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| 1 | Interplay between post-translational cyclooxygenase-2 modifications and the metabolic and proteomic profile in a colorectal cancer cohort显示文摘BACKGROUND Colorectal cancer(CRC) is the second most common cause of cancer death worldwide. It is broadly described that cyclooxygenase-2(COX-2) is mainly overexpressed in CRC but less is known regarding post-translational modifications of this enzyme that may regulate its activity, intracellular localization and stability. Since metabolic and proteomic profile analysis is essential for cancer prognosis and diagnosis, our hypothesis is that the analysis of correlations between these specific parameters and COX-2 state in tumors of a high number of CRC patients could be useful for the understanding of the basis of this cancer in humans.AIM To analyze COX-2 regulation in colorectal cancer and to perform a detailed analysis of their metabolic and proteomic profile.METHODS Biopsies from both healthy and pathological colorectal tissues were taken under informed consent from patients during standard colonoscopy procedure in the University Hospital of Bellvitge(Barcelona, Spain) and Germans Trias i Pujol University Hospital(Campus Can Ruti)(Barcelona, Spain). Western blot analysis was used to determine COX-2 levels. Deglycosylation assays were performed in both cells and tumor samples incubating each sample with peptide N-glycosidase F(PNGase F). Prostaglandin E2(PGE2) levels were determined using a specific ELISA. 1 H high resolution magic angle spinning(HRMAS) analysis was performed using a Bruker AVIII 500 MHz spectrometer and proteomic analysis was performed in a nano-liquid chromatography-tandem mass spectrometer(nano LC-MS/MS) using a QExactive HF orbitrap MS.RESULTS Our data show that COX-2 has a differential expression profile in tumor tissue of CRC patients vs the adjacent non-tumor area, which correspond to a glycosylated and less active state of the protein. This fact was associated to a lesser PGE2 production in tumors. These results were corroborated in vitro performing deglycosylation assays in HT29 cell line where COX-2 protein profile was modified after PNGase F incubation, showing higher PGE2 levels. Moreover,HRMAS analysis indicated that tumor tissue has altered metabolic features vs non-tumor counterparts, presenting increased levels of certain metabolites such as taurine and phosphocholine and lower levels of lactate. In proteomic experiments, we detected an enlarged number of proteins in tumors that are mainly implicated in basic biological functions like mitochondrial activity,DNA/RNA processing, vesicular trafficking, metabolism, cytoskeleton and splicing.CONCLUSION In our colorectal cancer cohort, tumor tissue presents a differential COX-2 expression pattern with lower enzymatic activity that can be related to an altered metabolic and proteomic profile. | Patricia Prieto Rafael I Jaén Daniel Calle María Gómez-Serrano Estefanía Nú?ez María Fernández-Velasco Paloma Martín-Sanz Sergio Alonso Jesús Vázquez Sebastián Cerdán Miguel ángel Peinado Lisardo Boscá | 2019 | World Journal of Gastroenterology2019，25，4： | 4 |
| 2 | Transcystic Common Bile Duct Exploration in the Management of Patients With Choledocholithiasis显示文摘 | Sergio Rojas-Ortega Daniel Arizpe-Bravo Eduardo R Mar??n López Rachid Cesin-Sánchez Gerardo Reed-San Roman Crispina Gómez | 2003 | Journal of Gastrointestinal Surgery2003，，4： | 3 |
