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11. OVERVIEW

Author

Brechot, C

Published
2006

12. Meeting the Challenge of Eliminating Chronic Hepatitis B Infection

Author

Revill, PA, Penicaud, C, Brechot, C, Zoulim, F, Revill, PA, Penicaud, C, Brechot, C, and Zoulim, F

Abstract

Over 257 million people live with chronic hepatitis B virus (HBV) infection and there is no known cure. The effective preventative vaccine has no impact on existing infection. Despite the existence of drugs which efficiently suppress viral replication, treatment is usually life-long and finite therapies that cure HBV infection are urgently required. However, even if such therapies were available today, it is unlikely they would reach all of those who need it most, due to chronic hepatitis B (CHB) being largely undiagnosed across the globe and to the dire need for health systems promoting access to therapy. Considerable challenges to developing and implementing an effective HBV cure remain. Nonetheless, important advances towards a cure are being made, both in the development of a multitude of new therapeutic agents currently undergoing clinical trials, and through the establishment of a new global initiative dedicated to an HBV cure, ICE-HBV, that is working together with existing organisations to fast-track an HBV cure available to all.

Published
2019

13. 2018 international meeting of the Global Virus Network

Author

Brechot, C, Bryant, J, Endtz, H, Garry, RF, Griffin, DE, Lewi, SR, Mercer, N, Osterhaus, A, Picot, V, Vahlne, A, Verjans, GMGM, Weaver, S, Brechot, C, Bryant, J, Endtz, H, Garry, RF, Griffin, DE, Lewi, SR, Mercer, N, Osterhaus, A, Picot, V, Vahlne, A, Verjans, GMGM, and Weaver, S

Abstract

The Global Virus Network (GVN) was established in 2011 to strengthen research and responses to emerging viral causes of human disease and to prepare against new viral pandemics. There are now 45 GVN Centers of Excellence and 7 Affiliate laboratories in 29 countries. The 10th International GVN meeting was held from November 28-30, 2018 in Veyrier du Lac, France and was co-hosted by the two GVN Centers of Excellence, the Mérieux Foundation and the University of Veterinary Medicine Hannover (TiHo). The theme of this 10th International GVN meeting was "Eradication and control of (re-) emerging viruses". This report highlights the recent accomplishments of GVN researchers in several important areas of medical virology, including strategies for the eradication of smallpox, measles, polio, SARS and vector-borne or zoonotic infections, emergence and intervention strategies for retroviruses and arboviruses, preparedness for outbreaks of Filo- and other hemophilic viruses, pathogenesis, impact and prevention of respiratory viruses, as well as, viruses affecting the central and peripheral nervous system. Also threats in crisis settings like refugee camps were presented.

Published
2019

15. Detection of hepatitis B virus (HBV) in HBsAg negative individuals with primary liver cancer

Author

Paterlini, P. and Brechot, C.

Subjects
Hepatitis B -- Complications, Liver cancer -- Risk factors, Health
Abstract

Primary liver cancer (PLC), cancer that infests the liver first, rather than spreading from a neighboring organ, is a relatively common form of cancer. Epidemiological studies have shown a close relationship between infection with hepatitis B virus (HBV), a potentially fatal form of hepatitis, which is spread by blood and blood products, and with PLC. HBV is often, but not always, characterized by the presence of hepatitis B surface antigen (HBsAg), a protein associated with HBV, in the blood. Although evidence is mounting that HBV may be causally involved in the development of PLC, it is not clear what role, if any, is played by HBV in the onset of PLC in patients who are negative for HBsAg (HBsAg-negative). One possibility is that the virus is present, but at concentrations too low to be detected by standard assay techniques. If this is the case, the use of the polymerase chain reaction (PCR) technique, a method for amplifying tiny amounts of DNA, might capable of detecting HBV DNA. To further investigate this possibility, nine HBsAg-negative Italian patients with PLC, but without evidence of HBV exposure, participated in a study in which DNA was isolated from their liver tumor and processed with PCR to amplify the HBV region (if present) infecting the DNA molecule. Twenty normal liver and white blood cell DNA samples were used as negative controls. In five of the nine tumor samples, HBV DNA was clearly detected; in the remaining cases, inconclusive, but suggestive, evidence of HBV DNA was found. In contrast, no evidence was found for HBV infection in the 20 control samples. (Consumer Summary produced by Reliance Medical Information, Inc.)

