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Biblio - Bibliographie IAL
Bibliographie IAL

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Recherche bibliographique scientifique

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Accueil > Références bibliographiques

biblio

2010

  • Petit, VW, Refregiers, M, Guettier, C, Jamme, F, Sebanayakam, K, Brunelle, A, Laprevote, O, Dumas, P & Le Naour, F 2010, « Multimodal spectroscopy combining time-of-flight-secondary ion mass spectrometry, synchrotron-FT-IR, and synchrotron-UV microspectroscopies on the same tissue section », Anal Chem, vol. 82, no. 9, p. 3963-8.
    Résumé : Mass spectrometry and spectroscopy-based approaches can provide an overview of the chemical composition of a tissue sample. This opens up the possibility to investigate in depth the subtle biochemical changes associated with pathological tissues. In this study, time-of-flight secondary ion mass spectrometry (TOF-SIMS) and synchrotron-FT-IR and -UV imaging were applied to the same tissue section by using the same sample holder. The tested sample involved liver cirrhosis, which is characterized by regeneration nodules surrounded by annular fibrosis. A tissue section from a cirrhotic liver was deposited on a gold coated glass slide and was initially analyzed by FT-IR microspectroscopy in order to image the distribution of lipids, proteins, sugars, and nucleic acids. This technique has identified collagen enrichment in fibrosis whereas esters were mostly distributed into the cirrhotic nodules. The exact same section was investigated using TOF-SIMS demonstrating that some molecular lipid species were differentially distributed into the fibrosis areas or cirrhotic nodules. Spectra of UV microspectroscopy obtained from the same section allowed visualizing high autofluorescence from fibrous septa confirming the presence of collagen. Altogether, these results demonstrated that TOF-SIMS and FT-IR/UV microspectroscopy analyses can be successfully performed on the same tissue section.
    Mots-clés : Fibrosis/pathology Humans Liver/ pathology Spectrometry, Fourier Transform Infrared/methods, Mass, Secondary Ion/methods Spectrophotometry, Ultraviolet/methods Spectroscopy.

  • Preudhomme, C, Guilhot, J, Nicolini, FE, Guerci-Bresler, A, Rigal-Huguet, F, Maloisel, F, Coiteux, V, Gardembas, M, Berthou, C, Vekhoff, A, Rea, D, Jourdan, E, Allard, C, Delmer, A, Rousselot, P, Legros, L, Berger, M, Corm, S, Etienne, G, Roche-Lestienne, C, Eclache, V, Mahon, FX, Guilhot, F & Interg, SIF 2010, « Imatinib plus Peginterferon Alfa-2a in Chronic Myeloid Leukemia », New England Journal of Medicine, vol. 363, no. 26, p. 2511-2521, viewed sans date, <<Go to ISI>://WOS:000285555600006>.
    Résumé : Background: Imatinib (400 mg daily) is considered the best initial therapy for patients with newly diagnosed chronic myeloid leukemia (CML) in the chronic phase. However, only a minority of patients treated with imatinib have a complete molecular remission. Methods: We randomly assigned 636 patients with untreated chronic-phase CML to receive imatinib alone at a dose of 400 mg daily, imatinib (400 mg daily) plus cytarabine (20 mg per square meter of body-surface area per day on days 15 through 28 of each 28-day cycle) or pegylated interferon (peginterferon) alfa-2a (90 microg weekly), or imatinib alone at a dose of 600 mg daily. Molecular and cytogenetic responses, time to treatment failure, overall and event-free survival, and adverse events were assessed. An analysis of molecular response at 12 months was planned. A superior molecular response was defined as a decrease in the ratio of transcripts of the tyrosine kinase gene BCR-ABL to transcripts of ABL of 0.01% or less, corresponding to a reduction of 4 log(sub 10) units or more from the baseline level, as assessed by means of a real-time quantitative polymerase-chain-reaction assay. Results: At 12 months, the rates of cytogenetic response were similar among the four groups. The rate of a superior molecular response was significantly higher among patients receiving imatinib and peginterferon alfa-2a (30%) than among patients receiving 400 mg of imatinib alone (14%) (P=0.001). The rate was significantly higher among patients treated for more than 12 months than among those treated for 12 months or less. Gastrointestinal events were more frequent among patients receiving cytarabine, whereas rash and depression were more frequent among patients receiving peginterferon alfa-2a. Conclusions: As compared with other treatments, the addition of peginterferon alfa-2a to imatinib therapy resulted in significantly higher rates of molecular response in patients with chronic-phase CML. (Funded by the French Ministry of Health and others; ClinicalTrials.gov number, NCT00219739.) N Engl J Med 2010;363:2511-21.
  • Roche, B, Roque-Afonso, AM, Sebagh, M, Delvart, V, Duclos-Vallee, JC, Castaing, D & Samuel, D 2010, « Escape hepatitis B virus mutations in recipients of antibody to hepatitis B core antigen-positive liver grafts receiving hepatitis B immunoglobulins », Liver Transpl, vol. 16, no. 7, p. 885-94.
    Résumé : A variety of prophylactic strategies are used to prevent the risk of hepatitis B virus (HBV) transmission from antibody to hepatitis B core antigen (anti-HBc)-positive donors. The mechanisms underlying the failure of HBV immunoglobulin monoprophylaxis have been poorly evaluated. Seventy-seven anti-HBc-positive grafts were used in 21 hepatitis B surface antigen (HBsAg)-positive recipients and 56 HBsAg-negative recipients. HBsAg-positive recipients received prophylaxis comprising hepatitis B immunoglobulins (HBIG) and antiviral agents, 45 HBsAg-negative recipients received a modified HBIG regimen, and 11 HBsAg-negative recipients received no prophylaxis. Both donors and recipients were screened for HBsAg, antibody to HBsAg (anti-HBs) and anti-HBc in their sera and for HBV DNA in both their sera and liver. S gene mutations were investigated after HBV reinfection. HBV infection occurred in 15 HBsAg-negative recipients (19.4%) at a median interval of 16 months (range = 6-67 months) post-transplant and in none of the HBsAg-positive recipients. HBV infections were observed in 31.6% of HBV-naive recipients and 7.7% of HBV-immune recipients receiving HBIG prophylaxis versus 100% of HBV-naive recipients (P = 0.0068) and 33% of HBV-immune recipients (P = 0.08) with no such prophylaxis. S gene mutations were identified in 9 recipients. In conclusion, priority should be given to using anti-HBc positive grafts for HBsAg-positive or HBV-immune recipients. Our study has confirmed the high risk of HBV transmission to naive recipients. HBIG monoprophylaxis was associated with a significant risk of de novo HBV infection and HBV escape mutations. In these patients, we therefore recommend prophylaxis with lamivudine or new nucleos(t)ides analogues. The potential benefits of HBIG prophylaxis combined with antiviral drugs require further evaluations. Long-term prophylaxis is needed because of the long interval of de novo HBV infection post-transplant in some patients.
    Mots-clés : &, Adolescent, Adult, Aged, Agents/therapeutic, Antigens/, Antiviral, B, B/epidemiology/immunology/, control, Envelope, Factors, genetics, Hepatitis, Humans, Immunoglobulins/, immunology, Incidence, Lamivudine/therapeutic, Liver, Longitudinal, Middle, Mutation/, Nucleosides/therapeutic, Outcome, prevention, Proteins/, Retrospective, Risk, Studies, Surface, therapeutic, Transplantation, Transplantation/, Treatment, use, Viral, Young.

  • Roche, B & Samuel, D 2010, « Hepatitis C virus: Up to the minute », Liver Transplantation, vol. 16, no. 10 Suppl 2, p. S26-S35, viewed sans date, .
  • Roche, B & Samuel, D 2010, « Are viral or host factors predictive of response to interferon-ribavirin in transplant patients with hepatitis C? », J Hepatol, vol. 52, no. 5, p. 630-2.
    Résumé : Roche, Bruno; Samuel, Didier; Comment; Editorial; England; J Hepatol. 2010 May;52(5):630-2. doi: 10.1016/j.jhep.2010.01.023. Epub 2010 Feb 18.
    Mots-clés : Antiviral Agents/therapeutic use Drug Therapy.
  • Roche, B & Samuel, D 2010, « Hepatitis: viral load predicts HBV recurrence after liver transplant », Nat Rev Gastroenterol Hepatol, vol. 7, no. 12, p. 657-8.
    Résumé : Roche, Bruno; Samuel, Didier; News; England; Nat Rev Gastroenterol Hepatol. 2010 Dec;7(12):657-8. doi: 10.1038/nrgastro.2010.165.
    Mots-clés : Chronic/ diagnosis/ virology Humans Liver Transplantation Postoperative Complications/diagnosis/virology Predictive Value of Tests Recurrence Viral Load, Hepatitis B.
  • Roque Afonso, AM, Desbois, D & Dussaix, E 2010, « Hepatitis A virus: serology and molecular diagnostics », Future Virology, vol. 5, no. 2, p. 233-242.
    Résumé : The diagnosis of hepatitis A virus (HAV) infection is based on the detection of anti-HAV IgM. Shortcomings of this serological approach include the persistence of IgM after normalization of liver enzymes or its detection during polyclonal activation of the immune system due to unrelated viral infection or autoimmune diseases. Molecular diagnosis of HAV along with anti-HAV IgG avidity measurement are helpful in case of positive IgM where laboratory evidence of acute hepatitis is absent and there is no epidemiologic link to other cases. Molecular epidemiology allows us to determine whether viruses from different locations are related to each other and provides further understanding of viral epidemiology by identifying sources and transmission modes. It has been demonstrated that the rapid turnover of HAV strains in low-endemicity countries is caused by their introduction by travelers, Growing sequence databases allow for the identification of geographic origin of viral strains. Collaboration between surveillance laboratories, including database sharing, should be promoted for deeper investigation of outbreaks and improved prevention approaches.

