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https://www.readbyqxmd.com/read/28542535/a-trichostatin-a-expression-signature-identified-by-tempo-seq-targeted-whole-transcriptome-profiling
#1
Joanne M Yeakley, Peter J Shepard, Diana E Goyena, Harper C VanSteenhouse, Joel D McComb, Bruce E Seligmann
The use of gene expression signatures to classify compounds, identify efficacy or toxicity, and differentiate close analogs relies on the sensitivity of the method to identify modulated genes. We used a novel ligation-based targeted whole transcriptome expression profiling assay, TempO-Seq®, to determine whether previously unreported compound-responsive genes could be identified and incorporated into a broad but specific compound signature. TempO-Seq exhibits 99.6% specificity, single cell sensitivity, and excellent correlation with fold differences measured by RNA-Seq (R2 = 0...
2017: PloS One
https://www.readbyqxmd.com/read/28542306/gene-signature-associated-with-benign-neurofibroma-transformation-to-malignant-peripheral-nerve-sheath-tumors
#2
Marta Martínez, Carlos O S Sorzano, Alberto Pascual-Montano, Jose M Carazo
Benign neurofibromas, the main phenotypic manifestations of the rare neurological disorder neurofibromatosis type 1, degenerate to malignant tumors associated to poor prognosis in about 10% of patients. Despite efforts in the field of (epi)genomics, the lack of prognostic biomarkers with which to predict disease evolution frustrates the adoption of appropriate early therapeutic measures. To identify potential biomarkers of malignant neurofibroma transformation, we integrated four human experimental studies and one for mouse, using a gene score-based meta-analysis method, from which we obtained a score-ranked signature of 579 genes...
2017: PloS One
https://www.readbyqxmd.com/read/28529481/topical-ophthalmic-formulation-of-trichostatin-a-and-surr9-c84a-for-quick-recovery-post-alkali-burn-of-corneal-haze
#3
Kislay Roy, Chun Hei Antonio Cheung, Rupinder K Kanwar, Rajat Sandhir, Jagat R Kanwar
Alkali burn injury is a true ocular emergency of the conjunctiva and cornea that requires immediate precision. Lack of an immediate therapy can lead to a substantial damage in the ocular surface and anterior segment further causing visual impairment and disfigurement. We explored the regenerative capability of dominant negative survivin protein (SurR9-C84A) and histone deacetylase inhibitor trichostatin-A (TSA) in vivo, in a rat alkali burn model. A topical insult in rat eyes with NaOH led to degradation of the conjunctival and corneal epithelium...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28526911/dynamics-of-post-translationally-modified-histones-during-barley-pollen-embryogenesis-in-the-presence-or-absence-of-the-epi-drug-trichostatin-a
#4
Pooja Pandey, Diaa S Daghma, Andreas Houben, Jochen Kumlehn, Michael Melzer, Twan Rutten
Improving pollen embryogenesis. Despite the agro-economic importance of pollen embryogenesis, the mechanisms underlying this process are still poorly understood. We describe the dynamics of chromatin modifications (histones H3K4me2, H3K9ac, H3K9me2, and H3K27me3) and chromatin marks (RNA polymerase II CDC phospho-Ser5, and CENH3) during barley pollen embryogenesis. Immunolabeling results show that, in reaction to stress, immature pollen rapidly starts reorganizing several important chromatin modifications indicative of a change in cell fate...
May 19, 2017: Plant Reproduction
https://www.readbyqxmd.com/read/28525378/irf5-is-elevated-in-childhood-onset-sle-and-regulated-by-histone-acetyltransferase-and-histone-deacetylase-inhibitors
#5
Jin Shu, Ling Li, Lan-Bo Zhou, Jun Qian, Zhi-Dan Fan, Li-Li Zhuang, Lu-Lu Wang, Rui Jin, Hai-Guo Yu, Guo-Ping Zhou
Interferon regulatory factor 5 (IRF5) plays a critical role in the induction of type I interferon, proinflammatory cytokines and chemokines, and participates in the pathogenesis of autoimmune diseases such as systemic lupus erythematosus (SLE). However, the relationship between IRF5 and childhood-onset SLE remains elusive. In the present study, we demonstrated that levels of mRNA expression of IRF5, IFN-α, and Sp1 were significantly increased in childhood-onset SLE, as seen on quantitative real-time PCR, and the expression of Sp1 and IFN-α was positively correlated with IRF5...
