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Histone deacetylase

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https://www.readbyqxmd.com/read/28319066/nucleus-accumbens-associated-protein-1-promotes-glycolysis-and-survival-of-hypoxic-tumor-cells-via-the-hdac4-hif-1%C3%AE-axis
#1
Y Zhang, Y-J Ren, L-C Guo, C Ji, J Hu, H-H Zhang, Q-H Xu, W-D Zhu, Z-J Ming, Y-S Yuan, X Ren, J Song, J-M Yang
Nucleus accumbens-associated protein-1 (NAC1), a nuclear factor of the BTB/POZ gene family, has emerging roles in cancer. In this study, we identified the NAC1-HDAC4-HIF-1α axis as an important pathway in regulating glycolysis and hypoxic adaptation in tumor cells. We show that nuclear NAC1 binds to histone deacetylase type 4 (HDAC4), hindering phosphorylation of HDAC4 at Ser(246) and preventing its nuclear export that leads to cytoplasmic degradation of the deacetylase. Accumulation of HDAC4 in the nuclei results in an attenuation of HIF-1α acetylation, enhancing the stabilization and transcriptional activity of HIF-1α and strengthening adaptive response of cells to hypoxia...
March 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28317157/design-and-synthesis-of-novel-anti-plasmodial-histone-deacetylase-inhibitors-containing-an-alkoxyamide-connecting-unit
#2
Leandro A Alves Avelar, Jana Held, Jessica A Engel, Parichat Sureechatchaiyan, Finn K Hansen, Alexandra Hamacher, Matthias U Kassack, Benjamin Mordmüller, Katherine T Andrews, Thomas Kurz
Despite recent declines in mortality, malaria remains an important global health problem. New therapies are needed, including new drugs with novel modes of action compared to existing agents. Among new potential therapeutic targets for malaria, inhibition of parasitic histone deacetylases (HDACs) is a promising approach. Homology modeling of PfHDAC1, a known target of some anti-plasmodial HDAC inhibitors, revealed a unique threonine residue at the rim of the active site in close proximity to the location of the cap group of vorinostat-type HDAC inhibitors...
March 20, 2017: Archiv der Pharmazie
https://www.readbyqxmd.com/read/28315487/xpln-is-modulated-by-hdac-inhibitors-and-negatively-regulates-sparc-expression-by-targeting-mtorc2-in-human-lung-fibroblasts
#3
Koichiro Kamio, Arata Azuma, Jiro Usuki, Kuniko Matsuda, Minoru Inomata, Nobuhiko Nishijima, Shioto Itakura, Hiroki Hayashi, Takeru Kashiwada, Nariaki Kokuho, Kenichiro Atsumi, Tomoyoshi Yamaguchi, Kazue Fujita, Yoshinobu Saito, Shinji Abe, Kaoru Kubota, Akihiko Gemma
Pathogenesis of idiopathic pulmonary fibrosis (IPF) remains unclear. Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein that participates in the assembly and turnover of the extracellular matrix, whose expression is regulated by transforming growth factor (TGF)-β1 through activation of mammalian target of rapamycin complex 2 (mTORC2). Exchange factor found in platelets, leukemic, and neuronal tissues (XPLN) is an endogenous inhibitor of mTORC2. However, whether XPLN modulates SPARC expression remains unknown...
March 14, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28315173/ricolinostat-a-selective-hdac6-inhibitor-shows-anti-lymphoma-cell-activity-alone-and-in-combination-with-bendamustine
#4
Maria Cosenza, Monica Civallero, Luigi Marcheselli, Stefano Sacchi, Samantha Pozzi
Histone deacetylase inhibitors (HDACis) have emerged as a new class of anticancer agents, targeting the biological process including cell cycle and apoptosis. We investigated and explained the anticancer effects of an HDAC6 inhibitor, ricolinostat alone and in combination with bendamustine in lymphoma cell lines. Cell viability was measured by MTT assay. Apoptosis, reactive oxygen species (ROS) generation, Bcl-2 protein expression, cell cycle progression and tubuline expression were determined by flow cytometry...