  • Rousseau, A, Ayoubi, F, Deveaux, C, Charbit, B, Delmau, C, Christin-Maitre, S, Jaillon, P, Uzan, G & Simon, T 2010, « Impact of age and gender interaction on circulating endothelial progenitor cells in healthy subjects », Fertil Steril, vol. 93, no. 3, p. 843-6, viewed sans date, .
    Résumé : OBJECTIVE: To assess the level of circulating endothelial progenitor cells (CEPC) in cycling women compared with men and menopausal women. DESIGN: Controlled clinical study. SETTING: Healthy, nonsmoking volunteers. PATIENT(S): Twelve women, aged 18-40 years, with regular menstrual cycles, 12 menopausal women, and two groups of 12 age-matched men were recruited. Women did not receive any hormone therapy. INTERVENTION(S): Collection of 20 mL of peripheral blood. MAIN OUTCOME MEASURE(S): The number of CEPC, defined as (Lin-/7AAD-/CD34+/CD133+/KDR+) cells per 10(6) mononuclear cells (MNC), was measured by flow cytometry. RESULT(S): The number of CEPC was significantly higher in cycling women than in age-matched men and menopausal women (26.5 per 10(6) MNC vs. 10.5 per 10(6) MNC vs. 10 per 10(6) MNC, respectively). The number of CEPC was similar in menopausal women, age-matched, and young men. CONCLUSION(S): The number of CEPC is influenced by an age-gender interaction. This phenomenon may explain in part the better vascular repair and relative cardiovascular protection in younger women as compared with age-matched men.
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  • Ruschmann, J, Ho, V, Antignano, F, Kuroda, E, Lam, V, Ibaraki, M, Snyder, K, Kim, C, Flavell, RA, Kawakami, T, Sly, L, Turhan, AG & Krystal, G 2010, « Tyrosine phosphorylation of SHIP promotes its proteasomal degradation », Experimental Hematology, vol. 38, no. 5, p. 392-402, viewed sans date, <<Go to ISI>://WOS:000277015400006>.
    Résumé : Objective. The activity of the SH2-containing-phosphatidylinositol-5'-phosphatase (SHIP, also known as SHIN), a critical hematopoietic-restricted negative regulator of the PI3 kinase (PI3K) pathway, is regulated in large part via its protein levels. We sought to determine the mechanism(s) involved in its downregulation by BCR-ABL and by interleukin (IL)-4. Materials and Methods. We used Ba/F3(p210-tetOFF) cells to study the downregulation of SHIP by BCR-ABL and bone marrow derived macrophages to study SHIP's downregulation by IL-4. Results. We show herein that BCR-ABL downregulates SHIP, but not SHIP2 or PTEN, and this can be blocked with the Src kinase inhibitor PP2, which inhibits the tyrosine phosphorylation of SHIP, or with the proteasomal inhibitor MG-132. We also show, using anti-SHIP immunoprecipitates, that c-Cbl and Cbl-b are associated with SHIP and that BCR-ABL induces SHIP's polyubiquitination. This ubiquitination can be blocked with PP2, consistent with the tyrosine phosphorylation of SHIP acting as a signal for its ubiquitination. In bone marrow derived macrophages, IL-4 also leads to the proteasomal degradation of SHIP but, unlike in Ba/F3(p210-tetOFF) cells, SHIP2 is also proteasomally degraded and the degradation of both inositol phosphatases can be prevented with PP2 or MG-132. Conclusion. Our results suggest that SHIP protein levels can be reduced via BCR-ABL and/or Src family member-induced tyrosine phosphorylation of SHIP because this triggers its polyubiquitination and degradation within the proteasome. (C) 2010 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.
  • Sadanandam, A, Varney, ML, Singh, S, Ashour, AE, Moniaux, N, Deb, S, Lele, SM, Batra, SK & Singh, RK 2010, « High gene expression of semaphorin 5A in pancreatic cancer is associated with tumor growth, invasion and metastasis », Int J Cancer, vol. 127, no. 6, p. 1373-83.
    Résumé : Semaphorin 5A (SEMA5A) is an axonal regulator molecule, which belongs to the Semaphorin family of proteins. Previously, we identified SEMA5A as a putative marker for aggressive pancreatic tumors. However, the expression, localization and functional significance of SEMA5A in pancreatic tumors remain unclear. In our study, we hypothesized that SEMA5A expression modulates pancreatic tumor growth and metastasis. We analyzed the constitutive expression and localization of SEMA5A in patient pancreatic tumors (n = 33) and unmatched normal pancreatic (n = 8) tissues and human pancreatic cancer cell lines (n = 16) with different histopathological characteristics. We observed significantly higher expression of SEMA5A protein expression (p < 0.05) in human pancreatic tumor tissue samples compared to normal pancreatic tissues. Similarly, the pancreatic cancer cell lines with higher tumorigenic and metastatic potentials as xenografts in nude mice expressed higher levels of SEMA5A mRNA compared to those with lower tumorigenic and metastatic potentials. Furthermore, we examined the functional role of SEMA5A in pancreatic tumor growth and invasion. Ectopic expression of mouse full-length Sema5A in Panc1 (SEMA5A negative) cells significantly (p < 0.05) enhanced tumorigenesis, growth and metastasis in vivo as well as proliferation, invasiveness and homotypic aggregation in vitro. Together, these data demonstrate that the expression of SEMA5A in pancreatic cancer cells regulates tumorigenesis, growth, invasion and metastasis, and it also suggests a novel target for diagnosis and treatment of pancreatic cancer.
    Mots-clés : Animals Base Sequence Blotting, Inbred BALB C Mice, Messenger/genetics, Nude Neoplasm Invasiveness/ genetics Neoplasm Metastasis/ genetics Nerve Tissue Proteins/ genetics Pancreatic Neoplasms/ genetics/pathology RNA, Western Cell Division/ genetics DNA Primers Humans Immunohistochemistry Male Membrane Proteins/ genetics Mice Mice.
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  • Safdar, A, Ma, J, Saliba, F, Dupont, B, Wingard, JR, Hachem, RY, Mattiuzzi, GN, Chandrasekar, PH, Kontoyiannis, DP, Rolston, KV, Walsh, TJ, Champlin, RE & Raad, II 2010, « Drug-induced nephrotoxicity caused by amphotericin B lipid complex and liposomal amphotericin B: a review and meta-analysis », Medicine (Baltimore), vol. 89, no. 4, p. 236-44.
    Résumé : Lipid preparations of amphotericin B, commonly used to treat fungal infections, have been demonstrated to have reduced nephrotoxicity compared to conventional amphotericin B. However, to our knowledge, a comprehensive comparison of nephrotoxicity induced by different lipid preparations of amphotericin B has not been performed. We conducted a meta-analysis to evaluate nephrotoxicity associated with amphotericin B lipid complex (ABLC) and liposomal amphotericin B (L-AmB). We searched the PubMed MEDLINE database and abstracts presented at key scientific meetings, and identified 11 studies reported between 1995 and 2008 that compared nephrotoxicity resulting from the use of these agents. Eight of the 11 studies were included in the meta-analysis. The Cochran-Mantel-Haenszel test was used to determine odds ratio (OR) and relative risk (RR), and the Breslow-Day test was used to analyze homogeneity of ORs across different studies. Analysis of all 8 studies (n = 1160) included in the meta-analysis showed an increased probability of nephrotoxicity in patients treated with ABLC versus L-AmB (OR, 1.75; RR, 1.55), but there was a significant lack of homogeneity across these studies (p < 0.001). After excluding the study by Wingard et al, the probability of experiencing nephrotoxicity was more similar between the 2 AmB lipid preparations (OR, 1.31; RR, 1.24; n = 916), particularly when the analysis included only the salvage patient population reported by Hachem et al (OR, 1.12; RR, 1.09; n = 839); the 7 remaining studies were more homogenous by Breslow-Day test (p = 0.054). Our results suggest that nephrotoxicity is generally similar for ABLC and L-AmB in patients receiving antifungal therapy and prophylaxis.
    Mots-clés : Acute Kidney Injury/ chemically induced Amphotericin B/ adverse effects/therapeutic use Antifungal Agents/ adverse effects/therapeutic use Dose-Response Relationship, Drug Drug Delivery Systems Humans.
  • Saliba, F 2010, « Current review on Anidulafungin », Journal de Mycologie Médicale, vol. 20, no. 3, p. 206-11.
    Résumé : L’anidulafungine (Ecalta®) est un inhibiteur de la synthèse des β-(1,3)-d-glucanes entraînant une altération de la paroi des champignons. L’anidulafungine a une activité fongicide sur Candida et actif sur les souches fluconazole-résistantes. Elle a montré une excellente activité in vitro contre plusieurs souches d’Aspergillus avec une action inhibitrice au niveau des sites de croissance cellulaire des hyphes. Elle est indiquée dans le traitement des candidoses invasives chez l’adulte non neutropénique. La posologie est une dose de charge unique de 200 mg le premier jour, suivie d’une dose de 100 mg/j avec un état d’équilibre atteint en 24 heures. Les particularités essentielles de l’anidulafungine est au niveau de son métabolisme la distinguant des autres échinocandines : une dégradation chimique lente, absence de métabolisme hépatique et absence d’interaction significative avec les cytochromes P450, particulièrement la ciclosporine, le tacrolimus, le voriconazole et l’amphotéricine B liposomale. Elle ne nécessite pas d’ajustement en cas d’insuffisance hépatique ou rénale quelle que soit la sévérité. L’étude pivotale a montré la supériorité de l’anidulafungine au fluconazole dans le traitement des candidoses invasives des patients sévères en réanimation. Son efficacité sur la candidose œsophagienne prouvée endoscopiquement et microbiologiquement était comparable au fluconazole et ouvre une alternative aux patients intolérants ou porteurs de souches de sensibilité réduite ou résistantes.


  • Saliba, F, Ichaï, P, Azoulay, D, Habbouchi, H, Antonini, T, Sebagh, M, Adam, R, Castaing, D & Samuel, D 2010, « Successful long-term outcome of ABO-incompatible liver transplantation using antigen-specific immunoadsorption columns », Ther Apher Dial, vol. 14, no. 1, p. 116-23, viewed sans date, .
    Résumé : ABO-incompatible (ABO-I) liver transplantation has been performed essentially in patients with acute liver failure awaiting an urgent liver transplantation. Early results with ABO-I liver transplantation were disappointing with a very low graft survival rate (20-50%). The main risk is the occurrence of severe humoral and cellular rejection, vascular thrombosis, and biliary complications. In order to avoid humoral rejection and improve graft survival, total plasma exchange in combination with an intense immunosuppressive regimen has been proposed to decrease hemagglutinin titers in ABO-I liver grafts. In some centers, this regimen was associated with splenectomy, phototherapy, and portal or arterial intrahepatic infusion therapy; however, as these patients are at high risk of sepsis, a selective approach using antigen-specific immunoadsorption with immunoadsorbent columns has been successfully proposed for ABO-I living donor kidney transplantation. Few cases have been reported following liver transplantation. We report our recent experience with three adult patients (two patients with acute liver failure, and one with severe cirrhosis and hepatic encephalopathy) transplanted in an emergency situation with an ABO-I liver graft and managed with the use of GlycoSorb ABO immunoadsorbent columns and a quadruple immunosuppressive regimen with preservation of the spleen. Eight sessions were performed in the three patients. Antigen-specific immunoadsorption greatly lowered the anti-A hemagglutinin titers. None of the three patients developed acute humoral or cellular rejection. Two patients are alive at 1.5 and 3 years follow-up with a normally functioning graft. The third patient died with a functioning graft, one month after the transplantation, from septic complications.
    Mots-clés : ABO Blood-Group System/ immunology Adult Antibodies.
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  • Samuel, D 2010, « Focus », J Hepatol, vol. 52, no. 1, p. 3-4.
    Résumé : Samuel, Didier; Introductory; England; J Hepatol. 2010 Jan;52(1):3-4. doi: 10.1016/j.jhep.2009.10.017. Epub 2009 Oct 29.
    Mots-clés : Antineoplastic Agents/administration & dosage/therapeutic use Antiviral Agents/pharmacology/ therapeutic use Carcinoma, Combination Genotype Hepacivirus/drug effects/ genetics Hepatitis C/ drug therapy Humans Liver Neoplasms/drug therapy Ribavirin/ analogs & derivatives/therapeutic use Treatment Outcome, Hepatocellular/ drug therapy Drug Delivery Systems Drug Therapy.
  • Samuel, D 2010, « Welcome editorial », J Hepatol, vol. 52, no. 1, p. 5-6.
    Résumé : Samuel, Didier; Editorial; Introductory; England; J Hepatol. 2010 Jan;52(1):5-6. doi: 10.1016/j.jhep.2009.10.021.
    Mots-clés : Europe Gastroenterology Humans Periodicals as Topic/ trends Societies, Medical.

