p16 Mutation Spectrum in the Premalignant Condition Barrett's Esophagus

Background: Mutation, promoter hypermethylation and loss of heterozygosity involving the tumor suppressor gene p16 (CDKN2a/INK4a) have been detected in a wide variety of human cancers, but much less is known concerning the frequency and spectrum of p16 mutations in premalignant conditions. Methods and Findings: We have determined the p16 mutation spectrum for a cohort of 304 patients with Barrett’s esophagus, a premalignant condition that predisposes to the development of esophageal adenocarcinoma. Forty seven mutations were detected by sequencing of p16 exon 2 in 44 BE patients (14.5%) with a mutation spectrum consistent with that caused by oxidative damage and chronic inflammation. The percentage of patients with p16 mutations increased with increasing histologic grade. In addition, samples from 3 out of 19 patients (15.8%) who underwent esophagectomy were found to have mutations. Conclusions: The results of this study suggest the environment of the esophagus in BE patients can both generate an

Qualitative analysis of Adenomatous Polyposis Coli promoter: Hypermethylation, engagement and effects on survival of patients with esophageal cancer in a high risk region of the world, a potential molecular marker

<p>Abstract</p> <p>Background</p> <p>Squamous cell carcinoma of esophagus (SCCE) occurs at a high incidence rate in certain parts of the world. This feature necessitates that different aspects of the disease and in particular genetic characteristics be investigated in such regions. In addition, such investigations might lead to achievement of molecular markers helpful for early detection, successful treatment and follow up of the disease. Adenomatous Polyposis Coli (<it>APC</it>) promoter hypermethylation has been shown to be a suitable marker for both serum and solid tumors of adenocarcinoma of esophagus. We investigated the status of <it>APC </it>promoter hypermethylation in Iranian patients, compared the results with the former studies, and evaluated its applicability as a candidate molecular marker by examining association between survival of SCCE patients and <it>APC </it>promoter methylation.</p> <p>Methods</p> <p>For evaluating the status of <it>APC </it>promoter hypermethylation and its association with SCCE, a qualitative methylation specific PCR (MSP) was used. DNA was extracted and digested with an appropriate restriction enzyme, treated with sodium bisulfite in agarose beads and amplified in two-step PCR reaction by applying either methylated or unmethylated promoter specific primers. Universally methylated DNA and methylase treated blood DNA of healthy donors were used as positive controls as well. Survival of patients was followed up for two years after treatment and survival rate of patients with methylated <it>APC </it>promoter was compared with that of unmethylated patients.</p> <p>Results</p> <p>Assessment of <it>APC </it>promoter methylation revealed that normal tissues were unmethylated, while twenty out of forty five (44.4%) tumor tissues were hypermethylated either in one or both alleles of <it>APC</it>. Among the tissues in which methylation was detected, seven were hypermethylated in both alleles while the other thirteen were hypermethylated in one of the two alleles of <it>APC</it>. Analyzing two-year survival rate of patients with respect to promoter hypermethylation showed a lower rate of survival for patients with methylated <it>APC </it>promoter following their treatment. Further investigation into the association between promoter hypermethylation and tumor differentiation status indicated that patients with well differentiated tumors were more likely to develop promoter hypermethylation.</p> <p>Conclusion</p> <p>Observing similar level of <it>APC </it>promoter hypermethylation in patients with SCCE in this high risk region and comparing it with other parts of the world could support the hypothesis that a common molecular mechanism might be involved in tumorigenesis of SCCE. In addition, the higher rate of two-year survival for patients with unmethylated <it>APC </it>promoter as well as its relationship with tumor differentiation would suggest that this tumor suppressor could be an appropriate candidate molecular marker for evaluating tumor malignancy and predicting survival of patients subsequent to treatment.</p

Corrosion galvanique du magnesium avec le graphite en presence de chlorures

National audienc

Mg-Zr alloy corrosion in Na-geopolymer and its synthetic pore solution

International audienceLes géo-polymères sont des candidats pour constituer les liants de conditionnement des déchets magnésiens issus des réacteurs de la filière UNGG. Il est envisage d'utiliser un aluminosilicate active a la soude et avec ajout de NaF (qui est un inhibiteur de corrosion pour le magnésium). Le comportement en corrosion d'un alliage Mg-0.5%Zr a été étudié dans ce géopolymère ainsi que dans la solution porale correspondante. Les vitesses de corrosion (avec et sans couplage galvanique avec l'acier ou le graphite) ont été déterminées par gravimétrie et par des méthodes électrochimiques (Electrochemical Impedance Spectroscopy et Zero Resistance Ammeter). De plus, la conductivité du géopolymère ainsi que les produits de corrosion formes ont été caractérisés

9th International Conference on Fracture Mechanics of Concrete and Concrete Structures STUDY OF SHRINKAGE RESTRAINT EFFECTS AT EARLY-AGE IN ALKALI- ACTIVATED SLAG MORTARS