March 17, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28315153/effects-of-histone-deacetylase-inhibitory-prodrugs-on-epigenetic-changes-and-dna-damage-response-in-tumor-and-heart-of-glioblastoma-xenograft
#5
Nataly Tarasenko, Abraham Nudelman, Gabriela Rozic, Suzanne M Cutts, Ada Rephaeli
The histone deacetylase (HDAC) inhibitory prodrugs of butyric (AN7) and valproic (AN446) acids, which release the active acids upon metabolic degradation, were studied examining their differential effects on the viability, HDAC inhibitory activity and the DNA damage response (DDR), in glioblastoma cell and normal human astrocytes (NHAs). In xenografts of glioblastoma, AN7 or AN446 given or the combination of each of them with Dox augmented the anticancer activity of Dox and protected the heart from its toxicity...
March 17, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28314266/additive-interaction-of-cisplatin-and-histone-deacetylase-inhibitors-combined-treatment-in-rhabdomyosarcoma-cells-an-isobolographic-analysis
#6
Agata Jarząb, Jarogniew J Łuszczki, Małgorzata Guz, Ewelina Gumbarewicz, Krzysztof Polberg, Andrzej Stepulak
BACKGROUND/AIM: The aim of this study was to assess the anticancer effect and the type of pharmacologic drug-drug interaction of cisplatin (CDDP) and histone deacetylase inhibitors (HDIs) combined treatment on the rhabdomyosarcoma cell line. MATERIALS AND METHODS: The antiproliferative actions of cisplatin and suberoylanilide hydroxamic acid (SAHA, vorinostat), as well as valproic acid (VPA) alone and in combination, were evaluated using the tetrazolium dye-based MTT cell proliferation assay and isobolographic analysis...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28314258/antimetastatic-efficacy-of-the-combination-of-caffeine-and-valproic-acid-on-an-orthotopic-human-osteosarcoma-cell-line-model-in-nude-mice
#7
Kentaro Igarashi, Kei Kawaguchi, Tasuku Kiyuna, Takashi Murakami, Norio Yamamoto, Katsuhiro Hayashi, Hiroaki Kimura, Shinji Miwa, Hiroyuki Tsuchiya, Robert M Hoffman
AIM: We have previously reported that caffeine can enhance chemotherapy efficacy of bone and soft tissue sarcoma via cell-cycle perturbation. Valproic acid has histone deacetylase (HDAC) inhibitory activity. We have also reported the anti-tumor efficacy of combination treatment with caffeine and valproic acid against osteosarcoma primary tumors in a cell-line orthotopic mouse model. MATERIALS AND METHODS: In this study, we performed combination treatment of caffeine and valproic acid on osteosarcoma cell lines in vitro and in spontaneous and experimental lung metastasis mouse models of osteosarcoma...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28306192/histone-deacetylase-activity-mediates-acquired-resistance-towards-structurally-diverse-hsp90-inhibitors
#8
Ryan C Chai, Jessica L Vieusseux, Benjamin J Lang, Chau H Nguyen, Michelle M Kouspou, Kara L Britt, John T Price
Heat Shock Protein 90 (HSP90) regulates multiple signaling pathways critical for tumor growth. As such, HSP90 inhibitors have been shown to act as effective anticancer agents in preclinical studies but, for a number of reasons, the same effect has not been observed in the clinical trials to date. One potential reason for this may the presence of de novo or acquired resistance within the tumors. To investigate mechanisms of resistance, we generated resistant cell lines through gradual dose escalation of the HSP90 inhibitor 17-AAG...
March 17, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28304160/nucleosome-histone-tail-conformation-and-dynamics-impacts-of-lysine-acetylation-and-a-nearby-minor-groove-benzo-a-pyrene-derived-lesion
#9
Iwen Fu, Yuqin Cai, Nicholas E Geacintov, Yingkai Zhang, Suse Broyde
Histone tails in nucleosomes play critical roles in regulation of many biological processes including chromatin compaction, transcription and DNA repair. Moreover, post-translational modifications, notably lysine acetylation, are crucial to these functions. While the tails have been intensively studied, how the structures and dynamics of tails are impacted by the presence of a nearby bulky DNA lesion is a frontier research area, and how these properties are impacted by tail lysine acetylation remains unexplored...
March 17, 2017: Biochemistry
https://www.readbyqxmd.com/read/28301545/implication-of-the-intestinal-microbiome-as-a-potential-surrogate-marker-of-immune-responsiveness-to-experimental-therapies-in-autoimmune-diabetes
#10
James C Needell, Charles A Dinarello, Diana Ir, Charles E Robertson, Sarah M Ryan, Miranda E Kroehl, Daniel N Frank, Danny Zipris
Type 1 diabetes (T1D) is an autoimmune proinflammatory disease with no effective intervention. A major obstacle in developing new immunotherapies for T1D is the lack of means for monitoring immune responsiveness to experimental therapies. The LEW1.WR1 rat develops autoimmunity following infection with the parvovirus Kilham rat virus (KRV) via mechanisms linked with activation of proinflammatory pathways and alterations in the gut bacterial composition. We used this animal to test the hypothesis that intervention with agents that block innate immunity and diabetes is associated with a shift in the gut microbiota...
