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Biblio - Bibliographie IAL
Bibliographie IAL

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Recherche bibliographique scientifique

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Accueil > Références bibliographiques

biblio

2012


  • Palesh, OG, Mustian, KM, Peppone, LJ, Janelsins, M, Sprod, LK, Kesler, S, Innominato, PF, Roth, T, Manber, R, Heckler, C, Fiscella, K & Morrow, GR 2012, « Impact of paroxetine on sleep problems in 426 cancer patients receiving chemotherapy: a trial from the University of Rochester Cancer Center Community Clinical Oncology Program », Sleep Med, vol. 13, no. 9, p. 1184-90, viewed sans date, .
    Résumé : BACKGROUND: Sleep problems are a frequent distressing symptom in cancer patients, yet little is known about their treatment. Sleep problems and depression frequently co-occur, leading healthcare professionals to treat depression with the expectation that sleep problems will also improve. The purpose of this study was to compare the effect of paroxetine to placebo on sleep problems via a secondary data analysis of a RCT designed to compare the effects of paroxetine to placebo on fatigue in cancer patients undergoing chemotherapy. A previously published report found a significant effect of paroxetine on depression in this cohort. METHODS: A total of 426 patients were randomized following Cycle 2 of chemotherapy to receive either 20mg of paroxetine or placebo. Sleep problems were assessed using questions from the Hamilton Depression Inventory three times during chemotherapy. RESULTS: A total of 217 patients received paroxetine and 209 received placebo. Significantly fewer patients taking paroxetine reported sleep problems compared to patients on placebo (Paroxetine 79% versus Placebo 88%; p<0.05). These differences remained significant even after controlling for baseline sleep problems and depression (p<0.05). CONCLUSION: Paroxetine had a significant benefit on sleep problems in both depressed and non-depressed cancer patients. However, rates of sleep problems remained high even among those effectively treated for depression with paroxetine. There is a need to develop and deliver sleep-specific interventions to effectively treat sleep-related side effects of cancer treatments. These findings suggest that sleep problems and depression are prevalent and co-morbid. Cancer progression, its response to treatment, and overall patient survival are intricately linked to host factors, such as inflammatory response and circadian rhythms, including sleep/wake cycles. Sleep problems and depression are modifiable host factors that can influence inflammation and impact cancer progression and quality of life. Future research should focus on discovering the pathogenesis of sleep dysregulation and depression in cancer so that better treatment approaches can be developed to ameliorate these symptoms.
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  • Palesh, O, Peppone, L, Innominato, PF, Janelsins, M, Jeong, M, Sprod, L, Savard, J, Rotatori, M, Kesler, S, Telli, M & Mustian, K 2012, « Prevalence, putative mechanisms, and current management of sleep problems during chemotherapy for cancer », Nat Sci Sleep, vol. 4, p. 151-162, viewed sans date, .
    Résumé : Sleep problems are highly prevalent in cancer patients undergoing chemotherapy. This article reviews existing evidence on etiology, associated symptoms, and management of sleep problems associated with chemotherapy treatment during cancer. It also discusses limitations and methodological issues of current research. The existing literature suggests that subjectively and objectively measured sleep problems are the highest during the chemotherapy phase of cancer treatments. A possibly involved mechanism reviewed here includes the rise in the circulating proinflammatory cytokines and the associated disruption in circadian rhythm in the development and maintenance of sleep dysregulation in cancer patients during chemotherapy. Various approaches to the management of sleep problems during chemotherapy are discussed with behavioral intervention showing promise. Exercise, including yoga, also appear to be effective and safe at least for subclinical levels of sleep problems in cancer patients. Numerous challenges are associated with conducting research on sleep in cancer patients during chemotherapy treatments and they are discussed in this review. Dedicated intervention trials, methodologically sound and sufficiently powered, are needed to test current and novel treatments of sleep problems in cancer patients receiving chemotherapy. Optimal management of sleep problems in patients with cancer receiving treatment may improve not only the well-being of patients, but also their prognosis given the emerging experimental and clinical evidence suggesting that sleep disruption might adversely impact treatment and recovery from cancer.
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  • Panigrahi, R, Biswas, A, Banerjee, A, Singh, SP, Panigrahi, MK, Roque-Afonso, AM, Das, HS, Mahapatra, PK, Chakrabarti, S & Chakravarty, R 2012, « Subgenotype D5, BCP and MHR mutations in hepatic complications among hepatitis B virus infected patients from Orissa, India », Infect Genet Evol, vol. 12, no. 8, p. 1622-9.
    Résumé : The study was undertaken to investigate the clinical implications of hepatitis B virus (HBV) genotypes, basal core promoter (BCP), precore (PC) and surface gene mutations in HBV infected patients from Orissa, southeastern India. HBV infections were identified by serology testing and HBV DNA amplification by polymerase chain reaction among the 152 patients. After sequencing, surface gene mutation were studied by sequence analysis as well as by using BLOSUM scores and BCP mutations were studied only by sequence analysis. A high proportion of HBV/D5 (66.0%) was found among the study samples having significant relation with liver cirrhosis (LC) and hepatocellular carcinoma (HCC) patients (p<0.05). The BCP mutation, TA (81.4%) and C1753/TA (75.0%) was found in significant proportion (p<0.05) among HCC cases and in fact a gradual increase in these mutations were noted between inactive carriers (IC) to HCC group and also showed higher viral load. An increasing trend of major hydrophilic region (MHR) mutations in S gene was also observed from IC (56.0%) to chronic liver disease (CLD) (60.4%) to LC (72.4%) to HCC (95.0%) patients. In conclusion, our study suggests that the predominant HBV subgenotype HBV/D5 with high viral load and BCP mutations (double and triple) and high mutations in MHR region was significantly associated with advanced liver disease (LC and HCC) and might act as predictor of severe hepatic complications.
    Mots-clés : Adult Aged Amino Acid Sequence Carcinoma, Hepatocellular/virology Chi-Square Distribution Consensus Sequence DNA, Viral/genetics Female Genes.
  • Pathology, BWG on LA 2012, « Importance of liver biopsy findings in immunosuppression management: biopsy monitoring and working criteria for patients with operational tolerance », Liver Transpl, vol. 18, no. 10, p. 1154-70.
    Résumé : Obstacles to morbidity-free long-term survival after liver transplantation (LT) include complications of immunosuppression (IS), recurrence of the original disease and malignancies, and unexplained chronic hepatitis and graft fibrosis. Many programs attempt to minimize chronic exposure to IS by reducing dosages and stopping steroids. A few programs have successfully weaned a highly select group of recipients from all IS without apparent adverse consequences, but long-term follow-up is limited. Patients subjected to adjustments in IS are usually followed by serial liver chemistry tests, which are relatively insensitive methods for detecting allograft damage. Protocol biopsy has largely been abandoned for hepatitis C virus-negative recipients, at least in part because of the inability to integrate routine histopathological findings into a rational clinical management algorithm. Recognizing a need to more precisely categorize and determine the clinical significance of findings in long-term biopsy samples, the Banff Working Group on Liver Allograft Pathology has reviewed the literature, pooled the experience of its members, and proposed working definitions for biopsy changes that (1) are conducive to lowering IS and are compatible with operational tolerance (OT) and (2) raise concern for closer follow-up and perhaps increased IS during or after IS weaning. The establishment of guidelines should help us to standardize analyses of the effects of various treatments and/or weaning protocols and more rigorously categorize patients who are assumed to show OT. Long-term follow-up using standardized criteria will help us to determine the consequences of lowering IS and to define and determine the incidence and robustness of OT in liver allografts.
    Mots-clés : Adult Biopsy Child Dose-Response Relationship, Drug Follow-Up Studies Graft Rejection/prevention & control Humans Immunosuppressive Agents/ therapeutic use Liver/ pathology Liver Transplantation/ immunology Transplantation Tolerance/ immunology.
  • Patin, E, Kutalik, Z, Guergnon, J, Bibert, S, Nalpas, B, Jouanguy, E, Munteanu, M, Bousquet, L, Argiro, L, Halfon, P, Boland, A, Mullhaupt, B, Semela, D, Dufour, JF, Heim, MH, Moradpour, D, Cerny, A, Malinverni, R, Hirsch, H, Martinetti, G, Suppiah, V, Stewart, G, Booth, DR, George, J, Casanova, JL, Brechot, C, Rice, CM, Talal, AH, Jacobson, IM, Bourliere, M, Theodorou, I, Poynard, T, Negro, F, Pol, S, Bochud, PY & Abel, L 2012, « Genome-wide association study identifies variants associated with progression of liver fibrosis from HCV infection », Gastroenterology, vol. 143, no. 5, p. 1244-52 e1-12.
    Résumé : BACKGROUND & AIMS: Polymorphisms in IL28B were shown to affect clearance of hepatitis C virus (HCV) infection in genome-wide association (GWA) studies. Only a fraction of patients with chronic HCV infection develop liver fibrosis, a process that might also be affected by genetic factors. We performed a 2-stage GWA study of liver fibrosis progression related to HCV infection. METHODS: We studied well-characterized HCV-infected patients of European descent who underwent liver biopsies before treatment. We defined various liver fibrosis phenotypes on the basis of METAVIR scores, with and without taking the duration of HCV infection into account. Our GWA analyses were conducted on a filtered primary cohort of 1161 patients using 780,650 single nucleotide polymorphisms (SNPs). We genotyped 96 SNPs with P values <5 x 10(-5) from an independent replication cohort of 962 patients. We then assessed the most interesting replicated SNPs using DNA samples collected from 219 patients who participated in separate GWA studies of HCV clearance. RESULTS: In the combined cohort of 2342 HCV-infected patients, the SNPs rs16851720 (in the total sample) and rs4374383 (in patients who received blood transfusions) were associated with fibrosis progression (P(combined) = 8.9 x 10(-9) and 1.1 x 10(-9), respectively). The SNP rs16851720 is located within RNF7, which encodes an antioxidant that protects against apoptosis. The SNP rs4374383, together with another replicated SNP, rs9380516 (P(combined) = 5.4 x 10(-7)), were linked to the functionally related genes MERTK and TULP1, which encode factors involved in phagocytosis of apoptotic cells by macrophages. CONCLUSIONS: Our GWA study identified several susceptibility loci for HCV-induced liver fibrosis; these were linked to genes that regulate apoptosis. Apoptotic control might therefore be involved in liver fibrosis.
    Mots-clés : Adult Apoptosis/genetics Disease Progression Eye Proteins/genetics Female Genome-Wide Association Study Genotype Hepacivirus Hepatitis C, Chronic/ complications/virology Humans Lipase/genetics Liver Cirrhosis/ genetics/virology Logistic Models Male Membrane Proteins/genetics Phenotype Polymorphism, Single Nucleotide Proportional Hazards Models Proto-Oncogene Proteins/genetics Receptor Protein-Tyrosine Kinases/genetics Ubiquitin-Protein Ligases/genetics Young Adult.

