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https://www.readbyqxmd.com/read/29051480/nox4-functions-as-a-mitochondrial-energetic-sensor-coupling-cancer-metabolic-reprogramming-to-drug-resistance
#1
Karthigayan Shanmugasundaram, Bijaya K Nayak, William E Friedrichs, Dharam Kaushik, Ronald Rodriguez, Karen Block
The molecular mechanisms that couple glycolysis to cancer drug resistance remain unclear. Here we identify an ATP-binding motif within the NADPH oxidase isoform, NOX4, and show that ATP directly binds and negatively regulates NOX4 activity. We find that NOX4 localizes to the inner mitochondria membrane and that subcellular redistribution of ATP levels from the mitochondria act as an allosteric switch to activate NOX4. We provide evidence that NOX4-derived reactive oxygen species (ROS) inhibits P300/CBP-associated factor (PCAF)-dependent acetylation and lysosomal degradation of the pyruvate kinase-M2 isoform (PKM2)...
October 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/29050320/epigenetic-regulation-of-interleukin-8-expression-by-class-i-hdac-and-cbp-in-ovarian-cancer-cells
#2
Himavanth R Gatla, Yue Zou, Mohammad M Uddin, Ivana Vancurova
Although inhibitors of epigenetic regulators have been effective in the treatment of cutaneous T cell lymphoma (CTCL) and other hematopoietic malignancies, they have been less effective in solid tumors, including ovarian cancer (OC). We have previously shown that inhibition of histone deacetylase (HDAC) activity induces expression of the pro-inflammatory and pro-angiogenic chemokine interleukin-8 (CXCL8, IL-8) in OC cells, resulting in their increased survival and proliferation. Here, we show that in addition to ovarian cancer SKOV3, OVCAR3, and CAOV3 cells, HDAC inhibition induces the CXCL8 expression in HeLa cells, but not in CTCL Hut-78 cells...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29048941/patient-perceptions-of-the-adequacy-of-supplemental-oxygen-therapy-results-of-the-american-thoracic-society-nursing-assembly-oxygen-working-group-survey
#3
Susan S Jacobs, Kathleen O Lindell, Eileen G Collins, Chris M Garvey, Carme Hernandez, Sally McLaughlin, Ann M Schneidman, Paula M Meek
RATIONALE: Pulmonary clinicians and patients anecdotally report barriers to home supplemental oxygen services including inadequate supply, unacceptable portable options, and equipment malfunction. Limited evidence exists to describe or quantify these problems. OBJECTIVE: To describe the frequency and type of problems experienced by supplemental oxygen users in the United States. METHODS: The Patient Supplemental Oxygen Survey, a self-report questionnaire, was posted on the American Thoracic Society (ATS) Public Advisory Roundtable and patient and healthcare-affiliated websites...
October 19, 2017: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/29042928/long-non-coding-rna-ab209630-suppresses-cell-proliferation-and-metastasis-in-human-hepatocellular-carcinoma
#4
Teng Li, Yun Liu, Yanming Sun
Hepatocellular carcinoma (HCC) is one of the most prevalent cancers worldwide and the second most common cause of cancer-related mortalities. With a high potential for metastasis and recurrence, HCC is refractory to cure. The present study aimed to explore the role of a recent-discovered LncRNA, AB209630, in human HCC, in order to provide new insights useful for clinical HCC diagnosis and treatment. Reverse transcription-quantitative polymerase chain reaction was performed to examine the expression of AB209630 in clinical HCC samples and the adjacent non-cancerous tissues...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29018059/involvement-of-leptin-in-the-molecular-physiology-of-the-placenta
#5
Malena Schanton, Julieta Lorena Maymó, Antonio Pérez-Pérez, Victor Sanchez-Margalet, Cecilia Varone
Leptin is a homeostatic regulator in the placenta where it promotes proliferation, protein synthesis and the expression of tolerogenic maternal response molecules such as HLA-G. Leptin also exerts an anti-apoptotic action in placenta controlling the expression of p53 master cell cycle regulator under different stress conditions. On the other hand, leptin is an integrative target of different placental stimuli. The expression of leptin in placenta is regulated by hCG, insulin, steroids, hypoxia, and many other growth hormones, suggesting that it might have an important endocrine function in the trophoblastic cells...