2017: PloS One
https://www.readbyqxmd.com/read/28300476/ovarian-steroid-hormones-modulate-the-expression-of-progesterone-receptors-and-histone-acetylation-patterns-in-uterine-leiomyoma-cells
#11
Gabriela Dos Santos Sant'Anna, Ilma Simoni Brum, Gisele Branchini, Lolita Schneider Pizzolato, Edison Capp, Helena von Eye Corleta
Uterine leiomyomas are the most common benign smooth muscle cell tumors in women. Estrogen (E2), progesterone (P4) and environmental factors play important roles in the development of these tumors. New treatments, such as mifepristone, have been proposed. We evaluated the gene expression of total (PRT) and B (PRB) progesterone receptors, and the histone acetyltransferase (HAT) and deacetylase (HDAC) activity after treatment with E2, P4 and mifepristone (RU486) in primary cell cultures from uterine leiomyoma and normal myometrium...
March 16, 2017: Gynecological Endocrinology
https://www.readbyqxmd.com/read/28299833/unsupervised-pharmacophore-modeling-combined-with-qsar-analyses-revealed-novel-low-micromolar-sirt2-inhibitors
#12
Mohammad A Khanfar, Mutasem O Taha
Situin 2 (SIRT2) enzyme is a histone deacetylase that has important role in neuronal development. SIRT2 is clinically validated target for neurodegenerative diseases and some cancers. In this study, exhaustive unsupervised pharmacophore modeling was combined with quantitative structure-activity relationship (QSAR) analysis to explore the structural requirements for potent SIRT2 inhibitors using 146 known SIRT2 ligands. A computational workflow that combines genetic function algorithm with k-nearest neighbor or multiple linear regression was implemented to build self-consistent and predictive QSAR models based on combinations of pharmacophores and physicochemical descriptors...
March 15, 2017: Journal of Molecular Recognition: JMR
https://www.readbyqxmd.com/read/28299580/the-expression-of-hdac7-in-cancerous-gastric-tissues-is-positively-associated-with-distant-metastasis-and-poor-patient-prognosis
#13
Y Yu, F Cao, X Yu, P Zhou, Q Di, J Lei, Y Tai, H Wu, X Li, X Wang, W Zhang, P Li, Y Li
PURPOSE: To characterize the expression patterns of HDAC7 in patients with gastric cancer and evaluate the prognostic value of HDAC7 in gastric cancer. METHODS: The expression of histone deacetylase 7 (HDAC7) was detected in paraffin-embedded gastric cancer samples from 86 patients by immunohistochemistry, and the differences in the expression of HDAC7 between cancerous and corresponding adjacent noncancerous tissues were compared using the Wilcoxon matched-pairs signed rank test...
March 15, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/28298436/chromatin-remodeler-chd4-represses-aberrant-expression-of-tbx3-and-sustains-self-renewal-of-embryonic-stem-cells
#14
Haixin Zhao, Zhijun Han, Xinyuan Liu, Junjie Gu, Fan Tang, Gang Wei, Ying Jin
The unique properties of embryonic stem cells (ESCs), unlimited self-renewal and pluripotent differentiation potential, are sustained by integrated genetic and epigenetic networks composed of a series of transcriptional factors and epigenetic modulators. However, molecular mechanisms underlying the function of these regulators are not fully elucidated. Chd4, an ATPase subunit of the nucleosome remodeling and deacetylase (NuRD) complex, is highly expressed in ESCs. However, its function in the regulation of ESC properties remains elusive...
March 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28294989/a-flavone-constituent-from-myoporum-bontioides-induces-m-phase-cell-cycle-arrest-of-mcf-7-breast-cancer-cells
#15
Jing-Ru Weng, Li-Yuan Bai, Wei-Yu Lin, Chang-Fang Chiu, Yu-Chang Chen, Shi-Wei Chao, Chia-Hsien Feng
Myoporum bontioides is a traditional medicinal plant in Asia with various biological activities, including anti-inflammatory and anti-bacterial characteristics. To identify the bioactive constituents from M. bontioides, a newly-identified flavone, 3,4'-dimethoxy-3',5,7-trihydroxyflavone (compound 1), along with eight known compounds, were investigated in human MCF-7 breast cancer, SCC4 oral cancer, and THP-1 monocytic leukemia cells. Among these compounds, compound 1 exhibited the strongest antiproliferative activity with half-maximal inhibitory concentration (IC50) values ranging from 3...