  • Samuel, D & Ichai, P 2010, « Prognosis indicator in acute liver failure: Is there a place for cell death markers? », J Hepatol, vol. 53, no. 4, p. 593-5.
    Résumé : Samuel, Didier; Ichai, Philippe; Comment; Editorial; England; J Hepatol. 2010 Oct;53(4):593-5. doi: 10.1016/j.jhep.2010.06.002. Epub 2010 Jun 20.
    Mots-clés : Acute/ epidemiology Prognosis Risk Factors Severity of Illness Index Survival Analysis, Biological Markers/analysis Cell Death Humans Liver Failure.

  • Schmutz, V, Janel-Bintz, R, Wagner, J, Biard, D, Shiomi, N, Fuchs, RP & Cordonnier, AM 2010, « Role of the ubiquitin-binding domain of Pol eta in Rad18-independent translesion DNA synthesis in human cell extracts », Nucleic Acids Research, vol. 38, no. 19, p. 6456-6465, viewed sans date, <<Go to ISI>://WOS:000283682100019>.
    Résumé : In eukaryotic cells, the Rad6/Rad18-dependent monoubiquitination of the proliferating cell nuclear antigen (PCNA) plays an essential role in the switching between replication and translesion DNA synthesis (TLS). The DNA polymerase Pol eta binds to PCNA via a consensus C-terminal PCNA-interacting protein (PIP) motif. It also specifically interacts with monoubiquitinated PCNA thanks to a recently identified ubiquitin-binding domain (UBZ). To investigate whether the TLS activity of Pol eta is always coupled to PCNA monoubiquitination, we monitor the ability of cell-free extracts to perform DNA synthesis across different types of lesions. We observe that a cis-syn cyclobutane thymine dimer (TT-CPD), but not a N-2-acetylaminofluorene-guanine (G-AAF) adduct, is efficiently bypassed in extracts from Rad18-deficient cells, thus demonstrating the existence of a Pol eta-dependent and Rad18-independent TLS pathway. In addition, by complementing Pol eta-deficient cells with PIP and UBZ mutants, we show that each of these domains contributes to Pol eta activity. The finding that the bypass of a CPD lesion in vitro does not require Ub-PCNA but nevertheless depends on the UBZ domain of Pol eta, reveals that this domain may play a novel role in the TLS process that is not related to the monoubiquitination status of PCNA.
  • Schramm, C, Bubenheim, M, Adam, R, Karam, V, Buckels, J, O'Grady, JG, Jamieson, N, Pollard, S, Neuhaus, P, Manns, MM, Porte, R, Castaing, D, Paul, A, Traynor, O, Garden, J, Friman, S, Ericzon, BG, Fischer, L, Vitko, S, Krawczyk, M, Metselaar, HJ, Foss, A, Kilic, M, Rolles, K, Burra, P, Rogiers, X & Lohse, AW 2010, « Primary liver transplantation for autoimmune hepatitis: a comparative analysis of the European Liver Transplant Registry », Liver Transpl, vol. 16, no. 4, p. 461-9.
    Résumé : The principal aim of this study was to compare the probability of and potential risk factors for death and graft loss after primary adult and pediatric liver transplantation in patients undergoing transplantation for autoimmune hepatitis (AIH) to those in patients undergoing transplantation for primary biliary cirrhosis (PBC; used as the reference group) or alcoholic cirrhosis (used as an example of a nonautoimmune liver disease). The 5-year survival of patients undergoing transplantation for AIH (n = 827) was 0.73 [95% confidence interval (CI) = 0.67-0.77]. This was similar to that of patients undergoing transplantation for alcoholic cirrhosis (0.74, 95% CI = 0.72-0.76, n = 6424) but significantly worse than that of patients undergoing transplantation for PBC (0.83, 95% CI = 0.80-0.85, n = 1588). Fatal infectious complications occurred at an increased rate in patients with AIH (hazard ratio = 1.8, P = 0.002 with PBC as the reference). The outcome of pediatric AIH patients was similar to that of adult patients undergoing transplantation up to the age of 50 years. However, the survival of AIH patients undergoing transplantation beyond the age of 50 years (0.61 at 5 years, 95% CI = 0.51-0.70) was significantly reduced in comparison with the survival of young adult AIH patients (0.78 at 18-34 years, 95% CI = 0.70-0.86) and in comparison with the survival of patients of the same age group with PBC or alcoholic cirrhosis. In conclusion, age significantly affects patient survival after liver transplantation for AIH. The increased risk of dying of infectious complications in the early postoperative period, especially above the age of 50 years, should be acknowledged in the management of AIH patients with advanced-stage liver disease who are listed for liver transplantation. It should be noted that not all risk factors relevant to patient and graft survival could be analyzed with the European Liver Transplant Registry database.
    Mots-clés : Adolescent Adult Europe Female Hepatitis, Autoimmune/ diagnosis/ therapy Humans Ischemia Liver/surgery Liver Transplantation/ methods Male Middle Aged Registries Risk Factors Sex Factors Treatment Outcome.

