Ecosystem dynamics in the Liguro-Provençal Basin: the role of eddies in the biological production.

We study numerically the role of mesoscale structures in the Ligurian Sea (NW Mediterranean Sea) as a possible factor affecting the spatial distribution of the chlorophyll spring bloom. We use the Regional Ocean Modeling System (ROMS) configured for the NW Mediterranean Sea (ROMS_NWMed) and satellite derived Altimetric, Sea Surface Temperature and Chlorophyll concentration data, for years 2009 and 2010. Comparison of model output with satellite and in situ data shows agreement between numerical results and observations. There is a significant interannual variability in concentration and distribution of chlorophyll in the basin during the two years of the study. The ROMS_NWMed simulation reveals the formation of a number of mesoscale eddies along the Northern rim Current characterized by a long lifetime and closed streamlines. A significant higher number of eddies is found during the chlorophyll-rich year 2010. The high number of eddies, due to the “eddy pumping mechanism”, generate spatially and temporally localised fluxes of nutrient into the euphotic zone, thus contributing to the fertilization of the Ligurian Sea. Therefore, eddies in the Ligurian rim current can have important effects on the location of development of the main patch of chlorophyll spring bloom and consequently on the local ecosystem dynamics

Ecosystem dynamics in the Liguro-Provençal Basin: the role of eddies in the biological production

We study numerically the role of mesoscale structures in the Ligurian Sea (NW Mediterranean Sea) as a possible factor affecting the spatial distribution of the chlorophyll spring bloom. We use the Regional Ocean Modeling System (ROMS) configured for the NW Mediterranean Sea (ROMS_NWMed) and satellite derived Altimetric, Sea Surface Temperature and Chlorophyll concentration data, for years 2009 and 2010. Comparison of model output with satellite and in situ data shows agreement between numerical results and observations. There is a significant interannual variability in concentration and distribution of chlorophyll in the basin during the two years of the study. The ROMS_NWMed simulation reveals the formation of a number of mesoscale eddies along the Northern rim Current characterized by a long lifetime and closed streamlines. A significant higher number of eddies is found during the chlorophyll-rich year 2010. The high number of eddies, due to the "eddy pumping mechanism", generate spatially and temporally localised fluxes of nutrient into the euphotic zone, thus contributing to the fertilization of the Ligurian Sea. Therefore, eddies in the Ligurian rim current can have important effects on the location of development of the main patch of chlorophyll spring bloom and consequently on the local ecosystem dynamics

Contribution of angiogenesis and rationale for use of targeted therapies in digestive neuroendocrine tumours

Ces dernières années, la compréhension des bases moléculaires de la tumorigenèse endocrine digestive a fait des progrès considérables. Ainsi, il a été montré que l’angiogenèse jouait un rôle essentiel dans le développement des tumeurs endocrines. Parallèlement, de nouvelles drogues qui ciblent l’angiogenèse et la transduction du signal des récepteurs des facteurs de croissance vasculaire ont été mises au point, potentiellement très utiles dans ces tumeurs hypervascularisées. Le but de ce travail est de faire une revue des données actuelles concernant l’angiogenèse tumorale et ses voies principales de signalisation dans les tumeurs neuroendocrines digestives.During these last years, the understanding of the molecular bases of digestive neuroendocrine tumor genesis made considerable progress. Angiogenesis has been demonstrated to play a major role in the development of endocrine tumors. In parallel, new drugs were developed targeting angiogenesis and the signal transduction by vascular growth factor receptors, yielding major usefulness in these hyper vascularised tumors.The aim of this work is to present a review of the current data available on angiogenesis and its main signaling pathways in digestive neuroendocrine tumors

NETest in advanced high-grade gastroenteropancreatic neuroendocrine neoplasms.

Molecular blood biomarkers are lacking for high-grade (HG) gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN). To histologically distinguish between neuroendocrine carcinoma (NEC), neuroendocrine tumors G3 (NET G3), adenocarcinoma and MINEN is often challenging. The mRNA-based NETest has diagnostic, prognostic and predictive value in neuroendocrine tumors G1-2 but has not been studied in HG GEP-NEN. Patients with advanced HG GEP-NEN were prospectively included in an observational study. A blood sample was collected before the start of chemotherapy and pseudonymised before NETest was performed. NETest results are expressed as an activity index (NETest score) from 0 to 100. The normal score cut-off is 20. Histological sections were pseudonymised before centralized pathological re-evaluation. Samples from 60 patients were evaluable with the NETest. Main primary tumor sites were colon (14), rectum (12), pancreas (11) and esophagus (7). Re-classification: 30 NEC, 12 NET G3, 3 HG-NEN ambiguous morphology, 8 MiNEN, 3 adenocarcinomas with neuroendocrine differentiation (ADNE), 3 adenocarcinomas and 1 NET G2. Elevated NETest (>20) was seen in 38/45 (84%) HG GEP-NEN, all 17 large-cell NEC (100%), 11/13 (85%) small-cell NEC, all ambiguous cases and 7/12 (64%) NET G3. NETest was elevated in 5/8 (63%) MiNEN, 2/3 ADNE, however not in 3 adenocarcinomas. Median survival was 10.2 months (9.6-10.8 95%CI) for evaluable HG GEP-NEN treated with palliative chemotherapy (n = 39), and survival was significantly shorter in patients with NETest >60 with an OS of only 6.5 months. This is the first study to evaluate use of the NETest in advanced HG GEP-NEN. The NETest was almost always elevated in GEP-NEC and in all large-cell NEC. The NETest was also frequently elevated in NET G3 and MiNEN, however cases were limited. Baseline NETest was not predictive for benefit of chemotherapy, however a NETest >60 was prognostic with a shorter survival for patients receiving chemotherapy

