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• keyword#1
Rosa Pennisi, Antonio Antoccia, Stefano Leone, Paolo Ascenzi, Alessandra di Masi
The molecular chaperone heat shock protein 90 (Hsp90α) regulates cells proteostasis and mitigates the harmful effects of endogenous and exogenous stressors on the proteome. Indeed, the inhibition of Hsp90α ATPase activity affects the cellular response to ionizing radiation (IR). Although the interplay between Hsp90α and several DNA damage response (DDR) proteins has been reported, its role in the DDR is still unclear. Here, we show that ATM and NBN, but not 53BP1, RAD50, and MRE11, are Hsp90α clients as the Hsp90α inhibitor 17-(allylamino)-17-demethoxygeldanamycin (17-AAG) induces ATM and NBN polyubiquitination and proteosomal degradation in normal fibroblasts and lymphoblastoid cells lines...
June 20, 2017: FEBS Journal
#2
Zuwen Zhang, Jumei Zhao, Zhikuan Mi, Qiuxia Pang, Aihong Wang, Meini Chen, Xiaobin Liu, Xiaoli Wei, Tao Liu
The aim of the present study was to investigate the effects and mechanisms of 17‑AAG combined with salinomycin treatment on proliferation and apoptosis of the SGC‑7901 gastric cancer cell line. An MTT assay was used to detect the proliferation of SGC‑7901 cells. Morphological alterations of cells were observed under inverted phase‑contrast and fluorescence microscopes. Cell cycle and apoptosis were assessed by flow cytometry analysis. The protein expression of nuclear factor (NF)‑κB p65 and Fas‑ligand (L) were evaluated by immunocytochemistry...
June 9, 2017: Molecular Medicine Reports
#3
Shunsuke Imai, Tomohiro Otsuka, Akira Naito, Masamitsu Shimazawa, Hideaki Hara
BACKGROUND: Diabetic macular edema (DME) is resulted from the retinal microvascular leakage that accompanies the breakdown of blood-retinal barrier. Triamcinolone acetonide (TA) is a therapeutic agent for DME, but since the detailed mechanism of action of TA is not known, part of its action was examined. METHODS: In vitro model to enhance the permeability of human retinal microvascular endothelial cells (HRMECs) was constructed by using DME-related cytokines such as vascular endothelial growth factor (VEGF), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β)...
June 18, 2017: Current Neurovascular Research
#4
Asuka Yoshifuku, Koichi Yoneda, Yusuke Sakiyama, Osamu Higuchi, Shunya Nakane, Takuro Kanekura
Autoimmune autonomic ganglionopathy (AAG), clinically characterized by gastrointestinal dysmotility, orthostatic hypotension and tonic pupils, is an idiopathic acquired disorder of the autonomic nervous system elicited by antibodies against ganglionic acetylcholine receptor (gAChR). We encountered a 60-year-old man who presented with severe anhidrosis, difficulty in thermoregulation, orthostatic hypotension, gastrointestinal dysmotility, tonic pupils and ptosis. Histologically, an anhidrotic skin sample was normal...
June 16, 2017: Journal of Dermatology
#5
Daniel Glinatsi, Joshua F Baker, Merete L Hetland, Kim Hørslev-Petersen, Bo J Ejbjerg, Kristian Stengaard-Pedersen, Peter Junker, Torkell Ellingsen, Hanne M Lindegaard, Ib Hansen, Tine Lottenburger, Jakob M Møller, Lykke Ørnbjerg, Aage Vestergaard, Anne Grethe Jurik, Henrik S Thomsen, Trine Torfing, Signe Møller-Bisgaard, Mette B Axelsen, Mikkel Østergaard
OBJECTIVES: To examine whether MRI assessed inflammation and damage in the wrist of patients with early rheumatoid arthritis (RA) are associated with patient-reported outcomes (PROs). METHODS: Wrist and hand MRIs of 210 patients with early RA from two investigator-initiated, randomised controlled studies (CIMESTRA/OPERA) were assessed according to the Outcome Measures in Rheumatology RA MRI score (RAMRIS) for synovitis, tenosynovitis, osteitis, bone erosions and joint space narrowing (JSN) at baseline, 1 and 5 years follow-up...
