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https://www.readbyqxmd.com/read/28927052/synergistic-effects-of-phenylhexyl-isothiocyanate-and-ly294002-on-the-pi3k-akt-signaling-pathway-in-hl-60-cells
#1
Huicong Yang, Yiqun Huang, Yong Zou, Xudong Ma
The aim of the present study was to investigate the synergistic effect of phenylhexyl isothiocyanate (PHI) and LY294002 [an inhibitor of phosphoinositide 3-kinase (PI3K)] on the PI3K/protein kinase B (Akt) signaling pathway, modulating histone acetylation, inhibiting cell viability and inducing apoptosis in HL-60 cells. The inhibition of HL-60 cell viability was monitored using an MTT assay. Cell apoptosis was measured using flow cytometry. Expression of acetylated histone H3 and histone H4, and the Akt signaling pathway proteins phosphorylated Akt (p-Akt), phosphorylated mammalian target of rapamycin (p-mTOR) and phosphorylated ribosomal protein S6 kinase (p-p70S6K) was detected using western blotting...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28926431/epigenetic-regulation-of-dendritic-cell-development-and-function
#2
Yuanyuan Tian, Lijun Meng, Yi Zhang
The immune system is characterized by the generation of structurally and functionally heterogeneous immune cells that constitute complex innate and adaptive immunity. This heterogeneity of immune cells results from changes in the expression of genes without altering DNA sequence. To achieve this heterogeneity, immune cells orchestrate the expression and functional status of transcription factor (TF) networks, which can be broadly categorized into 3 classes: pioneer TFs that facilitate initial commitment and differentiation of hematopoietic cells, subset-specific TFs that promote the generation of selected cell lineages, and immune-signaling TFs that regulate specialized function in differentiated cells...
September 2017: Cancer Journal
https://www.readbyqxmd.com/read/28925507/-epigallocatechin-3-gallate-and-ezh2-inhibitor-gsk343-have-similar-inhibitory-effects-and-mechanisms-of-action-on-colorectal-cancer-cells
#3
Le Ying, Feng Yan, Bryan R G Williams, Ping Xu, Xin Li, Yueling Zhao, Yiqun Hu, Yuefei Wang, Dakang Xu, Jing Dai
Epigallocatechin-3-gallate (EGCG) is a type of catechin. It exhibits excellent antioxidant effects and anti-tumor activities for cancer chemoprevention. The mechanism of anti-tumor effects of EGCG on different cancers has been studied for the past few decades, but remains controversial. To investigate the potential role that EGCG may play in the epigenetic regulation of colorectal cancer (CRC) cell line, we integrated bioinformatics analysis with experimental validation. We found that levels of the enhancer of zeste homolog 2 (EZH2) were significantly higher in CRC tissues compared to normal adjacent tissues, based on the Genomic Data Commons (GDC) data portal...
September 19, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28923959/ncor1-independent-mechanism-plays-a-role-in-the-action-of-the-unliganded-thyroid-hormone-receptor
#4
Arturo Mendoza, Inna Astapova, Hiroaki Shimizu, Molly R Gallop, Lujain Al-Sowaimel, S M Dileas MacGowan, Tim Bergmann, Anders H Berg, Danielle E Tenen, Christopher Jacobs, Anna Lyubetskaya, Linus Tsai, Anthony N Hollenberg
Nuclear receptor corepressor 1 (NCoR1) is considered to be the major corepressor that mediates ligand-independent actions of the thyroid hormone receptor (TR) during development and in hypothyroidism. We tested this by expressing a hypomorphic NCoR1 allele (NCoR1ΔID), which cannot interact with the TR, in Pax8-KO mice, which make no thyroid hormone. Surprisingly, abrogation of NCoR1 function did not reverse the ligand-independent action of the TR on many gene targets and did not fully rescue the high mortality rate due to congenital hypothyroidism in these mice...
