27 research outputs found
Microsatellite instability and mismatch repair gene inactivation in sporadic pancreatic and colon tumours
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
The Cumulative Effects of Polymorphisms in the DNA Mismatch Repair Genes and Tobacco Smoking in Oesophageal Cancer Risk
The DNA mismatch repair (MMR) enzymes repair errors in DNA that occur during normal DNA metabolism or are induced by certain cancer-contributing exposures. We assessed the association between 10 single-nucleotide polymorphisms (SNPs) in 5 MMR genes and oesophageal cancer risk in South Africans. Prior to genotyping, SNPs were selected from the HapMap database, based on their significantly different genotypic distributions between European ancestry populations and four HapMap populations of African origin. In the Mixed Ancestry group, the MSH3 rs26279 G/G versus A/A or A/G genotype was positively associated with cancer (OR = 2.71; 95% CI: 1.34–5.50). Similar associations were observed for PMS1 rs5742938 (GG versus AA or AG: OR = 1.73; 95% CI: 1.07–2.79) and MLH3 rs28756991 (AA or GA versus GG: OR = 2.07; 95% IC: 1.04–4.12). In Black individuals, however, no association between MMR polymorhisms and cancer risk was observed in individual SNP analysis. The interactions between MMR genes were evaluated using the model-based multifactor-dimensionality reduction approach, which showed a significant genetic interaction between SNPs in MSH2, MSH3 and PMS1 genes in Black and Mixed Ancestry subjects, respectively. The data also implies that pathogenesis of common polymorphisms in MMR genes is influenced by exposure to tobacco smoke. In conclusion, our findings suggest that common polymorphisms in MMR genes and/or their combined effects might be involved in the aetiology of oesophageal cancer
Improvement of the interaction formulae for beam columns in Eurocode 3
This paper presents a new proposal for beam-column interaction formulae initially based on second-order in-plane elastic theory, as an alternative to those proposed in the Eurocode 3 pre-standard [1]. It has been derived according to the following requirements: theoretical background, clear physical meaning, consistency with the other related formulae of Eurocode 3 and accuracy. Besides that, the suggested formulae cover all required continuities: between the cross-section classes, from plasticity to elasticity as slenderness and axial force increase, and continuity between all the individual stability member checks and cross-section verifications. Further to the presentation of the formulae and their background, the good agreement of the proposal is shown through an extensive comparison with more than 15,000 results of finite element numerical simulations. (C) 2002 Civil-Comp Ltd. and Elsevier Science Ltd. All rights reserved
Swaged bolts: modelling of the installation process and numerical analysis of the mechanical behaviour
peer reviewedSwaged bolts are an alternative to high strength (HS) bolts for connections in steel structures. To clarify the different steps involved during their specific installation process, a numerical modelling has been carried out. It allows the relevant phenomena to be described and to be evaluated. This numerical calculation accounts for mechanical plasticity and friction contact between the components of swaged bolts. The finite element code "Lagamine" designed for the forming analysis that requires the modelling of the friction between plastically deformable solids has been used with an original and quite efficient way to take into account the contact. The drawing of the stress distributions during and after the swaging process is the main result of this research
New interaction formulae for beam-columns in Eurocode 3: The French-Belgian approach
peer reviewedThis paper presents one of the two new proposals for beam-column interaction formulae, which will be made available in the forthcoming EN version of Eurocode 3. It is based on second-order in-plane elasticity, and has been derived in order to exhibit an understandable physical background, as well as accuracy and consistency with the other resistance and stability formulae of the code. The formulae ensure all the required continuities: between the cross-section classes, from plasticity to elasticity when slenderness and axial force are increasing, and continuity between all the individual stability member checks and cross-section verifications. The paper shows how the basic format may be extended to cover a wider range of cases, i.e. spatial elastic-plastic behaviour with possible lateral-torsional buckling. Through an extensive comparison with the results of FEM numerical simulations of about 15 000 beam-columns, the proposal is found to be safe and accurate. (C) 2003 Elsevier Ltd. All rights reserved
Génération de polysulfures lors de la radiolyse de l'eau porale de matériaux cimentaires avec laitier
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