Foraminifera as potential bio-indicators of the “

Benthic foraminifera are used as potential bio-indicators of pollution due to the “Erika” oil spill. The foraminiferal assemblages from a site situated on the tidal mudflat of the southern Bay of Bourgneuf (Vendée, France) have been sampled 19 times on a monthly/bimonthly scale. The field study reveals uncommon low densities and poor faunas in the first 21 months of the survey. In order to understand the effect of the “Erika” fuel, foraminiferal cultures with 0 to 72.0 mg per 100 ml of “Erika” oil were maintained in controlled conditions in the laboratory. In the laboratory, an experiment with 5.5 mg per 100 ml of oil shows morphological abnormalities, cellular modifications and a low rate of reproduction. These first results confirm the potential toxicity of the fuel No. 2 from “Erika” and the sensitivity of foraminifera to this pollutant

Predicting drug response and toxicity based on gene polymorphisms

International audienceThe sequencing of the human genome has allowed the identification of thousands of gene polymorphisms, most often single nucleotide polymorphims (SNP), which may play an important role in the expression level and activity of the corresponding proteins. When these polymorphisms occur at the level of drug metabolising enzymes or transporters, the disposition of the drug may be altered and, consequently, its efficacy may be compromised or its toxicity enhanced. Polymorphisms can also occur at the level of proteins directly involved in drug action, either when the protein is the target of the drug or when the protein is involved in the repair of drug-induced lesions. There again, these polymorphisms may lead to alterations in drug efficacy and/or toxicity. The identification of functional polymorphisms in patients undergoing chemotherapy may help the clinician prescribe the optimal drug combination or schedule and predict with more accuracy the response to these prescriptions. We have recorded in this review the polymorphisms that have been identified up till now in genes involved in anticancer drug activity. Some of them appear especially important in predicting drug toxicity and should be determined in routine before drug administration; this is the case of the most common variations of thiopurine methyltransferase for 6-mercaptopurine and of dihydropyrimidine dehydrogenase for fluorouracil. Other appear determinant for drug response, such as the common SNPs found in glutathione S-transferase P1 or xereoderma pigmentosum group D enzyme for the activity of oxaliplatin. However, confusion factors may exist between the role of gene polymorphisms in cancer risk or overall prognosis and their role in drug response

Identification des différences de traitement des évènements internes, agressions internes et agressions naturelles extrêmes, lors de l’évaluation du risque d’une installation industrielle.

International audienceCet article présente les travaux effectués dans le cadre du projet IMdR P18-1 (souscrit par EDF, INERIS, IRSN, TOTAL), qui vise à améliorer l'évaluation de risques, dans le cas où des installations industrielles ou nucléaires peuvent se trouver menacées par des agressions naturelles extrêmes. L'objectif final est de permettre aux industriels de poursuivre l'inter-comparaison de leurs pratiques et de leur proposer un formalisme de traitement cohérent et de portée générale des évènements internes et agressions internes ou agressions externes ainsi que des éléments pouvant contribuer à arbitrer des actions d'amélioration possibles de leurs systèmes

Major Efficacy of Trabectedin in 2 Metastatic Osteosarcoma Patients with Wild-Type Asp1104 ERCC5 Tumor Status

International audienc

Development of a molecular recognition based approach for multi-residue extraction of estrogenic endocrine disruptors from biological fluids coupled to liquid chromatography-tandem mass spectrometry measurement

International audienceMulti-residue methods permitting the high-throughput and affordable simultaneous determination of an extended range of endocrine disrupting chemicals (EDCs) with reduced time and cost of analysis is of prime interest in order to characterize a whole set of bioactive compounds. Such a method based on UHPLC-MS/MS measurement and dedicated to 13 estrogenic EDCs was developed and applied to biological matrices. Two molecular recognition-based strategies, either molecular imprinted polymer (MIP) with phenolic template or estrogen receptors (ERα) immobilized on a sorbent, were assessed in terms of recovery and purification efficiency. Both approaches demonstrated their suitability to measure ultra-trace levels of estrogenic EDCs in aqueous samples. Applicability of the MIP procedure to urine and serum samples has also been demonstrated

Role of Calcium Signaling in GA101-Induced Cell Death in Malignant Human B Cells

GA101/obinutuzumab is a novel type II anti-CD20 monoclonal antibody (mAb), which is more effective than rituximab (RTX) in preclinical and clinical studies when used in combination with chemotherapy. Ca2+ signaling was shown to play a role in RTX-induced cell death. This report concerns the effect of GA101 on Ca2+ signaling and its involvement in the direct cell death induced by GA101. We reveal that GA101 triggered an intracellular Ca2+ increase by mobilizing intracellular Ca2+ stores and activating Orai1-dependent Ca2+ influx in non-Hodgkin lymphoma cell lines and primary B-Cell Chronic Lymphocytic Leukemia (B-CLL) cells. According to the cell type, Ca2+ was mobilized from two distinct intracellular compartments. In Raji, BL2, and B-CLL cells, GA101 induced a Ca2+ release from lysosomes, leading to the subsequent lysosomal membrane permeabilization and cell death. Inhibition of this calcium signaling reduced GA101-induced cell death in these cells. In SU-DHL-4 cells, GA101 mobilized Ca2+ from the endoplasmic reticulum (ER). Inhibition of ER replenishment, by blocking Orai1-dependent Ca2+ influx, led to an ER stress and unfolded protein response (UPR) which sensitized these cells to GA101-induced cell death. These results revealed the central role of Ca2+ signaling in GA101’s action mechanism, which may contribute to designing new rational drug combinations improving its clinical efficacy

Comparison of ACR 1987 and ACR/EULAR 2010 criteria for predicting a 10-year diagnosis of rheumatoid arthritis.

International audienceOBJECTIVE: To compare the diagnostic accuracy of the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) and 1987 ACR criteria for rheumatoid arthritis (RA) in a cohort of patients with recent-onset arthritis followed-up for 10 years. METHODS: One hundred and sixty-four patients with recent-onset arthritis of less than 1 year's duration were included prospectively between 1995 and 1997. The diagnosis of RA was defined as having a diagnosis of RA made by the office-based rheumatologist 10 years after enrolment. We compared the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the criteria sets at baseline. RESULTS: At baseline, 60 of the 164 patients had alternative diagnoses better explaining the arthritis and 13 had erosions typical for RA; of the 91 remaining patients, 33 had at least 6 ACR/EULAR points (indicating definite RA), and 58 had fewer than 6 points. The ACR/EULAR criteria had a quite similar sensitivity than the 1987 ACR criteria (33/57 [57.9%] for ACR/EULAR criteria vs 34/57 [59.6%] for the 1987 ACR criteria), but higher specificity, PPV, and NPV (95/107 [88.8%], 34/46 [73.9%], and 95/118 [80.5%], respectively) than the 1987 ACR criteria (80/107 [74.8%], 33/63 [52.4%], and 80/104 [76.9%], respectively). CONCLUSION: ACR/EULAR criteria performed substantially better than ACR 1987 criteria for predicting a diagnosis of RA after 10 years. Much of the improvement was ascribable to the use of exclusion criteria. BULLET POINTS: (1) The ACR/EULAR criteria had the same sensitivity, but higher specificity, PPV, and NPV than the 1987 ACR criteria; (2) Much of the improvement was ascribable to the use of exclusion criteria