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Le Touquet – Paris-Plage, France

Geles K.G.,Pfizer | Zhong W.,Pfizer | O'Brien S.K.,Pfizer | Baxter M.,Pfizer | And 4 more authors.
Translational Oncology | Year: 2016

Intratumoral heterogeneity in non–small cell lung cancer (NSCLC) has been appreciated at the histological and cellular levels, but the association of less differentiated pathology with poor clinical outcome is not understood at the molecular level. Gene expression profiling of intact human tumors fails to reveal the molecular nature of functionally distinct epithelial cell subpopulations, in particular the tumor cells that fuel tumor growth, metastasis, and disease relapse. We generated primary serum-free cultures of NSCLC and then exposed them to conditions known to promote differentiation: the air-liquid interface (ALI) and serum. The transcriptional network of the primary cultures was associated with stem cells, indicating a poorly differentiated state, and worse overall survival of NSCLC patients. Strikingly, the overexpression of RNA splicing and processing factors was a prominent feature of the poorly differentiated cells and was also observed in clinical datasets. A genome-wide analysis of splice isoform expression revealed many alternative splicing events that were specific to the differentiation state of the cells, including an unexpectedly high frequency of events on chromosome 19. The poorly differentiated cells exhibited alternative splicing in many genes associated with tumor progression, as exemplified by the preferential expression of the short isoform of telomeric repeat-binding factor 1 (TERF1), also known as Pin2. Our findings demonstrate the utility of the ALI method for probing the molecular mechanisms that underlie NSCLC pathogenesis and provide novel insight into posttranscriptional mechanisms in poorly differentiated lung cancer cells. © 2016 The Authors. Published by Elsevier Inc.

Vasconcelos D.M.,University of Porto | Vasconcelos D.M.,Abel Salazar Biomedical Sciences Institute | Falentin-Daudre C.,CNRS Laboratory of Chemistry, Structures, Biomaterials Properties and Therapeutic Agents | Blanquaert D.,CERAVER | And 4 more authors.
Materials Science and Engineering C | Year: 2014

Joint implant-related infections, namely by Staphylococci, are a worldwide problem, whose consequences are dramatic. Various methods are studied to fight against these infections. Here, the proposed solution consists in grafting a bioactive polymer on joint implant surfaces in order to allow the control of the interactions with the living system. In this study, sodium styrene sulfonate, bearing sulfonate groups, was grafted on the surface of titanium alloys. Scanning Electron Microscopy, colorimetric method, Fourier-transformed infrared spectroscopy and contact angle measurements were applied to characterize the surfaces. Bacterial adhesion studies were studied on poly(sodium styrene sulfonate) grafted Ti6Al4V and Ti6Al4V surfaces previously adsorbed by proteins involved in the bacteria adhesion process. Fibrinogen and fibronectin were demonstrated to increase staphylococcal adhesion on Ti6Al4V surfaces. Ti6Al4V grafted sodium styrene sulfonate surfaces inhibited the adhesion of Staphylococcus epidermidis in 37% and 13% on pre-adsorbed surfaces with fibrinogen and fibronectin, respectively. The mechanism of the observed inhibiting bacteria adhesion properties is related to the differences of proteic conformations induced by poly(sodium styrene sulfonate) grafting. © 2014 Elsevier B.V.

