Ebp1 expression in benign and malignant prostate

<p>Abstract</p> <p>Background</p> <p>ErbB3-binding protein 1 (Ebp1) is a member of the <it>PA2G4 </it>family of proliferation-regulated proteins that is expressed in multiple malignant and non-malignant cells. ErbB3 and other members of the EGFR family have been implicated in cancer progression, it however remains unknown whether Ebp1 participate in prostate cancer progression <it>in vivo</it>. Therefore, the present study examines Ebp1 expression in cancerous and non-cancerous prostates tissues. Ebp1 expression was also correlated to known Ebp1 regulated proteins (Androgen receptor (AR), Cyclin D1 & ErbB3) and the proliferation marker Ki67. Furthermore we evaluated whether Ebp1 expression correlated with biochemical recurrence (BCR) following radical prostatectomy.</p> <p>Methods</p> <p>The expression of Ebp1, AR, Cyclin D1, ErbB3 and Ki67 were evaluated by immunohistochemistry using three separate tissue micro-arrays containing normal prostate tissues, non-cancerous tissue adjacent to the primary tumor, hormone-sensitive and hormone-refractory cancerous tissues. Multivariate COX regression analysis was performed with four clinical parameters in order to correlate Ebp1 expression with PCa progression.</p> <p>Results</p> <p>The expression of Ebp1 significantly increased with the progression from normal to hormone sensitive and to hormone refractory PCa. Furthermore, we observed strong correlation between Ebp1 expression and the nuclear expression of AR, Cyclin D1 and ErbB3 in both normal adjacent and cancer tissues. The expression of AR, Cyclin D1 and ErbB3 in normal adjacent tissues correlated with PSA relapse, whereas Ebp1 on its own did not significantly predict PSA relapse. Finally, in a multivariate analysis with a base clinical model (Gleason, Pre-op PSA, surgical margins and P-stage) we identified the multi-marker combination of Ebp1+/Cyclin D1- as an independent predictor of PSA relapse with a hazard ratio of 4.79.</p> <p>Conclusion</p> <p>Although not related to disease recurrence, this is the first <it>in vivo </it>study to report that Ebp1 expression correlates with PCa progression.</p

Airborne fluorescent pseudomonads : What potential for virulence?

International audienc

Les ateliers du hameau Les Noires Terres à Messein (Meurthe-et-Moselle, Lorraine, France) :