Published
1991

16. Polymerase chain reaction to detect hepatitis B virus DNA and RNA sequences in primary liver cancers from patients negative for hepatitis B surface antigen

Author

Paterlini, P., Gerken, G., Nakajima, E., Terre, S., D'Errico, W., Grigioni, B., Nalpas, B., Franco, D., Wands, J., Kew, M., Pisi, E., Tiollais, P., and Brechot, C.

Subjects
Hepatitis B virus -- Identification and classification, Hepatitis B -- Diagnosis, Liver cancer -- Causes of, Liver cirrhosis -- Causes of, Hepatitis B -- Complications, Hepatitis associated antigen -- Measurement, Polymerase chain reaction -- Usage
Abstract

Results of epidemiologic studies strongly suggest that chronic infection with hepatitis B virus (HBV) is associated with liver cancer. HBV infection also contributes to liver cirrhosis (a chronic, degenerative disease), and cirrhosis is also correlated with liver cancer. These results are best established in patients who are HBsAg-positive (have antigens associated with hepatitis B virus on the surfaces of their cells), but the possible role of HBV in HBsAg-negative patients with liver cancer has not been as extensively explored. To better evaluate this issue, 28 HBsAg-negative patients with liver cancer were studied, using a highly sensitive assay (the polymerase chain reaction). The patients came from Italy (nine), France (10), South Africa (eight), and Japan (one). Cirrhosis was present in 22 patients. Tumor tissue was evaluated for HBV viral DNA and RNA (genetic material), and blood samples were taken to determine the presence of HBsAg and antibodies against hepatitis B proteins (anti-HBc or anti-HBs). Results showed that 10 of 23 patients had anti-HBc antibodies, anti-HBs, or both, while 13 had no markers for HBV. Eight of these 10 patients were from South Africa. HBV DNA was detected in liver tissue from 17 of the 28 patients; five from Italy, six from South Africa, five from France, and the one patient from Japan. Eight were positive for one of the anti-hepatitis B antibodies, and six had no HBV markers. Fourteen of these HBV DNA-positive tumors were from patients with cirrhosis, and three were associated with normal liver. Of the 22 patients with cirrhosis, HBV DNA was found in 14. Further investigation indicated that in some tumors the viral DNA was partially deleted. The findings suggest that in patients who are positive for anti-HBc or anti-HBs and who develop liver cancer, the viral genome may decline, resulting in HBsAg-negative test results. The persistence of HBV DNA sequences in people who have been exposed to the disease represents a risk for cancer through an unexplained mechanism. Overall, HBV DNA capable of replication was present in patients with liver cancer, even though they tested negative for HBsAg. (Consumer Summary produced by Reliance Medical Information, Inc.)

Published
1990

27. Identification and assembly of genomes and genetic elements in complex metagenomic samples without using reference genomes

