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| 1 | COX-2 in liver,from regeneration to hepatocarcinogenesis:What we have learned from animal models?显示文摘The use of animals lacking genes or expressing genes under the control of cell-specific promoters has signifi cantly increased our knowledge of the genetic and molecular basis of physiopathology,allowing testing of functional hypotheses and validation of biochemical and pharmacologic approaches in order to understand cell function.However,with unexpected frequency,gene knockout animals and,more commonly,animal models of transgenesis give experimental support to even opposite conclusions on gene function.Here we summarize what we learned on the role of cyclooxygenase 2(COX-2) in liver and revise the results obtained in 3 independent models of mice expressing a COX-2 transgene specifi cally in the hepatocyte.Upon challenge with pro-inflammatory stimuli,the animals behave very differently,some transgenic models having a protective effect but others enhancing the injury.In addition,one transgene exerts differential effects on normal liver physiology depending on the transgenic animal model used. | Paloma Martín-Sanz Rafael Mayoral Marta Casado Lisardo Boscá | 2010 | World Journal of Gastroenterology2010，16，12： | 12 |
| 2 | Cyclooxygenase 2 in liver dysfunction and carcinogenesis: Facts and perspectives显示文摘The biosynthesis of prostaglandins and thromboxanes has been a focus of interest in the management of many liver diseases.Cyclooxygenases are the enzymes involved in the first step of the biosynthesis of these lipid mediators and selective inhibitors for these isoenzymes as well as pharmacological analogues of prostaglandins have been developed and are currently applied therapeutically.Here we discuss the implications of these enzymes in the onset of metabolic and lipid disorders in the liver and their potential role in the progression of the diseases towards fibrosis and hepatocellular carcinogenesis. | Paloma Martín-Sanz Marta Casado Lisardo Boscá | 2017 | World Journal of Gastroenterology2017，23，20： | 7 |
| 3 | Post-translational modifications of prostaglandin-endoperoxide synthase 2 in colorectal cancer:An update显示文摘The biosynthesis of prostanoids is involved in both physiological and pathological processes. The expression of prostaglandin-endoperoxide synthase 2(PTGS2; also known as COX-2) has been traditionally associated to the onset of several pathologies, from inflammation to cardiovascular, gastrointestinal and oncologic events. For this reason, the search of selective PTGS2 inhibitors has been a focus for therapeutic interventions. In addition to the classic non-steroidal anti-inflammatory drugs, selective and specific PTGS2 inhibitors, termed coxibs, have been generated and widely used. PTGS2 activity is less restrictive in terms of substrate specificity than the homeostatic counterpart PTGS1, and it accounts for the elevated prostanoid synthesis that accompanies several pathologies. The main regulation of PTGS2 occurs at the transcription level. In addition to this, the stability of the mRNA is finely regulated through the interaction with several cytoplasmic elements, ranging from specificmicroR NAs to proteins that control mR NA degradation. Moreover, the protein has been recognized to be the substrate for several post-translational modifications that affect both the enzyme activity and the targeting for degradation via proteasomal and non-proteasomal mechanisms. Among these modifications, phosphorylation, glycosylation and covalent modifications by reactive lipidic intermediates and by free radicals associated to the proinflammatory condition appear to be the main changes. Identification of these post-translational modifications is relevant to better understand the role of PTGS2 in several pathologies and to establish a correct analysis of the potential function of this protein in diseases progress. Finally, these modifications can be used as biomarkers to establish correlations with other parameters, including the immunomodulation dependent on molecular pathological epidemiology determinants, which may provide a better frame for potential therapeutic interventions. | Rafael I Jaén Patricia Prieto Marta Casado Paloma Martín-Sanz Lisardo Boscá | 2018 | World Journal of Gastroenterology2018，24，48： | 5 |