L’occupation altomédiévale (VIe-VIIIe s.) au lieu-dit Les Noires Terres sur la commune de Messein, au sud de Nancy (Meurthe-et-Moselle, France, fouille 2003-2004), associe des unités composées d’un bâtiment d’habitation et de structures de type agricole (greniers, silos, enclos, cabanes excavées…) à des ateliers de production et de travail du fer (préparation du minerai, fabrication du charbon de bois, fourneaux de réduction, forgeage du fer). La présence des déchets relevant d’une chaîne opératoire complète (de la préparation du minerai à l’élaboration de produits finis), documentée par l’étude paléométallurgique, ainsi que le volume de production estimé au vu de leur quantité (plusieurs dizaines de tonnes de fer), suggèrent qu’il s’agit de l’activité principale des occupants et non pas d’une activité d’appoint aux pratiques agricoles. La nature de l’occupation est donc discutée : les vestiges découverts correspondraient aux unités d’habitation d’artisans spécialisés, avec leurs ateliers, comportant l’ensemble des installations et équipements nécessaires à leur subsistance et à leur vie quotidienne. On peut ainsi émettre l’hypothèse qu’il s’agit d’une des formes d’organisation de la production du fer dans le monde franc au cours du premier Moyen Âge, et qu’elle correspond peut-être à ce que nous laissent entrevoir les polyptiques de la période carolingienne.The Altomedieval occupation (6th-8th c.) at Les Noires Terres in Messein, to the south of Nancy (Meurthe-et-Moselle, France, excavation 2003-2004), associates elements composed of a dwelling and agricultural structures (granaries, silos, enclosures, excavated huts, etc.) with iron production and transformation workshops (iron ore preparation, wood charcoal production, reduction furnaces, iron forging). The presence of waste products corresponding to a complete chaîne opératoire (production sequence) (from iron ore preparation to finished products), documented by the paleo-metallurgical study and the production volume estimated from their quantity (several dozen tons of iron), suggest that this was the main activity of the occupants, rather than an activity secondary to agricultural activities. The nature of the occupation is thus discussed : the remains discovered could correspond to the dwellings of the specialized artisans, with their workshops, including all the installations and equipment necessary for their subsistence and daily life. We can thus propose the hypothesis that this was one of the forms of iron production organization employed by the Franks during the Early Middle Ages, and that if might correspond to that which is suggested by the polyptyques of the Carolingian period.Die frühmittelalterliche Besiedlung (6.-8. Jh.) von Les Noires Terres auf dem Gebiet der Gemeinde Messein, südlich von Nancy (Departement Meurthe-et-Moselle, Frankreich, Ausgrabung 2003-2004), besteht aus Siedlungseinheiten, die sich jeweils aus einem Wohnbau mit landwirtschaftlichen Einrichtungen (Speicherbauten, Silos, Einfriedungen, Grubenhäuser…) und Werkstätten für die Eisengewinnung und -verarbeitung (Erzaufbereitung, Holzkohlengewinnung, Rennöfen, Eisenschmieden) zusammensetzen. Die Abfälle, die von einem kompletten, durch die paläometallurgische Studie dokumentierten Verhüttungsprozess (von der Erzaufbereitung bis hin zur Formgebung der Endprodukte) zeugen, sowie das anhand der Abfälle geschätzte Produktionsvolumen (mehrere Dutzend Tonnen Eisen) legen nahe, dass es sich hier um die Hauptbeschäftigung der Bewohner handelte und nicht um eine Nebentätigkeit. Demzufolge steht die Art der Besiedlung zur Diskussion: Die Funde und Befunde würden einer auf die Eisengewinnung und -verarbeitung spezialisierte Handwerkersiedlung entsprechen mit allen für die Arbeit und den Alltag der Bewohner notwendigen Anlagen und Einrichtungen, Wohnhäusern und Werkstätten. So können wir die Hypothese vorlegen, dass es sich um eine der Organisationsformen der frühmittelalterlichen fränkischen Eisenmetallurgie handelt, welche die Urbare der karolingischen Periode erahnen lassen

Clinical Relevance of Tumor Cells with Stem-Like Properties in Pediatric Brain Tumors

BACKGROUND: Primitive brain tumors are the leading cause of cancer-related death in children. Tumor cells with stem-like properties (TSCs), thought to account for tumorigenesis and therapeutic resistance, have been isolated from high-grade gliomas in adults. Whether TSCs are a common component of pediatric brain tumors and are of clinical relevance remains to be determined. METHODOLOGY/PRINCIPAL FINDINGS: Tumor cells with self-renewal properties were isolated with cell biology techniques from a majority of 55 pediatric brain tumors samples, regardless of their histopathologies and grades of malignancy (57% of embryonal tumors, 57% of low-grade gliomas and neuro-glial tumors, 70% of ependymomas, 91% of high-grade gliomas). Most high-grade glioma-derived oncospheres (10/12) sustained long-term self-renewal akin to neural stem cells (>7 self-renewals), whereas cells with limited renewing abilities akin to neural progenitors dominated in all other tumors. Regardless of tumor entities, the young age group was associated with self-renewal properties akin to neural stem cells (P = 0.05, chi-square test). Survival analysis of the cohort showed an association between isolation of cells with long-term self-renewal abilities and a higher patient mortality rate (P = 0.013, log-rank test). Sampling of low- and high-grade glioma cultures showed that self-renewing cells forming oncospheres shared a molecular profile comprising embryonic and neural stem cell markers. Further characterization performed on subsets of high-grade gliomas and one low-grade glioma culture showed combination of this profile with mesenchymal markers, the radio-chemoresistance of the cells and the formation of aggressive tumors after intracerebral grafting. CONCLUSIONS/SIGNIFICANCE: In brain tumors affecting adult patients, TSCs have been isolated only from high-grade gliomas. In contrast, our data show that tumor cells with stem cell-like or progenitor-like properties can be isolated from a wide range of histological sub-types and grades of pediatric brain tumors. They suggest that cellular mechanisms fueling tumor development differ between adult and pediatric brain tumors