  • Pestana, JO, Grinyo, JM, Vanrenterghem, Y, Becker, T, Campistol, JM, Florman, S, Garcia, VD, Kamar, N, Lang, P, Manfro, RC, Massari, P, Rial, MD, Schnitzler, MA, Vitko, S, Duan, T, Block, A, Harler, MB & Durrbach, A 2012, « Three-year outcomes from BENEFIT-EXT: a phase III study of belatacept versus cyclosporine in recipients of extended criteria donor kidneys », Am J Transplant, vol. 12, no. 3, p. 630-9, viewed sans date, .
    Résumé : Recipients of extended-criteria donor (ECD) kidneys have poorer long-term outcomes compared to standard-criteria donor kidney recipients. We report 3-year outcomes from a randomized, phase III study in recipients of de novo ECD kidneys (n = 543) assigned (1:1:1) to either a more intensive (MI) or less intensive (LI) belatacept regimen, or cyclosporine. Three hundred twenty-three patients completed treatment by year 3. Patient survival with a functioning graft was comparable between groups (80% in MI, 82% in LI, 80% in cyclosporine). Mean calculated GFR (cGFR) was 11 mL/min higher in belatacept-treated versus cyclosporine-treated patients (42.7 in MI, 42.2 in LI, 31.5 mL/min in cyclosporine). More cyclosporine-treated patients (44%) progressed to GFR <30 mL/min (chronic kidney disease [CKD] stage 4/5) than belatacept-treated patients (27-30%). Acute rejection rates were similar between groups. Posttransplant lymphoproliferative disorder (PTLD) occurrence was higher in belatacept-treated patients (two in MI, three in LI), most of which occurred during the first 18 months; four additional cases (3 in LI, 1 in cyclosporine) occurred after 3 years. Tuberculosis was reported in two MI, four LI and no cyclosporine patients. In conclusion, at 3 years after transplantation, immunosuppression with belatacept resulted in similar patient survival, graft survival and acute rejection, with better renal function compared with cyclosporine. As previously reported, PTLD and tuberculosis were the principal safety findings associated with belatacept in this study population.
    Mots-clés : Adult Cyclosporine/therapeutic use Female Follow-Up Studies Glomerular Filtration Rate Graft Rejection/*prevention & control Graft Survival Humans Immunoconjugates/*therapeutic use Immunosuppressive Agents/*therapeutic use Kidney Failure, Chronic/complications/*surgery Kidney Function Tests *Kidney Transplantation Lymphoproliferative Disorders/chemically induced Male Middle Aged *Postoperative Complications Prognosis Risk Factors Survival Rate.

  • Poaty, H, Coullin, P, Leguern, E, Dessen, P, Valent, A, Afoutou, J-M, Peko, J-F, Candelier, J-J, Gombé-Mbalawa, C, Picard, J-Y & Bernheim, A 2012, « [Cytogenomic studies of hydatiform moles and gestational choriocarcinoma] », Bulletin Du Cancer, vol. 99, no. 9, p. 827-843.
    Résumé : The complete hydatidiform mole (CHM), a gestational trophoblastic disease, is usually caused by the development of an androgenic egg whose genome is exclusively paternal. Due to parental imprinting, only trophoblasts develop in the absence of a fetus. CHM are diploid and no abnormal karyotype is observed. It is 46,XX in most cases and less frequently 46,XY. The major complication of this disease is gestational choriocarcinoma, a metastasizing tumor and a true allografted malignancy. This complication is infrequent in developed countries, but is more common in the developing countries and is then worsened by delayed care. The malignancies are often accompanied by acquired, possibly etiological genomic abnormalities. We investigated the presence of recurrent cytogenetic abnormalities in CHM and post-molar choriocarcinoma using metaphasic CGH (mCGH) and high-resolution 244K aCGH techniques. The 10 CHM studied by mCGH showed no chromosomal gains or losses. For post-molar choriocarcinoma, 11 tumors, whose diagnosis was verified by histopathology, were investigated by aCGH. Their androgenic nature and the absence of tumor DNA contamination by maternal DNA were verified by the analysis of microsatellite markers. Three choriocarcinoma cell lines (BeWo, JAR and JEG) were also analyzed by aCGH. The results allowed us to observe some chromosomal rearrangements in primary tumors, and more in the cell lines. Chromosomal abnormalities were confirmed by FISH and functional effect by immunohistochemical analysis of gene expression. Forty minimum critical regions (MCR) were defined on chromosomes. Candidate genes implicated in choriocarcinoma oncogenesis were selected. The presence in the MCR of many miRNA clusters whose expression is modulated by parental imprinting has been observed, for example in 14q32 or in 19q13.4. This suggests that, in gestational choriocarcinoma, the consequences of gene abnormalities directly linked to acquired chromosomal abnormalities are superimposed upon those of imprinted genes altered at fertilization.
    Mots-clés : Cell Line, Tumor, choriocarcinoma, Chromosome Aberrations, Comparative Genomic Hybridization, Female, Genotype, Humans, Hydatidiform Mole, Immunohistochemistry, In Situ Hybridization, Fluorescence, Pregnancy.

  • Poaty, H, Coullin, P, Peko, JF, Dessen, P, Diatta, AL, Valent, A, Leguern, E, Prévot, S, Gombé-Mbalawa, C, Candelier, J-J, Picard, J-Y & Bernheim, A 2012, « Genome-wide high-resolution aCGH analysis of gestational choriocarcinomas », PloS One, vol. 7, no. 1, p. e29426.
    Résumé : Eleven samples of DNA from choriocarcinomas were studied by high resolution CGH-array 244 K. They were studied after histopathological confirmation of the diagnosis, of the androgenic etiology and after a microsatellite marker analysis confirming the absence of contamination of tumor DNA from maternal DNA. Three cell lines, BeWo, JAR, JEG were also studied by this high resolution pangenomic technique. According to aCGH analysis, the de novo choriocarcinomas exhibited simple chromosomal rearrangements or normal profiles. The cell lines showed various and complex chromosomal aberrations. 23 Minimal Critical Regions were defined that allowed us to list the genes that were potentially implicated. Among them, unusually high numbers of microRNA clusters and imprinted genes were observed.
    Mots-clés : Cell Line, Tumor, choriocarcinoma, Comparative Genomic Hybridization, Female, Genome, Human, Genotype, Humans, Immunohistochemistry, In Situ Hybridization, Fluorescence, Microsatellite Repeats, Pregnancy, Pregnancy Complications, Sequence Analysis, DNA, Uterine Neoplasms.

  • Poitou, C, Francois, H, Bellanne-Chantelot, C, Noel, C, Jacquet, A, Clauin, S, Beaudreuil, S, Damieri, H, Hebibi, H, Hammoudi, Y, Benoit, G, Charpentier, B & Durrbach, A 2012, « Maturity onset diabetes of the young: clinical characteristics and outcome after kidney and pancreas transplantation in MODY3 and RCAD patients: a single center experience », Transpl Int, vol. 25, no. 5, p. 564-72, viewed sans date, .
    Résumé : The diabetes and renal phenotype of patients with maturity-onset diabetes of the young (MODY) on a transplantation waiting list is not known; neither is their outcome after pancreas (PT) and/or kidney transplantation (KT). Between 2002 and 2009, we screened 50 of 150 patients referred for kidney and pancreas transplantation to the Kremlin-Bicetre center for HNF1B and HNF1A mutations if one or more of the following criteria was present (i) an atypical history of diabetes (ii) diabetes with at least one affected parent or two affected relatives, (iii) an absence of auto-antibodies at diagnosis (iv) a persistent secretion of fasting C peptide (v) a personal or a family history of renal cysts or dysplasia. Their phenotype and their outcome were analyzed. Four HNF1A (MODY3) and eight HNF1B mutations [renal cysts and diabetes (RCAD)] were identified. All MODY3 patients had diabetic nephropathy, but only 50% of RCAD patients. Four patients underwent a kidney and pancreas transplantation and two a kidney transplant alone. After 4.1 +/- 1.1 years of follow-up, 83% of patients still have a functioning kidney and 75% a functioning pancreas. PT can be proposed with good results for MODY3 and RCAD patients.
    Mots-clés : Adult Central Nervous System Diseases/genetics/*surgery Cohort Studies Dental Enamel/abnormalities/surgery Diabetes Mellitus, Cystic/genetics/*surgery *Kidney Transplantation/physiology Male Middle Aged Mutation Survival Analysis, Type 2/genetics/*surgery Female Follow-Up Studies Graft Survival Hepatocyte Nuclear Factor 1-alpha/genetics Hepatocyte Nuclear Factor 1-beta/genetics Humans *Islets of Langerhans Transplantation/physiology Kidney Diseases.