  • Sorel, N, Mayeur-Rousse, C, Deverrière, S, Roy, L, Brottier-Mancini, E, Guilhot, F, Turhan, AG & Chomel, JC 2010, « Comprehensive characterization of a novel intronic pseudo-exon inserted within an e14/a2 BCR-ABL rearrangement in a patient with chronic myeloid leukemia », J Mol Diagn, vol. 12, no. 4, p. 520-4, viewed sans date, .
    Résumé : We identified a novel breakpoint cluster region-ABL rearrangement in a chronic myeloid leukemia (CML) patient. The e14/a2 (b3/a2) type BCR-ABL mRNA incorporated a 42-nucleotide intronic insertion of ABL intron Ib between BCR exon e14 and ABL exon a2. As we hypothesized that the rearrangement between BCR and ABL genes occurred near the inserted sequence and because of the relative small size of BCR intron 14, we determined the BCR-ABL breakpoint at the genomic DNA level. Using a PCR-based method, this analysis revealed that i) BCR intron 14 brought a potential lariat branch point and the polypyrimidine tract, ii) the BCR-ABL breakpoint created a chimeric acceptor site, and iii) the inserted sequence of ABL intron Ib carried at its 3' end a well-conserved donor splice site. Therefore, the inserted sequence was flanked by canonical consensus splice sites and recognized as a pseudo-exon (as shown by splice site prediction and exon finder software). Moreover, the insertion did not disrupt the reading frame between BCR and ABL and did not produce a premature stop codon. Instead, this novel BCR-ABL chimeric transcript encoded a functional oncoprotein with an in-frame insertion of 15 new amino acids.
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  • Steimer, J-L, Dahl, SG, De Alwis, DP, Gundert-Remy, U, Karlsson, MO, Martinkova, J, Aarons, L, Ahr, H-J, Clairambault, J, Freyer, G, Friberg, LE, Kern, SE, Kopp-Schneider, A, Ludwig, W-D, De Nicolao, G, Rocchetti, M & Troconiz, IF 2010, « Modelling the genesis and treatment of cancer: the potential role of physiologically based pharmacodynamics », Eur J Cancer, vol. 46, no. 1, p. 21-32, viewed sans date, .
    Résumé : Physiologically based modelling of pharmacodynamics/toxicodynamics requires an a priori knowledge on the underlying mechanisms causing toxicity or causing the disease. In the context of cancer, the objective of the expert meeting was to discuss the molecular understanding of the disease, modelling approaches used so far to describe the process, preclinical models of cancer treatment and to evaluate modelling approaches developed based on improved knowledge. Molecular events in cancerogenesis can be detected using 'omics' technology, a tool applied in experimental carcinogenesis, but also for diagnostics and prognosis. The molecular understanding forms the basis for new drugs, for example targeting protein kinases specifically expressed in cancer. At present, empirical preclinical models of tumour growth are in great use as the development of physiological models is cost and resource intensive. Although a major challenge in PKPD modelling in oncology patients is the complexity of the system, based in part on preclinical models, successful models have been constructed describing the mechanism of action and providing a tool to establish levels of biomarker associated with efficacy and assisting in defining biologically effective dose range selection for first dose in man. To follow the concentration in the tumour compartment enables to link kinetics and dynamics. In order to obtain a reliable model of tumour growth dynamics and drug effects, specific aspects of the modelling of the concentration-effect relationship in cancer treatment that need to be accounted for include: the physiological/circadian rhythms of the cell cycle; the treatment with combinations and the need to optimally choose appropriate combinations of the multiple agents to study; and the schedule dependence of the response in the clinical situation.
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  • Syhavong, B, Rasachack, B, Smythe, L, Rolain, JM, Roque-Afonso, AM, Jenjaroen, K, Soukkhaserm, V, Phongmany, S, Phetsouvanh, R, Soukkhaserm, S, Thammavong, T, Mayxay, M, Blacksell, SD, Barnes, E, Parola, P, Dussaix, E, Raoult, D, Humphreys, I, Klenerman, P, White, NJ & Newton, PN 2010, « The infective causes of hepatitis and jaundice amongst hospitalised patients in Vientiane, Laos », Trans R Soc Trop Med Hyg, vol. 104, no. 7, p. 475-83.
    Résumé : There is little information on the diverse infectious causes of jaundice and hepatitis in the Asiatic tropics. Serology (hepatitis A, B, C and E, leptospirosis, dengue, rickettsia), antigen tests (dengue), PCR assays (hepatitis A, C and E) and blood cultures (septicaemia) were performed on samples from 392 patients admitted with jaundice or raised transaminases (> or =x3) to Mahosot Hospital, Vientiane, Laos over 3 years. Conservative definitions suggested diagnoses of dengue (8.4%), rickettsioses (7.3%), leptospirosis (6.8%), hepatitis B (4.9%), hepatitis C (4.9%), community-acquired septicaemia (3.3%) and hepatitis E (1.6%). Although anti-hepatitis A virus (HAV) IgM antibody results suggested that 35.8% of patients had acute HAV infections, anti-HAV IgG antibody avidity and HAV PCR suggested that 82% had polyclonal activation and not acute HAV infections. Scrub typhus, murine typhus or leptospirosis were present in 12.8% of patients and were associated with meningism and relatively low AST and ALT elevation. These patients would be expected to respond to empirical doxycycline therapy which, in the absence of virological diagnosis and treatment, may be an appropriate cost-effective intervention in Lao patients with jaundice/hepatitis.
    Mots-clés : Adolescent Adult Child Child, Endemic Flea-Borne/diagnosis Young Adult, Human/diagnosis/ etiology Hospitalization Humans Infant Infant, Newborn Jaundice/ microbiology/virology Laos Leptospirosis/diagnosis Male Middle Aged RNA, Preschool Community-Acquired Infections/diagnosis Dengue/diagnosis Female Fever/microbiology Hepatitis, Viral, Viral/isolation & purification Rickettsia Infections/diagnosis Scrub Typhus/diagnosis Serologic Tests/methods Typhus.
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  • Tan, MH, Wong, CF, Tan, HL, Yang, XJ, Ditlev, J, Matsuda, D, Khoo, SK, Sugimura, J, Fujioka, T, Furge, KA, Kort, E, Giraud, S, Ferlicot, S, Vielh, P, Amsellem-Ouazana, D, Debre, B, Flam, T, Thiounn, N, Zerbib, M, Benoit, G, Droupy, S, Molinie, V, Vieillefond, A, Tan, PH, Richard, S & Teh, BT 2010, « Genomic expression and single-nucleotide polymorphism profiling discriminates chromophobe renal cell carcinoma and oncocytoma », BMC Cancer, vol. 10, p. 196, viewed sans date, .
    Résumé : BACKGROUND: Chromophobe renal cell carcinoma (chRCC) and renal oncocytoma are two distinct but closely related entities with strong morphologic and genetic similarities. While chRCC is a malignant tumor, oncocytoma is usually regarded as a benign entity. The overlapping characteristics are best explained by a common cellular origin, and the biologic differences between chRCC and oncocytoma are therefore of considerable interest in terms of carcinogenesis, diagnosis and clinical management. Previous studies have been relatively limited in terms of examining the differences between oncocytoma and chromophobe RCC. METHODS: Gene expression profiling using the Affymetrix HGU133Plus2 platform was applied on chRCC (n = 15) and oncocytoma specimens (n = 15). Supervised analysis was applied to identify a discriminatory gene signature, as well as differentially expressed genes. High throughput single-nucleotide polymorphism (SNP) genotyping was performed on independent samples (n = 14) using Affymetrix GeneChip Mapping 100 K arrays to assess correlation between expression and gene copy number. Immunohistochemical validation was performed in an independent set of tumors. RESULTS: A novel 14 probe-set signature was developed to classify the tumors internally with 93% accuracy, and this was successfully validated on an external data-set with 94% accuracy. Pathway analysis highlighted clinically relevant dysregulated pathways of c-erbB2 and mammalian target of rapamycin (mTOR) signaling in chRCC, but no significant differences in p-AKT or extracellular HER2 expression was identified on immunohistochemistry. Loss of chromosome 1p, reflected in both cytogenetic and expression analysis, is common to both entities, implying this may be an early event in histogenesis. Multiple regional areas of cytogenetic alterations and corresponding expression biases differentiating the two entities were identified. Parafibromin, aquaporin 6, and synaptogyrin 3 were novel immunohistochemical markers effectively discriminating the two pathologic entities. CONCLUSIONS: Gene expression profiles, high-throughput SNP genotyping, and pathway analysis effectively distinguish chRCC from oncocytoma. We have generated a novel transcript predictor that is able to discriminate between the two entities accurately, and which has been validated both in an internal and an independent data-set, implying generalizability. A cytogenetic alteration, loss of chromosome 1p, common to renal oncocytoma and chRCC has been identified, providing the opportunities for identifying novel tumor suppressor genes and we have identified a series of immunohistochemical markers that are clinically useful in discriminating chRCC and oncocytoma.
    Mots-clés : Adenoma, Biological/analysis/*genetics Tumor Suppressor Proteins/analysis, Differential Gene Dosage *Gene Expression Profiling *Gene Expression Regulation, Human, Oxyphilic/chemistry/diagnosis/*genetics Aquaporin 6/analysis Carcinoma, Pair 1 Cytogenetic Analysis Diagnosis, Renal Cell/chemistry/diagnosis/*genetics *Chromosomes, Single Nucleotide Predictive Value of Tests Reproducibility of Results Synaptogyrins Tumor Markers.
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  • Tarte, K, Gaillard, J, Lataillade, J-J, Fouillard, L, Becker, M, Mossafa, H, Tchirkov, A, Rouard, H, Henry, C, Splingard, M, Dulong, J, Monnier, D, Gourmelon, P, Gorin, N-C, Sensebé, L & Cellulaire, SF de G de M et T 2010, « Clinical-grade production of human mesenchymal stromal cells: occurrence of aneuploidy without transformation », Blood, vol. 115, no. 8, p. 1549-53, viewed sans date, .
    Résumé : Clinical-grade human mesenchymal stromal cells (MSCs) have been expanded in vitro for tissue engineering or immunoregulatory purposes without standardized culture conditions or release criteria. Although human MSCs show poor susceptibility for oncogenic transformation, 2 recent studies described their capacity to accumulate chromosomal instability and to give rise to carcinoma in immunocompromised mice after long-term culture. We thus investigated the immunologic and genetic features of MSCs expanded with fetal calf serum and fibroblast growth factor or with platelet lysate in 4 cell-therapy facilities during 2 multicenter clinical trials. Cultured MSCs showed a moderate expression of human leukocyte antigen-DR without alteration of their low immunogenicity or their immunomodulatory capacity. Moreover, some transient and donor-dependent recurring aneuploidy was detected in vitro, independently of the culture process. However, MSCs with or without chromosomal alterations showed progressive growth arrest and entered senescence without evidence of transformation either in vitro or in vivo.
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  • Tham, TN, Gouin, E, Rubinstein, E, Boucheix, C, Cossart, P & Pizarro-Cerda, J 2010, « Tetraspanin CD81 is required for Listeria monocytogenes invasion », Infect Immun, vol. 78, no. 1, p. 204-9, viewed sans date, .
    Résumé : Listeria monocytogenes is an intracellular bacterial pathogen that invades epithelial cells by subverting two cellular receptors, E-cadherin and Met. We recently identified type II phosphatidylinositol 4-kinases alpha and beta (PI4KIIalpha and PI4KIIbeta) as being required for bacterial entry downstream of Met. In this work, we investigated whether tetraspanins CD9, CD63, and CD81, which figure among the few described molecular partners of PI4KIIalpha, function as molecular adaptors recruiting PI4KIIalpha to the bacterial entry site. We observed by fluorescence microscopy that CD9, CD63, and CD81 are expressed and detected at the cellular surface and also within intracellular compartments, particularly in the case of CD63. In resting cells, colocalization of tetraspanins and PI4KIIalpha is detectable only in restricted areas of the perinuclear region. Upon infection with Listeria, endogenous CD9, CD63, and CD81 were recruited to the bacterial entry site but did not colocalize strictly with endogenous PI4KIIalpha. Live-cell imaging confirmed that tetraspanins and PI4KIIalpha do not follow the same recruitment dynamics to the Listeria entry site. Depletion of CD9, CD63, and CD81 levels by small interfering RNA demonstrated that CD81 is required for bacterial internalization, identifying for the first time a role for a member of the tetraspanin family in the entry of Listeria into target cells. Moreover, depletion of CD81 inhibits the recruitment of PI4KIIalpha but not that of the Met receptor to the bacterial entry site, suggesting that CD81 may act as a membrane organizer required for the integrity of signaling events occurring at Listeria entry sites.
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  • Tosca, L, Brisset, S, Petit, FM, Lecerf, L, Rousseau, G, Bas, C, Laroudie, M, Maurin, M-L, Tapia, S, Picone, O, Prevot, S, Goossens, M, Labrune, P & Tachdjian, G 2010, « Recurrent 70.8 Mb 4q22.2q32.3 duplication due to ovarian germinal mosaicism », Eur J Hum Genet, vol. 18, no. 8, p. 882-8, viewed sans date, .
    Résumé : A mosaicism is defined by the presence of two or more populations of cells with different genotypes in one individual. Chromosomal germinal mosaicism occurs in germ cells before the onset of meiosis. Previously, few studies have described germinal mosaicism. In this study, we report on two siblings who carried identical pure and direct interstitial 4q22.2q32.3 duplication. Procedure investigations included complete clinical description, conventional cytogenetic analysis, fluorescence in situ hybridization (FISH), comparative genomic hybridization (CGH) array experiments and microsatellite study searching for parental origin of the duplication. Microarray CGH and further FISH experiments with BAC clones showed the same 70.8 Mb direct duplication, dup(4)(q22.2q32.3). Molecular studies of the 4q duplication were consistent with maternal origin associated with mitotic or meiotic rearrangements. This structural chromosomal aberration was associated in both cases with increased nuchal translucency, growth retardation and dysmorphy. Cardiopathy and lung malformations were only evident in the first case. These clinical manifestations are similar to those previously reported in previous studies involving pure 4q trisomy of the same region, except for thumb and renal abnormalities that were not obvious in the presented cases. The amplified region included genes involved in neurological development (NEUROG2, MAB21L2, PCDH10/18 and GRIA2). The recurrent 4q duplication in these siblings is consistent with a maternal ovarian germinal mosaicism. This is the first description of germinal mosaicism for a large chromosomal duplication and highlights that genetic counselling for apparently de novo chromosome aberration should be undertaken with care.
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  • Touboul, T, Hannan, NRF, Corbineau, S, Martinez, A, Martinet, C, Branchereau, S, Mainot, S, Strick-Marchand, H, Pedersen, R, Di Santo, J, Weber, A & Vallier, L 2010, « Generation of functional hepatocytes from human embryonic stem cells under chemically defined conditions that recapitulate liver development », Hepatology, vol. 51, no. 5, p. 1754-65, viewed sans date, .
    Résumé : UNLABELLED: Generation of hepatocytes from human embryonic stem cells (hESCs) could represent an advantageous source of cells for cell therapy approaches as an alternative to orthotopic liver transplantation. However, the generation of differentiated hepatocytes from hESCs remains a major challenge, especially using a method compatible with clinical applications. We report a novel approach to differentiate hESCs into functional hepatic cells using fully defined culture conditions, which recapitulate essential stages of liver development. hESCs were first differentiated into a homogenous population of endoderm cells using a combination of activin, fibroblast growth factor 2, and bone morphogenetic protein 4 together with phosphoinositide 3-kinase inhibition. The endoderm cells were then induced to differentiate further into hepatic progenitors using fibroblast growth factor 10, retinoic acid, and an inhibitor of activin/nodal receptor. After further maturation, these cells expressed markers of mature hepatocytes, including asialoglycoprotein receptor, tyrosine aminotransferase, alpha1-antitrypsin, Cyp7A1, and hepatic transcription factors such as hepatocyte nuclear factors 4alpha and 6. Furthermore, the cells generated under these conditions exhibited hepatic functions in vitro, including glycogen storage, cytochrome activity, and low-density lipoprotein uptake. After transduction with a green fluorescent protein-expressing lentivector and transplantation into immunodeficient uPA transgenic mice, differentiated cells engrafted into the liver, grew, and expressed human albumin and alpha1-antitrypsin as well as green fluorescent protein for at least 8 weeks. In addition, we showed that hepatic cells could be generated from human-induced pluripotent cells derived from reprogrammed fibroblasts, demonstrating the efficacy of this approach with pluripotent stem cells of diverse origins. CONCLUSION: We have developed a robust and efficient method to differentiate pluripotent stem cells into hepatic cells, which exhibit characteristics of human hepatocytes. Our approach should facilitate the development of clinical grade hepatocytes for transplantation and for research on drug discovery.
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  • Touboul, T, Vallier, L & Weber, A 2010, « Robust differentiation of fetal hepatocytes from human embryonic stem cells and iPS », Med Sci (Paris), vol. 26, no. 12, p. 1061-6, viewed sans date, .
    Résumé : Hepatocyte transplantation is considered as an alternative to organ transplantation in particular for the treatment of liver metabolic diseases. However, due to the difficulties to obtain a large number of hepatocytes, new sources of cells are needed. These cells could be either of hepatic origin (hepatic stem cells) or extrahepatic such as mesenchymal stem cells or pluripotent stem cells (human embryonic stem cells [hESC] or iPS). We developed a new method to differentiate hESCs into fetal hepatocytes. These conditions recapitulate the main liver developmental stages, using fully defined medium devoid of animal products or unknown factors. The differentiated cells express many fetal hepatocytes markers (cytochrome P450 3A7, albumin, alpha-1-antitrypsin, etc.). The cells display specific hepatic functions (ammonia metabolism, excretion of indocyanin green) and are capable to engraft and express hepatic proteins two months after transplantation into newborn uPAxrag2gc-/- mouse liver. We have also showed that this approach is transposable to human iPS, and further studies on animal models will allow us to compare the in vivo potential of these two sources of pluripotent cells. Finally, only studies on large animals such as nonhuman primates will validate an eventual clinical application.
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  • Trunecka, P, Boillot, O, Seehofer, D, Pinna, AD, Fischer, L, Ericzon, BG, Troisi, RI, Baccarani, U, Ortiz de Urbina, J & Wall, W 2010, « Once-daily prolonged-release tacrolimus (ADVAGRAF) versus twice-daily tacrolimus (PROGRAF) in liver transplantation », Am J Transplant, vol. 10, no. 10, p. 2313-23, viewed sans date, .
    Résumé : The efficacy and safety of dual-therapy regimens of twice-daily tacrolimus (BID; Prograf) and once-daily tacrolimus (QD; Advagraf) administered with steroids, without antibody induction, were compared in a multicenter, 1:1-randomized, two-arm, parallel-group study in 475 primary liver transplant recipients. A double-blind, double-dummy 24-week period was followed by an open extension to 12 months posttransplant. The primary endpoint, event rate of biopsy-proven acute rejection (BPAR) at 24 weeks, was 33.7% for tacrolimus BID versus 36.3% for tacrolimus QD (Per-protocol set; p = 0.512; treatment difference 2.6%, 95% confidence interval -7.3%, 12.4%), falling within the predefined 15% noninferiority margin. At 12 months, BPAR episodes requiring treatment were similar for tacrolimus BID and QD (28.1% and 24.7%). Twelve-month patient and graft survival was 90.8% and 85.6% for tacrolimus BID and 89.2% and 85.3% for tacrolimus QD. Adverse event (AE) profiles were similar for both tacrolimus BID and QD with comparable incidences of AEs and serious AEs. Tacrolimus QD was well tolerated with similar efficacy and safety profiles to tacrolimus BID.
  • Vaghefi, P, Marchadier, E, Dussaix, E & Roque-Afonso, AM 2010, « [Hepatitis C virus genotyping: comparison of the Abbott RealTime HCV Genotype II assay and NS5B sequencing] », Pathol Biol (Paris), vol. 58, no. 2, p. 175-8.
    Résumé : PURPOSE OF THE STUDY: Hepatitis C virus genotyping is needed for treatment decision and monitoring. The results of a genotyping assay based on real-time PCR and TaqMan chemistry were compared with the results of NS5B region sequencing. MATERIALS AND METHODS: One hundred and two sera (genotypes 1-6) were tested. Amplification and detection of viral RNA were performed with the Abbott RealTime HCV Genotype II assay targeting 5'non-coded region (5'NC) for the identification of genotypes 1 to 6 and NS5B, for 1a and 1b subtypes detection. Sequencing of 5'NC fragment was used to resolve discrepant results. RESULTS: No indeterminate results were obtained. Concordance with NS5B sequencing was 93% (95 on 102), 96% at the genotype level (98 on 102) and 93% for genotype 1 subtyping (40 on 43). Discordant genotyping results were a 2f subtype identified as 5, a 6a typed as 1, a 3a identified as a 1-3 co-infection and a 4r identified as a 1-4 co-infection. Discordant subtyping results were 2 1b subtypes only typed as 1 and a 1e identified as 1a. CONCLUSION: Abbott RealTime HCV Genotype II assay is a rapid, automated and simple to interpret method for HCV genotyping. It allows the detection of possible mixed infections which might have a negative impact on therapeutic response. However, the discrepant results found in this small series underline the need for assay optimization.
    Mots-clés : Chronic/blood/virology Humans Polymerase Chain Reaction/ methods Prospective Studies RNA, Computer Systems Genotype Hepacivirus/classification/ genetics/isolation & purification Hepatitis C, Diagnostic Sequence Analysis, RNA/ methods Taq Polymerase Time Factors Viremia/virology, Viral/blood/ genetics/isolation & purification Reagent Kits.