Author

Nielsen, H.B., Almeida, M., Sierakowska Juncker, A., Rasmussen, S., Li, J., Sunagawa, S., Plichta, D.R., Gautier, L., Pedersen, A.G., Le Chatelier, E., Pelletier, E., Bonde, I., Nielsen, T., Manichanh, C., Arumugam, M., Batto, J.M., Quintanilha dos Santos, M.B., Blom, N., Borruel, N., Burgdorf, K.S., Boumezbeur, F., Casellas, F., Doré, J., Dworzynski, P., Guarner, F., Hansen, T., Hildebrand, F., Kaas, R.S., Kennedy, S., Kristiansen, K., Kultima, J.R., Leonard, P., Levenez, F., Lund, O., Moumen, B., Le Paslier, D., Pons, N., Pedersen, O., Prifti, E., Qin, J., Raes, J., Sørensen, S., Tap, J., Tims, S., Ussery, D.W., Yamada, T., Jamet, A., Mérieux, A., Cultrone, A., Torrejon, A., Quinquis, B., Brechot, C., Delorme, C., M'Rini, C., de Vos, W.M., Maguin, E., Varela, E., Guedon, E., Gwen, F., Haimet, F., Artiguenave, F., Vandemeulebrouck, G., Denariaz, G., Khaci, G., Blottière, H., Knol, J., Weissenbach, J., van Hylckama Vlieg, J.E., Torben, J., Parkhil, J., Turner, K., van de Guchte, M., Antolin, M., Rescigno, M., Kleerebezem, M., Derrien, M., Galleron, N., Sanchez, N., Grarup, N., Veiga, P., Oozeer, R., Dervyn, R., Layec, S., Bruls, T., Winogradski, Y., Zoetendal, E.G., Renault, D., Sicheritz-Ponten, Bork, P., Wang, J., Brunak, S., Ehrlich, S.D., Center for Biological Sequence Analysis, Technical University of Denmark [Lyngby] (DTU), Novo Nordisk Foundation Center for Biosustainability, MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Department of Computer Science [Baltimore], Johns Hopkins University (JHU), BGI Hong Kong Researche Institute, BGI Shenzhen, School of Bioscience and Biotechnology, Southern University of Science and Technology [Shenzhen] (SUSTech), European Molecular Biology Laboratory, US 1367 MetaGénoPolis, Institut National de la Recherche Agronomique (INRA)-Département Microbiologie et Chaîne Alimentaire (MICA), Institut National de la Recherche Agronomique (INRA)-MetaGénoPolis (MGP), Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Université d'Évry-Val-d'Essonne (UEVE), Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR), Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Digestive System Research Unit, Vall d'Hebron University Hospital [Barcelona], Faculty of Health Sciences, University of Southern Denmark (SDU), Department of Structural Biology, Flanders Institute for Biotechnology, Department of Bioscience Engineering, Vrije Universiteit [Brussels] (VUB), 8National Food Institute - Division for Epidemiology and Microbial Genomics, Department of Biology [Copenhagen], Faculty of Science [Copenhagen], Hagedorn Research Institute, Faculty of Health, Aarhus University [Aarhus], BGI Hong Kong research Institute, Rega Institute - Department of Microbiology and Immunology, Université Catholique de Louvain (UCL), VIB Center for the Biology of Disease, Section of Microbiology [Copenhagen], University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU)-Faculty of Science [Copenhagen], Laboratory of Microbiology, Wageningen University and Research Centre [Wageningen] (WUR), Department of Biological Information, Tokyo Institute of Technology [Tokyo] (TITECH), Max-Delbrück Center for Molecular Medicine, Princess Al Jawhara Center of Excellence in the Research of Hereditary Disorders, King Abdulaziz University, Centre for Host-Microbiome Interactions, Dental Institute Central Office, Guy’s Hospital, King‘s College London, Département Microbiologie et Chaîne Alimentaire (MICA), Institut National de la Recherche Agronomique (INRA), European Community's Seventh Framework Programme [FP7-HEALTH-F4-2007-201052, FP7-HEALTH-2010-261376], OpenGPU FUI collaborative research projects, DGCIS, Instituto de Salud Carlos III (Spain), Ministere de la Recherche et de l'Education Nationale (France), [ANR-11-DPBS-0001], Danmarks Tekniske Universitet = Technical University of Denmark (DTU), Beijing Genomics Institute [Shenzhen] (BGI), Southern University of Science and Technology (SUSTech), MetaGenoPolis, Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Vrije Universiteit Brussel (VUB), Université Catholique de Louvain = Catholic University of Louvain (UCL), University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH)-Faculty of Science [Copenhagen], Wageningen University and Research [Wageningen] (WUR), Max Delbrück Center for Molecular Medicine [Berlin] (MDC), Helmholtz-Gemeinschaft = Helmholtz Association, European Project: 201052,EC:FP7:HEALTH,FP7-HEALTH-2007-A,METAHIT(2008), Department of Systems Biology, Center for Biological Sequence Analysis, Ctr Biol Sequence Anal, National University of Singapore (NUS), European Molecular Biology Laboratory [Heidelberg] (EMBL), Department of Mathematics and Computer Science [Odense] (IMADA), Génomique métabolique (UMR 8030), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), Vall d’Hebron Research Institute (VHIR), Faculty of Health and Medical Sciences, The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen = Københavns Universitet (KU), INRA US1367 MetaGenoPolis, European Molecular Biology Laboratory [Grenoble] (EMBL), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP], Center for Biological Sequence Analysis [Lyngby], Chinese Academy of Agricultural Mechanization Sciences (CCCME), 1Génétique Microbienne, INRA, Domaine de Vilvert, 78352 Jouy en Josas Cedex, and Department of Bio-engineering Sciences