Diaxonhit | Date: 2013-03-29

Pharmaceutical products for the treatment of diseases; chemical and biological reagents for medical use for diagnostics, namely chemical and biological reagents for use in tests based on blood or biological biomarkers enabling the identification of patients affected by diseases or being at risk of developing a disease and for enabling the identification of patients responding to specific personalized medical treatments; biological acidic products and preparations for pharmaceutical purposes, namely pharmaceutical preparations for diagnosing diseases; capsules sold empty for medicines and diagnostic tests;chemico-pharmaceutical preparations for diagnosing, preventing and treating diseases; biopharmaceutical products for diagnosing, preventing and treating diseases; chemical preparations for medical, pharmaceutical or veterinary purposes, especially chemical preparations for diagnosing diseases and in particular infectious diseases, neurodegenerative diseases and cancers; medical and clinical diagnostic products namely beads, microspheres, nucleic acid or antigen banks, nucleic acids, antigens on beads, or on microspheres, on biochips or on other media; DNA libraries, RNA libraries and antigen libraries, namely biological materials for medical diagnosis and companion diagnosis for medical purposes; nucleic acid or antigen sequences, namely biological materials intended for medical use and medical diagnosis, namely for decoding the genes and proteins affected by diseases or revealing the transcriptomic signature of patients affected by diseases and for the detection of specific antibodies produced by patients affected by diseases; enzymes or enzyme preparations for medical or veterinary purposes namely enzyme stabilizers and enzymatic substrates for use as ingredients in medicines for the treatment of diseases; chemical reagents for medical use contained in diagnostic testing kits for collecting biological samples required for the preservation of the biological material under analysis to carry out the test in appropriate conditions. Surgical, medical, dental and veterinary apparatus and instruments, especially apparatus and instruments, including fluorescent instruments used for identifying diseases, assessing the severity of these diseases, assessing prognoses of these diseases, measuring the progression of a disease; medical devices using beads, microspheres and fluorescent instruments, or biopsies for analyzing blood or other biological materials; apparatus for medical use for analyzing blood or other products of the human body; apparatus for for medical diagnosis, namely, kits for taking samples of blood or other products of the human body comprising medical instruments for taking blood, DNA collection for diagnosing diseases, and materials required for the preservation of any product of the human body under analysis to carry out the test under good conditions; spoons for administering medicine; containers specially adapted to the application of medicines namely small bags and pouches used for administering medicines;probes for medical use; syringes for medical use; galvanic therapeutic appliances particularly for diagnosing diseases; probes and kits for medical and clinical diagnosis. Research and development for others of pharmaceutical molecules or biological markers for diagnostic purposes and medicines for treating diseases; chemical analysis; chemical research; chemistry services, namely analysis of RNA genes, antigens, tissue and samples of blood or other biological materials; biotechnological project studies for identifying people suffering from diseases and to measure the severity of these diseases, the prognoses, progression and conversion of the disease and to determine the responsiveness of patients to treatments, especially personalized medical treatments; research and development of new products for others;biological research; biotechnological research; technical research in the field of biotechnology; biotechnological analysis services; laboratory analysis, namely quantification of nucleic acid content intended for medical and scientific research. Medical services; veterinary services; medical assistance; consultancy in the field of biotechnology and pharmacy namely to assist in the selection of people suffering from diseases for clinical trials and to offer targeted care and personalized medical solutions; hospital services; services for the pharmaceutical industry and pharmacists (preparation of prescriptions) namely immunology, infectiology, cancerology, geriatric and/or neurological services, in order to facilitate diagnoses and undertaking therapy; health care services; telemedicine services.

Diaxonhit | Date: 2012-08-17

The present invention relates to novel thiazolo[5,4-f]quinazoline compounds and methods that are useful in the amelioration, treatment or control of Downs syndrome or early Alzheimers disease or in the amelioration, treatment or control of cancers, especially solid tumors. More specifically, the invention relates to DYRK1A and/or DYRK1B inhibitors and to methods for preparing such compounds.

Marmor S.,Service de chirurgie orthopedique | Bauer T.,Service de Chirurgie Orthopedique et Traumatologie | Desplaces N.,Service de microbiologie | Heym B.,Laboratoire Of Microbiologie | And 13 more authors.
Journal of Clinical Microbiology | Year: 2016

We developed and evaluated a multiplex antibody detection-based immunoassay for the diagnosis of prosthetic joint infections (PJIs). Sixteen protein antigens from three Staphylococcus species (Staphylococcus aureus, Staphylococcus epidermidis, and Staphylococcus lugdunensis) (8 antigens), Streptococcus agalactiae (4 antigens), and Propionibacterium acnes (4 antigens) were selected by comparative immunoproteomics using serum samples from PJI cases versus controls. A bead-based multiplex immunoassay that measured serum IgG against purified, recombinant forms of each of the 16 antigens was developed. We conducted a prospective study to evaluate the performance of the assay. A PJI was defined by the presence of a sinus tract and/or positive intraoperative sample cultures (at least one sample yielding a virulent organism or at least two samples yielding the same organism). A total of 455 consecutive patients undergoing revision or resection arthroplasty (hip, 66.3%; knee, 29.7%; shoulder, 4%) at two French reference centers for the management of PJI were included: 176 patients (38.7%) were infected and 279 (61.3%) were not. About 60% of the infections involved at least one of the species targeted by the assay. The sensitivity/specificity values were 72.3%/80.7% for targeted staphylococci, 75%/92.6% for S. agalactiae, and 38.5%/84.8% for P. acnes. The assay was more sensitive for infections occurring>3 months after arthroplasty and for patients with an elevated C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR). However, it detected 64.3% and 58.3% of targeted staphylococcal infections associated with normal CRP and ESR values, respectively. This new multiplex immunoassay approach is a novel noninvasive tool to evaluate patients suspected of having PJIs and provides information complementary to that from inflammatory marker values. © Copyright 2016, American Society for Microbiology. All Rights Reserved.

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