  • Vanneaux, V, El-Ayoubi, F, Delmau, C, Driancourt, C, Lecourt, S, Grelier, A, Cras, A, Cuccuini, W, Soulier, J, Lataillade, J-J, Lebousse-Kerdiles, M-C, Oury, JF, Sibony, O, Marolleau, J-P, Benbunan, M, Uzan, G & Larghero, J 2010, « In vitro and in vivo analysis of endothelial progenitor cells from cryopreserved umbilical cord blood: are we ready for clinical application? », Cell Transplant, vol. 19, no. 9, p. 1143-55, viewed sans date, .
    Résumé : Umbilical cord blood (CB) represents a main source of circulating endothelial progenitor cells (cEPCs). In view of their clinical use, in either the autologous or allogeneic setting, cEPCs should likely be expanded from CB kept frozen in CB banks. In this study, we compared the expansion, functional features, senescence pattern over culture, and in vivo angiogenic potential of cEPCs isolated from fresh or cryopreserved CB (cryoCB). cEPCs could be isolated in only 59% of cryoCB compared to 94% for fresh CB, while CB units were matched in terms of initial volume, nucleated and CD34(+) cell number. Moreover, the number of endothelial colony-forming cells was significantly decreased when using cryoCB. Once cEPCs culture was established, the proliferation, migration, tube formation, and acetylated-LDL uptake potentials were similar in both groups. In addition, cEPCs derived from cryoCB displayed the same senescence status and telomeres length as that of cEPCs derived from fresh CB. Karyotypic aberrations were found in cells obtained from both fresh and cryoCB. In vivo, in a hind limb ischemia murine model, cEPCs from fresh and cryoCB were equally efficient to induce neovascularization. Thus, cEPCs isolated from cryoCB exhibited similar properties to those of fresh CB in vitro and in vivo. However, the low frequency of cEPCs colony formation after cryopreservation shed light on the need for specific freezing conditions adapted to cEPCs in view of their future clinical use.
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  • Verine, J, Lehmann-Che, J, Soliman, H, Feugeas, JP, Vidal, JS, Mongiat-Artus, P, Belhadj, S, Philippe, J, Lesage, M, Wittmer, E, Chanel, S, Couvelard, A, Ferlicot, S, Rioux-Leclercq, N, Vignaud, JM, Janin, A & Germain, S 2010, « Determination of angptl4 mRNA as a diagnostic marker of primary and metastatic clear cell renal-cell carcinoma », PLoS One, vol. 5, no. 4, p. e10421, viewed sans date, .
    Résumé : BACKGROUND: We have previously shown that angiopoietin-like 4 (angptl4) mRNA, a hypoxia-inducible gene, is highly expressed in clear cell renal-cell carcinoma (ccRCC), the most common subtype of RCC for which no specific marker is available. We here investigated whether angptl4 mRNA 1) could be a useful diagnostic and/or prognostic marker of ccRCC in a large and comprehensive retrospective series, 2) induction is dependent on the VHL status of tumors. METHODOLOGY/PRINCIPAL FINDINGS: Using in situ hybridization, we report that angptl4 mRNA is expressed in 100% of both sporadic (n = 102) and inherited (n = 6) primary ccRCCs, without any statistical association with nuclear grade (p = 0.39), tumor size (p = 0.09), stage grouping (p = 0.17), progression-free survival (p = 0.94), and overall survival (p = 0.80). Angptl4 mRNA was also expressed in 26 (87%) of 30 secondary ccRCCs but neither in any other secondary RCCs (n = 7). In contrast, angptl4 mRNA was neither expressed in 94% non-ccRCC renal tumors (papillary RCCs (n = 46), chromophobe RCCs (n = 28), and oncocytomas (n = 9)), nor in non-renal clear cell carcinomas (n = 39). Angptl4 expression was also examined in tumors associated (n = 23) or not associated (n = 66) with VHL disease. 40 (98%) hemangioblastomas expressed angptl4 whereas all pheochromocytomas (n = 23) and pancreatic tumors (n = 25) were angptl4-negative, whatever their VHL status. CONCLUSIONS/SIGNIFICANCE: Angptl4 mRNA expression was highly associated with ccRCC (p = 1.5 10(-49), Chi square test) allowing to define its expression as a diagnosis marker for primary ccRCC. Moreover, angptl4 mRNA allows to discriminate the renal origin of metastases of clear-cell carcinomas arising from various organs. Finally, inactivation of VHL gene is neither necessary nor sufficient for angptl4 mRNA induction.
    Mots-clés : Angiopoietins/*genetics Biological Markers Carcinoma, Differential Humans In Situ Hybridization *Molecular Diagnostic Techniques Neoplasm Metastasis RNA, Messenger/*analysis RNA, Neoplasm/analysis Retrospective Studies, Renal Cell/*diagnosis/pathology/secondary Diagnosis.
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  • Vibert, E, Azoulay, D, Hoti, E, Iacopinelli, S, Samuel, D, Salloum, C, Lemoine, A, Bismuth, H, Castaing, D & Adam, R 2010, « Progression of alphafetoprotein before liver transplantation for hepatocellular carcinoma in cirrhotic patients: a critical factor », Am J Transplant, vol. 10, no. 1, p. 129-37, viewed sans date, .
    Résumé : Liver transplantation (LT) for cirrhotic/Hepatocellular carcinoma (HCC) is associated with reduced survival in patients with poor histological features. Preoperative levels of alphafetoprotein (AFP) could predict negative biological features. AFP progression could be more relevant than static AFP levels in predicting LT outcomes. A total of 252 cirrhotic/HCC patients transplanted between 1985 and 2005 were reviewed. One hundred fifty-three patients were analyzed, 99 excluded (for nonsecreting tumors and/or salvage transplantation). Using receiver operating characteristics analysis for recurrence after LT, 'progression' of AFP was defined by >15 microg/L per month before LT. A total of 127 (83%) were transplanted under and 26 (16%) over this threshold. After 45 months of follow-up (median), 5-year overall survival (OS) and recurrence free-survival (RFS) were 72% and 69%, respectively. Five-year survival in the progression group was lower than the nonprogression group (OS 54% vs. 77%; RFS 47% vs. 74%). Multivariate analysis showed progression of AFP>15 microg/L per month and preoperative nodules>3 were associated with decreased OS. Progression group and age>60 years were associated with decreased RFS. Male gender, progression of AFP and size of tumor>30 mm were associated with satellite nodules and/or vascular invasion. In conclusion, increasing AFP>15 microg/L/month while waiting for LT is the most relevant preoperative prognostic factor for low OS/DFS. AFP progression could be a pathological preoperative marker of tumor aggressiveness.
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  • Vibert, E, Dokmak, S & Belghiti, J 2010, « Surgical strategy of biliary papillomatosis in Western countries », J Hepatobiliary Pancreat Sci, vol. 17, no. 3, p. 241-5.
    Résumé : Surgical resection, considered the optimal treatment of biliary papillomatosis, often remains incomplete due to high risk of recurrence in view of positive margins or recurrence on the remnant bile duct because of its multifocality. Resection of the whole biliary tree by liver transplantation and duodenopancreatectomy can be regarded as the only curative treatment. However, this approach has resulted in unfavorable results in patients with advanced tumor invasion and/or positive lymph nodes. For the majority of biliary tumors, preoperative assessment is often insufficient. Therefore, we advocate initial partial resection as a first step to eliminate both advanced tumor invasion and/or positive lymph nodes on definitive analysis of the specimen. We propose the strategy of initial resection for selecting the patients who would actually benefit from liver transplantation.
    Mots-clés : Bile Duct Neoplasms/pathology/ surgery Bile Ducts, Extrahepatic/pathology Bile Ducts, Intrahepatic/pathology Dilatation, Pathologic Fatal Outcome Female France Humans Liver Transplantation/contraindications Magnetic Resonance Imaging Male Middle Aged Neoplasm Invasiveness Pancreatectomy Pancreaticoduodenectomy Papilloma/pathology/ surgery Patient Selection Tomography, X-Ray Computed.
  • Vienne, A, Hobeika, E, Gouya, H, Lapidus, N, Fritsch, J, Choury, AD, Chryssostalis, A, Gaudric, M, Pelletier, G, Buffet, C, Chaussade, S & Prat, F 2010, « Prediction of drainage effectiveness during endoscopic stenting of malignant hilar strictures: the role of liver volume assessment », Gastrointest Endosc, vol. 72, no. 4, p. 728-35.
    Résumé : BACKGROUND: The optimal endoscopic approach to the drainage of malignant hilar strictures remains controversial, especially with regard to the extent of desirable drainage and unilateral or bilateral stenting. OBJECTIVE: To identify useful criteria for predicting successful endoscopic drainage. DESIGN AND SETTING: Retrospective 2-center study in the greater Paris area in France. PATIENTS: A total of 107 patients who had undergone endoscopic stenting for hilar tumors Bismuth type II, III, or IV and a set of contemporaneous cross-sectional imaging data available. INTERVENTIONS: The relative volumetry of the 3 main hepatic sectors (left, right anterior, and right posterior) was assessed on CT scans. The liver volume drained was estimated and classified into 1 of 3 classes: less than 30%, 30% to 50%, and more than 50% of the total liver volume. MAIN OUTCOME MEASUREMENTS: The primary outcome was effective drainage, defined as a decrease in the bilirubin level of more than 50% at 30 days after drainage. Secondary outcomes were early cholangitis rate and survival. RESULTS: The main factor associated with drainage effectiveness was a liver volume drained of more than 50% (odds ratio 4.5, P = .001), especially in Bismuth III strictures. Intubating an atrophic sector (<30%) was useless and increased the risk of cholangitis (odds ratio 3.04, P = .01). A drainage > 50% was associated with a longer median survival (119 vs 59 days, P = .005). LIMITATIONS: Heterogeneous population and volume assessment methodology to improve in further prospective studies. CONCLUSION: Draining more than 50% of the liver volume, which frequently requires bilateral stent placement, seems to be an important predictor of drainage effectiveness in malignant, especially Bismuth III, hilar strictures. A pre-ERCP assessment of hepatic volume distribution on cross-sectional imaging may optimize endoscopic procedures.
    Mots-clés : Aged Atrophy Bile Duct Neoplasms/complications Bile Ducts, Endoscopic Retrograde Cholangitis/epidemiology/surgery Cholestasis/mortality/ surgery Digestive System Neoplasms/ complications/pathology Drainage/ methods Endoscopy, Intrahepatic Bilirubin/blood Cholangiocarcinoma Cholangiopancreatography, X-Ray Computed Treatment Outcome.

