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https://www.readbyqxmd.com/read/28222071/combination-of-the-histone-deacetylase-inhibitor-vorinostat-with-bevacizumab-in-patients-with-clear-cell-renal-cell-carcinoma-a-multicentre-single-arm-phase-i-ii-clinical-trial
#1
Roberto Pili, Glenn Liu, Sreenivasulu Chintala, Hendrick Verheul, Shabnam Rehman, Kristopher Attwood, Martin A Lodge, Richard Wahl, James I Martin, Kiersten Marie Miles, Silvia Paesante, Remi Adelaiye, Alejandro Godoy, Serina King, James Zwiebel, Michael A Carducci
BACKGROUND: Class II histone deacetylase (HDAC) inhibitors induce hypoxia-inducible factor-1 and -2α degradation and have antitumour effects in combination with vascular endothelial growth factor (VEGF) inhibitors. In this study, we tested the safety and efficacy of the HDAC inhibitor vorinostat and the VEGF blocker bevacizumab in metastatic clear-cell renal cell carcinoma (ccRCC) patients previously treated with different drugs including sunitinib, sorafenib, axitinib, interleukin-2, interferon, and temsirolimus...
February 21, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28222070/inhibition-of-polypyrimidine-tract-binding-protein-3-induces-apoptosis-and-cell-cycle-arrest-and-enhances-the-cytotoxicity-of-5-fluorouracil-in-gastric-cancer-cells
#2
Xin Liang, Haiyang Shi, Liyan Yang, Cen Qiu, Shengchao Lin, Yingxue Qi, Jiyu Li, Aiguang Zhao, Jianwen Liu
BACKGROUND: Human polypyrimidine tract binding protein 3 (PTBP3) was first discovered in 1999 and has been well characterised as a differentiation regulator. However, its role in human cancer has rarely been reported. Our previous study revealed increased PTBP3 protein level in gastric cancer tissues. Downregulation of PTBP3 suppressed the proliferation and differentiation of gastric cancer cells in vivo. METHODS: PTBP3 mRNA levels in human gastric cancer and adjuvant non-tumour tissues were detected...
February 21, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28221861/inhibiting-histone-deacetylase-as-a-means-to-reverse-resistance-to-angiogenesis-inhibitors-phase-i-study-of-abexinostat-plus-pazopanib-in-advanced-solid-tumor-malignancies
#3
Rahul Aggarwal, Scott Thomas, Nela Pawlowska, Imke Bartelink, Jennifer Grabowsky, Thierry Jahan, Amy Cripps, Armand Harb, Jim Leng, Anne Reinert, Ilaria Mastroserio, Thach-Giao Truong, Charles J Ryan, Pamela N Munster
Purpose This phase I trial evaluated epigenetic modulation of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor by using a histone deacetylase abexinostat in combination with pazopanib to enhance response and reverse resistance. Patients and Methods Pazopanib was administered once a day on days 1 to 28 and abexinostat was administered orally twice a day on days 1 to 5, 8 to 12, and 15 to 19 (schedule A) or on days 1 to 4, 8 to 11, and 15 to 18 (schedule B). Dose escalation (3 + 3 design) in all solid tumors was followed by dose expansion in renal cell carcinoma (RCC)...
February 21, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28220120/neutrophil-extracellular-traps-and-its-implications-in-inflammation-an-overview
#4
REVIEW
Vidal Delgado-Rizo, Marco A Martínez-Guzmán, Liliana Iñiguez-Gutierrez, Alejandra García-Orozco, Anabell Alvarado-Navarro, Mary Fafutis-Morris
In addition to physical barriers, neutrophils are considered a part of the first line of immune defense. They can be found in the bloodstream, with a lifespan of 6-8 h, and in tissue, where they can last up to 7 days. The mechanisms that neutrophils utilize for host defense are phagocytosis, degranulation, cytokine production, and, the most recently described, neutrophil extracellular trap (NET) production. NETs are DNA structures released due to chromatin decondensation and spreading, and they thus occupy three to five times the volume of condensed chromatin...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28219702/genetic-alterations-in-krebs-cycle-and-its-impact-on-cancer-pathogenesis
#5
REVIEW
Karishma Sajnani, Farhadul Islam, Robert Anthony Smith, Vinod Gopalan, Alfred King-Yin Lam
Cancer cells exhibit alterations in many cellular processes, including oxygen sensing and energy metabolism. Glycolysis in non-oxygen condition is the main energy production process in cancer rather than mitochondrial respiration as in benign cells. Genetic and epigenetic alterations of Krebs cycle enzymes favour the shift of cancer cells from oxidative phosphorylation to anaerobic glycolysis. Mutations in genes encoding aconitase, isocitrate dehydrogenase, succinate dehydrogenase, fumarate hydratase, and citrate synthase are noted in many cancers...