October 9, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/29016683/the-epigenetic-factor-pcaf-regulates-vascular-inflammation-and-is-essential-for-intimal-hyperplasia-development
#6
Rob C M de Jong, Mark M Ewing, Margreet R de Vries, Jacco C Karper, Antonius J N M Bastiaansen, Hendrika A B Peters, Fabiana Baghana, Peter J van den Elsen, Céline Gongora, J Wouter Jukema, Paul H A Quax
OBJECTIVE: Genetic P300/CBP-associated factor (PCAF) variation affects restenosis-risk in patients. PCAF has lysine acetyltransferase activity and promotes nuclear factor kappa-beta (NFκB)-mediated inflammation, which drives post-interventional intimal hyperplasia development. We studied the contributing role of PCAF in post-interventional intimal hyperplasia. METHODS AND RESULTS: PCAF contribution to inflammation and intimal hyperplasia was assessed in leukocytes, macrophages and vascular smooth muscle cells (vSMCs) in vitro and in a mouse model for intimal hyperplasia, in which a cuff is placed around the femoral artery...
2017: PloS One
https://www.readbyqxmd.com/read/28986367/inhibition-of-p300-cbp-suppresses-castration-resistant-prostate-cancer
#7
(no author information available yet)
A virtual ligand screen led to generation of A-485, a potent selective p300/CBP catalytic inhibitor.
October 6, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28974455/melatonin-as-an-angiogenesis-inhibitor-to-combat-cancer-mechanistic-evidence
#8
REVIEW
Nasser Hashemi Goradel, Mohammad Hossein Asghari, Milad Moloudizargari, Babak Negahdari, Hamed Haghi-Aminjan, Mohammad Abdollahi
Melatonin, a pineal indolamine, participates in different body functions and is shown to possess diverse biological activities such as anti-tumor action. Angiogenesis inhibition is one of the mechanisms by which melatonin exerts its oncostatic effects. Increased angiogenesis is a major feature of tumor progression, thus angiogenesis inhibition is a critical step in cancer therapy. Melatonin employs a variety of mechanisms to target nutrients and oxygen supply to cancer cells. At the transcriptional level, hypoxia induced factor-1α (HIF-1α) and the genes under its control, such as vascular endothelial growth factor (VEGF) are the main targets of melatonin for inhibition of angiogenesis...
November 15, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28967086/intestinal-mucosal-barrier-dysfunction-in-sap-patients-with-mods-ameliorated-by-continuous-blood-purification
#9
Qing Shen, Zhengrong Li, Shanshan Huang, Liman Li, Hua Gan, Xiao-Gang Du
BACKGROUND: Dysfunction of the intestinal mucosal barrier plays an important role in the pathophysiology of severe acute pancreatitis (SAP). Continuous blood purification (CBP) has been shown to improve the prognosis of SAP patients. In order to investigate the effect of CBP on intestinal mucosal barrier dysfunction in SAP patients with MODS, we conducted in vivo and in vitro experiments to explore the underlying mechanisms. METHODS: The markers for the assessment of intestinal mucosal barrier function including serum diamine oxidase (DAO), endotoxin and intestinal epithelial monolayer permeability were detected during CBP therapy...
September 14, 2017: International Journal of Artificial Organs
https://www.readbyqxmd.com/read/28953875/discovery-of-a-selective-catalytic-p300-cbp-inhibitor-that-targets-lineage-specific-tumours
#10
Loren M Lasko, Clarissa G Jakob, Rohinton P Edalji, Wei Qiu, Debra Montgomery, Enrico L Digiammarino, T Matt Hansen, Roberto M Risi, Robin Frey, Vlasios Manaves, Bailin Shaw, Mikkel Algire, Paul Hessler, Lloyd T Lam, Tamar Uziel, Emily Faivre, Debra Ferguson, Fritz G Buchanan, Ruth L Martin, Maricel Torrent, Gary G Chiang, Kannan Karukurichi, J William Langston, Brian T Weinert, Chunaram Choudhary, Peter de Vries, John H Van Drie, David McElligott, Ed Kesicki, Ronen Marmorstein, Chaohong Sun, Philip A Cole, Saul H Rosenberg, Michael R Michaelides, Albert Lai, Kenneth D Bromberg
The dynamic and reversible acetylation of proteins, catalysed by histone acetyltransferases (HATs) and histone deacetylases (HDACs), is a major epigenetic regulatory mechanism of gene transcription and is associated with multiple diseases. Histone deacetylase inhibitors are currently approved to treat certain cancers, but progress on the development of drug-like histone actyltransferase inhibitors has lagged behind. The histone acetyltransferase paralogues p300 and CREB-binding protein (CBP) are key transcriptional co-activators that are essential for a multitude of cellular processes, and have also been implicated in human pathological conditions (including cancer)...