  • Proust, R, Bertoglio, J & Gesbert, F 2012, « The adaptor protein SAP directly associates with CD3ζ chain and regulates T cell receptor signaling », PLoS One, vol. 7, no. 8, p. e43200, viewed sans date, .
    Résumé : Mutations altering the gene encoding the SLAM associated protein (SAP) are responsible for the X-linked lymphoproliferative disease or XLP1. Its absence is correlated with a defective NKT cells development, a decrease in B cell functions and a reduced T cells and NK cells cytotoxic activities, thus leading to an immunodeficiency syndrome. SAP is a small 128 amino-acid long protein that is almost exclusively composed of an SH2 domain. It has been shown to interact with the CD150/SLAM family of receptors, and in a non-canonical manner with SH3 containing proteins such as Fyn, βPIX, PKCθ and Nck1. It would thus play the role of a minimal adaptor protein. It has been shown that SAP plays an important function in the activation of T cells through its interaction with the SLAM family of receptors. Therefore SAP defective T cells display a reduced activation of signaling events downstream of the TCR-CD3 complex triggering. In the present work, we evidence that SAP is a direct interactor of the CD3ζ chain. This direct interaction occurs through the first ITAM of CD3ζ, proximal to the membrane. Additionally, we show that, in the context of the TCR-CD3 signaling, an Sh-RNA mediated silencing of SAP is responsible for a decrease of several canonical T cell signaling pathways including Erk, Akt and PLCγ1 and to a reduced induction of IL-2 and IL-4 mRNA. Altogether, we show that SAP plays a central function in the T cell activation processes through a direct association with the CD3 complex.
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  • Redelsperger, F, Lekbaby, B, Mandouri, Y, Giang, E, Duriez, M, Desire, N, Roque Afonso, AM, Brichler, S, Dubreuil, P, Dobrin, A, Perlemuter, G, Prevot, S, Bacon, N, Grange, JD, Zatla, F, Le Pendeven, C, Pol, S, Strick-Marchand, H, Di Santo, J, Kremsdorf, D & Soussan, P 2012, « Production of hepatitis B defective particles is dependent on liver status », Virology, vol. 431, no. 1-2, p. 21-8.
    Résumé : Defective hepatitis B virus (dHBV) generated from spliced RNA is detected in the sera of HBV-chronic carriers. Our study was designed to determine whether the proportion of dHBV changed during the course of infection, and to investigate whether dHBV might interfere with HBV replication. To achieve this, HBV wild-type and dHBV levels were determined by Q-PCR in sera from 56 untreated chronic patients and 23 acute patients, in sequential samples from 4 treated-patients and from liver-humanized mice after HBV infection. The proportion of dHBV was higher in patients with severe compared to null/moderate liver disease or with acute infection. Follow-up showed that the proportion of dHBV increased during disease progression. By contrast, a low and stable proportion of dHBV was observed in the humanized-mouse model of HBV infection. Our results highlight a regulation of the proportion of dHBV during liver disease progression that is independent of interference with viral replication.
    Mots-clés : Adult Animals Defective Viruses/ growth & development/isolation & purification Disease Models, Animal Female Hepatitis B virus/ growth & development/isolation & purification Hepatitis B, Chronic/ virology Humans Liver/pathology/ virology Male Mice Mice, SCID Middle Aged Real-Time Polymerase Chain Reaction Serum/virology Viral Load Virus Replication.
  • Renou, C, Pariente, A, Roque-Afonso, AM & Nicand, E 2012, « [Autochthonous hepatitis E: an emerging and still unrecognized disease] », Rev Prat, vol. 62, no. 7, p. 903-8.
    Résumé : In developed countries, HEV infection was still recently considered as rare, and as an imported disease from endemic areas by travellers. Hepatitis E virus is now mainly recognized as an autochthonous disease in these countries. Although the sources and the routes of contamination remain uncertain, several cases of foodborne (zoonotic transmission) and blood borne transmission have been recently reported. HEV infection may evolve towards a chronic hepatitis in immunocompromised patients (mostly in solid organ transplant recipients and patients with HIV) which can evolve to cirrhosis. The mortality rates in industrialized countries seem to be higher than in endemic areas. By contrast, whereas mortality rate reaches 20% during pregnancy in developing countries, no death in pregnant woman secondary to an autochthonous case has been reported so far in developed countries.
    Mots-clés : Animals Communicable Diseases, Emerging/epidemiology/virology Developing Countries Disease Reservoirs/virology Hepatitis E/ epidemiology/ transmission/virology Humans.
  • Roche, B & Samuel, D 2012, « Hepatitis C virus treatment pre- and post-liver transplantation », Liver Int, vol. 32 Suppl 1, p. 120-8.
    Résumé : Liver disease caused by the hepatitis C virus is the main indication for liver transplantation in Western countries. However, HCV re-infection post-transplantation is constant and recent data confirm that it significantly impairs patient and graft survival. Chronic HCV infection develops in 75-90% of patients, and 5-30% ultimately progress to cirrhosis within 5 years. Because of the impact of HCV recurrence on graft and patient survival, several treatment strategies have been evaluated. Antiviral therapy could be administered before transplantation to suppress viral replication and reduce the risk of recurrence. However, this approach is applicable in around 50% of patients and tolerance is poor, particularly in patients with decompensated cirrhosis. Pre-emptive therapy in the early post-transplant period is limited by the high rate of side effects. Frequently, antiviral therapy is initiated when HCV recurs to obtain viral eradication and/or reduce disease progression. Treatment of established graft lesions with Pegylated Interferon (PEG-IFN) and Ribavirin (RBV) combination therapy results in a sustained virological response (SVR) in around 30% of patients. The new classes of potent and direct antiviral agents (DAA) will certainly improve the results of pre- and post-transplant antiviral therapy. However, at the present time, no data are available on the use of these drugs in patients with decompensated cirrhosis or post-transplant hepatitis.
    Mots-clés : Antiviral Agents/ therapeutic use Disease Progression Drug Administration Schedule Hepatitis C.
  • Roche, B & Samuel, D 2012, « Liver transplantation in delta virus infection », Semin Liver Dis, vol. 32, no. 3, p. 245-55.
    Résumé : Liver transplantation is the only therapy for patients with end-stage liver disease, hepatocellular carcinoma, or fulminant hepatitis due to hepatitis D virus (HDV) and hepatitis B virus (HBV) coinfection or superinfection. Patients chronically coinfected with HDV are less at risk of HBV recurrence and have a better survival rate than patients infected with HBV alone. Patients coinfected with HDV generally do not require pretransplant antiviral therapy. Rates of recurrent HBV-HDV infection are lower than 5% using low-dose intramuscular (IM) HBIg and antiviral prophylaxis in combination. Few studies have evaluated the possibility of using shorter-term HBIg (12-24 months) then switching to antiviral therapy. Although HBV replication can be controlled by potent HBV-polymerase inhibitors, reappearance of HBsAg and/or the persistence of HBV DNA in serum, liver, or peripheral blood mononuclear cells might have deleterious consequences in the setting of HBV-HDV coinfection as they may provide the biologic substrate to the reactivation of HDV. No effective antiviral drug is available for the treatment of graft infection with HDV.
    Mots-clés : Antiviral Agents/therapeutic use Carcinoma, Chronic/complications/drug therapy/surgery Humans Immunization, Passive Liver Neoplasms/ surgery/virology Liver Transplantation Postoperative Care Preoperative Care Recurrence/prevention & control Superinfection/complications.

  • Rossignol, A, Levescot, A, Jacomet, F, Robin, A, Basbous, S, Giraud, C, Roy, L, Guilhot, F, Turhan, AG, Barra, A, Herbelin, A & Gombert, J-M 2012, « Evidence for BCR-ABL-dependent dysfunctions of iNKT cells from chronic myeloid leukemia patients », Eur J Immunol, vol. 42, no. 7, p. 1870-5, viewed sans date, .
    Résumé : Chronic myeloid leukemia (CML) is a clonal hematopoietic stem-cell malignancy characterized by the presence of the chimeric BCR-ABL oncoprotein with deregulated tyrosine-kinase (TK) activity. Although conventional T cells are acknowledged as important players in the control of CML, a possible modification of invariant NKT (iNKT) cells, known for their antitumoral activity, has not been established as yet. Here, we showed that the expression of perforin, CD95L, and promyelocytic leukemia zinc finger, a transcription factor required for maintenance of iNKT cell functions, was reduced or suppressed in CML patients at diagnosis, as compared with healthy individuals. The proliferation rate of blood iNKT cells in response to their cognate ligand was likewise diminished. These functional deficiencies were corrected in patients having achieved complete cytogenetic remission following TK inhibitor or IFN-α therapy. iNKT cells from CML patients in the chronic phase did not display increased TK activity, which argued against a direct autonomous action of BCR-ABL. Instead, we found that their anergic status originated from both intrinsic and APC-dependent dysfunctions. Our data demonstrate that chronic phase CML is associated with functional deficiencies of iNKT cells that are restored upon remission. These results suggest a possible contribution to disease control by TK inhibitor therapies.
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  • Rostaing, L, Saliba, F, Calmus, Y, Dharancy, S & Boillot, O 2012, « Review article: use of induction therapy in liver transplantation », Transplant Rev (Orlando), vol. 26, no. 4, p. 246-60.
    Résumé : Induction therapy is used relatively infrequently in liver transplantation, but developments in induction regimens and strategies for their use are prompting a re-examination of its benefits. Rabbit antithymocyte globulin (rATG) induces protracted, dose-dependent lymphocytopenia with preferential reconstitution of regulatory T-lymphocytes. Non-depleting interleukin-2 receptor antagonists (IL-2RA) act selectively on activated T-lymphocytes with a shorter duration of effect. IL-2RA induction with delayed and reduced calcineurin inhibitor (CNI) exposure appears to preserve efficacy, while more aggressive CNI minimisation has been attempted successfully using rATG. Steroid-free tacrolimus monotherapy with rATG or IL-2RA induction is effective if adequate tacrolimus exposure is maintained. Early concerns that addition of induction to a conventional maintenance regimen could lead to accelerated progression of hepatitis C disease, or to an increased risk of hepatocellular cancer recurrence, now appear unfounded using modern regimens. Similarly, with routine use of systemic prophylaxis, recent prospective and retrospective data have not shown a higher rate of infections overall, or cytomegalovirus infection specifically, using rATG or IL-2RA induction. Historical evidence that lymphocyte-depleting agents increased the risk of non-Hodgkin lymphoma has not been confirmed for rATG. Wider use of induction in liver transplantation is now merited, using individualized strategies to support reduced CNI exposure or steroid-free immunosuppression.
    Mots-clés : Antibodies, Monoclonal, Monoclonal/therapeutic use Antibodies.

