Pooled analysis of prognostic impact of urokinase-type plasminogen activator and its inhibitor PAI-1 in 8377 breast cancer patients

BACKGROUND: Urokinase-type plasminogen activator (uPA) and its inhibitor (PAI-1) play essential roles in tumor invasion and metastasis. High levels of both uPA and PAI-1 are associated with poor prognosis in breast cancer patients. To confirm the prognostic value of uPA and PAI-1 in primary breast cancer, we reanalyzed individual patient data provided by members of the European Organization for Research and Treatment of Cancer-Receptor and Biomarker Group (EORTC-RBG). METHODS: The study included 18 datasets involving 8377 breast cancer patients. During follow-up (median 79 months), 35% of the patients relapsed and 27% died. Levels of uPA and PAI-1 in tumor tissue extracts were determined by different immunoassays; values were ranked within each dataset and divided by the number of patients in that dataset to produce fractional ranks that could be compared directly across datasets. Associations of ranks of uPA and PAI-1 levels with relapse-free survival (RFS) and overall survival (OS) were analyzed by Cox multivariable regression analysis stratified by dataset, including the following traditional prognostic variables: age, menopausal status, lymph node status, tumor size, histologic grade, and steroid hormone-receptor status. All P values were two-sided. RESULTS: Apart from lymph node status, high levels of uPA and PAI-1 were the strongest predictors of both poor RFS and poor OS in the analyses of all patients. Moreover, in both lymph node-positive and lymph node-negative patients, higher uPA and PAI-1 values were independently associated with poor RFS and poor OS. For (untreated) lymph node-negative patients in particular, uPA and PAI-1 included together showed strong prognostic ability (all P<.001). CONCLUSIONS: This pooled analysis of the EORTC-RBG datasets confirmed the strong and independent prognostic value of uPA and PAI-1 in primary breast cancer. For patients with lymph node-negative breast cancer, uPA and PAI-1 measurements in primary tumors may be especially useful for designing individualized treatment strategies

Pleiotropic Effects of Sox2 during the Development of the Zebrafish Epithalamus

The zebrafish epithalamus is part of the diencephalon and encompasses three major components: the pineal, the parapineal and the habenular nuclei. Using sox2 knockdown, we show here that this key transcriptional regulator has pleiotropic effects during the development of these structures. Sox2 negatively regulates pineal neurogenesis. Also, Sox2 is identified as the unknown factor responsible for pineal photoreceptor prepatterning and performs this function independently of the BMP signaling. The correct levels of sox2 are critical for the functionally important asymmetrical positioning of the parapineal organ and for the migration of parapineal cells as a coherent structure. Deviations from this strict control result in defects associated with abnormal habenular laterality, which we have documented and quantified in sox2 morphants

La S.F.I.O. à Roubaix de 1904 à 1914

Quillien N. La S.F.I.O. à Roubaix de 1904 à 1914. In: Revue du Nord, tome 51, n°201, Avril-juin 1969. Roubaix. Ve Centenaire de la Charte des Drapiers 1469-1969. pp. 275-289

La méiofaune benthique, bon indicateur biologique des impacts de l'eutrophisation par les macroalgues vertes ?

International audienceEn Bretagne, l'eutrophisation des cours d'eau côtiers induit la prolifération de macroalgues vertes dans de nombreuses baies sableuses. Les indicateurs écologiques benthiques les plus employés pour le suivi des écosystèmes côtiers sont dérivés des paramètres écologiques des communautés d'herbiers de phanérogames marines, de macrofaune et d'épiphytes. Du fait des difficultés d'identification taxinomique dues à la très petite taille des individus, la méiofaune est peu utilisée pour ces suivis. Pourtant, ce compartiment benthique, et notamment le groupe majoritaire des nématodes, possède de nombreux intérêts en tant qu'indicateur biologique. Dans notre étude, nous nous intéressons à l'impact des marées d'algues vertes sur la méiofaune des plages de sables fins. Deux sites ont été choisis en baie de Douarnenez (sud du Finistère, France) : la plage de Saint-Nic (site impacté) et l'anse de Dinan (site non impacté). De grandes différences de composition et de diversité de la méiofaune ont été observées entre le site impacté et le site non impacté. Cette étude suggère que la méiofaune pourrait être un bon indicateur pour les études d'impact de l'eutrophisation due aux blooms de macroalgues vertes

Green tides on inter- and subtidal sandy shores: differential impacts on infauna and flatfish

This study was supported by the national interdisciplinary Ecosphere Continentale et Cotiere EC2CO-INSU 'MAVERIQ', the Region Bretagne, the Universite de Bretagne Occidentale, and Abo Akademi University. This study was conducted as part of the PhD thesis of N. Quillien for Universite de Bretagne Occidentale and Abo Akademi University. E. Bonsdorff and M. C. Nordstrom were funded through the Abo Akademi University Endowment.International audienceBeach ecosystems extend from dune to offshore areas along most coasts, and provide essential services that are not provided by any other ecosystem. Indeed, sandy systems contain unique biodiversity and supply nursery and foraging areas for numerous commercially important marine species, such as flatfish. However, these systems are threatened by increasing anthropogenic pressure. Green tides (GT, i.e. accumulations of green opportunistic macroalgae) are a major human-induced threat to marine ecosystems, from inshore to nearshore. This eutrophication process greatly affects both benthic invertebrate communities and flatfish communities, within sheltered and non- or microtidal systems. However, the responses of dynamic open macrotidal sandy systems to eutrophication in the form of macroalgal mats are not yet fully understood. In particular, understanding the effects of GT on two connected biological compartments (infauna and flatfish) within two connected habitats (intertidal and subtidal) is crucial. Here, we set out to assess the influence of several environmental variables, including Ulva biomass, on the variability in infauna and flatfish communities in both the intertidal and the subtidal at four sites impacted or not by GT. In total, 110 biodiversity samples were analysed with classic and novel analytical approaches. Our results demonstrate that the presence of GT specifically impacts intertidal macroinvertebrate communities. However, small effects of GT on subtidal infauna communities, as well as on species-specific flatfish at both intertidal and subtidal, were still detectable. Our findings underline the vulnerability of highly dynamic ecosystems exposed to anthropogenic stress, in particular intertidal sandy shores

A strategy for proteomic identification of ubiquitinated proteins: application to antigen screening in glioblastoma

Poste

Whole transcriptome sequencing and biomineralization gene architecture associated with cultured pearl quality traits in the pearl oyster, Pinctada margaritifera

Abstract Background Cultured pearls are unique gems produced by living organisms, mainly molluscs of the Pinctada genus, through the biomineralization properties of pearl sac tissue. Improvement of P. margaritifera pearl quality is one of the biggest challenges that Polynesian research has faced to date. To achieve this goal, a better understanding of the complex mechanisms related to nacre and pearl formation is essential and can now be approached through the use of massive parallel sequencing technologies. The aim of this study was to use RNA-seq to compare whole transcriptome expression of pearl sacs that had producing pearls with high and low quality. For this purpose, a comprehensive reference transcriptome of P. margaritifera was built based on multi-tissue sampling (mantle, gonad, whole animal), including different living stages (juvenile, adults) and phenotypes (colour morphotypes, sex). Results Strikingly, few genes were found to be up-regulated for high quality pearls (n = 16) compared to the up-regulated genes in low quality pearls (n = 246). Biomineralization genes up-regulated in low quality pearls were specific to prismatic and prism-nacre layers. Alternative splicing was further identified in several key biomineralization genes based on a recent P. margaritifera draft genome. Conclusion This study lifts the veil on the multi-level regulation of biomineralization genes associated with pearl quality determination