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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 | Diagnostic yield and clinical outcomes after capsule endoscopy in 100 consecutive patients with obscure gastrointestinal bleeding显示文摘 | Emilio Estévez Benito González-Conde José Luis Vázquez-Iglesias Maria de los Angeles Vázquez-Millán Sonia Pértega Pedro A. Alonso Joan Clofent Eva Santos José Luis Ulla Eloy Sánchez | 2006 | European Journal of Gastroenterology & Hepatology2006，，8： | 3 |
| 3 | 遗传性肥胖与心房颤动的关系显示文摘观察性研究已经确定了体质量指数(body mass index,BMI)与心房颤动之间的关联。然而,从观察性研究中推断因果关系会受到混杂因素、逆因果关系和偏倚的影响。该研究的主要目的是应用BMI的遗传学预测因子评估BMI与心房颤动之间的因果关系。方法:纳入1987-2002年期间在美国、冰岛和荷兰实施的7个前瞻性人群队列研究中基线无心房颤动的欧洲血统个体51 646人, | 刘莉 叶鹏 Chatterjee NA Giulianini F Geelhoed B Lunetta KL Misialek JR Niemeijer MN Rienstra M Rose LM Smith AV Arking DE Ellinor PT Heeringa J Lin H Lubitz SA Soliman EZ Verweij N Alonso A Benjamin EJ Gudnason V Stricker BH van der Harst P Chasman DI Albert CM | 2017 | 中华高血压杂志2017，25，2： | 2 |
| 4 | Is cisplatin-induced cell death always produced by apoptosis?显示文摘 | GONZALEZ V M FUERTES M A ALONSO C | 2001 | Mol Pharmaeol2001，59，4： | 1 |
| 5 | On-line preconcentration using chelating and ion-exchange minicolumns for the speciation of chromium(iii) and chrontium(vi) and their quantitative determination in natural waters by inductively coupled plasma mass spectrometry显示文摘 | GUERRERO M M L ALONSO E V PAVON J M C | 2012 | Journal of Analytical Atomic Spectrometry2012，27，4： | 1 |
| 6 | Secondary compression of clays as a local dehydration process显示文摘 | Navarro V Alonso E E | 2001 | Geotechnique2001，51，10： | 1 |
| 7 | Genetic and epigenetic modifications of Sox2 contribute to the invasive phenotype of malignant gliomas显示文摘 | Alonso M M Diez V R Manterola L | 2011 | PLoS One2011，6，26： | 1 |
| 8 | Lactic acid from wood 显示文摘 | PARAJO J C ALONSO J L SANTOS V | 1996 | Process Biochemistry1996，31，3： | 1 |
| 9 | Case report: sonographic apperance of cavernous hemangioma of testis 显示文摘 | Lozano V Alonso P Marcos-Robles J | 1994 | Clin Radiol1994，49，4： | 1 |
| 10 | Comparison of the clinical efficacy and safety of carbamide peroxide and hydrogen peroxide in at-home bleaching gels显示文摘 | Alonso de la Pea V Balboa Cabrita O | 2006 | Quintessence Int2006，37，7： | 1 |
| 11 | Preparation of MoS2 and WS2 catalysts by in situ decomposition of ammonium thiosalts显示文摘 | Alonso G Del Valle M Cruz J Petranovskii V LiceaClaverie A Fuentes S | | 0，，： | 1 |
| 12 | Phytoestrogen modulation of bone-related cytokines and its impact on cell viability in human prostate cancer cells显示文摘 | Alonso V Perez-Martinez FC Calahorra FJ | | 0，，11： | 1 |
| 13 | High-performance liquid chromatography with amperometric detection applied to the screening of 1,4-dihydropyridines inhuman plasma显示文摘 | Lopez JA Martinez V Alonso RM | 2000 | Journal of Chromatography A2000，870，： | 1 |
| 14 | Inhibin A serum levels in proteinuric and nonproteinuric pregnancy-induced hypertension: Evidence for placental involvement in gestational hypertension显示文摘 | Casals E Gomez O Aibar C Cararach V Alonso PL Fortuny A | 2000 | Hypertens Preg2000，19，3： | 1 |
| 15 | Two-dimensional channel flows over rough surface显示文摘 | Coleman N L Alonso C V | 1983 | J Hydraul Eng1983，109，2： | 1 |
| 16 | Baseline of butyltin pollution in coastal sediments within the Basque Country (northern Spain), in 2007-2008显示文摘 | Rodriguez J G~ Solaun O Larreta J Segarra M J B Franco J Alonso J I G Sariego C Valencia V Borja A | 2010 | Marine Pollution Bulletin2010，60，1： | 1 |
| 17 | Modeling the compres sive properties of glass fiber reinforced epoxy foam using the a nalysis of variance approaeh显示文摘 | ALONSO M V AUAD M L NUTT S | 2006 | Composites Science and Teeh nology2006，66，13： | 1 |
| 18 | Graphene for toughand electroconductive alumina ceramics 显示文摘 | CENTENO A ROCHA V G ALONSO B | 2013 | J Eur Ceram Soc2013，33，32： | 1 |
| 19 | Modification of ammonium lignasulfanate hy phenolation for use in phenolic resins显示文摘 | Alonso M V Oliet M Rodnguez F | 2005 | Bioresurce technology2005，96，9： | 1 |
| 20 | Characterization of a novolac resin substituting phenol by ammonium lignosul- fonate as filler or extender显示文摘 | Perez J M Rodriguez F Alonso M V | 2007 | BioResources2007，2，2： | 1 |
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