May 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28524836/effect-of-histone-deacetylase-inhibition-on-the-expression-of-multidrug-resistance-associated-protein-2-in-a-human-placental-trophoblast-cell-line
#6
Hong-Yu Duan, Dan Ma, Kai-Yu Zhou, Tao Wang, Yi Zhang, Yi-Fei Li, Jin-Lin Wu, Yi-Min Hua, Chuan Wang
BACKGROUND: Placental multidrug resistance-associated protein 2 (MRP2), encoded by ABCC2 gene in human, plays a significant role in regulating drugs' transplacental transfer rates. Studies on placental MRP2 regulation could provide more therapeutic targets for individualized and safe pharmacotherapy during pregnancy. Currently, the roles of epigenetic mechanisms in regulating placental drug transporters are still unclear. This study aimed to investigate the effect of histone deacetylases (HDACs) inhibition on MRP2 expression in the placental trophoblast cell line and to explore whether HDAC1/2/3 are preliminarily involved in this process...
June 5, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28516379/panobinostat-enhances-growth-suppressive-effects-of-progestin-on-endometrial-carcinoma-by-increasing-progesterone-receptor-and-mitogen-inducible-gene-6
#7
Hirofumi Ando, Tsutomu Miyamoto, Hiroyasu Kashima, Shotaro Higuchi, Koichi Ida, David Hamisi Mvunta, Tanri Shiozawa
Although progestin has been used to treat endometrial hyperplasia and endometrial carcinoma (EC), its therapeutic efficacy is limited. In order to improve this, the underlining mechanisms of the effects of progestin need to be elucidated in more detail. In the present study, we examined the involvement of mitogen-inducible gene-6 (MIG6), a negative regulator of the EGF receptor, in the progestin-mediated growth suppression of endometrial epithelia. The immunohistochemical expression of MIG6 was elevated in the early to mid-secretory phases of normal endometrium and also with endometrial hyperplasia after medroxyprogesterone acetate (MPA) therapy...
May 17, 2017: Hormones & Cancer
https://www.readbyqxmd.com/read/28506198/naturally-occurring-benzoic-acid-derivatives-retard-cancer-cell-growth-by-inhibiting-histone-deacetylases-hdac
#8
Preethi G Anantharaju, Bandi Deepa Reddy, Mahesh A Padukudru, Ch M Kumari Chitturi, Manjunath G Vimalambike, SubbaRao V Madhunapantula
Histone deacetylases (HDACs), which modulate the expression of genes, are potential therapeutic targets in several cancers. Targeted inhibition of HDAC prevents the expression of oncogenes thereby help in the treatment of cancers. Hence, several pharmaceutical companies developed inhibitors of HDAC and tested them in preclinical models and in clinical trials. SAHA (suberanilohydroxamic acid) is one such HDAC inhibitor developed for treating breast and colorectal carcinomas. However, due to poor efficacy in clinical trials the utility of SAHA for treating cancers was discouraged...
May 16, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28500053/manipulating-the-mitochondrial-genome-to-enhance-cattle-embryo-development
#9
Kanokwan Srirattana, Justin C St John
The mixing of mitochondrial DNA (mtDNA) from the donor cell and the recipient oocyte in embryos and offspring derived from somatic cell nuclear transfer (SCNT) compromises genetic integrity and affects embryo development. We set out to generate SCNT embryos that inherited their mtDNA from the recipient oocyte only, as is the case following natural conception. Whilst SCNT blastocysts produced from Holstein (Bos Taurus) fibroblasts depleted of their mtDNA and oocytes derived from Angus (Bos Taurus) cattle possessed oocyte mtDNA only, the co-existence of donor cell and oocyte mtDNA resulted in blastocysts derived from non-depleted cells...
May 12, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28497964/biosynthetic-origin-of-the-hydroxamic-acid-moiety-of-trichostatin-a-identification-of-unprecedented-enzymatic-machinery-involved-in-hydroxylamine-transfer
#10
Kei Kudo, Taro Ozaki, Kazuo Shin-Ya, Makoto Nishiyama, Tomohisa Kuzuyama
Trichostatin A (TSA) is widely used in the field of epigenetics because it potently inhibits histone deacetylase (HDAC). In-depth studies have revealed that the hydroxamic acid group in TSA chelates the zinc(II) ion in the active site of HDAC to realize the inhibitory activity. Here we report the first identification of a complete TSA biosynthetic gene cluster from Streptomyces sp. RM72 and the heterologous production of TSA in Streptomyces albus. Biochemical analyses unambiguously demonstrate that unprecedented biosynthetic machinery catalyzes the direct transfer of hydroxylamine from a nonproteinogenic amino acid, l-glutamic acid γ-monohydroxamate, to the carboxylic acid group of trichostatic acid to form the hydroxamic acid moiety of TSA...