September 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28919959/chromosome-mapping-in-abracris-flavolineata-de-geer-1773-orthoptera-from-the-igua%C3%A3-u-national-park-foz-do-igua%C3%A3-u-paran%C3%A3-brazil
#5
Mariana Bozina Pine, Raquel Bozini Gallo, Carlos Roberto Maximiano da Silva, Larissa Forim Pezenti, Fernando Campos De Domenico, Vilma Loreto, Renata da Rosa
In this paper, we present the cytomolecular analysis of a population of Abracris flavolineata collected in the largest fragment of the Brazilian Atlantic forest, the Iguaçu National Park. The diploid number in males was 23 (22+X0), with two large pairs (1-2), 7 medium (3-9), 2 small (10-11) and the X chromosome of medium size. Heterochromatic blocks were evident in the pericentromeric regions of all chromosomes. Heterogeneity in the distribution of heterochromatin was observed, with a predominance of DAPI(+) blocks...
2017: Comparative Cytogenetics
https://www.readbyqxmd.com/read/28919888/the-sporothrix-schenckii-gene-encoding-for-the-ribosomal-protein-l6-has-constitutive-and-stable-expression-and-works-as-an-endogenous-control-in-gene-expression-analysis
#6
Elías Trujillo-Esquivel, José A Martínez-Álvarez, Diana M Clavijo-Giraldo, Nahúm V Hernández, Alberto Flores-Martínez, Patricia Ponce-Noyola, Héctor M Mora-Montes
Sporothrix schenckii is one of the causative agents of sporotrichosis, a worldwide-distributed mycosis that affects humans and other mammals. The interest in basic and clinical features of this organism has significantly increased in the last years, yet little progress in molecular aspects has been reported. Gene expression analysis is a set of powerful tools that helps to assess the cell response to changes in the extracellular environment, the genetic networks controlling metabolic pathways, and the adaptation to different growth conditions...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28918353/antitumor-platinum-iv-derivatives-of-carboplatin-and-the-histone-deacetylase-inhibitor-4-phenylbutyric-acid
#7
Awatif Rashed Z Almotairy, Valentina Gandin, Liam Morrison, Cristina Marzano, Diego Montagner, Andrea Erxleben
Five new platinum(IV) derivatives of carboplatin each incorporating the histone deacetylase inhibitor 4-phenylbutyrate in axial position were synthesized and characterized by (1)H and (195)Pt NMR spectroscopy, electrospray ionization mass spectrometry and elemental analysis, namely cis,trans-[Pt(CBDCA)(NH3)2(PBA)(OH)] (1), cis,trans-[Pt(CBDCA)(NH3)2(PBA)2] (2), cis,trans-[Pt(CBDCA)(NH3)2(PBA)(bz)] (3), cis,trans-[Pt(CBDCA)(NH3)2(PBA)(suc)] (4) and cis,trans-[Pt(CBDCA)(NH3)2)(PBA)(ac)] (5) (PBA=4-phenylbutyrate, CBDCA=1,1-cyclobutane dicarboxylate, bz=benzoate, suc=succinate and ac=acetate)...
September 10, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28916721/loss-of-cardiac-carnitine-palmitoyltransferase-2-results-in-rapamycin-resistant-acetylation-independent-hypertrophy
#8
Andrea S Pereyra, Like Y Hasek, Kate L Harris, Alycia G Berman, Frederick W Damen, Craig J Goergen, Jessica M Ellis
Cardiac hypertrophy is closely linked to impaired fatty acid oxidation, but the molecular basis of this link is unclear. Here, we investigated the loss of an obligate enzyme in mitochondrial long-chain fatty acid oxidation, carnitine palmitoyltransferase 2 (CPT2), on muscle and heart structure, function, and molecular signatures in a muscle- and heart-specific CPT2-deficient mouse (Cpt2M-/-) model. CPT2 loss in heart and muscle reduced complete oxidation of long-chain fatty acids by 87% and 69%, respectively, without altering body weight, energy expenditure, respiratory quotient, or adiposity...