| 4 | 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 |
| 5 | Powdered cellulose as excipient for extrusion - spheronization pellets of a cohesive hydrophobic drug显示文摘 | Lisardo Alvarez | 2003 | European Journal of Pharmaceutics and Biopharmaceutics2003，，55： | 1 |
| 6 | Thromboxane A2-Induced Inhibition of Voltage-Gated K+ Channels and Pulmonary Vaso- constriction Role of Protein Kinase C 显示文摘 | Angel Cogolludo Laura Moreno Lisardo Bosca | 2003 | Circulation Research2003，93，7： | 1 |
| 7 | Kinetics of the deep oxidation of benzene,toluene,n-hexane and their binary mixtures over a platinum on γ-alumina catalyst显示文摘 | SALVADOR Ordónez LISARDO Bello HERMINIO Sastre | 2002 | Appl Catal B:Environmental2002，38，： | 1 |
| 8 | Ubiquitin enhances the Th2 cytokine response and attenuates ischemia-reperfusion injury in the lung显示文摘 | Lisardo Garcia-Covarrubias Eddie W. Manning Luis T. Sorell Si M. Pham Matthias Majetschak | 2008 | Critical Care Medicine2008，，3： | 1 |
| 9 | Prostaglandin E2 promotes migration and adhesion in hepatocellular carcinoma cells显示文摘 | Rafae M Amalia FM Lisardo B | 2005 | Carcinogenisis2005，26，4： | 1 |
| 10 | Microcalorimetrics Study of the Effect of Temperature on Microbial Activity in Soils显示文摘 | Isabel Barja M Jorge Proupin Lisardo Munez | 1997 | Thermochimica Acta1997，，303： | 1 |
| 11 | Microcalorimetric Measurements of the Influence of Glucose Concentration on Microbial Activity in Soils显示文摘 | Isabel Barja Lisardo Nunnez | 1999 | Soil Biology and Biochemistry1999，，31： | 1 |
| 12 | Kinetics of the deep oxidation of benzene,toluene,nhexane and their binary mixtures over a platinum on γ-α-lumina catalyst显示文摘 | SALVADOR Ordonez LISARDO BeHo HERMINIO Sastre | 2002 | Appl Catal Environmental2002，38，： | 1 |
| 13 | Thermogravimetric study of the decomposition process of the system BADGE (n = 0)/1, 2 DCH 显示文摘 | Lisardo Nunez Fraga F Nunez M R | 2000 | Polymer2000，41，： | 1 |
| 14 | Transgenic Mice Expressing Cyclooxygenase-2 in Hepatocytes Reveal a Minor Contribution of This Enzyme to Chemical Hepatocarcinogenesis显示文摘 | Cristina Llorente Izquierdo Rafael Mayoral Juana María Flores Pilar García-Palencia Carme Cucarella Lisardo Boscá Marta Casado Paloma Martín-Sanz | 2011 | The American Journal of Pathology2011，，3： | 1 |
| 15 | Phase I trial of neoadjuvant chemoradiotherapy (CRT) with capecitabine and weekly irinotecan followed by laparoscopic total mesorectal excision (LTME) in rectal cancer patients显示文摘 | Lisardo Ugidos Salvadora Delgado Carlos Conill Angels Ginés Rosa Gallego Juan Ramón Ayuso Rosa Miquel Monica Tosca Antonio Lacy Antoni Castells Joan Maurel | 2009 | Investigational New Drugs2009，，3： | 1 |
| 16 | Thromboxane A2-Induced Inhibition of Voltage-Gated K+ Channels and Pulmonary Vasoconstriction: Role of Protein Kinase Cζ显示文摘 | Angel Cogolludo Laura Moreno Lisardo Bosca Juan Tamargo Francisco Perez-Vizcaino | 2003 | Circulation Research: Journal of the American Heart Association2003，，7： | 1 |
| 17 | Powdered cellulose as excipient for extrusion-spheronization pellets of a cohesive hydrophobic drug显示文摘 | Lisardo Alvarez Angel Concheiro Jose' Luis Go'mez-Amoza | 2003 | European Journal of Pharmaceutics and Biopharmaceutics2003，55，3： | 1 |
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