  • Vincenti, F, Blancho, G, Durrbach, A, Friend, P, Grinyo, J, Halloran, PF, Klempnauer, J, Lang, P, Larsen, CP, Muhlbacher, F, Nashan, B, Soulillou, JP, Vanrenterghem, Y, Wekerle, T, Agarwal, M, Gujrathi, S, Shen, J, Shi, R, Townsend, R & Charpentier, B 2010, « Five-year safety and efficacy of belatacept in renal transplantation », J Am Soc Nephrol, vol. 21, no. 9, p. 1587-96, viewed sans date, .
    Résumé : Belatacept is a first-in-class co-stimulation blocker in development for primary maintenance immunosuppression. A Phase II study comparing belatacept with cyclosporine (CsA) for prevention of acute rejection and protection of renal function in kidney transplant recipients demonstrated similar efficacy and significantly higher measured GFR at 1 year for belatacept, but the incidence of posttransplantation lymphoproliferative disorder was higher. Here, we present the results for the extension of this trial, which aimed to assess long-term safety and efficacy of belatacept. Seventy-eight of 102 patients who were receiving belatacept and the 16 of 26 who were receiving CsA completed the long-term extension period. GFR remained stable in patients who were receiving belatacept for 5 years, and the incidences of death/graft loss or acute rejection were low. The frequencies of serious infections were 16% for belatacept and 27% for CsA, and neoplasms occurred in 12% of each group. No patients who were treated with belatacept and one patient who was treated with CsA developed posttransplantation lymphoproliferative disorder during the follow-up period. Serious gastrointestinal disorders occurred more frequently with belatacept (12% belatacept versus 8% CsA), and serious cardiac disorders occurred more frequently with CsA (2% belatacept versus 12% CsA). Pharmacokinetic analyses showed consistent exposure to belatacept over time. CD86 receptor saturation was higher in patients who were receiving belatacept every 4 weeks (74%) compared with every 8 weeks (56%). In conclusion, this study demonstrated high patient persistence with intravenous belatacept, stable renal function, predictable pharmacokinetics, and good safety with belatacept over 5 years.
    Mots-clés : Acute Disease Adult Antigens, CD86/analysis Cardiovascular Diseases/etiology Glomerular Filtration Rate Graft Rejection Humans Immunoconjugates/*adverse effects/immunology/pharmacokinetics Immunosuppressive Agents/*adverse effects *Kidney Transplantation/adverse effects/mortality.
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  • Vullierme, MP, Paradis, V, Chirica, M, Castaing, D, Belghiti, J, Soubrane, O, Barbare, JC & Farges, O 2010, « Hepatocellular carcinoma–what's new? », J Visc Surg, vol. 147, no. 1, p. e1-12.
    Résumé : The increasing incidence of hepatocellular carcinoma (HCC) has led several countries to standardize and update its management. This review aims at summarizing these evolutions through six questions focusing on diagnosis and treatment. The radiological diagnosis of this tumor has been refined. Besides being hypervascular at the arterial phase, the "washout" in particular at the late phase of injection has become a prominent feature. Although routine ultrasound remains the corner stone of screening, contrast ultrasound has become a very reliable characterization tool as it allows continuous monitoring of the vascular kinetics. Biopsy of the tumor allows identification of conventional or molecular prognosis features, some of which could be used in current practice. The metabolic syndrome is an increasing etiology of HCC and carcinogenesis in this context may not always require the development of formal underlying cirrhosis. Associated (in particular cardiovascular) conditions account for an increased morbidity-mortality following surgery. Liver transplantation is the most effective treatment of early-stage tumors. The limited availability of grafts has led some countries including France to implement new allocation rules that are still evaluated and might need to be refined. Sorafenib is the first medical treatment shown to be effective in the treatment of HCC. This efficacy is however still limited and its indication is therefore restricted to Child-Pugh A, OMS 0-2 patients in whom a potentially curative treatment is contraindicated.
    Mots-clés : Antineoplastic Agents/therapeutic use Benzenesulfonates/therapeutic use Carcinoma, Hepatocellular/ diagnosis/etiology/ therapy Hepatectomy Humans Liver Neoplasms/ diagnosis/etiology/ therapy Liver Transplantation Metabolic Syndrome X/complications Prognosis Pyridines/therapeutic use Risk Factors Treatment Outcome.