Abstract: Alkali-activated materials are being increasingly studied nowadays as hydraulic binders. In order to be enrolled in different civil engineering applications, several properties must be characterized. This study focuses on their cracking risk by shrinkage restraints. The current paper summarizes the experimental and numerical results of a project assessing the development of early age properties of an alkali-activated slag mortar. First, an experimental campaign was held in order to quantify hydration heat release and hydration kinetics, to determine the time evolution of the Young modulus and the tensile strength and to measure free shrinkage strains, all in autogenous conditions. Second, two modelling approaches for mechanical properties and shrinkage development were compared. The results showed that the classical approach to characterize the hydration kinetics based on semi-adiabatic calorimetry results isn&apos;t suitable for the studied binder because of slow hydration and low heat release. Numerical work was finally conducted in order to predict stress development of a massive structure of alkali-activated slag mortar subjected to internal (self) and external strains&apos; restraints (at mesoscopic and macroscopic scales)

Corrosion behaviour of Mg alloys cladding from nuclear reactors fuel in alkaline solutions

International audienceThe reprocessing of spent fuel from the French UNGG (Graphite Gas Natural Uranium) nuclear power plants generates cladding wastes such are Mg-Mn alloys. A storage strategy is to encapsulate these wastes into cement matrix. The main issue is hydrogen evolution as the main consequence of the corrosion of Mg alloys, regardless of concrete radiolysis. In fact Mg acts as an anode in most of galvanic corrosion systems and the hydrogen can be produced either by water reduction or by Anodic Hydrogen Evolution (AHE). In the last case, an increase in the rate of hydrogen production with increasing applied potential is observed. This phenomenon called "Neg-ative Different Effect" (NDE) is in contradiction with the conventional Tafel equation. The corrosion of magnesium may produce Mg$^+$ cations which react quickly with water to produce hydrogen and stable Mg$^{2+}$ cations. The interstitial solution in concrete pores is characterized by a very high pH. To reproduce the pH solution around 13, 0.1M NaOH solutions were prepared and used as electrolytes from electrochemical experiments. Stainless steel, platinum and graphite were used as cathode to investigate basic galvanic coupling as it can be encountered in the real wastes. The purpose of this work was to investigate the galvanic corrosion of Mg alloys in the high pH solutions. The study of Mg corrosion behaviour was carried out using elec-trochemical measurement: ZRA mode. The analysis of the surface and the corrosion products were performed by Raman spectroscopy. The first results showed a galvan-ic corrosion rate more important with stainless steel rather than with graphite

Impact of fluoride concentration on general corrosion of Mg-Zr alloy in a Na-geopolymer and alkaline solutions

International audienc

UNGG Waste Retrieval Comparison of general and galvanic corrosion of Magnesium alloy coupled to graphite in ordinary Portland cement and alkali-activated slag binders

International audienceGraphite and magnesium alloys wastes were generated during the reprocessing phase of spent fuel assemblies of the former nuclear reactors in France. Conditioning of these low to intermediate level wastes in cementitious materials is being addressed here. The study is aiming to develop a numerical model able to predict the generation of stresses in such waste packages during their lifetime. Magnesium is one of the most reactive metals with a standard potential of -2.37V/SHE [1]. Once embedded in a hydraulic binder with alkaline pH and high internal humidity, oxidation reactions occur. The subsequent formation of corrosion products around the alloy may result in tensile stresses development in the surrounding binder that could lead to cracking risks. Thus, general and galvanic corrosion (when coupled with graphite) of the metal in the packages should be properly addressed.Hence, weight losses, electrochemical techniques and microscopic observations together with chemical analysis methods (Raman and SEM/EDX) are used to characterize the metal's corrosion in three binders. These latter consist of two different ordinary Portland cement and an alkali-activated blast furnace slag mortars [2]. The results prove that the use of alkali-activated slag (AAS) is beneficial for the metal's galvanic corrosion while the general corrosion behavior is comparable in all studied mortars.Additionally, the electrical conductance of the hydraulic binders was determined using electrochemical impedance spectroscopy technique (EIS). These tests were performed on graphite and magnesium electrodes embedded in the binders, from 7 to 180 days of hydration. The analysis of the results, using an equivalent electrical circuit, showed that the electrical conductance of AAS binder was lower than ordinary Portland cement binders, at a given hydration age.In order to explain this lower conductance of the AAS binder, an investigation of its porosity (total porosity and porosity size distribution) and a characterization of the pore solution are undertaken. Therefore, on one hand, mercury intrusion porosimetry and BET nitrogen adsorption tests are performed on the different binders in order to compare the pore structure. On the other hand, pH measurements and liquid ion chromatography techniques are used to monitor the evolution of the AAS binder's pore solution. The latter results are compared to those for OPC binders found in the literature