| 3 | Chronic intestinal pseudo-obstruction in patients with systemic lupus erythematosus: report of four cases显示文摘 | Federico Ceccato Adrián Salas Vanina Góngora Santiago Ruta Susana Roverano Juan Carlos Marcos Mercedes Garcìa Sergio Paira | 2008 | Clinical Rheumatology2008，，3： | 2 |
| 4 | Physiology and Pathology of Ovarian Hyperstimulation Syndrome显示文摘 | Raúl Gómez Sergio Soares Cristiano Busso Juan Garcia-Velasco Carlos Simón Antonio Pellicer | 2010 | Semin Reprod Med2010，，06： | 1 |
| 5 | Residual Flexure Capacity of Corroded Reinforced Concrete Beams 显示文摘 | ANDRS A TORRES A SERGIO N G | 2007 | Engineering Structures2007，29，6： | 1 |
| 6 | Commercial refrigeration system using CO2 as the refrigerant显示文摘 | SILVIA M PETTER N | 2004 | International Journal of Refrigeration2004，27，： | 1 |
| 7 | Recy- cled polyethylene composites reinforced with jute fabric from sack- cloth : part I - preparation and preliminary assessment显示文摘 | Amanda C Lima Sergio N Monteiro Kestur G Satyanarayana | 2012 | Journal of Polymers and the Environment2012，19，4： | 1 |
| 8 | Reversible myocardial dysfunction after cardiopulmonary resuscitation显示文摘 | Manuel Ruiz-Bailén Eduardo Aguayo de Hoyos Silvia Ruiz-Navarro Miguel ángel Díaz-Castellanos Luis Rucabado-Aguilar Francisco Javier Gómez-Jiménez Sergio Martínez-Escobar Rafael Melgares Moreno Javier Fierro-Rosón | 2005 | Resuscitation2005，，2： | 1 |
| 9 | 显示文摘 | KWAN H N SERGIO G S LAWRENCE L T | 2003 | Ind Eng Chem Res2003，42，： | 1 |
| 10 | A Neural Network for Nonuniformity and Ghosting Cor rection of Infrared Image Sequence显示文摘 | Sergio N Torres Cesar San Martin Daniel G Sbarbaro etal | 2005 | Lecture Notes in Computer Science(S1611-3349)2005，3656，： | 1 |
| 11 | Agrobacterium tumefaciens-mediated transformation of the aromatic shrub Lavandula latifolia显示文摘 | Sergio G N Isabel A Lucas del C A | 2000 | Mol Breeding2000，6，6： | 1 |
| 12 | Agrobacterium tumefaciens-mediated transformation of the aromatic shrub Lavandula latifolia显示文摘 | Sergio G N Isabel A Lucas del C A | | 0，，： | 1 |
| 13 | Developmental exposure to low dose PBDE 99: Effects on male fertility and neurobehavior in rat offspring 显示文摘 | Sergio N K Chris E T Konstanze G | 2005 | Environmental Health Per spectives2005，113，： | 1 |
| 14 | An object-oriented appr-oach for flexible manufacturing control systems analysis and design using the unified modeling language显示文摘 | Bruccoleri M Sergio N L D Perrone G | 2003 | The International Journal of Flexible Manufacturing Systems2003，15，3： | 1 |
| 15 | Transcystic Common Bile Duct Exploration in the Management of Patients With Choledocholithiasis显示文摘 | Sergio Rojas-Ortega Daniel Arizpe-Bravo Eduardo R Mar??n López Rachid Cesin-Sánchez Gerardo Reed-San Roman Crispina Gómez | 2003 | Journal of Gastrointestinal Surgery2003，，4： | 1 |
| 16 | Reaction of chlorine di- oxide with emergent water pollutants : product study of the reaction of three -lactam antibiotics with CIOz 显示文摘 | Sergio N Mereedes A Hermenegildo G | 2008 | Water Re- search2008，42，89： | 1 |
| 17 | Diversity and colonization of arbuscular mycorrhizal fungi in the tree fern Al- sophilafirma in rainy and dry season 显示文摘 | Luis A L P Juan C N C Sergio H G | 2014 | Symbiosis2014，62，3： | 1 |