September 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28916515/reversing-thyroid-hormone-mediated-repression-of-a-hsv-1-promoter-via-computationally-guided-mutagenesis
#9
Robert W Figliozzi, Feng Chen, Shaochung V Hsia
Thyroid hormones (TH or T3) and their DNA binding nuclear receptors (TRs), direct transcriptional regulation in diverse ways depending on the host cell environment and specific promoter characteristics of TH sensitive genes. This study sought to elucidate the impact on transcriptional repression of nucleotide sequence/orientation within TR binding sites, TR elements, (TREs) of TH sensitive promoters, to better understand ligand dependent transcriptional repression of wild-type promoters. Computational analysis of the HSV-1 thymidine kinase (TK) gene TRE bound by TR and RXR revealed a single TRE point mutation sufficient to reverse the TRE orientation...
September 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28915612/the-roles-of-ing5-in-gliomas-a-good-marker-for-tumorigenesis-and-a-potential-target-for-gene-therapy
#10
Shuang Zhao, Zhi-Juan Zhao, Hao-Yu He, Ji-Cheng Wu, Xiao-Qing Ding, Lei Yang, Ning Jia, Zhi-Jie Li, Hua-Chuan Zheng
To elucidate the anti-tumor effects and molecular mechanisms of ING5 on glioma cells, we overexpressed it in U87 cells, and examined the phenotypes and their relevant molecules. It was found that ING5 overexpression suppressed proliferation, energy metabolism, migration, invasion, and induced G2/M arrest, apoptosis, dedifferentiation, senescence, mesenchymal- epithelial transition and chemoresistance to cisplatin, MG132, paclitaxel and SAHA in U87 cells. There appeared a lower expression of N-cadherin, Twist, Slug, Zeb1, Zeb2, Snail, Ac-H3, Ac-H4, Cdc2, Cdk4 and XIAP, but a higher expression of Claudin 1, Histones 3 and 4, p21, p53, Bax, β-catenin, PI3K, Akt, and p-Akt in ING5 transfectants...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915584/a-phase-1-dose-escalation-study-of-the-oral-histone-deacetylase-inhibitor-abexinostat-in-combination-with-standard-hypofractionated-radiotherapy-in-advanced-solid-tumors
#11
Eric Deutsch, Elizabeth Cohen-Jonathan Moyal, Vanesa Gregorc, Paolo Andrea Zucali, Jean Menard, Jean-Charles Soria, Ioana Kloos, Jeff Hsu, Ying Luan, Emily Liu, Remus Vezan, Thorsten Graef, Sofia Rivera
Current treatments for advanced solid tumors tend to be only palliative. Although radiotherapy is administered with a curative intent, radioresistance and dose-limiting toxicities pose limitations to treatment. Abexinostat, an oral pan-histone deacetylase inhibitor, demonstrated enhanced sensitivity to radiation in various solid tumor cell lines. We conducted an exploratory, phase 1, dose-escalation study of abexinostat in combination with standard hypofractionated radiotherapy in patients with advanced solid tumors treated in a palliative setting...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28914393/costunolide-induces-micronuclei-formation-chromosomal-aberrations-cytostasis-and-mitochondrial-mediated-apoptosis-in-chinese-hamster-ovary-cells
#12
Soma Shiva Nageswara Rao Singireesu, Sunil Misra, Sujan Kumar Mondal, Suresh Yerramsetty, Nivedita Sahu, Suresh Babu K
Costunolide (CE) is a sesquiterpene lactone well-known for its antihepatotoxic, antiulcer, and anticancer activities. The present study focused on the evaluation of the cytogenetic toxicity and cellular death-inducing potential of CE in CHO cells, an epithelial cell line derived from normal ovary cells of Chinese hamster. The cytotoxic effect denoting MTT assay has shown an IC50 value of 7.56 μM CE, where 50% proliferation inhibition occurs. The oxidative stress caused by CE was confirmed based on GSH depletion induced cell death, conspicuously absent in N-acetylcysteine (GSH precursor) pretreated cells...