June 13, 2017: Annals of the Rheumatic Diseases
#6
Aage Kristian Olsen Alstrup, Ole Lajord Munk, Trine Hammer Jensen, Lasse Fast Jensen, Abdi Hedayat, Brian Hansen
BACKGROUND: Scanning techniques such as magnetic resonance imaging (MRI) and computed tomography (CT) are useful tools in veterinary and human medicine. Here we demonstrate the usefulness of these techniques in the study of the anatomy of wild marine mammals as part of a necropsy. MRI and CT scans of sperm whale teeth (n = 4) were performed. The methods were compared and further compared to current standard methods for evaluation of tooth layering. For MRI a zero echo time sequence was used, as previously done for imaging of intact human teeth...
June 12, 2017: Acta Veterinaria Scandinavica
#7
James D McKay, Rayjean J Hung, Younghun Han, Xuchen Zong, Robert Carreras-Torres, David C Christiani, Neil E Caporaso, Mattias Johansson, Xiangjun Xiao, Yafang Li, Jinyoung Byun, Alison Dunning, Karen A Pooley, David C Qian, Xuemei Ji, Geoffrey Liu, Maria N Timofeeva, Stig E Bojesen, Xifeng Wu, Loic Le Marchand, Demetrios Albanes, Heike Bickeböller, Melinda C Aldrich, William S Bush, Adonina Tardon, Gad Rennert, M Dawn Teare, John K Field, Lambertus A Kiemeney, Philip Lazarus, Aage Haugen, Stephen Lam, Matthew B Schabath, Angeline S Andrew, Hongbing Shen, Yun-Chul Hong, Jian-Min Yuan, Pier Alberto Bertazzi, Angela C Pesatori, Yuanqing Ye, Nancy Diao, Li Su, Ruyang Zhang, Yonathan Brhane, Natasha Leighl, Jakob S Johansen, Anders Mellemgaard, Walid Saliba, Christopher A Haiman, Lynne R Wilkens, Ana Fernandez-Somoano, Guillermo Fernandez-Tardon, Henricus F M van der Heijden, Jin Hee Kim, Juncheng Dai, Zhibin Hu, Michael P A Davies, Michael W Marcus, Hans Brunnström, Jonas Manjer, Olle Melander, David C Muller, Kim Overvad, Antonia Trichopoulou, Rosario Tumino, Jennifer A Doherty, Matt P Barnett, Chu Chen, Gary E Goodman, Angela Cox, Fiona Taylor, Penella Woll, Irene Brüske, H-Erich Wichmann, Judith Manz, Thomas R Muley, Angela Risch, Albert Rosenberger, Kjell Grankvist, Mikael Johansson, Frances A Shepherd, Ming-Sound Tsao, Susanne M Arnold, Eric B Haura, Ciprian Bolca, Ivana Holcatova, Vladimir Janout, Milica Kontic, Jolanta Lissowska, Anush Mukeria, Simona Ognjanovic, Tadeusz M Orlowski, Ghislaine Scelo, Beata Swiatkowska, David Zaridze, Per Bakke, Vidar Skaug, Shanbeh Zienolddiny, Eric J Duell, Lesley M Butler, Woon-Puay Koh, Yu-Tang Gao, Richard S Houlston, John McLaughlin, Victoria L Stevens, Philippe Joubert, Maxime Lamontagne, David C Nickle, Ma'en Obeidat, Wim Timens, Bin Zhu, Lei Song, Linda Kachuri, María Soler Artigas, Martin D Tobin, Louise V Wain, Thorunn Rafnar, Thorgeir E Thorgeirsson, Gunnar W Reginsson, Kari Stefansson, Dana B Hancock, Laura J Bierut, Margaret R Spitz, Nathan C Gaddis, Sharon M Lutz, Fangyi Gu, Eric O Johnson, Ahsan Kamal, Claudio Pikielny, Dakai Zhu, Sara Lindströem, Xia Jiang, Rachel F Tyndale, Georgia Chenevix-Trench, Jonathan Beesley, Yohan Bossé, Stephen Chanock, Paul Brennan, Maria Teresa Landi, Christopher I Amos
Although several lung cancer susceptibility loci have been identified, much of the heritability for lung cancer remains unexplained. Here 14,803 cases and 12,262 controls of European descent were genotyped on the OncoArray and combined with existing data for an aggregated genome-wide association study (GWAS) analysis of lung cancer in 29,266 cases and 56,450 controls. We identified 18 susceptibility loci achieving genome-wide significance, including 10 new loci. The new loci highlight the striking heterogeneity in genetic susceptibility across the histological subtypes of lung cancer, with four loci associated with lung cancer overall and six loci associated with lung adenocarcinoma...