| 18 | Observatory science with eXTP显示文摘In this White Paper we present the potential of the enhanced X-ray Timing and Polarimetry(eXTP) mission for studies related to Observatory Science targets. These include flaring stars, supernova remnants, accreting white dwarfs, low and high mass X-ray binaries, radio quiet and radio loud active galactic nuclei, tidal disruption events, and gamma-ray bursts. eXTP will be excellently suited to study one common aspect of these objects: their often transient nature. Developed by an international Consortium led by the Institute of High Energy Physics of the Chinese Academy of Science, the eXTP mission is expected to be launched in the mid 2020s. | Jean J.M.in 't Zand Enrico Bozzo JinLu Qu Xiang-Dong Li Lorenzo Amati Yang Chen Immacolata Donnarumma Victor Doroshenko Stephen A.Drake Margarita Hernanz Peter A.Jenke Thomas J.Maccarone Simin Mahmoodifar Domitilla de Martino Alessandra De Rosa Elena M.Rossi Antonia Rowlinson Gloria Sala Giulia Stratta Thomas M.Tauris Joern Wilms XueFeng Wu Ping Zhou Iván Agudo Diego Altamirano Jean-Luc Atteia Nils A.andersson M.Cristina Baglio David R.Ballantyne Altan Baykal Ehud Behar Tomaso Belloni Sudip Bhattacharyya Stefano Bianchi Anna Bilous Pere Blay Joao Braga Sφren Brandt Edward F.Brown Niccolo Bucciantini Luciano Burderi Edward M.Cackett Riccardo Campana Sergio Campana Piergiorgio Casella Yuri Cavecchi Frank Chambers Liang Chen Yu-Peng Chen Jér?me Chenevez Maria Chernyakova ChiChuan Jin Riccardo Ciolfi Elisa Costantini Andrew Cumming Antonino D'Aì Zi-Gao Dai Filippo D'Ammando Massimiliano De Pasquale Nathalie Degenaar Melania Del Santo Valerio D'Elia Tiziana Di Salvo Gerry Doyle Maurizio Falanga XiLong Fan Robert D.Ferdman Marco Feroci Federico Fraschetti Duncan K.Galloway Angelo F.Gambino Poshak Gandhi MingYu Ge Bruce Gendre Ramandeep Gill Diego G?tz Christian Gouiffès Paola Grandi Jonathan Granot Manuel Güdel Alexander Heger Craig O.Heinke Jeroen Homan Rosario Iaria Kazushi Iwasawa Luca Izzo Long Ji Peter G.Jonker Jordi José Jelle S.Kaastra Emrah Kalemci Oleg Kargaltsev Nobuyuki Kawai Laurens Keek Stefanie Komossa Ingo Kreykenbohm Lucien Kuiper Devaky Kunneriath Gang Li En-Wei Liang Manuel Linares Francesco Longo FangJun Lu Alexander A.Lutovinov Denys Malyshev Julien Malzac Antonios Manousakis Ian McHardy Missagh Mehdipour YunPeng Men Mariano Méndez Roberto P.Mignani Romana Mikusincova M.Coleman Miller Giovanni Miniutti Christian Motch Joonas Nättilä Emanuele Nardini Torsten Neubert Paul T.O'Brien Mauro Orlandini Julian P.Osborne Luigi Pacciani Stéphane Paltani Maurizio Paolillo Iossif E.Papadakis Biswajit Paul Alberto Pellizzoni Uria Peretz Miguel A.Pérez Torres Emanuele Perinati Chanda Prescod-Weinstein Pablo Reig Alessandro Riggio Jerome Rodriguez Pablo Rodríguez-Gil Patrizia Romano Agata Rózańska Takanori Sakamoto Tuomo Salmi Ruben Salvaterra andrea Sanna andrea Santangelo Tuomas Savolainen Stéphane Schanne Hendrik Schatz LiJing Shao andy Shearer Steven N.Shore Ben W.Stappers Tod E.Strohmayer Valery F.Suleimanov Jirí Svoboda F.-K.Thielemann Francesco Tombesi Diego F.Torres Eleonora Torresi Sara Turriziani andrea Vacchi Stefano Vercellone Jacco Vink Jian-Min Wang JunFeng Wang Anna L.Watts ShanShan Weng Nevin N.Weinberg Peter J.Wheatley Rudy Wijnands Tyrone E.Woods Stan E.Woosley ShaoLin Xiong YuPeng Xu Zhen Yan George Younes WenFei Yu Feng Yuan Luca Zampieri Silvia Zane andrzej A.Zdziarski Shuang-Nan Zhang Shu Zhang Shuo Zhang Xiao Zhang Michael Zingale | 2019 | Science China(Physics,Mechanics & Astronomy)2019，62，2： | 0 |
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