Subjects
Cellular immunity, polypeptide, [SDV]Life Sciences [q-bio], SHORT READ ALIGNMENT SEQUENCES SYSTEMS ALGORITHMS MICROBIOTA PROTEIN LIFE SETS TREE TOOL, complex metagenomic sample, Applied Microbiology and Biotechnology, Genome, Microbiologie, Databases, Genetic, genetic element, Cluster Analysis, sets, short read alignment, ComputingMilieux_MISCELLANEOUS, Genetics, 0303 health sciences, tool, metagenomic, tree, Lactococcus lactis, IL-12, Molecular Medicine, Biotechnology, life, Microbial Genomes, antigen specific immune response, Biomedical Engineering, Bioengineering, Computational biology, [SDV.BID]Life Sciences [q-bio]/Biodiversity, cellular immunity, Biology, algorithms, Microbiology, 03 medical and health sciences, Genetic variation, microbiota, Microbiome, Gene, genome, 030304 developmental biology, adjuvant activity, VLAG, 030306 microbiology, Metagenomics, WIAS, Microbial genetics, sequences, systems, protein
Abstract

Most current approaches for analyzing metagenomic data rely on comparisons to reference genomes, but the microbial diversity of many environments extends far beyond what is covered by reference databases. De novo segregation of complex metagenomic data into specific biological entities, such as particular bacterial strains or viruses, remains a largely unsolved problem. Here we present a method, based on binning co-abundant genes across a series of metagenomic samples, that enables comprehensive discovery of new microbial organisms, viruses and co-inherited genetic entities and aids assembly of microbial genomes without the need for reference sequences. We demonstrate the method on data from 396 human gut microbiome samples and identify 7,381 co-abundance gene groups (CAGs), including 741 metagenomic species (MGS). We use these to assemble 238 high-quality microbial genomes and identify affiliations between MGS and hundreds of viruses or genetic entities. Our method provides the means for comprehensive profiling of the diversity within complex metagenomic samples.

