-beta-cells-improves-glucose-tolerance-via-increased-insulin-secretion
#12
Jarrett R Remsberg, Benjamin N Ediger, Wesley Y Ho, Manashree Damle, Zhenghui Li, Christopher Teng, Cristina Lanzillotta, Doris A Stoffers, Mitchell A Lazar
OBJECTIVE: Histone deacetylases are epigenetic regulators known to control gene transcription in various tissues. A member of this family, histone deacetylase 3 (HDAC3), has been shown to regulate metabolic genes. Cell culture studies with HDAC-specific inhibitors and siRNA suggest that HDAC3 plays a role in pancreatic β-cell function, but a recent genetic study in mice has been contradictory. Here we address the functional role of HDAC3 in β-cells of adult mice. METHODS: An HDAC3 β-cell specific knockout was generated in adult MIP-CreERT transgenic mice using the Cre-loxP system...
January 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28117030/three-combined-treatment-a-novel-hdac-inhibitor-obp-801-ym753-5-fluorouracil-and-paclitaxel-induces-g2-phase-arrest-through-the-p38-pathway-in-human-ovarian-cancer-cells
#13
Makoto Akiyama, Yoshihiro Sowa, Tomoyuki Taniguchi, Motoki Watanabe, Shingo Yogosawa, Jo Kitawaki, Toshiyuki Sakai
Ovarian cancer is the most lethal disease among gynecological malignancies. More effective therapy is required to counter the high recurrence rates and chemotherapy resistance. We investigated the efficacy and molecular mechanisms of three-combined treatment, a novel histone deacetylase (HDAC) inhibitor OBP-801/YM753, 5-fluorouracil (5-FU) and paclitaxel (PTX), in human ovarian cancer SKOV-3 and OVCAR-3 cells. The inhibition of cell growth was stronger with the three-combined treatment than with each single agent and with two-combined treatment...
January 23, 2017: Oncology Research
https://www.readbyqxmd.com/read/28107195/a-new-hdac-inhibitor-cinnamoylphenazine-shows-antitumor-activity-in-association-with-intensive-macropinocytosis
#14
Bing-Yan Zhu, Bo-Yang Shang, Yue Du, Yi Li, Liang Li, Xian-Dong Xu, Yong-Su Zhen
Previous studies have shown that intensive macropinocytosis occurs in cancer cells and neutral red (NR) is noted for its capability to enter into the cell massively through a process mimetic to macropinocytosis. In addition, trans-cinnamic acid (tCA) has been found to be an inhibitor of histone deacetylase (HDAC). In the present study, cinnamoylphenazine (CA-PZ) that consists of NR and tCA moieties was synthesized and evaluated. As shown, CA-PZ massively entered into colon carcinoma HT-29 cells and pancreatic carcinoma MIA PaCa-2 cells and this entry was blocked by 5-(N-ethyl-N-isopropyl) amiloride (EIPA, an inhibitor of macropinocytosis), indicating a macropinocytosis-mediated uptake...
January 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28103535/down-regulation-of-histone-deacetylase-4-5-and-6-as-a-mechanism-of-synergistic-enhancement-of-apoptosis-in-human-lung-cancer-cells-treated-with-the-combination-of-a-synthetic-retinoid-am80-and-green-tea-catechin
#15
Yukiko Oya, Anupom Mondal, Anchalee Rawangkan, Sonthaya Umsumarng, Keisuke Iida, Tatsuro Watanabe, Miki Kanno, Kaori Suzuki, Zhenghao Li, Hiroyuki Kagechika, Koichi Shudo, Hirota Fujiki, Masami Suganuma
(-)-Epigallocatechin gallate (EGCG), a green tea catechin, acts as a synergist with various anticancer drugs, including retinoids. Am80 is a synthetic retinoid with a different structure from all-trans-retinoic acid: Am80 is now clinically utilized as a new drug for relapsed and intractable acute promyelocytic leukemia patients. Our experiments showed that the combination of EGCG and Am80 synergistically induced both apoptosis in human lung cancer cell line PC-9 and up-regulated expressions of growth arrest and DNA damage-inducible gene 153 (GADD153), death receptor 5, and p21(waf1) genes in the cells...