May 12, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28489652/histone-deacetylase-inhibitors-enhance-cytotoxicity-towards-breast-tumors-while-preserving-the-wound-healing-function-of-adipose-derived-stem-cells
#11
Kiavash R Koko, Shaohua Chang, Ashleigh L Hagaman, Marc W Fromer, Ryan S Nolan, John P Gaughan, Ping Zhang, Jeffrey P Carpenter, Spencer A Brown, Martha Matthews, Dorothy Bird
INTRODUCTION: Paclitaxel improves the oncologic response of breast cancer resections; however, it may negatively affect the wound-healing potential of human adipose-derived stem cells (hASCs) for fat grafting and reconstructive surgery. Histone deacetylase inhibitors (HDACis) modify the epigenetic regulation of gene expression and stabilize microtubules similarly to paclitaxel, thus, creating a synergistic mechanism of cell cycle arrest. We aim to combine these drugs to enhance cytotoxicity towards breast cancer cells, while preserving the wound-healing function of hASCs for downstream reconstructive applications...
June 2017: Annals of Plastic Surgery
https://www.readbyqxmd.com/read/28481734/hlj1-dnajb4-gene-is-a-novel-biomarker-candidate-in-breast-cancer
#12
Tolga Acun, Natalie Doberstein, Jens K Habermann, Timo Gemoll, Christoph Thorns, Emin Oztas, Thomas Ried
Breast cancer is the most common cancer type and cause of cancer-related mortality among women worldwide. New biomarker discovery is crucial for diagnostic innovation and personalized medicine in breast cancer. Heat shock proteins (HSPs) have been increasingly reported as biomarkers and potential drug targets for cancers. HLJ1 (DNAJB4) belongs to the DNAJ (HSP40) family of HSPs and is regarded as a tumor suppressor gene in lung, colon, and gastric cancers. However, the role of the HLJ1 gene in breast cancer is currently unknown...
May 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28474205/chaperone-co-inducer-bgp-15-inhibits-histone-deacetylases-and-enhances-the-heat-shock-response-through-increased-chromatin-accessibility
#13
Marek A Budzyński, Tim Crul, Samu V Himanen, Noemi Toth, Ferenc Otvos, Lea Sistonen, Laszlo Vigh
Defects in cellular protein homeostasis are associated with many severe and prevalent pathological conditions such as neurodegenerative diseases, muscle dystrophies, and metabolic disorders. One way to counteract these defects is to improve the protein homeostasis capacity through induction of the heat shock response. Despite numerous attempts to develop strategies for chemical activation of the heat shock response by heat shock transcription factor 1 (HSF1), the underlying mechanisms of drug candidates' mode of action are poorly understood...
May 4, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/28467484/chromatin-modifying-agents-convert-fibroblasts-to-oct4-and-vegfr-2-capillary-tube-forming-cells
#14
Anita Wary, Neil Wary, Jugajyoti Baruah, Victoria Mastej, Kishore K Wary
RATIONALE: The human epigenome is plastic. The goal of this study was to address if fibroblast cells can be epigenetically modified to promote neovessel formation. METHODS AND RESULTS: Here, we used highly abundant human adult dermal fibroblast cells (hADFCs) that were treated with the chromatin-modifying agents 5-aza-2'-deoxycytidine and trichostatin A, and subsequently subjected to differentiation by activating Wnt signaling. Our results show that these epigenetically modified hADFCs increasingly expressed β-catenin, pluripotency factor octamer-binding transcription factor-4 (OCT4, also known as POU5F1), and endothelial cell (EC) marker called vascular endothelial growth factor receptor-2 (VEGFR-2, also known as Fetal Liver Kinase-1)...
2017: PloS One
https://www.readbyqxmd.com/read/28463020/treatment-of-donor-cells-and-reconstructed-embryos-with-a-combination-of-trichostatin-a-and-5-aza-2-deoxycytidine-improves-the-developmental-competence-and-quality-of-buffalo-embryos-produced-by-handmade-cloning-and-alters-their-epigenetic-status-and-gene-expression
#15
Monika Saini, Naresh L Selokar, Himanshu Agrawal, Suresh Kumar Singla, Manmohan Singh Chauhan, Radheysham S Manik, Prabhat Palta
The application of cloning technology on a large scale is limited by very low offspring rate primarily due to aberrant or incomplete epigenetic reprogramming. Trichostatin A (TSA), a histone deacetylase inhibitor, and 5-aza-2'-deoxycytidine (5-aza-dC), an inhibitor of DNA methyltransferases, are widely used for altering the epigenetic status of cloned embryos. We optimized the doses of these epigenetic modifiers for production of buffalo embryos by handmade cloning and examined whether combined treatment with these epigenetic modifiers offered any advantage over treatment with the individual epigenetic modifier...