Published
2014

30. Enterotypes of the human gut microbiome

Author

Arumugam, M., Raes, J., Pelletier, E., Le Paslier, D., Yamada, Takuji, Mende, D. R., Fernandes, G. R., Tap, J., Bruls, T., Batto, J. M., Bertalan, M., Borruel, N., Casellas, F., Fernandez, L., Gautier, L., Hansen, T., Hattori, M., Hayashi, T., Kleerebezem, M., Kurokawa, K., Leclerc, M., Levenez, F., Manichanh, C., Nielsen, H. B., Nielsen, T., Pons, N., Poulain, J., Qin, J., Sicheritz-Ponten, T., Tims, S., Torrents, D., Ugarte, E., Zoetendal, E. G., Wang, J., Guarner, F., Pedersen, O., de Vos, W. M., Brunak, S., Dor�, J., Antol匤, M., Artiguenave, F., Blottiere, H. M., Almeida, M., Brechot, C., Cara, C., Chervaux, C., Cultrone, A., Delorme, C., Denariaz, G., Dervyn, R., Foerstner, K. U., Friss, C., van de Guchte, M., Guedon, E., Haimet, F., Huber, W., van Hylckama-Vlieg, J., Jamet, A., Juste, C., Kaci, G., Knol, J., Lakhdari, O., Layec, S., Le Roux, K., Maguin, E., M駻ieux, A., Melo Minardi, R., M'rini, C., Muller, J., Oozeer, R., Parkhill, J., Renault, P., Rescigno, M., Sanchez, N., Sunagawa, S., Torrejon, A., Turner, K., Vandemeulebrouck, G., Varela, E., Winogradsky, Y., Zeller, G., Weissenbach, J., Ehrlich, S. D., Bork, P., Consortium, MetaHIT, Microbiota Interaction with Human and Animal (MIHA), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech-Institut National de la Recherche Agronomique (INRA)-AgroParisTech, AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), European Molecular Biology Laboratory [Heidelberg] (EMBL), Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Center for Biological Sequence Analysis [Lyngby], Technical University of Denmark [Lyngby] (DTU), Digestive System Research Unit, Vall d'Hebron University Hospital [Barcelona], Barcelona Supercomputing Center - Centro Nacional de Supercomputacion (BSC - CNS), Centre Interlangues - Texte, Image, Langage (TIL), Université de Bourgogne (UB), Hagedorn Research Institute, Faculty of Health Sciences, University of Southern Denmark (SDU), NIZO [Ede, Netherlands], Institut National de la Recherche Agronomique (INRA), Génomique métabolique (UMR 8030), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), Beijing Genomics Institute [Shenzhen] (BGI), Laboratory of Microbiology, Wageningen University and Research [Wageningen] (WUR), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Lundbeck Foundation Centre for Applied Medical Genomics in Personalized Disease Prediction, Prevention and Care (LuCAMP), Novo Nordisk Foundation, International Science and Technology Cooperation Project in China [0806], Agence Nationale de la Recherche (ANR), Institute for the encouragement of Scientific Research and Innovation of Brussels (ISRIB), Fund for Scientific Research Flanders (FWO), European Project: 201052,EC:FP7:HEALTH,FP7-HEALTH-2007-A,METAHIT(2008), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, NIZO FOOD RESEARCH (NIZO), Nizo food research, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université d'Évry-Val-d'Essonne (UEVE), Wageningen University and Research Centre [Wageningen] (WUR), Danmarks Tekniske Universitet = Technical University of Denmark (DTU), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, intestinal microbiota, catalog, obesity, [SDV]Life Sciences [q-bio], pathways, Biodiversity, Biology, Microbiology, Article, diversity, 03 medical and health sciences, Feces, Human gut, mucin, Phylogenetics, Microbiologie, Humans, bacterial, Microbiome, genes, Phylogeny, 030304 developmental biology, VLAG, 2. Zero hunger, 0303 health sciences, metagenomics, Multidisciplinary, Bacteria, colon, 030306 microbiology, Host (biology), Ecology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Bacterial Typing Techniques, Europe, Intestines, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Evolutionary biology, Metagenomics, Metagenome, Enterotype, Biological Markers, Female, Biomarkers, Human Microbiome Project
Abstract

International audience; Our knowledge of species and functional composition of the human gut microbiome is rapidly increasing, but it is still based on very few cohorts and little is known about variation across the world. By combining 22 newly sequenced faecal metagenomes of individuals from four countries with previously published data sets, here we identify three robust clusters (referred to as enterotypes hereafter) that are not nation or continent specific. We also confirmed the enterotypes in two published, larger cohorts, indicating that intestinal microbiota variation is generally stratified, not continuous. This indicates further the existence of a limited number of well-balanced host-microbial symbiotic states that might respond differently to diet and drug intake. The enterotypes are mostly driven by species composition, but abundant molecular functions are not necessarily provided by abundant species, highlighting the importance of a functional analysis to understand microbial communities. Although individual host properties such as body mass index, age, or gender cannot explain the observed enterotypes, data-driven marker genes or functional modules can be identified for each of these host properties. For example, twelve genes significantly correlate with age and three functional modules with the body mass index, hinting at a diagnostic potential of microbial markers.