September 27, 2017: Nature
https://www.readbyqxmd.com/read/28952836/a-molecular-mechanism-for-il-4-suppression-of-loricrin-transcription-in-epidermal-keratinocytes-implication-for-atopic-dermatitis-pathogenesis
#11
Lei Bao, Girish C Mohan, Jaime B Alexander, Caroline Doo, Kui Shen, Jeremy Bao, Lawrence S Chan
Skin barrier defects play an important role in atopic dermatitis (AD) pathogenesis. Loricrin, an important barrier protein suppressed in human AD, is down-regulated by IL-4 in keratinocytes. However, the molecular mechanism is unknown. Since loricrin transcription requires p300/CBP, and Stat6 also recruits this common coactivator for its stimulated factors, we hypothesize that IL-4-activated Stat6 competes for the available endogenous p300/CBP, leading to loricrin transcription inhibition. First, we showed that loricrin is suppressed in the skin of IL-4 transgenic mice, an AD mouse model...
January 1, 2017: Innate Immunity
https://www.readbyqxmd.com/read/28949514/identifying-dysregulated-epigenetic-enzyme-activity-in-castrate-resistant-prostate-cancer-development
#12
Jin-Hee Lee, Bing Yang, Anastasia J Lindahl, Nathan Damaschke, Melissa D Boersma, Wei Huang, Eva Corey, David F Jarrard, John M Denu
There is a tremendous need for novel strategies aimed at directly assessing activities of histone modifiers to probe epigenetic determinants associated with disease progression. Here, we developed a high-throughput peptide microarray assay to identify altered histone lysine (de)acetylation activity in prostate cancer (PCa). This microarray-based activity assay revealed up-regulated histone acetyltransferase (HAT) activity against specific histone H3 sites in a castrate-resistant (CR) PCa cell line compared to its hormone-sensitive (HS) isogenic counterpart...
October 11, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28948506/comparative-analysis-of-arterial-parameters-variations-associated-with-inter-individual-variations-in-peripheral-and-aortic-blood-pressure-cross-sectional-study-in-healthy-subjects-aged-2-84%C3%A2-years
#13
Yanina Zócalo, Santiago Curcio, Victoria García-Espinosa, Pedro Chiesa, Gustavo Giachetto, Daniel Bia
INTRODUCTION: The association between arterial parameters and blood pressure (BP) interindividual variations could depend on the arterial segment, BP component (systolic, SBP; diastolic, DBP; pulse pressure, PP) and/or on whether central (cBP) or peripheral (pBP) BP variations are considered. AIM: To assess and compare arterial parameters variations associated with interindividual variations in cBP and pBP. METHODS: Healthy subjects (n = 923; 488 males, 2-84 years) were included...
September 25, 2017: High Blood Pressure & Cardiovascular Prevention: the Official Journal of the Italian Society of Hypertension
https://www.readbyqxmd.com/read/28947650/contribution-of-streptococcus-mutans-strains-with-collagen-binding-proteins-in-the-presence-of-serum-to-the-pathogenesis-of-infective-endocarditis
#14
Masatoshi Otsugu, Ryota Nomura, Saaya Matayoshi, Noboru Teramoto, Kazuhiko Nakano
Streptococcus mutans, a major pathogen of dental caries, is considered to be one of the causative agents of infective endocarditis (IE). Recently, bacterial DNA encoding 120 kDa cell surface collagen-binding proteins (CBPs) has been frequently detected from S. mutans-positive IE patients. In addition, some of the CBP-positive S. mutans strains lacked a 190 kDa protein antigen (PA), whose absence strengthened the adhesion to and invasion of endothelial cells. The interaction between pathogenic bacteria and serum or plasma is considered an important virulence factor in developing systemic diseases; thus, we decided to analyze the pathogenesis of IE induced by S...