  • Ru, Z, Xiao, W, Pajot, A, Kou, Z, Sun, S, Maillere, B, Zhao, G, Ojcius, DM, Lone, YC & Zhou, Y 2012, « Development of a humanized HLA-A2.1/DP4 transgenic mouse model and the use of this model to map HLA-DP4-restricted epitopes of HBV envelope protein », PLoS One, vol. 7, no. 3, p. e32247, viewed sans date, .
    Résumé : A new homozygous humanized transgenic mouse strain, HLA-A2.1(+/+)HLA-DP4(+/+) hCD4(+/+)mCD4(-/-)IAbeta(-/-)beta2m(-/-) (HLA-A2/DP4), was obtained by crossing the previously characterized HLA-A2(+/+)beta2m(-/-) (A2) mouse and our previously created HLA-DP4(+/+) hCD4(+/+)mCD4(-/-)IAbeta(-/-) (DP4) mouse. We confirmed that the transgenes (HLA-A2, HLA-DP4, hCD4) inherited from the parental A2 and DP4 mice are functional in the HLA-A2/DP4 mice. After immunizing HLA-A2/DP4 mice with a hepatitis B DNA vaccine, hepatitis B virus-specific antibodies, HLA-A2-restricted and HLA-DP4-restricted responses were observed to be similar to those in naturally infected humans. Therefore, the present study demonstrated that HLA-A2/DP4 transgenic mice can faithfully mimic human cellular responses. Furthermore, we reported four new HLA-DP4-restricted epitopes derived from HBsAg that were identified in both vaccinated HLA-A2/DP4 mice and HLA-DP4-positive human individuals. The HLA-A2/DP4 mouse model is a promising preclinical animal model carrying alleles present to more than a quarter of the human population. This model should facilitate the identification of novel HLA-A2- and HLA-DP4-restricted epitopes and vaccine development as well as the characterization of HLA-DP4-restricted responses against infection in humans.
    Mots-clés : Animals Antibodies, DNA/immunology Viral Envelope Proteins/*immunology Viral Vaccines/immunology, Humoral/immunology Mice Mice, Monoclonal, Transgenic Phenotype Vaccines.
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  • Sala-Valdés, M, Ailane, N, Greco, C, Rubinstein, E & Boucheix, C 2012, « Targeting tetraspanins in cancer », Expert Opin Ther Targets, vol. 16, no. 10, p. 985-97, viewed sans date, .
    Résumé : INTRODUCTION: Tetraspanins are a family of small proteins that cross the membrane four times and form complexes by interacting between themselves and with a variety of transmembrane and cytosolic proteins, building a network of interactions referred to as tetraspanin web or tetraspanin enriched microdomains (TEMs). These domains provide a signaling platform involved in many important cellular functions and malignant processes. AREAS COVERED: The authors describe the methods and the rationale for targeting tetraspanins in the therapy of cancer in this review. EXPERT OPINION: Targeting tetraspanins in cancer may be a promising therapy due to the importance of tetraspanins in several steps of tumor formation, communication with the environment, dissemination, and metastasis.
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  • Saliba, F 2012, « Emerging fungal infections », Expert Rev Anti Infect Ther, vol. 10, no. 4, p. 419-21.
    Résumé : Trends in Medical Mycology is one of the most attractive international meetings completely dedicated to clinical and fundamental research in the field of medical mycology. It is organized by the European Confederation of Medical Mycology and the Infectious Diseases Group of the European Organization for Research and Treatment of Cancer. Approximately 1500 participants, mainly microbiologists, clinicians and basic researchers, from more than 40 countries exchanged the most important advances in mycology from basic science to clinical research. A quick focus on some relevant clinical presentations is presented here.
    Mots-clés : Antifungal Agents/classification/therapeutic use Aspergillosis/epidemiology/microbiology Candidemia/epidemiology/microbiology Communicable Diseases, Emerging/ epidemiology/microbiology Humans Mycoses/ epidemiology/microbiology Organ Transplantation/ adverse effects Zygomycosis/epidemiology/microbiology.
  • Samuel, D & Roche, B 2012, « Combined prophylaxis might still be better than monoprophylaxis with entecavir following liver transplantation for hepatitis B », Gastroenterology, vol. 142, no. 1, p. e34; author reply e34-5.
    Résumé : Samuel, Didier; Roche, Bruno; Comment; Letter; United States; Gastroenterology. 2012 Jan;142(1):e34; author reply e34-5. doi: 10.1053/j.gastro.2011.09.052. Epub 2011 Nov 21.
    Mots-clés : Antiviral Agents/ therapeutic use Carcinoma, Chronic/ drug therapy/ surgery Humans Liver Cirrhosis/ surgery Liver Neoplasms/ surgery Liver Transplantation Male, Hepatocellular/ surgery Female Guanine/ analogs & derivatives Hepatitis B.

  • Sandt, C, Féraud, O, Oudrhiri, N, Bonnet, ML, Meunier, MC, Valogne, Y, Bertrand, A, Raphaël, M, Griscelli, F, Turhan, AG, Dumas, P & Bennaceur-Griscelli, A 2012, « Identification of spectral modifications occurring during reprogramming of somatic cells », PLoS One, vol. 7, no. 4, p. e30743, viewed sans date, .
    Résumé : Recent technological advances in cell reprogramming by generation of induced pluripotent stem cells (iPSC) offer major perspectives in disease modelling and future hopes for providing novel stem cells sources in regenerative medicine. However, research on iPSC still requires refining the criteria of the pluripotency stage of these cells and exploration of their equivalent functionality to human embryonic stem cells (ESC). We report here on the use of infrared microspectroscopy to follow the spectral modification of somatic cells during the reprogramming process. We show that induced pluripotent stem cells (iPSC) adopt a chemical composition leading to a spectral signature indistinguishable from that of embryonic stem cells (ESC) and entirely different from that of the original somatic cells. Similarly, this technique allows a distinction to be made between partially and fully reprogrammed cells. We conclude that infrared microspectroscopy signature is a novel methodology to evaluate induced pluripotency and can be added to the tests currently used for this purpose.
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  • Saulnier, N, Guihard, S, Holy, X, Decembre, E, Jurdic, P, Clay, D, Feuillet, V, Pagès, G, Pouysségur, J, Porteu, F & Gaudry, M 2012, « ERK1 regulates the hematopoietic stem cell niches », PloS One, vol. 7, no. 1, p. e30788.
    Résumé : The mitogen-activated protein kinases (MAPK) ERK1 and ERK2 are among the major signal transduction molecules but little is known about their specific functions in vivo. ERK activity is provided by two isoforms, ERK1 and ERK2, which are ubiquitously expressed and share activators and substrates. However, there are not in vivo studies which have reported a role for ERK1 or ERK2 in HSCs and the bone marrow microenvironment. The present study shows that the ERK1-deficient mice present a mild osteopetrosis phenotype. The lodging and the homing abilities of the ERK1(-/-) HSC are impaired, suggesting that the ERK1(-/-)-defective environment may affect the engrafment of HSCs. Serial transplantations demonstrate that ERK1 is involved in the maintenance of an appropriate medullar microenvironment, but that the intrinsic properties of HSCs are not altered by the ERK1(-/-) defective microenvironment. Deletion of ERK1 impaired in vitro and in vivo osteoclastogenesis while osteoblasts were unaffected. As osteoclasts derive from precursors of the monocyte/macrophage lineage, investigation of the monocytic compartment was performed. In vivo analysis of the myeloid lineage progenitors revealed that the frequency of CMPs increased by approximately 1.3-fold, while the frequency of GMPs significantly decreased by almost 2-fold, compared with the respective WT compartments. The overall mononuclear-phagocyte lineage development was compromised in these mice due to a reduced expression of the M-CSF receptor on myeloid progenitors. These results show that the cellular targets of ERK1 are M-CSFR-responsive cells, upstream to osteoclasts. While ERK1 is well known to be activated by M-CSF, the present results are the first to point out an ERK1-dependent M-CSFR regulation on hematopoietic progenitors. This study reinforces the hypothesis of an active cross-talk between HSCs, their progeny and bone cells in the maintenance of the homeostasis of these compartments.
    Mots-clés : Animals, Bone and Bones, Bone Density, Bone Marrow, Cell Compartmentation, Cell Differentiation, Cell Lineage, Cell Movement, Cell Proliferation, Cellular Microenvironment, Gene Deletion, Hematopoietic Stem Cells, Macrophages, Mice, Mice, Inbred C57BL, Mitogen-Activated Protein Kinase 3, Monocytes, Osteoblasts, Osteoclasts, Osteogenesis, Stem Cell Niche.