Published
2011

31. Liver hepatocyte growth factor does not always correlate with hepatocellular proliferation in human liver lesions: Its specific receptor c- met does

Author

D'Errico A., Fiorentino M., Ponzetto A., Daikuhara Y., Tsubouchi H., Brechot C., Scoazec J. -Y., Grigioni W. F., D'Errico A., Fiorentino M., Ponzetto A., Daikuhara Y., Tsubouchi H., Brechot C., Scoazec J.-Y., and Grigioni W.F.

Subjects
Hepatology, c-met, hepatocellular carcinoma, digestive system diseases
Abstract

Increased levels of expression of hepatocyte growth factor (HGF) and its specific receptor c-met have been shown in the liver of several benign and malignant pathologies, both in experimental models and humans. We investigated by immunohistochemistry the presence of both HGF and c-met protooncogene product (c-met pp) in 20 hepatocellular carcinomas (HCCs), 5 focal nodular hyperplasias (FNHs), 4 cases of fulminant hepatitis (FH), and 1 case of regenerated liver. The c-met protooncogene product was expressed in all cases with marked overexpression in the HCCs and in ductular metaplasia. HGF was detected in the Ito cells of all cases and in neoplastic hepatocytes of 9 of 20 HCCs (45%). The proliferative index of each lesion was evaluated by means of the polyclonal antibody anti-cyclin A. When the level of expression of HGF and c-met protooncogene product with the percentage of cyclin A+ nuclei were compared, the closest relationship was between c-met protooncogene product and cyclin A. In 11 of 20 HCCs (55%), there was no correlation between HGF positivity and cyclin A. This seems to suggest that, independently of the levels of native liver HGF, c-met protooncogene product is the most active modulator of liver cell proliferation.

Published
1996

33. HIP/PAP stimulates liver regeneration after partial hepatectomy and combines mitogenic and antiapoptotic functions through the PKA signaling pathway

Author

Simon, M.T., Pauloin, Alain, Normand, Guillaume, Lieu, H.T., Mouly, H., Pivert, G., Carnot, F., Tralhao, J.G., Brechot, C., Christa, L., Unité de recherche génomique et physiologie de la lactation (GPL), Institut National de la Recherche Agronomique (INRA), and ProdInra, Migration

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], [INFO]Computer Science [cs], [INFO] Computer Science [cs], GENE HIP-PAP, CANCER, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2003

37. High expression of the human hepatocarcinoma-intestine-pancreas/pancreatic-associated protein (HIP/PAP) gene in the mammary glang of lactating transgenic mice

Author

Christa, L., Pauloin, Alain, Simon, M.T., Stinnakre, M.G., Fontaine, M.L., Delpal, Serge, OLLIVIER-BOUSQUET, M., Brechot, C., Devinoy, Eve, Unité de biologie cellulaire et moléculaire, Institut National de la Recherche Agronomique (INRA), and ProdInra, Migration

Subjects
[SDV] Life Sciences [q-bio], EXPRESSION DU GENE, [SDV]Life Sciences [q-bio], BIOLOGIE MOLECULAIRE, ComputingMilieux_MISCELLANEOUS, GENE HIP/PAP
Abstract

International audience

Published
2000

38. Impact of HBV HCV and GBV-C/HGV on hepatocellular carcinomas in Europe: results of a European concerted action

Author

Brechot, C Jaffredo, F Lagorce, D Gerken, G zum Buschenfelde, KM Papakonstontinou, A Hadziyannis, S Romeo, R and Colombo, M Rodes, J Bruix, J Williams, R Naoumov, N