September 15, 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/28912064/cell-cycle-and-histone-modification-genes-were-decreased-in-placenta-tissue-from-unexplained-early-miscarriage
#13
Yuanchang Zhu, Bing Li, Tonghua Wu, Lijun Ye, Yong Zeng, Yaou Zhang
Genetic defect is a major cause of early miscarriage, but still in many cases the etiology are not fully understood. Recent studies have shown that dysregulation of genes in placenta tissue are participated in the pathogenesis of unexplained early miscarriage. The aim of our study is to explore mRNA expression profile in placental chorionic villi and to reveal the underlying mechanism of unexplained early miscarriage. Chorionic villous were isolated and extracted from early miscarriage (n=3) and control pregnancy (n=3) placenta with normal chromosome karyotype using MLPA assay, and then mRNA expression profiles were determined by microarray...
September 11, 2017: Gene
https://www.readbyqxmd.com/read/28911547/multifunctions-of-dietary-polyphenols-in-the-regulation-of-intestinal-inflammation
#14
REVIEW
Makoto Shimizu
Food for specified health use is a type of functional food approved by the Japanese government, with more than 1250 products in 10 health-claim categories being approved as of April 2016. Polyphenols are currently used as functional ingredients in seven of the 10 categories. Although they have not yet been used for the food-for-specified-health-use category of "gut health promotion," polyphenols are expected to contribute to the future development of gut-modulating food. Intestinal functions include digestion/absorption, acting as a barrier, recognition of external factors, and signal transduction...
January 2017: Journal of Food and Drug Analysis
https://www.readbyqxmd.com/read/28911066/prevention-of-chemotherapy-toxicity-by-agents-that-neutralize-or-degrade-cell-free-chromatin
#15
I Mittra, K Pal, N Pancholi, A Shaikh, B Rane, P Tidke, S Kirolikar, N K Khare, K Agrawal, H Nagare, N K Nair
Background: Toxicity associated with chemotherapy is a major therapeutic challenge and is caused by chemotherapy-induced DNA damage and inflammation. We have recently reported that cell-free chromatin (cfCh) fragments released from dying cells can readily enter into healthy cells of the body to integrate into their genomes and induce DNA double-strand breaks, apoptosis and inflammation in them. We hypothesized that much of the toxicity of chemotherapy might be due to release of large quantities of cfCh from dying cells that could trigger an exaggerated DNA damage, apoptotic and inflammatory response in healthy cells over and above that caused by the drugs themselves...
September 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28905188/novel-inhibitors-of-lysine-k-specific-demethylase-4a-with-anticancer-activity
#16
Hyo Jeong Lee, Bo-Kyoung Kim, Kyoung Bin Yoon, Yong-Chul Kim, Sun-Young Han
Lysine (K)-specific demethylase 4A (KDM4A) is a histone demethylase that removes methyl residues from trimethylated or dimethylated histone 3 at lysines 9 and 36. Overexpression of KDM4A is found in various cancer types. To identify KDM4A inhibitors with anti-tumor functions, screening with an in vitro KDM4A enzyme activity assay was carried out. The benzylidenehydrazine analogue LDD2269 was selected, with an IC50 of 6.56 μM of KDM4A enzyme inhibition, and the binding mode was investigated using in silico molecular docking...