Airway Epithelial Cell Migration Dynamics: Mmp-9 Role in Cell–Extracellular Matrix Remodeling

Cell spreading and migration associated with the expression of the 92-kD gelatinase (matrix metalloproteinase 9 or MMP-9) are important mechanisms involved in the repair of the respiratory epithelium. We investigated the location of MMP-9 and its potential role in migrating human bronchial epithelial cells (HBEC). In vivo and in vitro, MMP-9 accumulated in migrating HBEC located at the leading edge of a wound and MMP-9 expression paralleled cell migration speed. MMP-9 accumulated through an actin-dependent pathway in the advancing lamellipodia of migrating cells and was subsequently found active in the extracellular matrix (ECM). Lamellipodia became anchored through primordial contacts established with type IV collagen. MMP-9 became amassed behind collagen IV where there were fewer cell–ECM contacts. Both collagen IV and MMP-9 were involved in cell migration because when cell–collagen IV interaction was blocked, cells spread slightly but did not migrate; and when MMP-9 activation was prevented, cells remained fixed on primordial contacts and did not advance at all. These observations suggest that MMP-9 controls the migration of repairing HBEC by remodeling the provisional ECM implicated in primordial contacts

A whole-genome sequence and transcriptome perspective on HER2-positive breast cancers.

HER2-positive breast cancer has long proven to be a clinically distinct class of breast cancers for which several targeted therapies are now available. However, resistance to the treatment associated with specific gene expressions or mutations has been observed, revealing the underlying diversity of these cancers. Therefore, understanding the full extent of the HER2-positive disease heterogeneity still remains challenging. Here we carry out an in-depth genomic characterization of 64 HER2-positive breast tumour genomes that exhibit four subgroups, based on the expression data, with distinctive genomic features in terms of somatic mutations, copy-number changes or structural variations. The results suggest that, despite being clinically defined by a specific gene amplification, HER2-positive tumours melt into the whole luminal-basal breast cancer spectrum rather than standing apart. The results also lead to a refined ERBB2 amplicon of 106 kb and show that several cases of amplifications are compatible with a breakage-fusion-bridge mechanism

RÔLE DE L'OCCUPATION DU SOL VIS À VIS DE LA MODÉLISATION DES FLUX ENERGÉTIQUES ET HYDRIQUES EN MILIEU URBAIN ET PÉRIURBAIN

National audienceLe projet Rosenhy vise à étudier l’impact de l’occupation du sol sur la modélisation météorologique et hydrologique en termes de flux énergétiques et hydriques, en milieu urbain et périurbain. Trois sites appartenant aux observatoires français OTHU et ONEVU sont au centre de ce projet. Le quartier urbain hétérogène du Pin sec (Nantes), imperméabilisé à environ 45%, a fait l’objet d’une campagne expérimentale durant le mois de juin 2012, visant à estimer les flux de chaleur sensible et latente avec une haute résolution spatiale et temporelle par rapport aux mesures réalisées en continu sur ce site depuis 5 ans. Deux bassins versant périurbains (La Chézine à Nantes et l’Yzeron à Lyon), avec un taux d’imperméabilisation moins important (environ 10%) mais grandissant depuis plusieurs décennies, sont aussi étudiés. Ces deux derniers sites bénéficient d’un suivi hydrométéorologique depuis 10 ans pour la Chézine et 15 ans pour l’Yzeron. Sur ces trois sites, différentes sources de données d’occupation du sol à différentes résolutions sont disponibles :différentes bases de données géographiques communément utilisées par la communauté scientifique et les collectivités et des données télédétectées (multispectrales et hyperspectrales). L’utilisation de ces données en entrée de différents modèles météorologiques et hydrologiques implique un travail d’analyse et de classification pour adapter les informations aux besoins des modèles. Dans ce projet, les différents modèles adaptés au milieu urbain ou périrubain sont évalués et améliorés. Ainsi, les modèles hydrologiques périrubains sont en développement pour prendre en compte les différentes pratiques de gestion des eaux pluviales existantes (noues, toitures végétalisées, ...). L’utilisation conjointe des données simulées par les différents modèles aidera à déterminer le rôle de la part des surfaces naturelles et artificielles sur les bilans énergétique et hydrique en milieu plus ou moins urbanisé. Le milieu périurbain étant en évolution, le projet s’intéressera aussi à des scénarios d’urbanisation prospectifs en regardant d’une part l’impact de la densification sur les scénarios construits pour l’Yzeron lors du projet AVuPUR (ANR-VMCS, 2008-2011) et d’autre part, en réfléchissant conjointement avec Nantes Métropole, aux possibles voies d’évolution sur le bassin de la Chézine