January 8, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28102966/histone-deacetylase-2-is-decreased-in-peripheral-blood-pro-inflammatory-cd8-t-and-nkt-like-lymphocytes-following-lung-transplant
#16
Greg Hodge, Sandra Hodge, Chien-Li Holmes-Liew, Paul N Reynolds, Mark Holmes
BACKGROUND AND OBJECTIVE: Immunosuppression therapy following lung transplantation fails to prevent chronic rejection in many patients, which is associated with lack of suppression of cytotoxic mediators and pro-inflammatory cytokines in peripheral blood T and natural killer T (NKT)-like cells. Histone acetyltransferases (HATs) and histone deacetylases (HDACs) upregulate/downregulate pro-inflammatory gene expression, respectively; however, differences in the activity of these enzymes following lung transplant are unknown...
February 2017: Respirology: Official Journal of the Asian Pacific Society of Respirology
https://www.readbyqxmd.com/read/28073598/hdac10-as-a-potential-therapeutic-target-in-ovarian-cancer
#17
Muhtadi M Islam, Tapahsama Banerjee, Colin Z Packard, Shweta Kotian, Karuppaiyah Selvendiran, David E Cohn, Jeffrey D Parvin
OBJECTIVE: We analyzed histone deacetylase 10 (HDAC10) for function in the context of the DNA damage response in BRCA1-null ovarian cancer cells as well as evaluated the potential of general HDAC inhibitors in primary ovarian carcinoma cells. HDAC10 had previously been shown to be highly stimulatory to the process of homology directed repair in HeLa cells, and in this study we investigated whether HDAC10 could impact in vitro the response to anticancer therapies. We hypothesized that the loss of HDAC10 would sensitize cells to platinum therapy...
January 7, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28056398/clinical-outcome-of-myeloid-sarcoma-in-adult-patients-and-effect-of-allogeneic-stem-cell-transplantation-results-from-a-multicenter-survey
#18
Davide Lazzarotto, Anna Candoni, Carla Filì, Fabio Forghieri, Livio Pagano, Alessandro Busca, Giuseppina Spinosa, Maria Elena Zannier, Erica Simeone, Miriam Isola, Erika Borlenghi, Lorella Melillo, Federico Mosna, Federica Lessi, Renato Fanin
INTRODUCTION: Myeloid Sarcoma (MS) is a rare hematologic myeloid neoplasm that can involve any site of the body. It can occur as an exclusively extramedullary form or it can be associated with an acute myeloid leukemia (AML), a chronic myeloproliferative neoplasm (MPN) or a myelodysplastic syndrome (MDS) at onset or at relapse. The rarity of MS does not enable prospective clinical trials and therefore a specific multicenter register can be useful for the clinical and biological studies of this rare disease...
February 2017: Leukemia Research
https://www.readbyqxmd.com/read/28053023/ricolinostat-the-first-selective-histone-deacetylase-6-inhibitor-in-combination-with-bortezomib-and-dexamethasone-for-relapsed-or-refractory-multiple-myeloma
#19
Dan T Vogl, Noopur S Raje, Sundar Jagannath, Paul G Richardson, Parameswaran Hari, Robert Z Orlowski, Jeffrey G Supko, David Tamang, Min Yang, Simon S Jones, Catherine Wheeler, Robert J Markelewicz, Sagar Lonial
PURPOSE: Histone deacetylase (HDAC) inhibition improves the efficacy of proteasome inhibition for multiple myeloma but adds substantial toxicity. Preclinical models suggest that the observed synergy is due to the role of HDAC6 in mediating resistance to proteasome inhibition via the aggresome/autophagy pathway of protein degradation. EXPERIMENTAL DESIGN: We conducted a phase 1/2 trial of the HDAC6-selective inhibitor ricolinostat to define the safety, preliminary efficacy, and recommended phase 2 dose in combination with standard proteasome inhibitor therapy...
January 4, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28046085/differential-hdac1-and-2-recruitment-by-members-of-the-mier-family
#20
Roya Derwish, Gary D Paterno, Laura L Gillespie
The mier family consists of three related genes encoding ELM2-SANT containing proteins. MIER1 has been well characterized and is known to function in transcriptional repression through its ability to recruit HDAC1 and 2. Little is known about MIER2 or MIER3 function and no study characterizing these two proteins has been published. In this report, we investigate MIER2 and MIER3 localization and function. Confocal analysis revealed that, while MIER2 and MIER3 are mainly nuclear proteins, a substantial proportion (32%) of MIER2 is localized in the cytoplasm...
2017: PloS One
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