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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 | Likely serotoninergic syndrome from an interaction between amitryptiline,paroxetine,and linezolid显示文摘 | Morales-Molina JA Mateu-de Antonio J Grau Cerrato S Marín Casino M | 2005 | Farm Hosp2005，29，： | 1 |
| 3 | Inhibition of cell proliferation, invasion, tumor growth and metastasis by an oral non-antimicrobial tetracycline analog (COL-3) in a metastatic prostate cancer model显示文摘 | Jin Y Atkinson SJ Mars JA | 2002 | Int J Cancer2002，98，： | 1 |
| 4 | Effects of gamma-linolenic acid and oleic acid on paclitaxel cytotoxicity in human breast cancer cells 显示文摘 | Menendez JA del Mar Barbacid M Montero S | 2001 | Eur J Cancer2001，37，： | 1 |
| 5 | Virulence characteristics of Escherichia coli isolates obtained from broiler breeders with salpin- gitis 显示文摘 | MAR Monroy T Kn6bl JA Bottino | 2005 | Comparative Immunology Microbiology and Infectious Diseases2005，28，1： | 1 |
| 6 | Deter-mination of fosethyl-aluminium by spectrophotometric method 显示文摘 | DIMITR SVETLANA L MAR | 2001 | Pesticidi2001，16，2： | 1 |
| 7 | Analysis of therapeutic compliance in women with osteoporosis显示文摘 | Carbonell-Abella C Guaabens-Gay N Marín-Rives JA | 2011 | Reumatol Clin2011，7，5： | 1 |
| 8 | Effects of gamma-linolenie acid and oleie acid on paelitaxel eytotoxieity in human breast cancer cells 显示文摘 | Menendez JA del Mar Barbacid M Montero S | 2000 | Eur J Cancer2000，37，： | 1 |
| 9 | Ef- fects of gamma-linolenic acid and oleic acid on paclitaxel cytotoxicity in human breast cancer cells显示文摘 | Menendez JA del Mar Barbacid M Montero S | 2001 | Eur J Cancer2001，37，3： | 1 |
| 10 | MRI of idiopathic orbital inflammatory syndrome using fat saturation and Gd-DTPA 显示文摘 | Hardman JA Halpin SF Mars S | 1995 | Neuroradiology1995，37，： | 1 |
| 11 | Role of free radicals in vascular dysfunction induced by high tidal volume ventilation显示文摘 | Martínez-Caro L Lorente JA Marín-Corral J | 2009 | Intensive Care Med2009，35，6： | 1 |
| 12 | Recently confirmed inducing lead compounds isolated from marine potential relevance in cancer treatment显示文摘 | Essack M apoptosis sponge of Mar Drugs Bajic VB Archer JA | 2011 | 9= 1580--16062011，9，： | 1 |
| 13 | Inhibition of inducible nitric oxide synthase and cyclooxygenase-2 expression by flavonoids isolated from tanacetum microphyllum显示文摘 | José AG María FM María JA | 2006 | International Immunopharmacology2006，6，11： | 1 |
| 14 | Primary biliary cirrhosis and-CREST syndrome显示文摘 | Marín Gabriel JC Solís Herruzo JA | | 0，，03： | 1 |
| 15 | A new precursor for the radiosynthesis of FLT显示文摘 | Mar SJ Eisenbarth JA Wagner-Utermann U | 2002 | Nucl Med Biol2002，29，： | 1 |
| 16 | Ad 1 ibitum chol ineintake in healthy individuals meets or exceeds theproposed dequate intake level 显示文摘 | Fischer LM Scearce JA Mar MH | 2005 | J Nutr2005，135，： | 1 |
| 17 | Anatomical characterization of central, apical and minimal corneal thickness显示文摘·AIM: To anatomically locate the points of minimum corneal thickness and central corneal thickness(pupil center) in relation to the corneal apex.·METHODS: Observational, cross-sectional study, 299 healthy volunteers. Thickness at the corneal apex(AT),minimum corneal thickness(MT) and corneal thickness at the pupil center(PT) were determined using the pentacam. Distances from the corneal apex to MT(MD)and PT(PD) were calculated and their quadrant position(taking the corneal apex as the reference) determined:point of minimum thickness(MC) and point of central thickness(PC) depending on the quadrant position. Two multivariate linear regression models were constructed to examine the influence of age, gender, power of the flattest and steepest corneal axes, position of the flattest axis, corneal volume(determined using the Pentacam)and PT on MD and PD. The effects of these variables on MC and PC were also determined in two multinomial regression models.·RESULTS: MT was located at a mean distance of 0.909 mm from the apex(79.4% in the inferior-temporal quadrant). PT was located at a mean distance of 0.156 mm from the apex. The linear regression model for MD indicated it was significantly influenced by corneal volume(B =-0.024; 95% CI:-0.043 to-0.004). No significant relations were identified in the linear regression model for PD or the multinomial logisticregressions for MC and PC.·CONCLUSION: MT was typically located at the inferiortemporal quadrant of the cornea and its distance to the corneal apex tended to decrease with the increment of corneal volume. | Federico Saenz-Frances Martha Cecilia Bermúdez-Vallecilla Lara Borrego-Sanz Luis Jaez J osé Marìa Martinez-de-la-Casa Laura Morales-Fernandez Enrique Santos-Bueso Julián Garcia-Sanchez Julián Garcia-Feijoo | 2014 | International Journal of Ophthalmology(English edition)2014，7，4： | 0 |
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