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Hôpital-Camfrout, France

Pandiri A.R.,National Health Research Institute | Pandiri A.R.,Experimental Pathology Laboratories Inc. | Sills R.C.,National Health Research Institute | Ziglioli V.,North Carolina State University | And 9 more authors.
Toxicologic Pathology | Year: 2012

Lung cancer is the leading cause of cancer-related death in people and is mainly due to environmental factors such as smoking and radon. The National Toxicology Program (NTP) tests various chemicals and mixtures for their carcinogenic hazard potential. In the NTP chronic bioassay using B6C3F1 mice, the incidence of lung tumors in treated and control animals is second only to the liver tumors. In order to study the molecular mechanisms of chemically induced lung tumors, an understanding of the genetic changes that occur in spontaneous lung (SL) tumors from untreated control animals is needed. The authors have evaluated the differential transcriptomic changes within SL tumors compared to normal lungs from untreated age-matched animals. Within SL tumors, several canonical pathways associated with cancer (eukaryotic initiation factor 2 signaling, RhoA signaling, PTEN signaling, and mammalian target of rapamycin signaling), metabolism (Inositol phosphate metabolism, mitochondrial dysfunction, and purine and pyramidine metabolism), and immune responses (FcγR-mediated phagocytosis, clathrin-mediated endocytosis, interleukin 8 signaling, and CXCR4 signaling) were altered. Meta-analysis of murine SL tumors and human non-small cell lung cancer transcriptomic data sets revealed a high concordance. These data provide important information on the differential transcriptomic changes in murine SL tumors that will be critical to our understanding of chemically induced lung tumors and will aid in hazard analysis in the NTP 2-year carcinogenicity bioassays. © 2012 by The Author(s). Source


Gagneux-Brunon A.,Jean Monnet University | Delanaye P.,University of Liege | Maillard N.,Dialysis | Maillard N.,Jean Monnet University | And 8 more authors.
AIDS | Year: 2013

Objective: To validate glomerular filtration rate (GFR) estimating equations in white HIV-infected patients based on serum creatinine and/or serum cystatin C. Design: Single-center, cross-sectional evaluation of the predictive performance of GFR estimators. Methods: GFR was measured by iohexol plasma clearance. Serum creatinine (Scr) and serum cystatin C (Scyst) were measured by traceable and standardized methods. We evaluated the performance of the Modification of Diet in Renal Disease (MDRD) and the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equations. We also studied the performance of the cystatin C-based equation (CKD-EPI Scyst) and the combined cystatin and creatinine-based equation (CKD-EPI combined), as recently proposed by the CKD-EPI group. Results: Two hundred and three participants (18% of women) were included. Mean age was 49±10 years. Mean measured GFR (mGFR) was 95±24ml/min per 1.73m2. CKD-EPI and CKD-EPI combined significantly outperformed the MDRD equation. The percentage of estimating results within 30% of mGFR was 75, 82 and 81% for the MDRD, CKD-EPI and CKD-EPI combined equation, respectively. Results favoring the CKD-EPI and CKD-EPI combined equation were especially observed for patients with mGFR over 90 ml/min per 1.73 m2. Conclusion: In our European HIV cohort, we confirmed that the creatinine-based CKD-EPI equation should replace the MDRD study equation. However, global performance of this equation remains worse than the performance observed in the general population. This lesser performance is particularly relevant in patients with measured GFR under and around 60 ml/min per 1.73 m2. Moreover, the specific interest of Scyst-based equations is not confirmed in this population. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins. Source


Vallelian F.,University of Zurich | Garcia-Rubio I.,ETH Zurich | Garcia-Rubio I.,Centro Universitario Of La Defensa | Puglia M.,University of Zurich | And 6 more authors.
Free Radical Biology and Medicine | Year: 2015

Abstract Extracellular or free hemoglobin (Hb) accumulates during hemolysis, tissue damage, and inflammation. Heme-triggered oxidative reactions can lead to diverse structural modifications of lipids and proteins, which contribute to the propagation of tissue damage. One important target of Hb's peroxidase reactivity is its own globin structure. Amino acid oxidation and crosslinking events destabilize the protein and ultimately cause accumulation of proinflammatory and cytotoxic Hb degradation products. The Hb scavenger haptoglobin (Hp) attenuates oxidation-induced Hb degradation. In this study we show that in the presence of hydrogen peroxide (H2O2), Hb and the Hb:Hp complex share comparable peroxidative reactivity and free radical generation. While oxidation of both free Hb and Hb:Hp complex generates a common tyrosine-based free radical, the spin-trapping reaction with 5,5-dimethyl-1-pyrroline N-oxide (DMPO) yields dissimilar paramagnetic products in Hb and Hb:Hp, suggesting that radicals are differently redistributed within the complex before reacting with the spin trap. With LC-MS2 mass spectrometry we assigned multiple known and novel DMPO adduct sites. Quantification of these adducts suggested that the Hb:Hp complex formation causes extensive delocalization of accessible free radicals with drastic reduction of the major tryptophan and cysteine modifications in the β-globin chain of the Hb:Hp complex, including decreased βCys93 DMPO adduction. In contrast, the quantitative changes in DMPO adduct formation on Hb:Hp complex formation were less pronounced in the Hb α-globin chain. In contrast to earlier speculations, we found no evidence that free Hb radicals are delocalized to the Hp chain of the complex. The observation that Hb:Hp complex formation alters free radical distribution in Hb may help to better understand the structural basis for Hp as an antioxidant protein. © 2015 Elsevier Inc. Source

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