Do Surgeons Anticipate Women’s Hopes and Fears Associated with Prolapse Repair? A Qualitative Analysis in the PROSPERE Trial

Women’s preoperative perceptions of pelvic-floor disorders may differ from those of their physicians. Our objective was to specify women’s hopes and fears before cystocele repair, and to compare them to those that surgeons anticipate. We performed a secondary qualitative analysis of data from the PROSPERE trial. Among the 265 women included, 98% reported at least one hope and 86% one fear before surgery. Sixteen surgeons also completed the free expectations-questionnaire as a typical patient would. Women’s hopes covered seven themes, and women’s fears eleven. Women’s hopes were concerning prolapse repair (60%), improvement of urinary function (39%), capacity for physical activities (28%), sexual function (27%), well-being (25%), and end of pain or heaviness (19%). Women’s fears were concerning prolapse relapse (38%), perioperative concerns (28%), urinary disorders (26%), pain (19%), sexual problems (10%), and physical impairment (6%). Surgeons anticipated typical hopes and fears which were very similar to those the majority of women reported. However, only 60% of the women reported prolapse repair as an expectation. Women’s expectations appear reasonable and consistent with the scientific literature on the improvement and the risk of relapse or complication related to cystocele repair. Our analysis encourages surgeons to consider individual woman’s expectations before pelvic-floor repair

Rapid response to the M_w 4.9 earthquake of November 11, 2019 in Le Teil, Lower Rhône Valley, France

On November 11, 2019, a Mw 4.9 earthquake hit the region close to Montelimar (lower Rhône Valley, France), on the eastern margin of the Massif Central close to the external part of the Alps. Occuring in a moderate seismicity area, this earthquake is remarkable for its very shallow focal depth (between 1 and 3 km), its magnitude, and the moderate to large damages it produced in several villages. InSAR interferograms indicated a shallow rupture about 4 km long reaching the surface and the reactivation of the ancient NE-SW La Rouviere normal fault in reverse faulting in agreement with the present-day E-W compressional tectonics. The peculiarity of this earthquake together with a poor coverage of the epicentral region by permanent seismological and geodetic stations triggered the mobilisation of the French post-seismic unit and the broad French scientific community from various institutions, with the deployment of geophysical instruments (seismological and geodesic stations), geological field surveys, and field evaluation of the intensity of the earthquake. Within 7 days after the mainshock, 47 seismological stations were deployed in the epicentral area to improve the Le Teil aftershocks locations relative to the French permanent seismological network (RESIF), monitor the temporal and spatial evolution of microearthquakes close to the fault plane and temporal evolution of the seismic response of 3 damaged historical buildings, and to study suspected site effects and their influence in the distribution of seismic damage. This seismological dataset, completed by data owned by different institutions, was integrated in a homogeneous archive and distributed through FDSN web services by the RESIF data center. This dataset, together with observations of surface rupture evidences, geologic, geodetic and satellite data, will help to unravel the causes and rupture mechanism of this earthquake, and contribute to account in seismic hazard assessment for earthquakes along the major regional Cévenne fault system in a context of present-day compressional tectonics