February 17, 2017: Biochimie
https://www.readbyqxmd.com/read/28219521/butyrate-influences-intracellular-levels-of-adenine-and-adenine-derivatives-in-the-fungus-penicillium-restrictum
#6
Christoph Zutz, Yi Ming Chiang, Bettina Faehnrich, Markus Bacher, Roland Hellinger, Bernhard Kluger, Martin Wagner, Joseph Strauss, Kathrin Rychli
Butyrate, a small fatty acid, has an important role in the colon of ruminants and mammalians including the inhibition of inflammation and the regulation of cell proliferation. There is also growing evidence that butyrate is influencing the histone structure in mammalian cells by inhibition of histone deacetylation. Butyrate shows furthermore an antimicrobial activity against fungi, yeast and bacteria, which is linked to its toxicity at a high concentration. In fungi there are indications that butyrate induces the production of secondary metabolites potentially via inhibition of histone deacetylases...
April 2017: Microbiological Research
https://www.readbyqxmd.com/read/28214660/enhancer-of-zeste-homologue-2-plays-an-important-role-in-neuroblastoma-cell-survival-independent-of-its-histone-methyltransferase-activity
#7
Laurel T Bate-Eya, Hinco J Gierman, Marli E Ebus, Jan Koster, Huib N Caron, Rogier Versteeg, M Emmy M Dolman, Jan J Molenaar
Neuroblastoma is predominantly characterised by chromosomal rearrangements. Next to V-Myc Avian Myelocytomatosis Viral Oncogene Neuroblastoma Derived Homolog (MYCN) amplification, chromosome 7 and 17q gains are frequently observed. We identified a neuroblastoma patient with a regional 7q36 gain, encompassing the enhancer of zeste homologue 2 (EZH2) gene. EZH2 is the histone methyltransferase of lysine 27 of histone H3 (H3K27me3) that forms the catalytic subunit of the polycomb repressive complex 2. H3K27me3 is commonly associated with the silencing of genes involved in cellular processes such as cell cycle regulation, cellular differentiation and cancer...
February 16, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28213282/design-synthesis-and-biological-evaluation-of-thienopyrimidine-hydroxamic-acid-based-derivatives-as-structurally-novel-histone-deacetylase-hdac-inhibitors
#8
Jiang Wang, Mingbo Su, Tingting Li, Anhui Gao, Wei Yang, Li Sheng, Yi Zang, Jia Li, Hong Liu
New thienopyrimidine hydroxamic acid derivatives as HDACs inhibitors were designed, synthesized and evaluated. All compounds were evaluated for their ability to inhibit recombinant human HDAC1, HDAC3, and HDAC6 isoforms and in vitro anti-proliferative activity on tumor cell lines RMPI 8226 and HCT 116. Most of these compounds displayed good to excellent inhibitory activities against HDACs. The IC50 values of compound 9m against HDAC1, HDAC3, and HDAC6 was 29.81 ± 0.52 nM, 24.71 ± 1.16 nM, and 21.29 ± 0...
January 23, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28212444/sumo-modification-of-a-heterochromatin-histone-demethylase-jmjd2a-enables-viral-gene-transactivation-and-viral-replication
#9
Wan-Shan Yang, Mel Campbell, Pei-Ching Chang
Small ubiquitin-like modifier (SUMO) modification of chromatin has profound effects on transcription regulation. By using Kaposi's sarcoma associated herpesvirus (KSHV) as a model, we recently demonstrated that epigenetic modification of viral chromatin by SUMO-2/3 is involved in regulating gene expression and viral reactivation. However, how this modification orchestrates transcription reprogramming through targeting histone modifying enzymes remains largely unknown. Here we show that JMJD2A, the first identified Jumonji C domain-containing histone demethylase, is the histone demethylase responsible for SUMO-2/3 enrichment on the KSHV genome during viral reactivation...
February 17, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28212191/endothelial-cell-metabolism-an-update-anno-2017
#10
Laure-Anne Teuwen, Nihed Draoui, Charlotte Dubois, Peter Carmeliet
PURPOSE OF REVIEW: Endothelial cell metabolism has recently emerged as an important coregulator of angiogenesis and is therefore a promising new target in various angiogenesis-associated illnesses, like cancer. In this review, we discuss recent insights in endothelial cell metabolism in both physiological and pathological conditions and discuss possible translational implications. RECENT FINDINGS: Two metabolic pathways that determine the performance of endothelial cells are glycolysis and fatty acid oxidation (FAO)...