May 2, 2017: Cellular Reprogramming
https://www.readbyqxmd.com/read/28460463/set-oncoprotein-accumulation-regulates-transcription-through-dna-demethylation-and-histone-hypoacetylation
#16
Luciana O Almeida, Marinaldo P C Neto, Lucas O Sousa, Maryna A Tannous, Carlos Curti, Andreia M Leopoldino
Epigenetic modifications are essential in the control of normal cellular processes and cancer development. DNA methylation and histone acetylation are major epigenetic modifications involved in gene transcription and abnormal events driving the oncogenic process. SET protein accumulates in many cancer types, including head and neck squamous cell carcinoma (HNSCC); SET is a member of the INHAT complex that inhibits gene transcription associating with histones and preventing their acetylation. We explored how SET protein accumulation impacts on the regulation of gene expression, focusing on DNA methylation and histone acetylation...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28460447/sodium-butyrate-improves-porcine-host-defense-peptide-expression-and-relieves-the-inflammatory-response-upon-toll-like-receptor-2-activation-and-histone-deacetylase-inhibition-in-porcine-kidney-cells
#17
Xiujing Dou, Junlan Han, Wentao Song, Na Dong, Xinyao Xu, Wei Zhang, Anshan Shan
Host defense peptides (HDPs) are an important component of the innate immune system and possess direct antimicrobial and immunomodulatory activities. Dietary regulation of HDPs synthesis has emerged as a novel non-antibiotic approach to combat pathogen infection. There are species- and tissue-dependent characteristics of the regulation and mechanism of HDPs. In this study, we investigated whether the histone deacetylase inhibitor (HDACi) sodium butyrate (NaB) could induce HDP expression and the mechanism underlying NaB-regulated HDP expression in PK-15 cells...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28455414/hdac-inhibitors-disrupt-programmed-resistance-to-apoptosis-during-drosophila-development
#18
Yunsik Kang, Khailee Marischuk, Gina D Castelvecchi, Arash Bashirullah
We have previously shown that the ability to respond to apoptotic triggers is regulated during Drosophila development, effectively dividing the fly life cycle into stages that are either sensitive or resistant to apoptosis. Here, we show that the developmentally programmed resistance to apoptosis involves transcriptional repression of critical pro-apoptotic genes by histone deacetylases (HDACs). Administration of HDAC inhibitors (HDACi), like Trichostatin A (TSA) or Suberoylanilide Hydroxamic Acid (SAHA), increases expression of pro-apoptotic genes and is sufficient to sensitize otherwise resistant stages...
April 28, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28452069/the-hdac6-inhibitor-tubacin-induces-release-of-cd133-extracellular-vesicles-from-cancer-cells
#19
Olivia S Chao, Tim C Chang, Maria A Di Bella, Riccardo Alessandro, Fabio Anzanello, Germana Rappa, Oscar B Goodman, Aurelio Lorico
Tumor-derived extracellular vesicles (EVs) are emerging as an important mode of intercellular communication, capable of transferring biologically active molecules that facilitate the malignant growth and metastatic process. CD133 (Prominin-1), a stem cell marker implicated in tumor initiation, differentiation and resistance to anti-cancer therapy, is reportedly associated with EVs in various types of cancer. However, little is known about the factors that regulate the release of these CD133(+) EVs. Here, we report that the HDAC6 inhibitor tubacin promoted the extracellular release of CD133(+) EVs from human FEMX-I metastatic melanoma and Caco-2 colorectal carcinoma cells, with a concomitant downregulation of intracellular CD133...
April 27, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28439875/epigenetic-repression-of-mir-375-is-the-dominant-mechanism-for-constitutive-activation-of-the-pdpk1-rps6ka3-signalling-axis-in-multiple-myeloma
#20
Shotaro Tatekawa, Yoshiaki Chinen, Masaki Ri, Tomoko Narita, Yuji Shimura, Yayoi Matsumura-Kimoto, Taku Tsukamoto, Tsutomu Kobayashi, Eri Kawata, Nobuhiko Uoshima, Tomohiko Taki, Masafumi Taniwaki, Hiroshi Handa, Shinsuke Iida, Junya Kuroda
Cytogenetic/molecular heterogeneity is the hallmark of multiple myeloma (MM). However, we recently showed that the serine/threonine kinase PDPK1 and its substrate RPS6KA3 (also termed RSK2) are universally active in MM, and play pivotal roles in myeloma pathophysiology. In this study, we assessed involvement of aberrant miR-375 repression in PDPK1 overexpression in MM. An analysis of plasma cells from 30 pre-malignant monoclonal gammopathies of undetermined significance and 73 MM patients showed a significant decrease in miR-375 expression in patient-derived plasma cells regardless of the clinical stage, compared to normal plasma cells...
April 25, 2017: British Journal of Haematology
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