  • Sebagh, M, Samuel, D, Antonini, TM, Coilly, A, Degli Esposti, D, Roche, B, Karam, V, Dos Santos, A, Duclos-Vallée, J-C, Roque-Afonso, A-M, Ballot, E, Guettier, C, Blandin, F, Saliba, F & Azoulay, D 2012, « Twenty-year protocol liver biopsies: Invasive but useful for the management of liver recipients », J Hepatol, vol. 56, no. 4, p. 840-7, viewed sans date, .
    Résumé : BACKGROUND & AIMS: Most liver transplant centres have discontinued the practice of protocol liver biopsies (LB), mainly because of the perceived lack of therapeutic benefit. This study aimed to examine the usefulness of 20-year LBs. METHODS: Ten, 15, and 20-year protocol LBs from 147 patients surviving for >20 years were reviewed. Twenty-year biopsy findings were correlated with clinical data. RESULTS: Twenty-year-biopsy patients (N=91) and 20-year-non-biopsy patients (N=56) were similar in terms of transplant data, adverse events, and liver function tests (LFTs). Twenty-year LBs revealed a 90% prevalence of abnormalities, among which viral chronic hepatitis (VCH) was the most common (46%). Between 15 and 20 years, hepatic structural abnormalities were the only disorder to increase (p=0.008). An individual progression of abnormalities occurred in 56% of patients. At 20 years, the negative and positive predictive values (PV) of LFTs with respect to histological abnormalities were 95% and 18%, respectively; in VCH, Fibrotest and transient elastography displayed poor discriminative ability for fibrosis (80% and 81% discordance, respectively), but were satisfactory regarding significant fibrosis (negative PV of 77.7% and 80%, respectively). A decrease in immunosuppression was less frequent (14/91 vs. 20/56, p=0.008) while an increase was more common (15/91 vs. 2/56, p=0.017) in 20-year-biopsy patients than in non-biopsy patients. Antiviral therapy was administered in seven of the 20-year biopsy patients, but in none of the non-biopsy patients (p=0.04). CONCLUSIONS: Twenty-year LBs provided important histological information on graft function that was available to a limited degree from LFTs and non-invasive markers. They exerted an impact on immunosuppressive and antiviral therapies.
    Mots-clés : Adult Biopsy Disease Progression Female Graft Survival Hepatitis, Chronic/epidemiology Humans Liver/ pathology/physiology Liver Function Tests Liver Transplantation/ pathology/physiology Longitudinal Studies Male Middle Aged Predictive Value of Tests Prevalence Retrospective Studies Time Factors Treatment Outcome.
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  • Senapati, S, Gnanapragassam, VS, Moniaux, N, Momi, N & Batra, SK 2012, « Role of MUC4-NIDO domain in the MUC4-mediated metastasis of pancreatic cancer cells », Oncogene, vol. 31, no. 28, p. 3346-56.
    Résumé : MUC4 is a large transmembrane type I glycoprotein that is overexpressed in pancreatic cancer (PC) and has been shown to be associated with its progression and metastasis. However, the exact cellular and molecular mechanism(s) through which MUC4 promotes metastasis of PC cells has been sparsely studied. Here we showed that the nidogen-like (NIDO) domain of MUC4, which is similar to the G1-domain present in the nidogen or entactin (an extracellular matrix protein), contributes to the protein-protein interaction property of MUC4. By this interaction, MUC4 promotes breaching of basement membrane (BM) integrity, and spreading of cancer cells. These observations are corroborated with the data from our study using an engineered MUC4 protein without the NIDO domain, which was ectopically expressed in the MiaPaCa PC cells, lacking endogenous MUC4 and nidogen protein. The in vitro studies demonstrated an enhanced invasiveness of MiaPaCa cells expressing MUC4 (MiaPaCa-MUC4) compared with vector-transfected cells (MiaPaCa-Vec; P=0.003) or cells expressing MUC4 without the NIDO domain (MiaPaCa-MUC4-NIDO(Delta); P=0.03). However, the absence of NIDO-domain has no significant role on cell growth and motility (P=0.93). In the in vivo studies, all the mice orthotopically implanted with MiPaCa-MUC4 cells developed metastasis to the liver as compared with MiaPaCa-Vec or the MiaPaCa-MUC4-NIDO(Delta) group, hence, supporting our in vitro observations. Additionally, a reduced binding (P=0.0004) of MiaPaCa-MUC4-NIDO(Delta) cells to the fibulin-2 coated plates compared with MiaPaCa-MUC4 cells indicated a possible interaction between the MUC4-NIDO domain and fibulin-2, a nidogen-interacting protein. Furthermore, in PC tissue samples, MUC4 colocalized with the fibulin-2 present in the BM. Altogether, our findings demonstrate that the MUC4-NIDO domain significantly contributes to the MUC4-mediated metastasis of PC cells. This may be partly due to the interaction between the MUC4-NIDO domain and fibulin-2.
    Mots-clés : Animals Base Sequence Calcium-Binding Proteins/metabolism Cell Line, Neoplastic Humans Membrane Glycoproteins/ chemistry Mice Mucin-4/ chemistry/genetics/ metabolism Neoplasm Invasiveness Neoplasm Metastasis Pancreatic Neoplasms/genetics/metabolism/ pathology Protein Structure, Tertiary Protein Transport Sequence Deletion Transfection, Tumor Extracellular Matrix Proteins/metabolism Female Gene Expression Regulation.
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  • Si-Tayeb, K, Duclos-Vallee, JC & Petit, MA 2012, « Hepatocyte-like cells differentiated from human induced pluripotent stem cells (iHLCs) are permissive to hepatitis C virus (HCV) infection: HCV study gets personal », J Hepatol, vol. 57, no. 3, p. 689-91.
    Résumé : Si-Tayeb, Karim; Duclos-Vallee, Jean-Charles; Petit, Marie-Anne; Comment; England; J Hepatol. 2012 Sep;57(3):689-91. doi: 10.1016/j.jhep.2012.04.012. Epub 2012 May 5.
  • Snoeren, N, van Hooff, SR, Adam, R, van Hillegersberg, R, Voest, EE, Guettier, C, van Diest, PJ, Nijkamp, MW, Brok, MO, van Leenen, D, Koerkamp, MJ, Holstege, FC & Rinkes, IH 2012, « Exploring gene expression signatures for predicting disease free survival after resection of colorectal cancer liver metastases », PLoS One, vol. 7, no. 11, p. e49442.
    Résumé : BACKGROUND AND OBJECTIVES: This study was designed to identify and validate gene signatures that can predict disease free survival (DFS) in patients undergoing a radical resection for their colorectal liver metastases (CRLM). METHODS: Tumor gene expression profiles were collected from 119 patients undergoing surgery for their CRLM in the Paul Brousse Hospital (France) and the University Medical Center Utrecht (The Netherlands). Patients were divided into high and low risk groups. A randomly selected training set was used to find predictive gene signatures. The ability of these gene signatures to predict DFS was tested in an independent validation set comprising the remaining patients. Furthermore, 5 known clinical risk scores were tested in our complete patient cohort. RESULT: No gene signature was found that significantly predicted DFS in the validation set. In contrast, three out of five clinical risk scores were able to predict DFS in our patient cohort. CONCLUSIONS: No gene signature was found that could predict DFS in patients undergoing CRLM resection. Three out of five clinical risk scores were able to predict DFS in our patient cohort. These results emphasize the need for validating risk scores in independent patient groups and suggest improved designs for future studies.
    Mots-clés : Aged Area Under Curve Cohort Studies Colorectal Neoplasms/metabolism/ pathology Disease-Free Survival Female Gene Expression Profiling Gene Expression Regulation, Neoplastic Humans Liver Neoplasms/metabolism/ secondary Male Middle Aged Nucleic Acid Hybridization Oligonucleotide Array Sequence Analysis Proportional Hazards Models Recurrence Risk Treatment Outcome.
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  • Studach, LL, Menne, S, Cairo, S, Buendia, MA, Hullinger, RL, Lefrancois, L, Merle, P & Andrisani, OM 2012, « Subset of Suz12/PRC2 target genes is activated during hepatitis B virus replication and liver carcinogenesis associated with HBV X protein », Hepatology, vol. 56, no. 4, p. 1240-51.
    Résumé : Chronic hepatitis B virus (HBV) infection is a major risk factor for developing liver cancer, and the HBV X protein (pX) has been implicated as a cofactor in hepatocyte transformation. We have shown that HBV replication as well as in vitro transformation by pX are associated with induction of the mitotic polo-like kinase 1 (Plk1) and down-regulation of the chromatin remodeling components Suz12 and Znf198. Herein, we demonstrate the same inverse relationship between Plk1 and Suz12/Znf198 in liver tumors from X/c-myc bitransgenic mice and woodchuck hepatitis virus (WHV)-infected woodchucks. Employing these animal models and the HBV replicating HepAD38 cells we examined the effect of Suz12/Znf198 down-regulation on gene expression. Genes analyzed include hepatic cancer stem cell markers BAMBI, DKK1,2, DLK1, EpCAM, MYC, and proliferation genes CCNA1, CCND2, IGFII, MCM4-6, PLK1, RPA2, and TYMS. Suz12 occupancy at the promoters of BAMBI, CCND2, DKK2, DLK1, EpCAM, and IGFII was demonstrated by chromatin immunoprecipitation in untransformed hepatocytes, but was markedly reduced in pX-transformed and Suz12 knockdown cells. Accordingly, we refer to these genes as "Suz12 repressed" genes in untransformed hepatocytes. The Suz12 repressed genes and proliferation genes were induced in HBV-replicating HepAD38 cells and, interestingly, they exhibited distinct expression profiles during hepatocellular carcinoma (HCC) progression in X/c-myc bitransgenics. Specifically, CCND2, EpCAM, and IGFII expression was elevated at the proliferative and preneoplastic stages in X/c-myc bitransgenic livers, whereas BAMBI and PLK1 were overexpressed in hepatic tumors from X/c-myc bitransgenics and WHV-infected woodchucks. Importantly, most of these genes were selectively up-regulated in HBV-induced HCCs. Conclusion: The distinct expression profile of the identified Suz12 repressed genes in combination with the proliferation genes hold promise as biomarkers for progression of chronic HBV infection to HCC.
    Mots-clés : Animal Down-Regulation Gene Expression Regulation, Animals Carcinoma, Chronic/genetics/physiopathology Hepatocytes/pathology Liver Neoplasms/genetics/ virology Marmota Mice Mice, Cultured Disease Models, Hepatocellular/genetics/ virology Cell Cycle Proteins/ genetics/metabolism Cell Transformation, Neoplastic/genetics/pathology Cells, Viral Hepatitis B virus/ genetics Hepatitis B.
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  • Tamarat, R, Lataillade, JJ, Bey, E, Gourmelon, P & Benderitter, M 2012, « Stem cell therapy: from bench to bedside », Radiat Prot Dosimetry, vol. 151, no. 4, p. 633-9, viewed sans date, .
    Résumé : Several countries have increased efforts to develop medical countermeasures to protect against radiation toxicity due to acts of bioterrorism as well as cancer treatment. Both acute radiation injuries and delayed effects such as cutaneous effects and impaired wound repair depend, to some extent, on angiogenesis deficiency. Vascular damage influences levels of nutrients, oxygen available to skin tissue and epithelial cell viability. Consequently, the evolution of radiation lesions often becomes uncontrolled and surgery is the final option–amputation leading to a disability. Therefore, the development of strategies designed to promote healing of radiation injuries is a major therapeutic challenge. Adult mesenchymal stem cell therapy has been combined with surgery in some cases and not in others and successfully applied in patients with accidental radiation injuries. Although research in the field of radiation skin injury management has made substantial progress in the past 10 y, several strategies are still needed in order to enhance the beneficial effect of stem cell therapy and to counteract the deleterious effect of an irradiated tissue environment. This review summarises the current and evolving advances concerning basic and translational research based on stem cell therapy for the management of radiological burns.
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  • Teicher, E & Duclos-Vallee, JC 2012, « Opportunistic infections after liver transplantation in patients infected with human immunodeficiency virus », Liver Transpl, vol. 18, no. 3, p. 376-7; author reply 378-9.
    Résumé : Teicher, Elina; Duclos-Vallee, Jean-Charles; Comment; Letter; United States; Liver Transpl. 2012 Mar;18(3):376-7; author reply 378-9. doi: 10.1002/lt.22481.
    Mots-clés : AIDS-Related, C/, diagnosis/, Diseases/, epidemiology, Female, Hepatitis, HIV, Humans, Infections/, Liver, Male, Opportunistic, surgery/, Transplantation, virology.
  • Toledano, C, Gain, M, Kettaneh, A, Baudin, B, Johanet, C, Cherin, P, Riviere, S, Cabane, J & Tiev, KP 2012, « Aldolase predicts subsequent myopathy occurrence in systemic sclerosis », Arthritis Res Ther, vol. 14, no. 3, p. R152.
    Résumé : INTRODUCTION: Myopathy related to systemic sclerosis (Myo-SSc) is a disabling and unpredictable complication of SSc. We assessed the predictive value of serum aldolase, creatine kinase (CK), alanine transaminase (ALT), aspartate transaminase (AST) and C-reactive protein (CRP) to estimate the risk of developing Myo-SSc. METHODS: We enrolled 137 SSc patients without proximal muscle weakness in a prospective monocentric study to follow them longitudinally over a four-year period. The risk of occurrence of Myo-SSc was ascertained according to the European NeuroMuscular Centre criteria and was analyzed according to levels of plasma aldolase, CK, transaminase enzymes and CRP at inclusion. Performance of each parameter to predict Myo-SSc occurrence was assessed and compared with the others. RESULTS: The area under the receiver operating characteristic curves (ROC) of plasma aldolase for Myo-SSc occurrence prediction was 0.80 (95% CI: 0.67 to 0.94, P < 0.001), which was higher than that of plasma CK (0.75, P = 0.01), and that of ALT (0.63, P = 0.04). AST and CRP had no predictive value for Myo-SSc occurrence. The best cut-off of aldolase for prediction of Myo-SSc occurrence within three years after inclusion was 9 U/L and higher than the upper normality limit (7 U/L), unlike that of CK and ALT. Myo-SSc occurred more frequently in patients whose plasma aldolase was higher than 9 U/L. Adjusted Hazard Ratio for patients with aldolase > 9 U/L was 10.3 (95% CI: 2.3 to 45.5), P < 0.001. CONCLUSIONS: Increased plasma aldolase level accurately identified SSc patients with high risk to develop subsequent Myo-SSc. This could help initiate appropriate treatment when the disabling muscle damage is still in a reversible stage.
    Mots-clés : Area Under Curve Biological Markers/blood Female Fructose-Bisphosphate Aldolase/ blood Humans Male Middle Aged Muscular Diseases/ blood/enzymology/etiology Predictive Value of Tests ROC Curve Risk Factors Scleroderma, Systemic/blood/complications/ enzymology.
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  • Turato, C, Buendia, MA, Fabre, M, Redon, MJ, Branchereau, S, Quarta, S, Ruvoletto, M, Perilongo, G, Grotzer, MA, Gatta, A & Pontisso, P 2012, « Over-expression of SERPINB3 in hepatoblastoma: a possible insight into the genesis of this tumour? », Eur J Cancer, vol. 48, no. 8, p. 1219-26.
    Résumé : BACKGROUND: The serpin SERPINB3 (SB3) found over-expressed in human hepatocellular carcinoma and in regenerating liver in mice has been shown to induce apoptosis resistance, epithelial-to-mesenchymal transition and increasing cellular invasion. It has also been hypothesised that SB3 may provide a pro-proliferative stimulus for liver cells in vivo. No information is available on SB3 in hepatoblastoma (HB). Aims of the study were to analyse SB3 expression in HB specimens and to investigate its possible correlation with Myc expression and tumour extension at diagnosis as evaluated by the pre-treatment extent of disease evaluation system (PRETEXT). METHODS: Frozen tumour specimens from 42 children with HB were analysed for SB3 and Myc expression by real-time PCR. SB3 localisation in tumour specimens was assessed by immunohistochemistry. RESULTS: At transcription level SB3 was positive in 79% of the cases. By immunohistochemistry, SB3 expression was found mainly in the embryonic, blastemal, small cell undifferentiated (SCUD) components of HB, while it was not detectable in normal hepatocytes. High SB3 reactivity was also detected in neoplastic cell clusters of portal vein tumour thrombosis. A direct correlation was observed between SB3 gene expression, the up-regulation of Myc (r=0.598, p<0.0001) and tumour extension (PRETEXT III/IV versus I/II, p=0.013). CONCLUSIONS: SB3 is over-expressed in HB and its expression is positively correlated with Myc expression and high tumour stage. The role of SB3 in the genesis of HB and in defining the risk profile of children affected by this tumour is hypothesised.
    Mots-clés : Adult Antigens, Messenger/analysis Serpins/analysis/genetics/ physiology, myc Hepatoblastoma/ etiology/genetics/pathology Humans Immunohistochemistry Liver Neoplasms/ etiology/genetics/pathology Male Middle Aged Neoplasm Staging Prognosis RNA, Neoplasm/analysis/genetics/ physiology Female Genes.
  • Vergier, B & Guettier, C 2012, « [The use of virtual slide for pedagogy] », Med Sci (Paris), vol. 28, no. 11, p. 986-9.
    Résumé : Vergier, Beatrice; Guettier, Catherine; Review; France; Med Sci (Paris). 2012 Nov;28(11):986-9. doi: 10.1051/medsci/20122811019. Epub 2012 Nov 12.
    Mots-clés : Anatomy/ education Computer-Assisted Instruction/ methods Education, Clinical/ education/instrumentation/methods Photography/instrumentation/ methods Teaching Materials Universities User-Computer Interface, Computer-Assisted/instrumentation/ methods Microscopy/instrumentation/ methods Paris Pathology, Distance/methods Forecasting France Humans Image Processing.