February 15, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28211924/a-selfish-b-chromosome-induces-genome-elimination-by-disrupting-the-histone-code-in-the-jewel-wasp-nasonia-vitripennis
#11
John C Aldrich, Alexandra Leibholz, Manjinder S Cheema, Juan Ausiό, Patrick M Ferree
Intragenomic conflict describes a phenomenon in which genetic elements act 'selfishly' to gain a transmission advantage at the expense of the whole genome. A non-essential, selfish B chromosome known as Paternal Sex Ratio (PSR) induces complete elimination of the sperm-derived hereditary material in the jewel wasp Nasonia vitripennis. PSR prevents the paternal chromatin from forming chromosomes during the first embryonic mitosis, leading to its loss. Although paternally transmitted, PSR evades self-elimination in order to be inherited...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28211081/h3f3a-mutation-in-giant-cell-tumour-of-the-bone-is-detected-by-immunohistochemistry-using-a-monoclonal-antibody-against-the-g34w-mutated-site-of-the-histone-h3-3-variant
#12
Julian Lüke, Alexandra von Baer, Jordan Schreiber, Christoph Lübbehüsen, Thomas Breining, Kevin Mellert, Ralf Marienfeld, Markus Schultheiss, Peter Möller, Thomas Fe Barth
AIMS: Giant cell tumour of bone (GCTB) is a neoplasm predominantly of long bones characterised by the H3F3A mutation G34W. Conventional diagnostic is challenged by the tumour's giant cell-rich morphology, which overlaps with other giant cell containing lesions of the bone. Recently, a monoclonal antibody specific for the H3F3A mutation has been generated. Our aim was to test this antibody on a cohort of giant cell containing lesions. METHODS AND RESULTS: We used the antibody for analysis of 22 H3F3A-mutated GCTB, including two patients with recurrences; for comparison we analysed a cohort of 36 H3F3A-wild-type giant cell-rich lesions of the bone and soft tissue, containing one brown tumour, six aneurysmal bone cysts, six chondroblastomas, five non-ossifying-fibromas, two fibrous dysplasias, nine tenosynovial giant cell tumours, one giant cell-rich sarcoma and six osteosarcomas...
February 17, 2017: Histopathology
https://www.readbyqxmd.com/read/28209712/mycobacterium-tuberculosis-esxl-inhibit-mhc-ii-expression-by-promoting-hypermethylation-in-class-ii-transactivator-loci-in-macrophages
#13
Srabasti Sengupta, Saba Naz, Ishani Das, Abdul Ahad, Avinash Padhi, Sumanta Naik, Geetanjali Ganguli, Kaliprasad Patnaik, Sunil Kumar Raghav, Vinay Nandicoori, Avinash Sonawane
Mycobacterium tuberculosis (Mtb) is known to modulate the host immune responses to facilitate its persistence inside the host cells. One of the key mechanisms includes repression of class-II transactivator (CIITA) and MHC-II expression in infected macrophages. However, the precise mechanism of CIITA and MHC-II down-regulation is not well studied. Mtb 6-kDa early secretory antigenic target (ESAT-6) is a known potent virulence and antigenic determinant. Mtb genome encodes 23 such ESAT-6 family proteins. We herein report that Mtb and M...
February 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28207814/jmjd-5-kdm8-regulates-h3k36me2-and-is-required-for-late-steps-of-homologous-recombination-and-genome-integrity
#14
Pier Giorgio Amendola, Nico Zaghet, João J Ramalho, Jens Vilstrup Johansen, Mike Boxem, Anna Elisabetta Salcini
The eukaryotic genome is organized in a three-dimensional structure called chromatin, constituted by DNA and associated proteins, the majority of which are histones. Post-translational modifications of histone proteins greatly influence chromatin structure and regulate many DNA-based biological processes. Methylation of lysine 36 of histone 3 (H3K36) is a post-translational modification functionally relevant during early steps of DNA damage repair. Here, we show that the JMJD-5 regulates H3K36 di-methylation and it is required at late stages of double strand break repair mediated by homologous recombination...