September 14, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28903350/zeb1-confers-stem-cell-like-properties-in-breast-cancer-by-targeting-neurogenin-3
#17
Chen Zhou, Huimin Jiang, Zhen Zhang, Guomin Zhang, Hang Wang, Quansheng Zhang, Peiqing Sun, Rong Xiang, Shuang Yang
Cancer stem cells (CSCs) are a subpopulation of cancer cells believed to be implicated in cancer initiation, progression, and recurrence. Here, we report that ectopic expression of zinc finger E-box binding homeobox 1 protein (ZEB1) results in the acquisition of CSC properties by breast cancer cells, leading to tumor initiation and progression in vitro and in vivo. The neurogenin 3 gene (Ngn3) is a bona fide target of ZEB1, and its repression is a key factor contributing to ZEB1-induced cancer cell stemness...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28899740/histone-3-3-mutations-in-giant-cell-tumor-and-giant-cell-rich-sarcomas-of-bone
#18
Alberto Righi, Irene Mancini, Marco Gambarotti, Piero Picci, Gabriella Gamberi, Cristina Marraccini, Angelo Paolo Dei Tos, Lisa Simi, Pamela Pinzani, Alessandro Franchi
Mutually exclusive histone 3.3 gene mutations have been recognized in chondroblastoma and giant cell tumor of bone (GCTB), which may be useful for differential diagnostic purposes in morphologically ambiguous cases. While over 90% of GCTB presents histone 3.3 variants exclusively in the H3F3A gene, chondroblastoma is mutated mainly in H3F3B. In this study we examined a series of giant cell rich primary bone tumors, aiming to evaluate the possible diagnostic role of histone 3.3 mutations in the differential diagnosis between GCTB and giant cell rich sarcomas...
September 9, 2017: Human Pathology
https://www.readbyqxmd.com/read/28898696/a-dual-role-of-caspase-8-in-triggering-and-sensing-proliferation-associated-dna-damage-a-key-determinant-of-liver-cancer-development
#19
Yannick Boege, Mohsen Malehmir, Marc E Healy, Kira Bettermann, Anna Lorentzen, Mihael Vucur, Akshay K Ahuja, Friederike Böhm, Joachim C Mertens, Yutaka Shimizu, Lukas Frick, Caroline Remouchamps, Karun Mutreja, Thilo Kähne, Devakumar Sundaravinayagam, Monika J Wolf, Hubert Rehrauer, Christiane Koppe, Tobias Speicher, Susagna Padrissa-Altés, Renaud Maire, Jörn M Schattenberg, Ju-Seong Jeong, Lei Liu, Stefan Zwirner, Regina Boger, Norbert Hüser, Roger J Davis, Beat Müllhaupt, Holger Moch, Henning Schulze-Bergkamen, Pierre-Alain Clavien, Sabine Werner, Lubor Borsig, Sanjiv A Luther, Philipp J Jost, Ricardo Weinlich, Kristian Unger, Axel Behrens, Laura Hillert, Christopher Dillon, Michela Di Virgilio, David Wallach, Emmanuel Dejardin, Lars Zender, Michael Naumann, Henning Walczak, Douglas R Green, Massimo Lopes, Inna Lavrik, Tom Luedde, Mathias Heikenwalder, Achim Weber
Concomitant hepatocyte apoptosis and regeneration is a hallmark of chronic liver diseases (CLDs) predisposing to hepatocellular carcinoma (HCC). Here, we mechanistically link caspase-8-dependent apoptosis to HCC development via proliferation- and replication-associated DNA damage. Proliferation-associated replication stress, DNA damage, and genetic instability are detectable in CLDs before any neoplastic changes occur. Accumulated levels of hepatocyte apoptosis determine and predict subsequent hepatocarcinogenesis...
September 11, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28898261/aged-blood-factors-decrease-cellular-responses-associated-with-delayed-gingival-wound-repair
#20
María Paz Saldías, Christian Fernández, Alejandra Morgan, Catalina Díaz, Diego Morales, Fabián Jaña, Alvaro Gómez, Alonso Silva, Fernanda Briceño, Alejandro Oyarzún, Felipe Maldonado, Oscar Cerda, Patricio C Smith, Mónica Cáceres
Aging is a gradual biological process characterized by a decrease in cell and organism functions. Gingival wound healing is one of the impaired processes found in old rats. Here, we studied the in vivo wound healing process using a gingival repair rat model and an in vitro model using human gingival fibroblast for cellular responses associated to wound healing. To do that, we evaluated cell proliferation of both epithelial and connective tissue cells in gingival wounds and found decreased of Ki67 nuclear staining in old rats when compared to their young counterparts...
2017: PloS One
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