Oesophageal cancer and amplification of the human cyclin D gene CCND1/PRAD1.

The human CCND1/PRAD1 gene, located in the 11q13 chromosomal region, encodes a cyclin D protein with potential oncogenic capacity and is involved in several human malignancies. The amplification and expression status of CCND1 was investigated in a series of oesophageal tumours. CCND1 is amplified in 54% and overexpressed in 63% of the tumours of the squamous cell type

Probabilistic and predictive performance-based approach for assessing reinforced concrete structures lifetime: The applet project

International audienceConcrete deterioration results in different damage extents, from cracking to concrete spalling, from losses of reinforcement cross-sections to bond losses. A relevant prediction of this performance is the basis for a successful management of the concrete structures. Conversely, the large amount of uncertainties related to parameters and models require a specific analysis in order to provide relevant results. The APPLET project intends to develop a probabilistic and predictive performance-based approach by quantifying the various sources of variability (material and structure), studying the interaction between environmental aggressive agents and the concrete material, ensuring a transfer of the physical-chemical models at the material scale towards models at the structure level, including and understanding in a better manner the corrosion process, integrating interface models between reinforcement and concrete, proposing relevant numerical models, integrating know-how from monitoring or inspection. To provide answers, a consortium of 19 partners has been established and has promoted a research project funded by the French Research Science Agency (ANR). Started in May 2007, the project has ended in November 2010. This paper will resume the most significant advances targeted by this research project

Targeted molecular characterization shows differences between primary and secondary myelofibrosis

INTRODUCTION: In BCR-ABL1-negative myeloproliferative neoplasms, myelofibrosis (MF) is either primary (PMF) or secondary (SMF) to polycythemia vera or essential thrombocythemia. MF is characterized by an increased risk of transformation to acute myeloid leukemia (AML) and a shortened life expectancy. METHODS: Because natural histories of PMF and SMF are different, we studied by targeted next generation sequencing the differences in the molecular landscape of 86 PMF and 59 SMF and compared their prognosis impact. RESULTS: PMF had more ASXL1 (47.7%) and SRSF2 (14%) gene mutations than SMF (respectively 27.1% and 3.4%, P = .04). Poorer survival was associated with RNA splicing mutations (especially SRSF2) and TP53 in PMF (P = .0003), and with ASXL1 and TP53 mutations in SMF (P < .0001). These mutations of poor prognosis were associated with biological features of scoring systems (DIPSS and MYSEC-PM score). Mutations in TP53/SRSF2 in PMF or TP53/ASXL1 in SMF were more frequent as the risk of these scores increased. This allowed for a better stratification of MF patients, especially within the DIPSS intermediate-1 risk group (DIPSS) or the MYSEC-PM high risk group. AML transformation occurred faster in SMF than in PMF and patients who transformed to AML were more SRSF2-mutated and less CALR-mutated at MF sampling. CONCLUSIONS: PMF and SMF have different but not specific molecular profiles and different prognosis depending on the molecular profile. This may be due to differences in disease history. Combining mutations and existing scores should improve prognosis assessment

The Codevelopment of Mangroves and Infaunal Community Diversity in Response to the Natural Dynamics of Mud Deposition in French Guiana

The sustainability of mangrove ecosystems requires a knowledge of their spatiotemporal variability as a function of regional properties. The unique coastal ecosystems of the mangrove belt along the coast of the Guianas in South America are influenced by cycles of a massive accretion of mud supplied by the Amazon River and wave induced erosion. This study characterized, for the first time, how benthic infaunal assemblages, as proxies of mechanisms of mangrove resilience, were structured by the natural growth track of Avicennia germinans dominated mangroves in French Guiana. We sampled 4 mobile mud stations and 27 consolidated mud stations distributed over 9 tidal transects from bare to vegetated mudflats colonized by young mangroves during the dry season. We collected a complete dataset of sediment and vegetation variables together with the benthic meso- (>0.25 mm) and macrofauna (>1 mm). We used a combination of eigenvector based multivariate analyses and variance partitioning on this multiple set of variables to identify which environmental variables likely drive the benthic diversity patterns. Mangrove early development increased the alpha and beta diversities of the infaunal communities for the two size classes. A total of 20–30% and 7–12% of the beta diversity are explained by linear and nonlinear spatial variables, respectively. However, 7% to 9% of the variance partioning could be determined by other biotic/abiotic variables, biological interactions or neutral processes, not described here. This study has highlighted the necessity of taking into account mangrove dynamics at suitable spatial scales for benthic biodiversity evaluation and mangrove management or restoration plan

Clinical development of insulin-like growth factor receptor--1 (IGF-1R) inhibitors: at the crossroad?

Insulin like growth factor receptor (IGF-1R) targeting became one of the most investigated areas in anticancer drug development during the last decade. Strategies aiming to block IGF-1R activity include monoclonal antibodies, tyrosine kinase inhibitors and anti-ligands antibodies. Initial enthusiasm quickly encountered challenges. Unfortunately the validation of the efficacy of IGF-1R targeted agents in large clinical trials failed, however anecdotal single agent activity was seen in early studies. Consequently, questions regarding the selection of right target population and the appropriate trial design are arising. Despite the plethora of clinical trials conducted no predictive biomarker has been validated so far and resistance mechanisms to IGF-1R inhibitors remain unclear. The other issue to be addressed is how to best combine IGF-1R inhibitors with other therapeutic approaches. This review highlights the most relevant clinical data emphasizing the main tumor types where IGF-1R inhibition showed potential interest. We also tried to extract based on clinical and translational data some candidate biomarkers that could help better to select patient population who potentially could benefit most from this therapeutic approach.Journal ArticleReviewSCOPUS: re.jinfo:eu-repo/semantics/publishe