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Chêne-Bougeries, Switzerland

Gumy-Pause F.,University of Geneva | Pardo B.,University of Geneva | Khoshbeen-Boudal M.,University of Geneva | Ansari M.,University of Geneva | And 4 more authors.
Genes Chromosomes and Cancer | Year: 2012

Epigenetic modifications such as methylation of CpG islands in tumor-suppressor gene promoter regions have been associated with tumor development in many human cancers. Using methylation specific multiplex ligation-dependent probe amplification method, we analyzed the methylation status of 35 different genes in 16 neuroblastoma (NB) cell lines and 50 NB tumor samples (NBs), and investigated whether specific hypermethylation was associated with biological and/or clinical parameters. Among the genes found hypermethylated, the effect of GSTP1 hypermethylation on mRNA and protein expression was also explored. The median number of hypermethylated genes was higher in cell lines compared to NBs (5.5 vs. 2). For eight genes, aberrant methylation of CpG-islands in NB was not (ESR1, PAX5, WT1, CADM1, MSH6, and CDKN2B) or very rarely (CDH13 and GSTP1) reported in literature. GSTP1 was found hypermethylated in 44% of the NB cell lines and in 33% of the stage 4-11qLOH -non MYCN-amplified high risk NBs. Hypermethylation was correlated with reduced mRNA and protein expression. In the whole NBs cohort, GSTP1 hypermethylation was less frequently detected (8%), but found to be associated with lower event-free (EFS) and overall survival. Hypermethylation of GSTP1 showed also association with lower EFS in high risk subgroups as stage 4 and older patients (≥547 days). Our results suggest that, as in several adult cancers, aberrant methylation of GSTP1 may contribute to the carcinogenetic process in NB and could be potentially used as a new marker leading to define an ultra-high risk subgroup. © 2011 Wiley Periodicals, Inc. Source

Pineau A.,University of Nantes | Fauconneau B.,University of Poitiers | Sappino A.-P.,Clinique des Grangettes | Deloncle R.,University of Tours | Guillard O.,University of Poitiers
Journal of Trace Elements in Medicine and Biology | Year: 2014

Since aluminium (Al) pervades our environment, the scientific community has for many years raised concerns regarding its safety in humans. Al is present in numerous cosmetics such as antiperspirants, lipsticks and sunscreens. Al chlorohydrate is the active antiperspirant agent in underarm cosmetics and may constitute for Al a key exposure route to the human body and a potential source of damage. An in vitro study has demonstrated that Al from antiperspirant can be absorbed through viable human stripped skin. The potential toxicity of Al has been clearly shown and recent works convincingly argue that Al could be involved in cancerogenic processes. Nowadays, for example, Al is suspected of being involved in breast cancer. Recent work in cells in culture has lent credence to the hypothesis that this metal could accumulate in the mammary gland and selectively interfere with the biological properties of breast epithelial cells, thereby promoting a cascade of alterations reminiscent of the early phases of malignant transformation. In addition, several studies suggest that the presence of Al in human breast could influence metastatic process. As a consequence, given that the toxicity of Al has been widely recognized and that it is not a physiological component in human tissues, reducing the concentration of this metal in antiperspirants is a matter of urgency. © 2013 Elsevier GmbH. Source

Sappino A.-P.,Clinique des Grangettes | Buser R.,University of Geneva | Seguin Q.,University of Sfax | Fernet M.,Institute Curie | And 5 more authors.
Oncogenesis | Year: 2012