Subjects
virus diseases, digestive system diseases
Abstract

Background/Aims: To investigate the impact of hepatitis B (HBV) and C (HCV) infections on hepatocellular carcinoma (HCC) in Europe, Methods: Five hundred and three patients with HCC, from six liver centers, were included. All 503 sera and 80 liver samples were tested for HBV DNA and HCV RNA by polymerase chain reaction. GBV-C/HGV RNA was also tested in 57 sera. Results: HBsAg and anti-HCV were detected in 19% and 40.1% of the patients, respectively. Serum and liver HBV DNA were detected in 82% and 91% of the HBsAg positive subjects. HBV DNA was also detected in the serum and liver of 33% and 47% of HBsAg negative patients, In this group, serum HBV DNA was more prevalent in anti-HBs and/or anti-HBc patients (47.9%), compared to those without any HBV marker (25,1%), HCV RNA was detected in 89% and 7% of anti-HCV positive and negative cases, respectively, HCV Ib being the most prevalent genotype (80%), Coinfection with HBV and HCV was shown in 20.4% of patients, while only 29% had neither HBV nor HCV; GBV-C/HGV RNA was detected in only 4/57 sera, Conclusions: This study offers the first large analysis of HCC in Europe, based on both serology and molecular tests, It demonstrates the major impact of HBV and HCV, but not of GBV-C/HGV, in liver carcinogenesis in Northern as well as Southern Europe. It also stresses the need to use viral genome detection in epidemiological studies when serological tests are negative.

Published
1998

40. Liver-stage development of Plasmodium falciparum, in a humanized mouse model.

Author

Morosan, S., Hez-Deroubaix, S., Verduyn Lunel, F.M., Renia, L., Giannini, C., Rooijen, N. van, Battaglia, S., Blanc, C., Eling, W.M.C., Sauerwein, R.W., Hannoun, L., Belghiti, J., Brechot, C., Kremsdorf, D., Druilhe, P., Morosan, S., Hez-Deroubaix, S., Verduyn Lunel, F.M., Renia, L., Giannini, C., Rooijen, N. van, Battaglia, S., Blanc, C., Eling, W.M.C., Sauerwein, R.W., Hannoun, L., Belghiti, J., Brechot, C., Kremsdorf, D., and Druilhe, P.

Abstract

Item does not contain fulltext, BACKGROUND: The liver stage of the human malaria parasite Plasmodium falciparum is the least known, yet it holds the greatest promise for the induction of sterile immunity and the development of novel drugs. Progress has been severely limited by the lack of adequate in vitro and in vivo models. METHODS: Recently, it was found that immunodeficient mice transgenic for the urokinase plasminogen activator allow survival of differentiated human hepatocytes. We confirm this finding but show that hepatocyte survival is short lived unless nonadaptive defenses are simultaneously depleted. RESULTS: By controlling macrophages and NK cells, we readily effected the long-term secretion of human serum albumin and human alpha-1 antitrypsin in mouse serum (at 3 months, the proportion of repopulated mice increased from 0% to 60% and from 22% to 80%, respectively; P<.0001). P. falciparum sporozoites delivered intravenously into mice readily infected transplanted human hepatocytes and developed into liver schizonts. Their size was twice as large as what was seen in vitro and was comparable to that found in humans and chimpanzees. CONCLUSION: These results emphasize the importance of nonadaptive defenses against xenotransplantation and lead to development of small laboratory models that, because they can harbor human hepatocytes, provide novel opportunities to study intrahepatic pathogens, such as those causing malaria and hepatitis.

Published
2006

43. 1401 GENOME-WIDE ASSOCIATION STUDY IDENTIFIES VARIANTS ASSOCIATED WITH LIVER FIBROSIS PROGRESSION IN HCV-INFECTED PATIENTS

Author

Patin, E., primary, Kutalik, Z., additional, Guergnon, J., additional, Bibert, S., additional, Nalpas, B., additional, Jouanguy, E., additional, Munteanu, M., additional, Bousquet, L., additional, Argiro, L., additional, Halfon, P., additional, Boland, A., additional, Mullhaupt, B., additional, Semela, D., additional, Dufour, J.-F., additional, Heim, M.H., additional, Moradpour, D., additional, Cerny, A., additional, Malmvemi, R., additional, Hirsch, H., additional, Martinetti, G., additional, Suppiah, V., additional, Stewart, G., additional, Booth, D.R., additional, George, J., additional, Casanova, J.-L., additional, Brechot, C., additional, Rice, C.M., additional, Talal, A.H., additional, Jacobson, I.M., additional, Bourliere, M., additional, Theodorou, I., additional, Poynard, T., additional, Negro, F., additional, Pol, S., additional, Abel, L., additional, and Bochud, P.-Y., additional