June 12, 2017: Nature Genetics
#8
Robert Carreras-Torres, Mattias Johansson, Philip C Haycock, Kaitlin H Wade, Caroline L Relton, Richard M Martin, George Davey Smith, Demetrius Albanes, Melinda C Aldrich, Angeline Andrew, Susanne M Arnold, Heike Bickeböller, Stig E Bojesen, Hans Brunnström, Jonas Manjer, Irene Brüske, Neil E Caporaso, Chu Chen, David C Christiani, W Jay Christian, Jennifer A Doherty, Eric J Duell, John K Field, Michael P A Davies, Michael W Marcus, Gary E Goodman, Kjell Grankvist, Aage Haugen, Yun-Chul Hong, Lambertus A Kiemeney, Erik H F M van der Heijden, Peter Kraft, Mikael B Johansson, Stephen Lam, Maria Teresa Landi, Philip Lazarus, Loïc Le Marchand, Geoffrey Liu, Olle Melander, Sungshim L Park, Gad Rennert, Angela Risch, Eric B Haura, Ghislaine Scelo, David Zaridze, Anush Mukeriya, Milan Savić, Jolanta Lissowska, Beata Swiatkowska, Vladimir Janout, Ivana Holcatova, Dana Mates, Matthew B Schabath, Hongbing Shen, Adonina Tardon, M Dawn Teare, Penella Woll, Ming-Sound Tsao, Xifeng Wu, Jian-Min Yuan, Rayjean J Hung, Christopher I Amos, James McKay, Paul Brennan
BACKGROUND: Assessing the relationship between lung cancer and metabolic conditions is challenging because of the confounding effect of tobacco. Mendelian randomization (MR), or the use of genetic instrumental variables to assess causality, may help to identify the metabolic drivers of lung cancer. METHODS AND FINDINGS: We identified genetic instruments for potential metabolic risk factors and evaluated these in relation to risk using 29,266 lung cancer cases (including 11,273 adenocarcinomas, 7,426 squamous cell and 2,664 small cell cases) and 56,450 controls...
2017: PloS One
#9
Xiaoting Pei, Li Liu, Jialin Cai, Wenkai Wei, Yan Shen, Yaxuan Wang, Yanzi Chen, Panpan Sun, Mustapha Umar Imam, Zhiguang Ping, Xiaoli Fu
The aim of this study is to evaluate the effect of single-nucleotide polymorphisms (SNPs) of the PPARGC1A and UCP1 genes on impaired fasting glucose (IFG) or type 2 diabetes mellitus (T2DM) and the haplotype-based interaction between these genes.A cross-sectional study was conducted by cluster sampling in Henan province, China. Based on the level of fasting plasma glucose (FPG) and the history of T2DM, the participants were divided into 2 groups; 83 individuals were in the IFG+DM group (those with IFG or T2DM) and 445 individuals were in the NFPG group (those with normal FPG)...
