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Fogli A.,French Institute of Health and Medical Research | Fogli A.,French National Center for Scientific Research | Fogli A.,University of Auvergne | Chautard E.,University of Auvergne | And 26 more authors.
Carcinogenesis | Year: 2015

Malignant gliomas are the most common primary brain tumors. Grade III and IV gliomas harboring wild-type IDH1/2 are the most aggressive. In addition to surgery and radiotherapy, concomitant and adjuvant chemotherapy with temozolomide (TMZ) significantly improves overall survival (OS). The methylation status of the O6-methylguanine-DNA methyltransferase (MGMT) promoter is predictive of TMZ response and a prognostic marker of cancer outcome. However, the promoter regions the methylation of which correlates best with survival in aggressive glioma and whether the promoter methylation status predictive value could be refined or improved by other MGMT-associated molecular markers are not precisely known. In a cohort of 87 malignant gliomas treated with radiotherapy and TMZ-based chemotherapy, we retrospectively determined the MGMT promoter methylation status, genotyped single nucleotide polymorphisms (SNPs) in the promoter region and quantified MGMT mRNA expression level. Each of these variables was correlated with each other and with the patients' OS. We found that methylation of the CpG sites within MGMT exon 1 best correlated with OS and MGMT expression levels, and confirmed MGMT methylation as a stronger independent prognostic factor compared to MGMT transcription levels. Our main finding is that the presence of only the A allele at the rs34180180 SNP in the tumor was significantly associated with shorter OS, independently of the MGMT methylation status. In conclusion, in the clinic, rs34180180 SNP genotyping could improve the prognostic value of the MGMT promoter methylation assay in patients with aggressive glioma treated with TMZ. © The Author 2015. Published by Oxford University Press. All rights reserved. Source

Araujo A.P.,Portuguese Institute of Oncology of Porto | Costa B.M.,Life and Health science Research Institute ICVS | Pinto-Correia A.L.,Portuguese Institute of Oncology of Porto | Fragoso M.,Portuguese Institute of Oncology of Porto | And 8 more authors.
World Journal of Gastroenterology | Year: 2011

AIM: To investigate the association between epidermal growth factor (EGF) +61A/G polymorphism and susceptibility to gastric cancer, through a cross-sectional study. METHODS: Polymerase chain reaction resctriction fragment lenght polymorphism analyses were used to genotype EGF +61 in 207 patients with gastric lesions (162 patients with gastric adenocarcinomas, 45 with atrophy or intestinal metaplasia) and 984 controls. All subjects were Caucasian. RESULTS: Genotype distribution was 23.5% for GG and 76.5% for GA/AA in the control group, 18.4% for GG and 68.6% for GA/AA in the entire group with gastric lesions and 17.9% for GG and 82.1% for GA/AA in the group with gastric adenocarcinoma. No statistically significant associations were found between EGF +61 variants and risk for developing gastric cancer [odds ratios (OR) = 1.41, 95% confidence intervals (CI): 0.90-2.21, P = 0.116]. However, the stratification of individuals by gender revealed that males carrying A alleles (EGF +61A/G or AA) had an increased risk for developing gastric cancer as compared to GG homozygous males (OR = 1.55, 95% CI: 1.05-2.28, P = 0.021). CONCLUSION: In summary, we found that males who were A carriers for EGF +61 had an increased risk for developing gastric cancer. This result may be explained by the suggestion that women secrete less gastric acid than men. © 2011 Baishideng. Source

Costa-Pinto A.R.,European Institute of Excellence on Tissue Engineering and Regenerative Medicine | Costa-Pinto A.R.,PT Government Associate Laboratory | Martins A.M.,European Institute of Excellence on Tissue Engineering and Regenerative Medicine | Martins A.M.,PT Government Associate Laboratory | And 13 more authors.
Journal of Bioactive and Compatible Polymers | Year: 2014

In tissue engineering, the evaluation of the host response to the biomaterial implantation must be assessed to determine the extent of the inflammatory reaction. We studied the degradation of poly(butylene succinate) and chitosan in vitro using lipase and lysozyme enzymes, respectively. The subcutaneous implantation of the scaffolds was performed to assess tissue response. The type of inflammatory cells present in the surrounding tissue, as well as within the scaffold, was determined histologically and by immunohistochemistry. In the presence of lipase or lysozyme, the water uptake of the scaffolds increased. Based on the weight loss data and scanning electron microscopy analysis, the lysozyme combined with lipase had a notable effect on the in vitro degradation of the scaffolds. The in vivo implantation showed a normal inflammatory response, with presence of neutrophils, in a first stage, and macrophages, lymphocytes, and giant cells in a later stage. Vascularization in the surrounding tissue and within the implant increased with time. Moreover, the collagen deposition increased with time inside the implant. In vivo, the scaffolds maintained the structural integrity. The degradation in vitro was faster and greater compared to that observed in vivo within the same time periods. © The Author(s) 2014. Source

Ferreira D.,Life and Health science Research Institute ICVS | Dias N.,Life and Health science Research Institute ICVS
2012 IEEE 2nd Portuguese Meeting in Bioengineering, ENBENG 2012 | Year: 2012

With aging the body and the brain undergoes several changes. One of these changes is the loss of neuroplasticity, which leads to the decrease of cognitive abilities. Hence the necessity of stopping or reversing these changes is of utmost importance to contemporary society. In the present work, using electroencephalogram and the Wisconsin card sorting test (WCST) we try to understand which are the performance-related EEG phenotypes. The test was applied to young and elderly subjects due to the expected cognitive deficits with increasing age. The results showed that parietal theta desynchronization and the increase of the inter-frontal and intra-hemispheric coherence was associated to the group of good performers in the WCST. The implementation of an algorithm for low-resolution brain electromagnetic tomography (LORETA) showed that the WCST is not a specific test of the pre-frontal cortex. The identified performance-related EEG features have potential application on neurofeedback training protocols intended to hinder age-related cognitive decline. © 2012 IEEE. Source

Goncalves C.,IBB Institute for Biotechnology And Bioengineering | Torrado E.,Life and Health science Research Institute ICVS | Martins T.,Life and Health science Research Institute ICVS | Pereira P.,IBB Institute for Biotechnology And Bioengineering | And 2 more authors.
Colloids and Surfaces B: Biointerfaces | Year: 2010

The uptake of nanoparticles by cells of the mononuclear phagocytic system limits its use as colloidal drug carriers, reducing the blood circulation time and the ability to reach biological targets. In this work, the interaction between dextrin nanoparticles - recently developed in our laboratory - and murine bone marrow-derived macrophages was evaluated. Cytotoxicity and nitric oxide production were studied, using the MTT assay and the Griess method, respectively. FITC labelled nanoparticles were used to assess the phagocytic uptake and blood clearance after intravenous injection. The phagocytic uptake was analysed in vitro by confocal laser scanning microscopy and fluorescence activated cell sorting. The results show that the nanoparticles are not cytotoxic and do not stimulate the production of nitric oxide by macrophages, in the range of concentrations studied. Nanoparticles are phagocytosed by macrophages and are detected inside the cells, concentrated in cellular organelles. The blood clearance study showed that the blood removal of the nanoparticles occurs with a more pronounced rate in the first 3 h after intravenous administration, with about 30% of the material remaining in systemic circulation at this stage. Given the fairly high blood circulation time and biocompatibility, the dextrin nanoparticles are promising carriers for biomedical applications. Both applications targeting phagocytic, antigen-presenting cells (for vaccination purposes) and different tissues (as drug carriers) may be envisaged, by modulation of the surface properties. © 2009 Elsevier B.V. All rights reserved. Source

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