March 15, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28293123/pembrolizumab-in-the-treatment-of-metastatic-non-small-cell-lung-cancer-patient-selection-and-perspectives
#16
REVIEW
Ashwin Somasundaram, Timothy F Burns
Lung cancer is the leading killer of both men and women in the US, and the 5-year survival remains poor. However, the approval of checkpoint blockade immunotherapy has shifted the treatment paradigm and provides hope for improved survival. The ability of non-small-cell lung cancer (NSCLC) to evade the host immune system can be overcome by agents such as pembrolizumab (MK-3475/lambrolizumab), which is a monoclonal antibody targeting the programmed death 1 (PD-1) receptor. In early studies, treatment with pembrolizumab led to dramatic and durable responses in select patients (PD-L1+ tumors)...
2017: Lung Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/28290609/senescence-of-mesenchymal-stem-cells-review
#17
Yi Li, Qiong Wu, Yujia Wang, Li Li, Hong Bu, Ji Bao
Mesenchymal stem cells (MSCs) have been used in cell-based therapy for various diseases, due to their immunomodulatory and inflammatory effects. However, the function of MSCs is known to decline with age, a process that is called senescence. To date, the process of MSC senescence remains unknown as in-depth understanding of the mechanisms involved in cellular senescence is lacking. First, senescent MSCs are so heterogeneous that not all of them express the same phenotypic markers. In addition, the genes and signaling pathways which regulate this process in MSCs are still unknown...
March 9, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28288848/bcl11b-mediated-epigenetic-repression-is-a-crucial-target-for-histone-deacetylase-inhibitors-in-cutaneous-t-cell-lymphoma
#18
Wenjing Fu, Shengguo Yi, Lei Qiu, Jingru Sun, Ping Tu, Yang Wang
The treatment options for advanced cutaneous T-cell lymphoma (CTCL) are limited due to its unclear pathogenesis. HDAC inhibitors (HDACi) are recently developed therapeutics approved for refractory CTCL. However, the response rate is relatively low and unpredictable. Previously, we discovered that BCL11B, a key T-cell development regulator, was aberrantly overexpressed in mycosis fungoides (MF), the most common CTCL, as compared with benign inflammatory skin. In the current study, we identified positive correlation between BCL11B expression and the sensitivity to HDACi in CTCL lines...
March 10, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28288414/butyrate-induces-ros-mediated-apoptosis-by-modulating-mir-22-sirt-1-pathway-in-hepatic-cancer-cells
#19
Kishor Pant, Ajay K Yadav, Parul Gupta, Rakibul Islam, Anoop Saraya, Senthil K Venugopal
Butyrate is one of the short chain fatty acids, produced by the gut microbiota during anaerobic fermentation of dietary fibres. It has been shown that it can inhibit tumor progression via suppressing histone deacetylase and can induce apoptosis in cancer cells. However, the comprehensive pathway by which butyrate mediates apoptosis and growth arrest in cancer cells still remains unclear. In this study, the role of miR-22 in butyrate-mediated ROS release and induction of apoptosis was determined in hepatic cells...
March 7, 2017: Redox Biology
https://www.readbyqxmd.com/read/28288133/mta1-modulated-by-mir-30e-contributes-to-epithelial-to-mesenchymal-transition-in-hepatocellular-carcinoma-through-an-erbb2-dependent-pathway
#20
L Deng, J Tang, H Yang, C Cheng, S Lu, R Jiang, B Sun
MTA1 is a metastasis-associated protein, which is essential to epithelial-to-mesenchymal transition (EMT). However, information concerning its up- and downstream regulation is rare. We investigated its upstream regulation and downstream effector in human hepatocellular carcinoma (HCC). In total, 94 paired HCC and adjacent tissue samples were involved in the study, and the results indicated that decreased miR-30e levels were associated with increased MTA1 levels in human HCC. miR-30e exerted its regulation of MTA1 transcription by binding to its 3'-untranslated region, and was negatively associated with EMT...
March 13, 2017: Oncogene
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