  • Weber, A, Touboul, T, Mainot, S, Branger, J & Mahieu-Caputo, D 2010, « Human foetal hepatocytes: isolation, characterization, and transplantation », Methods Mol Biol, vol. 640, p. 41-55, viewed sans date, .
    Résumé : Hepatocyte transplantation has become an alternative to orthotopic liver transplantation for the treatment of liver metabolic diseases. However, there is an increasing lack of donor organs and isolated mature hepatocytes are difficult to manipulate and cannot be expanded in vitro. It is therefore necessary to find alternative sources of hepatocytes, and different approaches to evaluate the therapeutic potential of stem cells of different origins are being developed. Hepatic progenitors (hepatoblasts) and/or foetal hepatocytes isolated from foetal livers may be one potential source to generate fully differentiated hepatocytes. We have reported that human foetal liver cells can be isolated and cultured. These cells also engraft and differentiate into mature hepatocytes in situ after transplantation into immunodeficient mice. Foetal cell populations could also be used as targets for gene therapy since efficient gene transfer is achieved with retroviral vectors. Use of such experimental approaches will help design strategies for clinical applications of liver cell therapy with hepatic progenitors.
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  • Wicherts, DA, de Haas, RJ, Andreani, P, Sotirov, D, Salloum, C, Castaing, D, Adam, R & Azoulay, D 2010, « Impact of portal vein embolization on long-term survival of patients with primarily unresectable colorectal liver metastases », Br J Surg, vol. 97, no. 2, p. 240-50, viewed sans date, .
    Résumé : BACKGROUND: : Portal vein embolization (PVE) increases the resectability of initially unresectable colorectal liver metastases (CLM). This study evaluated long-term survival in patients with CLM who underwent hepatectomy following PVE. METHODS: : In a retrospective analysis patients treated by PVE before major hepatectomy were compared with those who did not have PVE, and with those who had PVE without resection. RESULTS: : Of 364 patients who underwent hepatectomy, 67 had PVE beforehand and 297 did not. Those who had PVE more often had more than three liver metastases (68 versus 40.9 per cent; P < 0.001) that were more frequently bilobar (78 versus 55.2 per cent; P < 0.001), and a higher proportion underwent extended hepatectomy (63 versus 18.1 per cent; P < 0.001). Postoperative morbidity rates were 55 and 41.1 per cent respectively (P = 0.035), and overall 3-year survival rates were 44 and 61.0 per cent (P = 0.001). Thirty-two other patients who were treated by PVE but did not undergo resection all died within 3 years. CONCLUSION: : PVE increased the resectability rate of initially unresectable CLM. Among patients who had PVE, long-term survival was better in those who had resection than in those who did not. PVE is of importance in the multimodal treatment of advanced CLM.
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  • Williamson, CT, Muzik, H, Turhan, AG, Zamo, A, O'Connor, MJ, Bebb, DG & Lees-Miller, SP 2010, « ATM Deficiency Sensitizes Mantle Cell Lymphoma Cells to Poly(ADP-Ribose) Polymerase-1 Inhibitors », Molecular Cancer Therapeutics, vol. 9, no. 2, p. 347-357, viewed sans date, <<Go to ISI>://WOS:000278487200010>.
    Résumé : Poly(ADP-ribose) polymerase-1 (PARP-1) inhibition is toxic to cells with mutations in the breast and ovarian cancer susceptibility genes BRCA1 or BRCA2, a concept termed synthetic lethality. However, whether this approach is applicable to other human cancers with defects in other DNA repair genes has yet to be determined. The ataxia telangiectasia mutated (ATM) gene is altered in several human cancers including mantle cell lymphoma (MCL). Here, we characterize a panel of MCL cell lines for ATM status and function and investigate the potential for synthetic lethality in MCL in the presence of small-molecule inhibitors of PARP-1. We show that Granta-519 and UPN2 cells have low levels of ATM protein, are defective in DNA damage-induced ATM-dependent signaling, are radiation sensitive, and have cell cycle checkpoint defects: all characteristics of defective ATM function. Significantly, Granta-519 and UPN2 cells were more sensitive to PARP-1 inhibition than were the ATM-proficient MCL cell lines examined. Furthermore, the PARP-1 inhibitor olaparib (known previously as AZD2281/KU-0059436) significantly decreased tumor growth and increased overall survival in mice bearing s.c. xenografts of ATM-deficient Granta-519 cells while producing only a modest effect on overall survival of mice bearing xenografts of the ATM-proficient cell line, Z138. Thus, PARP inhibitors have therapeutic potential in the treatment of MCL, and the concept of synthetic lethality extends to human cancers with ATM alterations. Mol Cancer Ther; 9(2); 347-57. (C) 2010 AACR.
  • Yan, XB, Chen, Z & Brechot, C 2010, « Associations among Genotype 1b Hepatitis C Virus Core Protein, Protein Kinase R, and Signal Transducer and Activator of Transcription 3 », Hepat Mon, vol. 10, no. 4, p. 275-84.
    Résumé : BACKGROUND AND AIMS: Because hepatitis C virus (HCV) core protein (Core), protein kinase R (PKR), and signal transducer and activator of transcription 3 (STAT3) all play relevant roles in the pathogenesis of HCV, persistent infection and hepatocellular carcinoma (HCC) and PKR may interact with HCV Core. In this study, we further investigate the associations among HCV Core, PKR, and STAT3 and the mechanisms involved in these interactions. MATERIALS AND METHODS: Expression levels of HCV Core, PKR, eukaryotic initiation factor 2 (eIF-2alpha), phosphorylated eIF- 2alpha (p-eIF-2alpha), STAT3, and phosphorylated-STAT3 (p-STAT3) were compared between Huh-7 and replicon cell-Huh-7 cells harboring the full length of genotype 1b HCV genomes. Co-immunoprecipitation and glutathione S-transferase (GST) pull-down assay were conducted for HCV Core, PKR, and STAT3. RESULTS: HCV may have induced the expression of STAT3 and the activity of PKR (p-eIF-2alpha). HCV Core, STAT3, and PKR appear to have interacted with one another. The N-terminal 1-126 amino acid (aa) of HCV Core contributed to an interaction between HCV Core and STAT3, and only full-length PKR bound to STAT3 and p-STAT3. CONCLUSIONS: These findings suggest that HCV Core, PKR, and STAT3 can interact with each other. Specifically, HCV Core may play its role through both PKR and STAT3. Alternatively, HCV Core's binding to and activation of STAT3 might be due to the interaction between HCV Core and PKR. The distinct interactions among these three molecules are important and may reveal a new molecular mechanism in the pathogenesis of HCV-persistent infection and HCV-related HCC.
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  • Zhang, D, Xu, L, Cao, F, Wei, T, Yang, C, Uzan, G & Peng, B 2010, « Celastrol regulates multiple nuclear transcription factors belonging to HSP90's clients in a dose- and cell type-dependent way », Cell Stress Chaperones, vol. 15, no. 6, p. 939-46, viewed sans date, .
    Résumé : Celastrol, a novel HSP90 inhibitor, has recently attracted much attention due to its potential in multiple applications, such as anti-inflammation use, degenerative neuron disease relief, and tumor management. At present, the studies in celastrol's effects on HSP90's clients have focused on the kinase sub-population, while another key sub-population, nuclear transcription factors (TFs), is not being well-explored. In this study, we observe the effects of celastrol on 18 TFs (belonging to HSP90 clients) in three human cell lines: MCF-7 (breast cancer), HepG2 (hepatoma), and THP-1 (monocytic leukemia). The results show that at least half of the detectable TFs were affected by celastrol, though the effect patterns varied with cell type and dosage. Bi-directional regulations of some TFs were identified, a phenomenon not yet seen with other HSP90 inhibitors. Celastrol's capability to affect multiple TFs was consistent with its altering HSP90/TFs interactions and disrupting HSP90/Hop interaction, in addition to the reported damaging HSP90/Cdc37 interaction. This work confirms, for the first time, that celastrol has broad effects on TFs belonging to HSP90's clients, casts new light on understanding these reported actions, and suggests new possible applications for celastrol, such as diabetes management.
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  • Zhao, G, Sun, S, Du, L, Xiao, W, Ru, Z, Kou, Z, Guo, Y, Yu, H, Jiang, S, Lone, Y, Zheng, BJ & Zhou, Y 2010, « An H5N1 M2e-based multiple antigenic peptide vaccine confers heterosubtypic protection from lethal infection with pandemic 2009 H1N1 virus », Virol J, vol. 7, p. 151, viewed sans date, .
    Résumé : BACKGROUND: A 2009 global influenza pandemic caused by a novel swine-origin H1N1 influenza A virus has posted an increasing threat of a potential pandemic by the highly pathogenic avian influenza (HPAI) H5N1 virus, driving us to develop an influenza vaccine which confers cross-protection against both H5N1 and H1N1 viruses. Previously, we have shown that a tetra-branched multiple antigenic peptide (MAP) vaccine based on the extracellular domain of M2 protein (M2e) from H5N1 virus (H5N1-M2e-MAP) induced strong immune responses and cross-protection against different clades of HPAI H5N1 viruses. In this report, we investigated whether such M2e-MAP presenting the H5N1-M2e consensus sequence can afford heterosubtypic protection from lethal challenge with the pandemic 2009 H1N1 virus. RESULTS: Our results demonstrated that H5N1-M2e-MAP plus Freund's or aluminum adjuvant induced strong cross-reactive IgG antibody responses against M2e of the pandemic H1N1 virus which contains one amino acid variation with M2e of H5N1 at position 13. These cross-reactive antibodies may maintain for 6 months and bounced back quickly to the previous high level after the 2nd boost administered 2 weeks before virus challenge. H5N1-M2e-MAP could afford heterosubtypic protection against lethal challenge with pandemic H1N1 virus, showing significant decrease of viral replications and obvious alleviation of histopathological damages in the challenged mouse lungs. 100% and 80% of the H5N1-M2e-MAP-vaccinated mice with Freund's and aluminum adjuvant, respectively, survived the lethal challenge with pandemic H1N1 virus. CONCLUSIONS: Our results suggest that H5N1-M2e-MAP has a great potential to prevent the threat from re-emergence of pandemic H1N1 influenza and possible novel influenza pandemic due to the reassortment of HPAI H5N1 virus with the 2009 swine-origin H1N1 influenza virus.
    Mots-clés : Animal *Disease Outbreaks Female Humans Influenza A Virus, Animals China/epidemiology *Cross Protection Disease Models, H1N1 Subtype/immunology/*physiology Influenza A Virus, H5N1 Subtype/chemistry/*immunology Influenza Vaccines/administration & dosage/*immunology Influenza, Human/epidemiology/*immunology/*prevention & control/virology Mice Mice, Inbred BALB C Peptides/immunology Protein Structure, Tertiary Viral Matrix Proteins/administration & dosage/chemistry/*immunology.
    Note Note
    <p>2912260</p>
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    <p>2912260</p>

2009


  • Aboura, A, Dupas, C, Tachdjian, G, Portnoï, M-F, Bourcigaux, N, Dewailly, D, Frydman, R, Fauser, B, Ronci-Chaix, N, Donadille, B, Bouchard, P & Christin-Maitre, S 2009, « Array comparative genomic hybridization profiling analysis reveals deoxyribonucleic acid copy number variations associated with premature ovarian failure », J Clin Endocrinol Metab, vol. 94, no. 11, p. 4540-6, viewed sans date, .
    Résumé : INTRODUCTION: Premature ovarian failure (POF) is defined by amenorrhea of at least 4- to 6-month duration, occurring before 40 yr of age, with two FSH levels in the postmenopausal range. Its etiology remains unknown in more than 80% of cases. Standard karyotypes, having a resolution of 5-10 Mb, have identified critical chromosomal regions, mainly located on the long arm of the X chromosome. Array comparative genomic hybridization (a-CGH) analysis is able to detect submicroscopic chromosomal rearrangements with a higher genomic resolution. We searched for copy number variations (CNVs), using a-CGH analysis with a resolution of approximately 0.7 Mb, in a cohort of patients with POF. PATIENTS AND METHODS: We prospectively included 99 women. Our study included a conventional karyotype and DNA microarrays comprising 4500 bacterial artificial chromosome clones spread on the entire genome. RESULTS: Thirty-one CNVs have been observed, three on the X chromosome and 28 on autosomal chromosomes. Data have been compared to control populations obtained from the Database of Genomic Variants (http://projects.tcag.ca/variation). Eight statistically significantly different CNVs have been identified in chromosomal regions 1p21.1, 5p14.3, 5q13.2, 6p25.3, 14q32.33, 16p11.2, 17q12, and Xq28. CONCLUSION: We report the first study of CNV analysis in a large cohort of Caucasian POF patients. In the eight statistically significant CNVs we report, we found five genes involved in reproduction, thus representing potential candidate genes in POF. The current study along with emerging information regarding CNVs, as well as data on their potential association with human diseases, emphasizes the importance of assessing CNVs in cohorts of POF women.
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    <p>19837940</p>