Molecular pathogenesis and targeted therapy of sporadic pancreatic neuroendocrine tumors

Over the past few years, knowledge regarding the molecular pathology of sporadic pancreatic neuroendocrine tumors (PNETs) has increased substantially, and a number of targeted agents have been tested in clinical trials in this tumor type. For some of these agents there is a strong biological rationale. Among them, the mammalian target of rapamycin inhibitor Everolimus and the antiangiogenic agent Sunitinib have both been approved for the treatment of PNETs. However, there is lack of knowledge regarding biomarkers able to predict their efficacy, and mechanisms of resistance. Other angiogenesis inhibitors, such as Pazopanib, inhibitors of Src, Hedgehog or of PI3K might all be useful in association or sequence with approved agents. On the other hand, the clinical significance, and potential for treatment of the most common mutations occurring in sporadic PNETs, in the MEN-1 gene and in ATRX and DAXX, remains uncertain. The present paper reviews the main molecular changes occurring in PNETs and how they might be linked with treatment options

Acinar Cell Cystadenoma (Acinar Cystic Transformation) of the Pancreas: the Radiologic-Pathologic Features

Acinar cystic transformation of the pancreas is also known as acinar cell cystadenoma (ACC), and this is an extremely rare benign lesion that was first described in April 2002. We report here on a case of a previously asymptomatic patient with pancreatic ACC and this was diagnosed by computed tomography (CT) and magnetic resonance imaging (MRI). To the best of our knowledge, there is no previous report concerning the CT or MRI features of ACC in the medical literature. We present here the CT, MRI and pathological findings of pancreatic ACC

Pancreatic ductal deletion of Hnf1b disrupts exocrine homeostasis, leads to pancreatitis and facilitates tumorigenesis

BACKGROUND AND AIMS: The exocrine pancreas consists of acinar cells that produce digestive enzymes transported to the intestine through a branched ductal epithelium. Chronic pancreatitis is characterized by progressive inflammation, fibrosis and loss of acinar tissue. These changes of the exocrine tissue are risk factors for pancreatic cancer. The cause of chronic pancreatitis cannot be identified in one-quarter of patients. Here, we investigated how duct dysfunction could contribute to pancreatitis development. METHODS: The transcription factor Hnf1b, first expressed in pancreatic progenitors, is strictly restricted to ductal cells from late embryogenesis. We have previously shown that Hnf1b is crucial for pancreas morphogenesis but its postnatal role still remains unelucidated. To investigate the role of pancreatic ducts in exocrine homeostasis, we inactivated Hnf1b gene in vivo in mouse ductal cells. RESULTS: We uncovered that postnatal Hnf1b inactivation in pancreatic ducts leads to chronic pancreatitis in adults. Hnf1bΔduct mutants display dilatation of ducts, loss of acinar cells, acinar-to-ductal metaplasia (ADM) and lipomatosis. We deciphered the early events involved, with downregulation of cystic disease-associated genes, loss of primary cilia, upregulation of signaling pathways, especially Yap pathway involved in ADM. Remarkably, Hnf1bΔduct mutants developed pancreatic intraepithelial neoplasia and promote PanIN progression in concert with KRAS. We further showed that adult Hnf1b inactivation in pancreatic ducts is associated with impaired regeneration after injury, with persistent metaplasia and initiation of neoplasia. CONCLUSION: Loss of Hnf1b in ductal cells leads to chronic pancreatitis and neoplasia. This reveals that Hnf1b deficiency may contribute to diseases of the exocrine pancreas and could gain further insight into the etiology of pancreatitis and tumorigenesis.Support to CH was received from theCentre National de la Recherche Scientifique (CNRS), the Universite Pierre et Marie Curie (UPMC)- Sorbonne Université , the GEFLUC - Les entreprises contre le Cancer, the Societe Francophone du Diabete (SFD)-Ypsomed, the programme Emergence UPMC. EQ was supported by a PhD fellowship from the French Ministère de la Recherche et de la Technologie. MF is an assistant engineer of the CNRS. TD and AS were supported by Sorbonne Université. MDV was supported by a PhD student fellowship from the European Marie Curie Initial Training Network (ITN)-Biology of Liver and Pancreatic Development and Disease (BOLD). O. O. was supported by a Master1 fellowship. RCP was supported by a postdoctoral fellowship from the American Heart Association (14POST20380262). MG was supported by the National Institutes of Health (U01 DK089540) and the Juvenile Diabetes Research Foundation (1-2011-592). CH is a permanent senior researcher of the Institut National de la Sante et de la Recherche Medicale (INSERM).S

Orographic disturbances of surface winds over the shelf waters adjacent to South Georgia

This study seeks to quantify the influence of South Georgia's orography on regional surface winds. A typical case study characterized by large-scale westerly winds is analysed using a high-resolution setup (3.3 km) of the Weather Research and Forecasting (WRF) regional model. The simulation produces significant fine-scale spatial variability which is in agreement with satellite-derived winds. The model simulation indicates that these orography-driven wind disturbances are responsible for strong wind stress curl and enhanced heat flux over the shelf waters surrounding South Georgia. Such surface forcing is entirely absent from the reanalysis, highlighting the need to use high-resolution forcing in regional ocean model simulation