The p53 tumor-suppressor protein has a key role in the induction of cellular senescence, an important barrier to cancer development. However, very little is known about the physiological mediators of cellular senescence induced by p53. CEACAM1 is an immunoglobulin superfamily member whose expression is frequently lost in human tumors and exhibits tumor-suppressor features in several experimental systems, including Ceacam1 knockout mice. There is currently little understanding of the pathways and mechanisms by which CEACAM1 exerts its tumor-suppressor function. Here we report that CEACAM1 is strongly upregulated during the cellular response to DNA double-strand breaks (DSBs) starting from the lowest doses of DSB inducers used, and that upregulation is mediated by the ataxia telangiectasia mutated (ATM)/p53 pathway. Stable silencing of CEACAM1 showed that CEACAM1 is required for p53-mediated cellular senescence, but not initial cell growth arrest, in response to DNA damage. These findings identify CEACAM1 as a key component of the ATM/p53-mediated cellular response to DNA damage, and as a tumor suppressor mediating cellular senescence downstream of p53. © 2012 Macmillan Publishers Limited. All rights reserved. Source

Taylor S.,Hopital Ambroise Pare | van Muylem A.,Hopital Erasme | Howarth N.,Clinique des Grangettes | Gevenois P.A.,Hopital Erasme | Tack D.,EpiCURA
European Radiology | Year: 2016

Objectives: To determine variability of volume computed tomographic dose index (CTDIvol) and dose–length product (DLP) data, and propose a minimum sample size to achieve an expected precision. Methods: CTDIvol and DLP values of 19,875 consecutive CT acquisitions of abdomen (7268), thorax (3805), lumbar spine (3161), cervical spine (1515) and head (4106) were collected in two centers. Their variabilities were investigated according to sample size (10 to 1000 acquisitions) and patient body weight categories (no weight selection, 67–73 kg and 60–80 kg). The 95 % confidence interval in percentage of their median (CI95/med) value was calculated for increasing sample sizes. We deduced the sample size that set a 95 % CI lower than 10 % of the median (CI95/med ≤ 10 %). Results: Sample size ensuring CI95/med ≤ 10 %, ranged from 15 to 900 depending on the body region and the dose descriptor considered. In sample sizes recommended by regulatory authorities (i.e., from 10–20 patients), mean CTDIvol and DLP of one sample ranged from 0.50 to 2.00 times its actual value extracted from 2000 samples. Conclusions: The sampling error in CTDIvol and DLP means is high in dose surveys based on small samples of patients. Sample size should be increased at least tenfold to decrease this variability. Key Points: • Variability of dose descriptors is high regardless of the body region. • Variability of dose descriptors depends on weight selection and the region scanned. • Larger samples would reduce sampling errors of radiation dose data in surveys. • Totally or partially disabling AEC reduces dose variability and increases patient dose. • Median values of dose descriptors depend on the body weight selection. © 2016 European Society of Radiology Source

Oliveri A.,Free University of Colombia | Howarth N.,Clinique des Grangettes | Gevenois P.A.,Hopital Erasme | Tack D.,EpiCURA
European Radiology | Year: 2016

Purpose: To test the hypothesis that quality clinical audits improve compliance with the procedures in computed tomography (CT) scanning. Materials and methods: This retrospective study was conducted in two hospitals, based on 6950 examinations and four procedures, focusing on the acquisition length in lumbar spine CT, the default tube current applied in abdominal un-enhanced CT, the tube potential selection for portal phase abdominal CT and the use of a specific “paediatric brain CT” procedure. The first clinical audit reported compliance with these procedures. After presenting the results to the stakeholders, a second audit was conducted to measure the impact of this information on compliance and was repeated the next year. Comparisons of proportions were performed using the Chi-square Pearson test. Results: Depending on the procedure, the compliance rate ranged from 27 to 88 % during the first audit. After presentation of the audit results to the stakeholders, the compliance rate ranged from 68 to 93 % and was significantly improved for all procedures (P ranging from <0.001 to 0.031) in both hospitals and remained unchanged during the third audit (P ranging from 0.114 to 0.999). Conclusion: Quality improvement through repeated compliance audits with CT procedures durably improves this compliance. Key Points: • Compliance with CT procedures is operator-dependent and not perfect. • Compliance differs between procedures and hospitals, even within a unified department. • Compliance is improved through audits followed by communication to the stakeholders. • This improvement is sustainable over a one-year period. © 2015, European Society of Radiology. Source

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