June 2017: Medicine (Baltimore)
#10
Svend B Jensen, Meeri Käkelä, Lars Jødal, Olli Moisio, Aage K O Alstrup, Sirpa Jalkanen, Anne Roivainen
Vascular adhesion protein 1 is a leukocyte homing-associated glycoprotein, which upon inflammation rapidly translocates from intracellular sources to the endothelial cell surface. It has been discovered that the cyclic peptide residues 283-297 of sialic acid-binding IgG-like lectin 9 (Siglec-9) "CARLSLSWRGLTLCPSK" bind to vascular adhesion protein 1 and hence makes the radioactive analogues of this compound ([(68) Ga]Ga-DOTA-Siglec-9) interesting as a noninvasive visualizing marker of inflammation. Three different approaches to the radiosynthesis of [(68) Ga]Ga-DOTA-Siglec-9 are presented and compared with previously published methods...
May 30, 2017: Journal of Labelled Compounds & Radiopharmaceuticals
#11
Rafid Salim Jabir, Gwo Fuang Ho, Muhammad Azrif Bin Ahmad Annuar, Johnson Stanslas
CONTEXT: Rash and oral mucositis are major non-haematological adverse events (AEs) of docetaxel, in addition to fatigue, nausea, vomiting and diarrhoea, which restrict the use of the drug in cancer therapy. Alpha-1-acid glycoprotein (AAG) is an acute phase reactant glycoprotein and is a primary carrier of docetaxel in the blood. Docetaxel has extensive binding (>98%) to plasma proteins such as AAG, lipoproteins and albumin. OBJECTIVE: To study the association between plasma AAG level and non-haematological AEs of docetaxel in Malaysian breast cancer patients of three major ethnic groups (Malays, Chinese and Indians)...
June 6, 2017: Biomarkers: Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals
#12
Hang Jung Lee, DO Hyung Kim, Seung Jin Lee
The proliferation status of tumor cells can be imaged using [(18)F]fluorothymidine ([(18)F]FLT), which is trapped by cell cycle-dependent thymidine kinase 1 (TK1). Targeting of heat shock protein 90 (HSP90) disrupts multiple client proteins, leading to heterogeneous cell-cycle phenotypes. To investigate whether [(18)F]FLT uptake reflects the growth arrest caused by various mechanisms of HSP90 inhibition, we used HCT116 cells that were arrested at G0/G1 phase, and Hep3B cells at G2/M phase, by the HSP90 inhibitor 17-AAG...
June 2017: Anticancer Research
#13
Susanne Schaefer, Tina H Svenstrup, Barbara Guerra
Many types of cancer express high levels of heat shock proteins (HSPs) that are molecular chaperones regulating protein folding and stability ensuring protection of cells from potentially lethal stress. HSPs in cancer cells promote survival, growth and spreading even in situations of growth factors deprivation by associating with oncogenic proteins responsible for cell transformation. Hence, it is not surprising that the identification of potent inhibitors of HSPs, notably HSP90, has been the primary research focus, in recent years...
2017: PloS One
#14
Kazuhiko Fujita, Haruhiko Tokuda, Gen Kuroyanagi, Naohiro Yamamoto, Shingo Kainuma, Tetsu Kawabata, Go Sakai, Rie Matsushima-Nishiwaki, Osamu Kozawa, Takanobu Otsuka
Heat shock protein 90 (HSP90) that is ubiquitously expressed in various tissues, is recognized to be a major molecular chaperone. We have previously reported that prostaglandin F2α (PGF2α), a potent bone remodeling mediator, stimulates the synthesis of interleukin-6 (IL-6) through p44/p42 mitogen-activated protein (MAP) kinase and p38 MAP kinase in osteoblast-like MC3T3-E1 cells, and that Rho-kinase acts at a point upstream of p38 MAP kinase. In the present study, we investigated the involvement of HSP90 in the PGF2α-stimulated IL-6 synthesis and the underlying mechanism in MC3T3-E1 cells...
2017: PloS One
#15
Ghassan K Abou-Alfa, Lionel D Lewis, Patricia LoRusso, Michael Maitland, Priya Chandra, Sravanthi Cheeti, Dawn Colburn, Sarah Williams, Brian Simmons, Richard A Graham
PURPOSE: Vismodegib is a Hedgehog pathway inhibitor approved for the treatment of advanced basal cell carcinoma. Currently, the pharmacokinetics (PK) and safety of vismodegib in patients with hepatic dysfunction are unknown and are the objective of this study. METHODS: Patients with advanced solid malignancies and hepatic impairment were enrolled into one of four cohorts: normal [bilirubin (bili) < upper limit of normal (ULN)], mild (ULN < bili ≤ 1...