Published
2012
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45. Alterations of cyclin-dependent kinase 4 inhibitor (p16INK4A/MTS1) gene structure and expression in acute lymphoblastic leukemias

Author

Alain Delmer, Tang R, Senamaud-Beaufort C, Paterlini P, Brechot C, and Zittoun R

Subjects
Base Sequence, Homozygote, Molecular Sequence Data, Gene Expression, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Polymerase Chain Reaction, Blotting, Southern, Cyclins, Humans, Genes, Tumor Suppressor, RNA, Messenger, Carrier Proteins, Protein Kinase Inhibitors, Cyclin-Dependent Kinase Inhibitor p16, Gene Deletion
Abstract

The cyclin-dependent kinase 4 (cdk4) inhibitor (p16INK4/MTS1/CDKN2) gene has been recently identified as a putative tumor suppressor gene because of the high frequency of homozygous deletion observed in numerous human tumor cell lines, including leukemias. However, results obtained from uncultured tumor samples have led to discussion of the relevance of these findings. Using reverse transcriptase polymerase chain reaction (RT-PCR) and Southern blot analysis, we have investigated p16INK4A gene at both RNA and genomic levels in various types of leukemias: acute myeloid leukemia (AML) (n = 23); acute lymphocytic leukemia (ALL) (n = 22) and B cell chronic lymphoproliferative disorders (CLPD) (n = 33). p16INK4A mRNA expression was not found in only 1/20 AML and 2/23 CLPD samples. Conversely, p16INK4A mRNA was not detected in 5/17 ALL cases, and intensity of PCR products were barely detectable in seven additional cases, possibly related to the contamination by normal cells in some cases. By Southern blotting, a homozygous deletion of p16INK4A gene was found in 6/17 ALL cases (35%) among which 4/6 were negative or weakly positive by RT-PCR assay. None of the five AML and 20 CLL samples studied had p16INK4A deletion. Sequence analysis of p16INK4A exon 2 did not show point mutation in two of these cases lacking mRNA expression. Our data provide further evidence that among hematological malignancies, ALL are the most likely to be associated with p16INK4A inactivation, mainly by homozygous gene deletion. Since most hematological malignancies-except ALL-are infrequently associated with p16INK4A and retinoblastoma (Rb) gene alteration it seems worthwhile to explore cdk4 and cdk6 expression to determine whether or not the disruption of the p16INK4A/Rb/cdk4/cdk6 regulatory loop might play a role in their pathogenesis.

Published
1995

46. Do Livers 'Stream'?

Author

Bralet, M-P., Branchereau, S., Brechot, C., and Ferry, N.

Subjects
Correspondence
Published
1995

49. Cell lineage study in the liver using retroviral mediated gene transfer. Evidence against the streaming of hepatocytes in normal liver

Author

Bralet, M. P., Branchereau, S., Brechot, C., and Ferry, N.

Subjects
Research Article
Abstract

The fate of normal hepatocytes in adult rat liver was studied after genetic labeling using the Escherichia coli beta-galactosidase gene coupled to a nuclear localization signal. The marker gene was introduced by direct in vivo retroviral-mediated gene transfer into hepatocytes 24 hours after partial hepatectomy. Analysis of beta-galactosidase expression in the liver at various time after gene transfer revealed that labeled hepatocytes were distributed throughout the entire lobule with a predominance in the periportal and mediolobular regions. Long-term experiments demonstrated that division of hepatocytes did occur as was revealed by the increasing number of beta-galactosidase-positive cells in isolated clusters. There was no evidence for the participation of stem cells in this process. Moreover, we found that after more than 1 year, the pattern of distribution of positive cells within the lobule was not modified. This suggests that hepatocytes do not migrate from the portal space to the perivenous region, as has been previously hypothesized.

Published
1994

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