  • Verhoeyen, E, Relouzat, F, Cambot, M, Costa, C, Nègre, D, Legrand, F, Joubert, C, Le Grand, R, Cosset, F-L, Leboulch, P, Dubart-Kupperschmitt, A & Prost, S 2012, « Stem cell factor-displaying simian immunodeficiency viral vectors together with a low conditioning regimen allow for long-term engraftment of gene-marked autologous hematopoietic stem cells in macaques », Hum Gene Ther, vol. 23, no. 7, p. 754-68, viewed sans date, .
    Résumé : Although clinical benefits have been reported in several human hematopoietic gene therapy trials, a remaining important goal is the transition to nonmyeloablative pretransplantation conditioning to decrease toxicity. Previous attempts at reduced intensity conditioning in nonhuman primates have resulted in only temporary vector marking of autologous blood cells or their persistence at low levels, well below the thresholds for clinical efficacy. In addition, we reasoned that lentiviral vector particles displaying cytokines at their surface have the potential to preserve stem cell fitness better than current ex vivo transduction protocols, which involve exposure to cytokine overstimulation. Here we show that the classically nonmyeloablative agent fludarabine (30 mg/m(2)/day for 3 days) together with low-level total body irradiation (2 Gy) and the use of a stem cell factor-displaying simian immunodeficiency virus-based vector, resulted in sustained, single-copy vector marking of autologous blood cells in two macaques over 3 years posttransplantation at levels averaging 1% of all lineages. This percentage is within the range of anticipated efficacy levels for hemophilia and related diseases and forms a basis for further improvement.
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  • Vibert, E & Ishizawa, T 2012, « Hepatocellular carcinoma: Western and Eastern surgeons' points of view », J Visc Surg, vol. 149, no. 5, p. e302-6.
    Résumé : Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide. Developed on a pathological liver in 90% of cases, theoretically liver transplantation (LT) is its best treatment because it cures both malignancy and cause of malignancy, the underlying pathological liver. Cadaveric donors are the main source of liver in Western countries as France and living donors are the rules in Eastern countries as Japan. Because organ shortage could impact choices in HCC treatments, it was interesting to compare a Western and Eastern surgeon's points of view about treatment of HCC to assess if the source of organs has modified therapeutic strategies. Hence, aim of this work was to compare points of view of two hepatobiliary and transplant surgeons specialized in the treatment of HCC in France and Japan concerning five keys points that are decisive to choose one of the two curative treatments in HCC on pathological liver: liver resection or LT. These questions included the definition of an oncological treatment of HCC, the assessment of liver function, the treatment of HCC recurrences, the incidence of pathological information on therapeutic strategy and potential future therapeutics strategies.
    Mots-clés : Carcinoma, Hepatocellular/ surgery Cultural Characteristics France Humans Japan Liver Neoplasms/ surgery Physician's Practice Patterns Questionnaires.

  • Villalva, C, Cortes, U, Wager, M, Tourani, J-M, Rivet, P, Marquant, C, Martin, S, Turhan, AG & Karayan-Tapon, L 2012, « O6-Methylguanine-Methyltransferase (MGMT) Promoter Methylation Status in Glioma Stem-Like Cells is Correlated to Temozolomide Sensitivity Under Differentiation-Promoting Conditions », Int J Mol Sci, vol. 13, no. 6, p. 6983-94, viewed sans date, .
    Résumé : Glioblastoma (GBM) is the most malignant type of primary brain tumor with a very poor prognosis. The actual standard protocol of treatment for GBM patients consists of radiotherapy and concomitant temozolomide (TMZ). However, the therapeutic efficacy of this treatment is limited due to tumor recurrence and TMZ resistance. Recently isolated, glioma stem-like cells (GSCs) are thought to represent the population of tumorigenic cells responsible for GBM resistance and recurrence following surgery and chemotherapy. In addition, MGMT (O6-methylguanine-methyltransferase) methylation is considered as one of the principal mechanisms contributing to TMZ sensitivity of GBM. In this study we have isolated GSCs from 10 adult GBM patients and investigated the relationship between MGMT methylation status and Temozolomide (TMZ) sensitivity of these lines grown either in stem-like or differentiation promoting conditions. Sensitivity to TMZ was significantly associated with MGMT methylation status in cells committed to differentiation but not in stem-like cells. In addition, patients harboring highly methylated MGMT promoters had a longer overall survival. These results reveal the importance of the differentiation process when considering the predictive value of MGMT status in GSCs for clinical response to TMZ.
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  • Winston, DJ, Saliba, F, Blumberg, E, Abouljoud, M, Garcia-Diaz, JB, Goss, JA, Clough, L, Avery, R, Limaye, AP, Ericzon, BG, Navasa, M, Troisi, RI, Chen, H, Villano, SA & Uknis, ME 2012, « Efficacy and safety of maribavir dosed at 100 mg orally twice daily for the prevention of cytomegalovirus disease in liver transplant recipients: a randomized, double-blind, multicenter controlled trial », Am J Transplant, vol. 12, no. 11, p. 3021-30.
    Résumé : Maribavir is an oral benzimidazole riboside with potent in vitro activity against cytomegalovirus (CMV), including some CMV strains resistant to ganciclovir. In a randomized, double-blind, multicenter trial, the efficacy and safety of prophylactic oral maribavir (100 mg twice daily) for prevention of CMV disease were compared with oral ganciclovir (1000 mg three times daily) in 303 CMV-seronegative liver transplant recipients with CMV-seropositive donors (147 maribavir; 156 ganciclovir). Patients received study drug for up to 14 weeks and were monitored for CMV infection by blood surveillance tests and also for the development of CMV disease. The primary endpoint was Endpoint Committee (EC)-confirmed CMV disease within 6 months of transplantation. In a modified intent-to-treat analysis, the noninferiority of maribavir compared to oral ganciclovir for prevention of CMV disease was not established (12% with maribavir vs. 8% with ganciclovir: event rate difference of 0.041; 95% CI: -0.038, 0.119). Furthermore, significantly fewer ganciclovir patients had EC-confirmed CMV disease or CMV infection by pp65 antigenemia or CMV DNA PCR compared to maribavir patients at both 100 days (20% vs. 60%; p < 0.0001) and at 6 months (53% vs. 72%; p = 0.0053) after transplantation. Graft rejection, patient survival, and non-CMV infections were similar for maribavir and ganciclovir patients. Maribavir was well-tolerated and associated with fewer hematological adverse events than oral ganciclovir. At a dose of 100 mg twice daily, maribavir is safe but not adequate for prevention of CMV disease in liver transplant recipients at high risk for CMV disease.
    Mots-clés : Acyclovir/administration & dosage Administration, Oral Antiviral Agents/ administration & dosage Benzimidazoles/ administration & dosage Cytomegalovirus Infections/diagnosis/ drug therapy Dose-Response Relationship.