September 25, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28943877/%C3%AE-catenin-directs-nuclear-factor-%C3%AE%C2%BAb-p65-output-via-creb-binding-protein-p300-in-human-airway-smooth-muscle
#15
Tim Koopmans, Roos Eilers, Mark Menzen, Andrew Halayko, Reinoud Gosens
β-Catenin is a multifunctional protein that apart from its role in proliferative and differentiation events, also acts upon inflammatory processes, mainly via interaction with nuclear factor-κB (NF-κB). However, there is still controversy as to whether β-catenin facilitates or represses NF-κB output. Insights into the molecular mechanisms underlying the interaction between β-catenin and NF-κB have highlighted the cofactors CREB-binding protein (CBP) and p300 as important candidates. Here, we hypothesized that the interaction of β-catenin with CBP/p300 directs NF-κB output...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28939763/a-novel-long-noncoding-rna-linc00460-upregulated-by-cbp-p300-promotes-carcinogenesis-in-esophageal-squamous-cell-carcinoma
#16
Yan Liang, Yuanyuan Wu, Xuedan Chen, Shixin Zhang, Kai Wang, Xingying Guan, Kang Yang, Juan Li, Yun Bai
Esophageal cancer is one of the leading causes of cancer related mortality because of poor prognosis. Long noncoding RNAs (lncRNAs) have been gradually demonstrated to play critical roles in cancer development. We indentified a novel long noncoding RNA named linc00460 by microarray analysis using esophageal squamous cell carcinoma (ESCC) clinical samples, which has not been studied before. Our research indicated that linc00460 was overexpressed in the majority of tumor tissues and ESCC cell lines. Linc00460 expression was positively correlated with ESCC TNM stage, lymph node metastasis and predicted poor prognosis...
September 22, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28933312/characterization-of-imatinib-resistant-cml-leukemic-stem-initiating-cells-and-their-sensitivity-to-cbp-catenin-antagonists
#17
Yi Zhao, Kaijin Wu, Yongfeng Wu, Elizabeth Melendez, Goar Smbatyan, David Massiello, Michael Kahn
The development of the tyrosine kinase inhibitor Imatinib (IM) represents a milestone breakthrough in CML (Chronic Myeloid Leukemia) treatment. However, it is not curative and patients develop IM resistance. IM resistance has been previously correlated with the emergence of drug-resistant LIC/LSC (Leukemia Initiating Cell/Leukemia Stem Cell) and increased nuclear catenin levels and enhanced Wnt signaling. It has been demonstrated previously that drug resistant CML LIC/LSC can be safely eliminated both in vitro and in vivo via disruption of the CBP/catenin interaction, utilizing the highly biochemically selective small molecule CBP/catenin antagonist ICG-001...
September 19, 2017: Current Molecular Pharmacology
https://www.readbyqxmd.com/read/28928281/engrailed-acts-with-nejire-to-control-decapentaplegic-expression-in-the-drosophila-ovarian-stem-cell-niche
#18
Lichao Luo, Chia Keng Siah, Yu Cai
Homeostasis of adult tissues is maintained by a small number of stem cells, which are sustained by their niches. In the Drosophila female germline stem cell (GSC) niche, Decapentaplegic (Dpp) is the primary factor that promotes GSC self-renewal. However, the mechanism regulating dpp expression in the niche is largely unknown. Here, we identify a 2.0 kb fragment located in a 5' cis-regulatory region of the dpp locus containing enhancer activity that drives its expression in the niche. This region is distinct from a previously characterized 3' cis-regulatory enhancer responsible for dpp expression in imaginal discs...
September 15, 2017: Development
https://www.readbyqxmd.com/read/28914629/association-between-ambulatory-blood-pressure-values-and-central-aortic-pressure-in-a-large-population-of-normotensive-and-hypertensive-patients
#19
Ana Rouxinol-Dias, Sara Araújo, José A Silva, Loide Barbosa, Jorge Polónia
OBJECTIVE: Our aim was to examine the association of ambulatory blood pressure monitoring (ABPM) and central blood pressure (CBP) data in a large set of normotensive and hypertensive patients and its relation with pulse wave velocity (PWV). PATIENTS AND METHODS: This cross-sectional study was carried out in a single centre and included 2864 individuals who carried out an ABPM, measurement of CBP from the aortic waveform (SphygmoCor) and carotid-femoral PWV (Complior)...
September 13, 2017: Blood Pressure Monitoring
https://www.readbyqxmd.com/read/28893318/icg-001-suppresses-growth-of-gastric-cancer-cells-and-reduces-chemoresistance-of-cancer-stem-cell-like-population
#20
Yi Liu, Hui Chen, Peiming Zheng, Yingxia Zheng, Qin Luo, Guohua Xie, Yanhui Ma, Lisong Shen
BACKGROUND: ICG-001, a small molecule, binds CREB-binding protein (CBP) to disrupt its interaction with β-catenin and inhibits CBP function as a co-activator of Wnt/β-catenin-mediated transcription. Given its ability to inhibit Wnt/β-catenin signaling pathway, ICG-001 has been used in some tumor types to exert its anticarcinogenic effect. Here, we examined ICG-001 and its potential role as a therapeutic in gastric cancer (GC). METHODS: The gastric cancer cell lines SGC-7901, MGC-803, BGC-823 and MKN-45 were used in vitro and in vivo...
September 11, 2017: Journal of Experimental & Clinical Cancer Research: CR
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