February 16, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28205129/remifentanil-postconditioning-ameliorates-histone-h3-acetylation-modification-in-h9c2-cardiomyoblasts-after-hypoxia-reoxygenation-via-attenuating-endoplasmic-reticulum-stress
#15
Manli Chen, Qin Liu, Lijian Chen, Lei Zhang, Erwei Gu
Remifentanil postconditioning (RPC) elicits cardioprotection against ischemia/reperfusion injury (IRI) by attenuating apoptosis associated with endoplasmic reticulum stress (ERS). Histone H3, acetylation modifications of histone H3, and histone deacetylases (HDAC) also have key roles in the mediation of the survival and apoptosis of cardiomyocytes. In this study, an in vitro IRI model was established with H9c2 cardiomyoblasts to investigate the role of histone H3 acetylation and HDAC3 in RPC-induced attenuation of ERS-associated apoptosis...
February 16, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28202597/histone-lysine-to-methionine-mutations-reduce-histone-methylation-and-cause-developmental-pleiotropy
#16
Dean Sanders, Shuiming Qian, Rachael Fieweger, Li Lu, James A Dowell, John M Denu, Xuehua Zhong
Epigenetic modifications play critical roles in diverse biological processes. Histone lysine to methionine (K-to-M) mutations act as gain-of-function mutations to inhibit a wide range of histone methyltransferases and are thought to promote tumorigenesis. However, it is largely unknown whether K-to-M mutations impact development at the whole organismal level. Using Arabidopsis as a model system, we discovered that a transgene exogenously expressing histone 3 lysine 36 to methionine mutation (K36M) acts in a dominant negative manner to cause global reduction of H3K36 methylation...
February 15, 2017: Plant Physiology
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
#17
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/28199194/regulation-of-mitochondrial-gene-expression-the-epigenetic-enigma
#18
Archibold Mposhi, Monique Gp Van der Wijst, Klaas Nico Faber, Marianne G Rots
Epigenetics provides an important layer of information on top of the DNA sequence and is essential for establishing gene expression profiles. Extensive studies have shown that nuclear DNA methylation and histone modifications influence nuclear gene expression. However, it remains unclear whether mitochondrial DNA (mtDNA) undergoes similar epigenetic changes to regulate mitochondrial gene expression. Recently, it has been shown that mtDNA is differentially methylated in various diseases such as diabetes and colorectal cancer...
March 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28195362/low-intensity-ultrasound-enhances-histone-acetylation-and-inhibition-of-interleukin-6-messenger-rna-expression-by-the-histone-deacetylase-inhibitor-sodium-butyrate-in-fibroblasts
#19
Noriaki Maeshige, Yuka Koga, Masayuki Tanaka, Michiko Aoyama-Ishikawa, Makoto Miyoshi, Makoto Usami, Hidemi Fujino
OBJECTIVES: Sodium butyrate, an inhibitor of histone deacetylase, has several therapeutic actions, including anti-inflammation. These actions depend on the concentration of sodium butyrate. In addition, lower concentrations have shown no effect on inflammation. Sonoporation by ultrasound can modify the permeability of the cell plasma membrane. Thus, the effects of sodium butyrate may be enhanced by the ultrasonic acoustics. Therefore, the facilitative effects of low-intensity ultrasound on histone acetylation and interleukin 6 (IL-6) regulation by sodium butyrate were investigated in this study...
February 3, 2017: Journal of Ultrasound in Medicine: Official Journal of the American Institute of Ultrasound in Medicine
https://www.readbyqxmd.com/read/28192098/anti-leukemic-effects-of-hdaci-belinostat-and-hmti-3-deazaneplanocin-a-on-human-acute-promyelocytic-leukemia-cells
#20
Giedrė Valiulienė, Ieva Stirblytė, Monika Jasnauskaitė, Veronika Borutinskaitė, Rūta Navakauskienė
Development of acute myeloid leukemia is usually sustained by deregulated epigenome. Alterations in DNA methylation and histone modifications are common manifestations of the disease. Acute promyelocytic leukemia (APL) is not an exception. Therefore, drugs that target epigenetic processes suggest an appealing strategy for APL treatment. In this study we tested the anti-leukemic activity of histone deacetylase inhibitor (HDACi) Belinostat (PXD101, (2E)-N-Hydroxy-3-[3-(phenylsulfamoyl)phenyl]prop-2-enamide), and histone methyltransferase inhibitor (HMTi) 3-Deazaneplanocin A (DZNep, 5R-(4-amino-1H-imidazo[4,5-c]pyridin-1-yl)-3-(hydroxymethyl)-3-cyclopentene-1S,2R-diol) combined with retinoic acid (RA) in APL cells NB4 and HL-60...
February 10, 2017: European Journal of Pharmacology
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