  • Wu, L-hua, Song, Z-xuan, Liu, X-hui, Li, S-zhu, Han, Z-chao & Uzan, G 2012, « [Method of expansion of late endothelial progenitor cells] », Zhonghua Yi Xue Za Zhi, vol. 92, no. 36, p. 2574-7, viewed sans date, .
    Résumé : OBJECTIVE: To validate a novel method of expanding late endothelial progenitor cells (EPC) in vitro. METHODS: We cultured mononuclear cells (MNC) from human peripheral blood on the plate with the feeder layer cells, i.e. irradiated late EPC or human umbilical vein endothelial cells. After 21 days, the numbers of late EPC colonies were counted separately. And the surface antigen of late EPC was detected by fluorescence-activated cell sorter (FACS) and their in vitro ability of forming vascular structure examined by matrigel. RESULTS: Both colony numbers of late EPC with feeder layer cell culturing were over 20 times than those without (40.0 ± 3.9, 39.3 ± 3.1 vs 2.0 ± 1.3, both P < 0.05). And the former's late EPC colony appeared earlier. The late EPC expressed CD31, CD34, eNOS, Flt-1, P1H12, Sendo, VE cadherin and CD117. And vascular structures were discerned. CONCLUSIONS: The method of feeder layer cells may vastly expand the quantity of late EPC. And microenvironment plays an important role in its expansion.
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  • Wu, L-hua, Song, Z-xuan, Liu, X-hui, Li, S-Z, Han, Z-chao & Uzan, G 2012, « Role of microenvironment in the process of expansion of late endothelial progenitor cell in vitro », Zhongguo Yi Xue Ke Xue Yuan Xue Bao, vol. 34, no. 3, p. 202-6, viewed sans date, .
    Résumé : OBJECTIVE: To study the role of the feeder layer cells as niche in the process of expansion of late endothelial progenitor cell in vitro. METHODS: We cultured mononuclear cells (MNC)from human peripheral blood (PB)on the plate with the feeder layer cells which were irradiated late endothelial progenitor cells(EPC)or human umbilical vein endothelial cells (HUVEC) by EGM-2. After 21 days, the numbers of obtained late EPC colonies were counted separately, and their surface antigen of the late EPC was verified by fluorescence-activated cell sorter (FACS) analysis, and their ability of forming vessel structure with Matrigel in vitro. The differentiation of single stem cell on the feeder layer cell was traced by video-microscopy. RESULTS: After 21 days of culture,(40.0±3.9)and(39.3±3.1)late EPC colonies that MNC of a handred milliliter PB were cultured, respectively, on the feeder layer cells of EPC and HUVEC were much more than (2.0±1.3) colonies cultured on without the feeder layer cells (all P <0.05). These cells also expressed CD31,CD34,eNOS,FLt-1,P1H12,Sendo,VEcadherin,and CD117, as shown by FACS analysis. Furthermore, they formed vessel structure with Matrigel in vitro. The video-microscopy showed the asymmetric cell division was participated by the feeder layer cell during the expansion of single stem cell. CONCLUSION: The massive expansion of late EPC can be achieved by the provision of the feeder layer cells, which may be involved in the stem cell asymmetric cell division.
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  • Young, J, Metay, C, Bouligand, J, Tou, B, Francou, B, Maione, L, Tosca, L, Sarfati, J, Brioude, F, Esteva, B, Briand-Suleau, A, Brisset, S, Goossens, M, Tachdjian, G & Guiochon-Mantel, A 2012, « SEMA3A deletion in a family with Kallmann syndrome validates the role of semaphorin 3A in human puberty and olfactory system development », Hum Reprod, vol. 27, no. 5, p. 1460-5, viewed sans date, .
    Résumé : BACKGROUND: Kallmann syndrome (KS) is a genetic disorder associating pubertal failure with congenitally absent or impaired sense of smell. KS is related to defective neuronal development affecting both the migration of olfactory nerve endings and GnRH neurons. The discovery of several genetic mutations responsible for KS led to the identification of signaling pathways involved in these processes, but the mutations so far identified account for only 30% of cases of KS. Here, we attempted to identify new genes responsible for KS by using a pan-genomic approach. METHODS: From a cohort of 120 KS patients, we selected 48 propositi with no mutations in known KS genes. They were analyzed by comparative genomic hybridization array, using Agilent 105K oligonucleotide chips with a mean resolution of 50 kb. RESULTS: One propositus was found to have a heterozygous deletion of 213 kb at locus 7q21.11, confirmed by real-time qPCR, deleting 11 of the 17 SEMA3A exons. This deletion cosegregated in the propositus' family with the KS phenotype, that was transmitted in autosomal dominant fashion and was not associated with other neurological or non-neurological clinical disorders. SEMA3A codes for semaphorin 3A, a protein that interacts with neuropilins. Mice lacking semaphorin 3A expression have been showed to have a Kallmann-like phenotype. CONCLUSIONS: SEMA3A is therefore a new gene whose loss-of-function is involved in KS. These findings validate the specific role of semaphorin 3A in the development of the olfactory system and in neuronal control of puberty in humans.
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  • Zemirli, N & Arnoult, D 2012, « Mitochondrial anti-viral immunity », Int J Biochem Cell Biol, vol. 44, no. 9, p. 1473-6, viewed sans date, .
    Résumé : In the cytosol, the sensing of RNA viruses by the RIG-I-like receptors (RLRs) triggers a complex signaling cascade where the mitochondrial antiviral signaling protein (MAVS) plays a crucial role in orchestrating the innate host response through the induction of antiviral and inflammatory responses. Hence, in addition to their known roles in the metabolic processes and the control of programmed cell death, mitochondria are now emerging as a fundamental hub for innate anti-viral immunity. This review summarizes the findings related to the MAVS adapter and mitochondria in the innate immune response to RNA viruses.
    Mots-clés : Cell Physiological Processes Humans *Immunity, Innate Mitochondria/*immunology/pathology/*virology Viruses/*immunology.