May 18, 2017: Cancer Chemotherapy and Pharmacology
#16
F Kosova, Z Kasar, I Tuglu, F Ozdal Kurt, S Gok, Z Ari, T Imren
AIM: The apoptotic effect of geldanamycin derivative may be important for the colorectal cancer therapy. The mechanisms of apoptosis require understanding of the behavior of colon cancer cell line Colo-205 which mimics colon adenocarcinoma. Therefore, the effect of IC50 dose of 17-allylamino-17-demethoxygeldanamycin (17-AAG) on the colon cancer cells in vitro was studied for its anti-apoptotic activity. METHOD: Apoptotic ratio of the Colo-205 cells was determined after 17-AAG application with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and apoptosis related genes...
2017: Bratislavské Lekárske Listy
#17
Anne M Landau, Aage Ko Alstrup, Helene Audrain, Steen Jakobsen, Mette Simonsen, Arne Møller, Poul Videbech, Gregers Wegener, Albert Gjedde, Doris J Doudet
Electroconvulsive therapy (ECT), a direct form of brain stimulation, is an effective antidepressant. We hypothesized that the beneficial effects of ECT are mediated by increased dopaminergic neurotransmission, in which the baseline activity of D1 receptors may predict the response to ECT. We established a novel model of brain stimulation in Göttingen minipigs based on the protocol of ECT applied in humans. With positron emission tomography (PET), we determined a measure of dopaminergic neurotransmission with the dopamine D1 receptor antagonist [(11)C]SCH23390...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
#18
Ayodeji Odunewu-Aderibigbe, Larry Fliegel
Na(+)/H(+) exchanger isoform one (NHE1) is a pH regulatory protein that is present in renal tissues and serves to remove protons from within cells and protect against intracellular acidification. NHE1 has a large 315 amino acid cytosolic regulatory domain that regulates the catalytic membrane domain. We examined protein-mediated regulation of NHE1 through the cytosolic domain. Affinity chromatography with the C-terminus of NHE1 yielded a number of NHE1 binding proteins including 14-3-3 protein, heat shock proteins (Hsp90 and Hsp70) and Na(+)/K(+) ATPase...
May 5, 2017: Cellular Signalling
#19
Andreas Nørgaard Glud, Johannes Bech, Laura Tvilling, Hamed Zaer, Dariusz Orlowski, Lise Moberg Fitting, Dora Ziedler, Michael Geneser, Ryan Sangill, Aage Kristian Olsen Alstrup, Carsten Reidies Bjarkam, Jens Christian Hedemann Sørensen
BACKGROUND: Stereotaxic neurosurgery in large animals is used widely in different sophisticated models, where precision is becoming more crucial as desired anatomical target regions are becoming smaller. Individually calculated coordinates are necessary in large animal models with cortical and subcortical anatomical differences. NEW METHOD: We present a convenient method to make an MRI-visible skull fiducial for 3D MRI-based stereotaxic procedures in larger experimental animals...
June 15, 2017: Journal of Neuroscience Methods
#20
Valli De Re, Ombretta Repetto, Stefania Zanussi, Mariateresa Casarotto, Laura Caggiari, Vincenzo Canzonieri, Renato Cannizzaro
BACKGROUND: Helicobacter pylori (H. pylori) represents a key factor in the etiology of autoimmune atrophic gastritis (AAG), duodenal ulcer (DU) and gastric cancer (GC). The aim of this study was to characterize the differential protein expression of H. pylori isolated from gastric biopsies of patients affected by either AAG, DU or GC. METHODS: The H. pylori strains were isolated from endoscopic biopsies from the stomach of patients with gastric disease. Protein profiles of H...
2017: Infectious Agents and Cancer
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