  • Adam, R & Hoti, E 2009, « Liver transplantation: the current situation », Semin Liver Dis, vol. 29, no. 1, p. 3-18, viewed sans date, .
    Résumé : Over the years, an improving liver transplant (LT) survival rate (1- and 5-year survival of 83% and 75%, respectively) has been instrumental in establishing transplant surgery as a durable therapy for all forms of end-stage liver disease and for some malignant conditions. The success of such treatment has resulted in a progressively increasing demand for liver transplantation. However, at the same time the availability of donor organs has diminished, resulting in the number of potential recipients for liver transplantation exceeding organ supply. Several strategies have been explored with the aim to increase access to liver transplantation, including: obtaining organs from non-heart-beating donors and live donors, and splitting and using livers from expanded donor criteria. This article discusses the utility of the mentioned techniques along with other strategies (e.g., Model for End-Stage Liver Disease [MELD] score), as well as the evolution of indications, contraindications, and postoperative care.
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    <p>19235656</p>
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    <p>19235656</p>

  • Adam, R, Hoti, E, Folprecht, G & Benson, AB 2009, « Accomplishments in 2008 in the management of curable metastatic colorectal cancer », Gastrointest Cancer Res, vol. 3, no. 5 Supplement 2, p. S15-22, viewed sans date, .
    Résumé : Overview of the Disease IncidencePrognosisCurrent Therapy Standards Colorectal Liver Metastases (CRLM) Resectable TumorsStrategies to Convert Nonresectable Liver Metastases to Resectable StatusSynchronous Colorectal Liver MetastasesPredictors of Survival After Resection of CRLMPeritoneal Carcinomatosis (PC) From Colorectal CancerColorectal Pulmonary Metastases (CRPM)Colorectal Liver Metastases With Extrahepatic DiseaseAccomplishments (or Lack of Accomplishments) During the Year Therapy New Staging SystemSystemic Chemotherapy in Resectable Liver MetastasesSystemic Chemotherapy in Nonresectable Liver MetastasesSelective Internal Radiation Therapy (SIRT)Selection of Patients for Liver ResectionRadiofrequency AblationBiomarkersWhat Needs To Be Done? Optimizing Patient CareFuture Directions Comments on ResearchObstacles to Overcome.
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    <p>20011559</p>
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    <p>20011559</p>
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    <p>20011559</p>
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    <p>20011559</p>


  • Adam, R, Wicherts, DA, de Haas, RJ, Ciacio, O, Lévi, F, Paule, B, Ducreux, M, Azoulay, D, Bismuth, H & Castaing, D 2009, « Patients with initially unresectable colorectal liver metastases: is there a possibility of cure? », J Clin Oncol, vol. 27, no. 11, p. 1829-35, viewed sans date, .
    Résumé : PURPOSE: Although oncosurgical strategies have demonstrated increased survival in patients with unresectable colorectal liver metastases (CLM), their potential for cure is still questioned. The aim of this study was to evaluate long-term outcome after combining downsizing chemotherapy and rescue surgery and to define prognostic factors of cure. PATIENTS AND METHODS: All patients with initially unresectable CLM who underwent rescue surgery and had a minimum follow-up of 5 years were included. Cure was defined as a disease-free interval > or = 5 years from last hepatic or extrahepatic resection until last follow-up. RESULTS: Mean age of 184 patients who underwent resection (April 1988 through July 2002) was 56.9 years. Patients had a mean number of 5.3 metastases (bilobar in 76%), associated to extrahepatic disease in 27%. Surgery was possible after one (74%) or more (26%) lines of chemotherapy. Five- and 10-year overall survival rates were 33% and 27%, respectively. Of 148 patients with a follow-up > or = 5 years, 24 patients (16%) were considered cured (mean follow-up, 118.6 months), six (25%) of whom were considered cured after repeat resection of recurrence. Twelve "cured" patients (50%) had a disease-free interval more than 10 years. Cured patients more often had three or fewer metastases less than 30 mm (P = .03) responding to first-line chemotherapy (P = .05). Multivariate analysis identified maximum size of metastases less than 30 mm at diagnosis, number of metastases at hepatectomy three or fewer, and complete pathologic response as independent predictors of cure. CONCLUSION: Cure can be achieved overall in 16% of patients with initially unresectable CLM resected after downsizing chemotherapy. In addition to increased survival, this oncosurgical approach has real potential for disease eradication.
    Mots-clés : Adult, Aged, Analysis, Colorectal, drug, Female, Humans, Liver, Male, Middle, Neoplasm, Neoplasms/, pathology, Prognosis, Staging, surgery, Survival, therapy/pathology/secondary/.
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    <p>19273699</p>
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    <p>19273699</p>

  • Albanese, P, Caruelle, D, Frescaline, G, Delbé, J, Petit-Cocault, L, Huet, E, Charnaux, N, Uzan, G, Papy-Garcia, D & Courty, J 2009, « Glycosaminoglycan mimetics-induced mobilization of hematopoietic progenitors and stem cells into mouse peripheral blood: structure/function insights », Exp Hematol, vol. 37, no. 9, p. 1072-83, viewed sans date, .
    Résumé : OBJECTIVE: Glycosaminoglycans (GAG) are major components of bone marrow extracellular matrix because they have the property to interact with cells and growth factors in hematopoietic niches. In this study, we investigated the effect of two different chemically defined GAG mimetics on mobilization of hematopoietic stem and progenitor cells (HSPCs) in mice peripheral blood. MATERIALS AND METHODS: Mobilization was achieved by intraperitoneal injection of GAG mimetics. Mobilized cells were characterized phenotypically by reverse transcription polymerase chain reaction and fluorescence-activated cell sorting analysis and functionally by colony-forming cell, cobblestone area-forming cell and long-term culture-initiating cell assays in vitro. Radioprotection assays were performed to confirm the functionality of primitive hematopoietic cells in vivo. Involvement of stromal-derived factor-1 (SDF-1) and matrix metalloproteinase-9 (MMP-9) were investigated. RESULTS: GAG mimetics treatment induces hyperleukocytosis and mobilization of HSPC. They synergize with the effects of granulocyte colony-stimulating factor or AMD3100 on hematopoietic progenitors mobilization. Reconstitution of lethally irradiated recipient mice with peripheral blood mononuclear cells from GAG mimetic-treated donor mice improves engraftment and survival. BiAcore studies indicate that the mimetics interact directly with SDF-1. In addition, GAG mimetics-induced mobilization is associated with increased levels of pro- and active MMP-9 from bone marrow cells and increased level of SDF-1 in peripheral blood. Finally, mobilization is partially inhibited by co-injection with anti-SDF-1 antibody. CONCLUSION: This study demonstrates that GAG mimetics induce efficient mobilization of HSPCs, associated with an activation of pro-MMP-9 and a modification in the SDF-1 concentration gradient between bone marrow and peripheral blood. We suggest that structural features of GAGs can modify the nature of mobilized cells.
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    <p>19539688</p>
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    <p>19539688</p>
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    <p>19539688</p>
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    <p>19539688</p>
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    <p>19539688</p>
  • Albano, L, Bretagne, S, Mamzer-Bruneel, MF, Kacso, I, Desnos-Ollivier, M, Guerrini, P, Le Luong, T, Cassuto, E, Dromer, F & Lortholary, O 2009, « Evidence that graft-site candidiasis after kidney transplantation is acquired during organ recovery: a multicenter study in France », Clin Infect Dis, vol. 48, no. 2, p. 194-202.
    Résumé : BACKGROUND: Infections of renal grafts with Candida species can induce life-threatening complications in the recipient. METHODS: A 9-year retrospective study involving all of the transplant centers in France was designed to determine the incidence, origin, characteristics, and outcome of graft-site candidiasis that occurred after kidney transplantation. Yeasts cultured from preservation or drainage solutions and graft specimens were recorded. RESULTS: Among 18,617 kidney grafts, 18 recipients corresponding to 12 donors developed culture-confirmed graft-site candidiasis (incidence, 1 case per 1000 grafts) a median of 25 days after the graft procedure. Clinical presentations included 14 cases of renal arteritis (13 were complicated by aneurysm), 1 urinoma, 2 graft site abscesses, and 1 surgical site infection. Candida albicans was involved in 13 cases. A unique C. albicans genotype or a single rare Candida species was involved in each episode. Together with the clinical history, these findings demonstrate that organ contamination followed by transmission to the recipient occurred during recovery. Therapeutic management varied from simple monitoring in 1 case to a combination of surgery (nephrectomy in 9 cases and arterial bypass in 9 cases) and antifungal therapy (14 cases). Overall, 3 of 18 kidney transplant recipients died, and 9 had their graft surgically removed. CONCLUSION: Graft-transmitted candidiasis that ends most often in fungal arteritis is associated with high morbidity and mortality after kidney transplantation and is related to organ contamination during recovery in the donor.
    Mots-clés : &, Adult, adverse, Aged, Candida/classification/genetics/, Candidiasis/, effects, epidemiology/etiology, Factors, Female, France/epidemiology, Genotype, Humans, Incidence, isolation, Kidney, Male, Middle, Outcome, purification, Retrospective, Risk, Studies, Transplantation/, Treatment.


  • André, M, Chambrion, C, Charrin, S, Soave, S, Chaker, J, Boucheix, C, Rubinstein, E & Le Naour, F 2009, « In situ chemical cross-linking on living cells reveals CD9P-1 cis-oligomer at cell surface », J Proteomics, vol. 73, no. 1, p. 93-102, viewed sans date, .
    Résumé : Tetraspanins are integral membrane proteins involved in a variety of physiological and pathological processes. They associate with each other in multimolecular complexes containing numerous membrane proteins. As a first step towards the study of the supramolecular organization of tetraspanin complexes, we have implemented a proteomic approach based on in situ protein cross-linking on living cells followed by affinity purification of tetraspanin complexes. This allowed observing the presence of high molecular weight protein complexes that were characterized as containing CD9P-1/CD315 using LC-MS/MS. Western blot analyses and the use of different tags demonstrated the presence of CD9P-1 oligomer in cis-association at cell surface. A significant amount of CD9P-1 oligomer was observed on various cell types. We have shown that CD9P-1 self-associates independently from its association with tetraspanins. However, the expression level of CD9 or CD81 that associate directly and specifically with CD9P-1, positively modulates the cross-linking efficiency of CD9P-1. Thus, tetraspanins can play a role on CD9P-1 oligomerization status.
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    <p>19703604</p>
  • Antonini, TM & Samuel, D 2009, « [Indications and results of liver transplantation (excluding hepatocellular carcinoma and fulminant hepatitis)] », Gastroenterol Clin Biol, vol. 33, no. 1 Pt 1, p. 44-50.
    Résumé : Antonini, T M; Samuel, D; France; Gastroenterol Clin Biol. 2009 Jan;33(1 Pt 1):44-50. doi: 10.1016/j.gcb.2008.11.004. Epub 2008 Dec 25.
    Mots-clés : &, Analysis, data, Diseases/mortality/, Donors, Europe, Humans, Liver, Living, numerical, surgery, Survival, Transplantation/statistics.

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