2011



  • Adam, R, de Haas, RJ, Wicherts, DA, Vibert, E, Salloum, C, Azoulay, D & Castaing, D 2011, « Concomitant extrahepatic disease in patients with colorectal liver metastases: when is there a place for surgery? », Ann Surg, vol. 253, no. 2, p. 349-59, viewed sans date, .
    Résumé : OBJECTIVE: To evaluate the impact of the location of extrahepatic disease (EHD) on survival and to determine patient outcome in a consecutive series of patients with both intrahepatic and extrahepatic colorectal metastases treated by an oncosurgical approach, combining repeat surgery and chemotherapy. BACKGROUND: Although recognized as poor prognostic factor, concomitant EHD is no more considered an absolute contraindication to surgery in patients with colorectal liver metastases (CLM). However, the impact of the location of EHD on survival and the benefit in patient outcome is still diversely appreciated. METHODS: From 840 patients resected for CLM between 1990 and 2006, 186(22%) also had resectable EHD. Sequential surgery was routinely combined with perioperative chemotherapy. Survival was compared with that of patients without EHD, prognostic factors were identified, and a predictive model was designed to better select surgical candidates. RESULTS: Patients resected for CLM with concomitant EHD experienced a lower 5-year survival than those without EHD (28% vs 55%, P < 0.001). Five poor prognostic factors were identified at multivariate analysis: EHD-location other than lung metastases (5-year survival: 23% vs 33%, P = 0.02), EHD concomitant to CLM recurrence (14% vs 34%, P < 0.001), carcinoembryonic antigen level at least 10 ng/mL (16% vs 37%, P=0.02), at least 6 CLM(9% vs 32%, P = 0.02), and right colon cancer (P = 0.02). Five-year survival ranged from 64% (0 factors) to 0% (>3 factors). In the EHD group, patients with an EHD-recurrence experienced better outcomes when resected than those treated by chemotherapy alone (5-year survival: 38% vs 21%, P = 0.05). CONCLUSION: Although sequential surgery is warranted for patients with 5 or less CLM with isolated lung metastases, low carcinoembryonic antigen levels,and no right colon primary tumor, it should be questioned in the presence of more than 3 of these prognostic factors.
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  • Adam, R, Hoti, E & Bredt, LC 2011, « [Oncosurgical strategies for metastatic liver cancer] », Cir Esp, vol. 89, no. 1, p. 10-9, viewed sans date, .
    Résumé : Patients with liver metastases from colorectal cancer (CRC) present a major public health challenge with approximately, 1,2 million cases of CRC occur yearly worldwide. Resection of colorectal liver metastases (CRLM) is the only treatment offering the possibility of cure and has been shown to provide clear survival benefits. However, only 10 to 20% of patients with CRLM are eligible for this procedure upfront. During the last decade, major advances in the management of CRLM have taken place involving three fields: oncology, interventional radiology, and surgery. These advances have increased the resectability rate to 20-30% of cases with a 5-year survival of 35-50%. Neoadjuvant treatment with chemotherapeutic agents such as irinotecan and oxaliplatin, and hepatic artery infusion combined with systemic therapy and biologic agents (bevacizumab, cetuximab) play an important role in increasing the number of patients eligible to secondary resection. However, with the progressive use of neoadjuvant chemotherapy further studies are necessary to answer questions such as the risk: benefit ratio in maximizing response rates versus vascular changes in the liver (current opinion still divided concerning their importance). These questions remain challenging and should not be underestimated. In this review, we have described the current oncosurgical strategies employed in patients with resectable and non resectable CRLM, their benefits, and future treatment strategies.
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  • Adams, D, Lacroix, C, Antonini, T, Lozeron, P, Denier, C, Kreib, AM, Epelbaum, S, Blandin, F, Karam, V, Azoulay, D, Adam, R, Castaing, D & Samuel, D 2011, « Symptomatic and proven de novo amyloid polyneuropathy in familial amyloid polyneuropathy domino liver recipients », Amyloid, vol. 18 Suppl 1, p. 174-7, viewed sans date, .
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  • Ahowesso, C, Li, X-M, Zampera, S, Peteri-Brunbäck, B, Dulong, S, Beau, J, Hossard, V, Filipski, E, Delaunay, F, Claustrat, B & Lévi, F 2011, « Sex and dosing-time dependencies in irinotecan-induced circadian disruption », Chronobiol Int, vol. 28, no. 5, p. 458-70, viewed sans date, .
    Résumé : Circadian disruption accelerates malignant growth; thus, it should be avoided in anticancer therapy. The circadian disruptive effects of irinotecan, a topoisomerase I inhibitor, was investigated according to dosing time and sex. In previous work, irinotecan achieved best tolerability following dosing at zeitgeber time (ZT) 11 in male and ZT15 in female mice, whereas worst toxicity corresponded to treatment at ZT23 and ZT3 in male and female mice, respectively. Here, irinotecan (50 mg/kg intravenous [i.v.]) was delivered at the sex-specific optimal or worst circadian timing in male and female B6D2F1 mice. Circadian disruption was assessed with rest-activity, body temperature, plasma corticosterone, and liver mRNA expressions of clock genes Rev-erbα, Per2, and Bmal1. Baseline circadian rhythms in rest-activity, body temperature, and plasma corticosterone were more prominent in females as compared to males. Severe circadian disruption was documented for all physiology and molecular clock endpoints in female mice treated at the ZT of worst tolerability. Conversely, irinotecan administration at the ZT of best tolerability induced slight alteration of circadian physiology and clock-gene expression patterns in female mice. In male mice, irinotecan produced moderate alterations of circadian physiology and clock-gene expression patterns, irrespective of treatment ZT. However, the average expression of Rev-erbα, Per2, and Bmal1 were down-regulated 2- to 10-fold with irinotecan at the worst ZT, while being minimally or unaffected at the best ZT, irrespective of sex. Corticosterone secretion increased acutely within 2 h with a sex-specific response pattern, resulting in a ZT-dependent phase-advance or -delay in both sex. The mRNA expressions of irinotecan clock-controlled metabolism genes Ce2, Ugt1a1, and Top1 were unchanged or down-regulated according to irinotecan timing and sex. This study shows that the circadian timing system represents an important toxicity target of irinotecan in female mice, where circadian disruption persists after wrongly timed treatment. As a result, the mechanisms underling cancer chronotherapeutics are expectedly more susceptible to disruption in females as compared to males. Thus, the optimal circadian timing of chemotherapy requires precise determination according to sex, and should involve the noninvasive monitoring of circadian biomarkers.
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  • Akesbi, J, Adam, R, Rodallec, T, Barale, P-O, Ayello-Scheer, S, Labbé, A, Laroche, L, Sahel, J-A & Nordmann, J-P 2011, « [Intraocular foreign bodies (IOFB) of the posterior segment: retrospective analysis and management of 57 cases] », J Fr Ophtalmol, vol. 34, no. 9, p. 634-40, viewed sans date, .
    Résumé : PURPOSE: To determine the influence of prognostic factors and the type of tamponade agent in surgical management of intraocular foreign bodies (IOFBs) for better visual outcome. PATIENTS AND METHODS: Fifty-seven consecutive cases were retrospectively reviewed at the XV-XX National Hospital (Paris) between 1 January 2004 and 31 December 2007. Univariate and multivariate analyses were performed to identify prognostic variables. Several parameters were measured: pre- and postoperatively: best corrected visual acuity (BCVA), material and size of the foreign body, entry site, time from trauma to surgical removal, IOFB location, initial retinal detachment, choice of vitreous tamponade agent (none, gas, silicone oil), postoperative visual outcome, and complications (siderosis, endophthalmitis, and vitreoproliferative retinal detachment). RESULTS: Metal IOFBs accounted for the majority with 80.7% (n=46). The inferior retinal segment was the most frequent location found: 47.4% (n=27). Initial and final mean BCVAs were, respectively, 1.47 (±0.99) and 1.03 (±0.96) (LogMar scale). The mean follow-up was 20.7 months (range, 12-60 months). Initial retinal detachment was found in 24.56% (n=14), with a statically worse prognosis. The BCVA was better in the group with gas tamponade (n=16) than in the group with silicone tamponade (n=21) and the group without a tamponade agent (n=20). Initial BCVA was the most important predictive factor for final BCVA. Time to surgery was a predictive factor of final visual outcome with a cut-off in the first week. The scleral or corneoscleral entry site had a better prognosis than the corneal site. Five cases of siderosis (8.7%) related to delayed management and two cases of endophthalmitis (3.5%) were found (despite use of prophylactic systemic antibiotics). No statistical difference was found regarding the IOFB location on the retina, its size, or the material. Finally, the retina remained detached in nine cases (15.78%). A final BCVA of 20/40 or more was obtained in 39.3 and 17.5% had light perception or worse. CONCLUSION: The prognosis of an IOFB injury is for the most part uncertain due to a complex combination of parameters. Nevertheless, good postoperative results can be achieved without a silicone tamponade agent. The main prognostic factors related to better visual outcome were initial BCVA, time to surgery (first week), initially attached retina, and the scleral entry site. The main complications were vitreoproliferative retinal detachment, endophthalmitis, and siderosis. The location, type, and size of IOFBs were not statistically significant predictive factors in this study.
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  • Antonini, TM, Sebagh, M, Roque-Afonso, AM, Teicher, E, Roche, B, Sobesky, R, Coilly, A, Vaghefi, P, Adam, R, Vittecoq, D, Castaing, D, Samuel, D & Duclos-Vallée, J-C 2011, « Fibrosing cholestatic hepatitis in HIV/HCV co-infected transplant patients-usefulness of early markers after liver transplantation », Am J Transplant, vol. 11, no. 8, p. 1686-95, viewed sans date, .
    Résumé : We characterized fibrosing cholestatic hepatitis (FCH) in a large cohort of HIV/HCV co-infected patients. Between 1999 and 2008, 59 HIV infected patients were transplanted for end-stage liver disease due to HCV. Eleven patients (19%) developed FCH within a mean period of 7 months [2-27] after liver transplantation (LT). At Week 1 post-LT, the mean HCV viral load was higher in the FCH group: 6.13 log(10) IU/mL ± 1.30 versus 4.9 log(10) IU/mL ± 1.78 in the non-FCH group, p = 0.05. At the onset of acute hepatitis after LT, activity was moderate to severe in 8/11 HIV+/HCV+ patients with FCH (73%) versus 13/28 (46%) HIV+/HCV+ non-FCH (p = 0.007) patients. A complete virological response to anti-HCV therapy was observed in 2/11 (18%) patients. Survival differed significantly between the two groups (at 3 years, 67% in non-FCH patients versus 15% in FCH patients, p = 0.004). An early diagnosis of FCH may be suggested by the presence of marked disease activity when acute hepatitis is diagnosed and when a high viral load is present. The initiation of anti-HCV therapy should be considered at this point.
    Mots-clés : Adult Aged Biological Markers/ blood Cholestasis, Intrahepatic Cohort Studies Female HIV Infections/ blood/complications Hepatitis C/blood/complications/ surgery Humans Immunosuppressive Agents/therapeutic use Liver Transplantation Male Middle Aged Viral Load.
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  • Araujo, LM, Chauvineau, A, Zhu, R, Diem, S, Bourgeois, EA, Levescot, A, Huerre, M, Gombert, JM, Bayry, J, Daeron, M, Bruhns, P, Kaveri, SV & Herbelin, A 2011, « Cutting Edge: Intravenous Ig Inhibits Invariant NKT Cell-Mediated Allergic Airway Inflammation through Fc gamma RIIIA-Dependent Mechanisms », Journal of Immunology, vol. 186, no. 6, p. 3289-3293, viewed sans date, <<Go to ISI>://WOS:000287923500002>.
    Résumé : Despite their increasing use in autoimmune, inflammatory, and allergic conditions, the mechanism of action of i.v. Igs (IVIg) is poorly understood. On the basis of the critical role of invariant NKT (iNKT) cells in allergic airway inflammation (AAI) and their constitutive expression of the low-affinity IgG receptor Fc gamma RIIIA, we surmised that IVIg targets iNKT cells to exert their anti-inflammatory effect. We found that IVIg treatment significantly inhibited AAI in OVA-sensitized C57BL/6 mice and downregulated alpha-galactosylceramide-induced iNKT cell activation and cytokine production. Allergic responses were restored in iNKT cell-deficient mice by transferring iNKT cells from PBS-but not from IVIg-treated mice, suggesting that IVIg acts directly on activated iNKT cells that have a critical role in AAI. The inhibitory effects of IVIg on both iNKT cell activation/function and OVA-driven AAI were lost in Fc gamma RIIIA(-/-) mice. Our data unravel an Fc gamma RIIIA-dependent inhibitory effect of IVIg on activated iNKT cells that confers protection in AAI. The Journal of Immunology, 2011, 186: 3289-3293.
  • Arcangeletti, MC, Dussaix, E, Ferraglia, F, Roque-Afonso, AM, Graube, A & Chezzi, C 2011, « Multicentric evaluation of new commercial enzyme immunoassays for the detection of immunoglobulin M and total antibodies against hepatitis A virus », Clin Vaccine Immunol, vol. 18, no. 8, p. 1391-4.
    Résumé : A multicentric clinical study was conducted on representative sera from 1,738 European and U.S. subjects for the evaluation of new anti-hepatitis A virus enzyme immunoassays from Bio-Rad Laboratories. Comparison with reference DiaSorin S.p.A. tests confirmed the good performance of Bio-Rad assays (99.85% and 99.47% overall agreement in detecting total antibodies and IgM, respectively).
    Mots-clés : A, A/, Antibodies/, Blood, Clinical, diagnosis, Hepatitis, Humans, Immunoenzyme, Immunoglobulin, immunology, Laboratory, M/, methods, Techniques/, Techniques/methods, virus/.
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    <p>3147345</p>
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  • Armengol, C, Cairo, S, Fabre, M & Buendia, MA 2011, « Wnt signaling and hepatocarcinogenesis: the hepatoblastoma model », Int J Biochem Cell Biol, vol. 43, no. 2, p. 265-70.
    Résumé : The Wnt/beta-catenin pathway plays a key role in liver development, regeneration and tumorigenesis. Among human cancers tightly linked to abnormal Wnt/beta-catenin signaling, hepatoblastoma (HB) presents with the highest rate (50-90%) of beta-catenin mutations. HB is the most common malignant tumor of the liver in childhood. This embryonic tumor differs from hepatocellular carcinoma by the absence of viral etiology and underlying liver disease, and by distinctive morphological patterns evoking hepatoblasts, the bipotent precursors of hepatocytes and cholangiocytes. Recent studies of the molecular pathogenesis of hepatoblastoma have led to identify two major tumor subclasses resembling early and late phases of prenatal liver development and presenting distinctive chromosomal alterations. It has been shown that the molecular signature of Wnt/beta-catenin signaling in hepatoblastoma is mainly imposed by liver context, but differs according to developmental stage. Finally, the differentiation stage of tumor cells strongly influences their invasive and metastatic properties, therefore affecting clinical behavior.
    Mots-clés : Animals Cell Differentiation Hepatoblastoma/ metabolism/pathology Hepatocytes/pathology Humans Liver Neoplasms/ metabolism/pathology Mice Mice, Knockout Mutation Signal Transduction Wnt Proteins/ physiology beta Catenin/genetics/physiology.

  • Arnoult, D, Soares, F, Tattoli, I & Girardin, SE 2011, « Mitochondria in innate immunity », EMBO Rep, vol. 12, no. 9, p. 901-10, viewed sans date, .
    Résumé : Mitochondria are cellular organelles involved in host-cell metabolic processes and the control of programmed cell death. A direct link between mitochondria and innate immune signalling was first highlighted with the identification of MAVS-a crucial adaptor for RIGI-like receptor signalling-as a mitochondria-anchored protein. Recently, other innate immune molecules, such as NLRX1, TRAF6, NLRP3 and IRGM have been functionally associated with mitochondria. Furthermore, mitochondrial alarmins-such as mitochondrial DNA and formyl peptides-can be released by damaged mitochondria and trigger inflammation. Therefore, mitochondria emerge as a fundamental hub for innate immune signalling.
    Mots-clés : Adaptor Proteins, Innate Mitochondria/genetics/*immunology/*metabolism Mitochondrial Proteins/genetics/immunology/metabolism Signal Transduction/*immunology, Signal Transducing/immunology/metabolism Animals Apoptosis Humans *Immunity.
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