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Genome-wide differences in hepatitis C-vs alcoholism-associated hepatocellular carcinoma

World Journal of Gastroenterology 2008年第11期14卷 1749-1758页

作者： Céline derambure Cédric Coulouarn frédérique Caillot Romain daveau Martine Hiron Michel Scotte Arnaud franois Celia duclos Odile Goria Marie Gueudin Catherine Cavard Benoit Terris Maryvonne daveau Jean-Philippe Salier inserm unité519 and institut fédératif de recherches multidisciplinaires sur les peptides Facultéde Médecine-PharmacieRouenFrance inserm unité519 and institut fédératif de recherches multidisciplinaires sur les peptides Facultéde Médecine-PharmacieRouenFrance Service de Chirurgie Générale et DigestiveCentre Hospitalier UniversitaireRouenFrance département de Pathologie Centre Hospitalier UniversitaireRouenFrance inserm unité519 and institut fédératif de recherches multidisciplinaires sur les peptides Facultéde Médecine-PharmacieRouenFrance Service d'Hépato-gastro-enterologieCentre Hospitalier UniversitaireRouenFrance Laboratoire de Virologie and UPRES EA 2646 Centre Hospitalier UniversitaireRouenFrance inserm unité567 CNRS UMR 8104 UniversitéParis 5Département GDPMInstitut CochinParis France

AIM:To look at a comprehensive picture of etiology- dependent gene abnormalities in hepatocellular carcinoma in Western Europe. METHOdS:With a liver-oriented microarray,transcript levels were compared in nodules and cirrhosis from a training set of patients with hepatocellular carcinoma (alcoholism,12;hepatitis C,10)and 5 *** or tight selection of informative transcripts with an abnormal abundance was statistically valid and the tightly selected transcripts were next quantified by qRTPCR in the nodules from our training set(12+10) and a test set(6+7). RESULTS:A selection of 475 transcripts pointed to significant gene over-representation on chromosome 8 (alcoholism)or-2(hepatitis C)and ontology indicated a predominant inflammatory response(alcoholism)or changes in cell cycle regulation,transcription factors and interferon responsiveness(hepatitis C).A stringent selection of 23 transcripts whose differences betweenetiologies were significant in nodules but not in cirrhotic tissue indicated that the above dysregulations take place in tumor but not in the surrounding *** 23 transcripts separated our test set according to etiologies. The inflammation-associated transcripts pointed to limited alterations of free iron metabolism in alcoholic vs hepatitis C tumors. CONCLUSION:Etiology-specific abnormalities(chromo- some preference;differences in transcriptomes and related functions)have been identified in hepatocellular carcinoma driven by alcoholism or hepatitis *** may open novel avenues for differential therapies in this disease.

关键词： Alcoholism Chromosome Cirrhosis Hepatitis C Transcriptomes Protein function

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Effects of glutamine supplementation on gut barrier,glutathione content and acute phase response in malnourished rats during inflammatory shock

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World Journal of Gastroenterology 2007年第20期13卷 2833-2840页

作者： Liliana Belmonte Mose Co■ffier florence Le Pessot Olga Miralles-Barrachina Martine Hiron Antony Leplingard Jean-franois Lemeland Bernadette Hecketsweiler Maryvonne daveau Philippe ducrotté Pierre déchelotte Appareil digestif Environnement Nutrition ADEN EA3234Institut Hospitalo-Universitaire de Recherche Biomédicale and Institut Fédératif de Recherches Multidisciplinaires sur les PeptidesFaculté de Médecine-PharmacieRouenFrance Service d’Anatomie Pathologique Centre Hospitalier UniversitaireRouenFrance inserm unit 519 Institut Hospitalo-Universitaire de Recherche Biomédicale and Institut Fédératif de Recherches Multidisciplinaires sur les PeptidesFaculté de Médecine-PharmacieRouenFrance Groupe de Recherche sur les Antimicrobiens et les Microorganismes GRAM EA2656Institut Hospitalo-Universitaire de Recherche Biomédicale and Institut Fédératif de Recherches Multidisciplinaires sur les PeptidesFaculté de Médecine-PharmacieRouenFrance

AIM: To evaluate the effect of glutamine on intestinal mucosa integrity,glutathione stores and acute phase response in protein-depleted rats during an inflammatory shock. METHOdS: Plasma acute phase proteins (APP),jejunal APP mRNA levels,liver and jejunal glutathione concentrations were measured before and one,three and seven days after turpentine injection in 4 groups of control,protein-restricted,protein-restricted rats supplemented with glutamine or protein powder. Bacterial translocation in mesenteric lymph nodes and intestinal morphology were also assessed. RESULTS: Protein deprivation and turpentine injection significantly reduced jejunal villus height,and crypt depths. Mucosal glutathione concentration significantly decreased in protein-restricted rats. Before turpentine oil,glutamine supplementation restored villus heights and glutathione concentration (3.24 ± 1.05 vs 1.72 ± 0.46 μmol/g tissue,P d low. Glutamine markedly increased jejunal α1-acid glycoprotein mRNA level after turpentine oil but did not affect its plasma concentration. Bacterial translocation in protein-restricted rats was not prevented by glutamine or protein powder supplementation. CONCLUSION: Glutamine restored gut glutathione stores and villus heights in malnourished rats but had no preventive effect on bacterial translocation in our model.

关键词： Acute phase response Glutamine Glutathione Intestine Malnutrition

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Transient and etiology-related transcription regulation in cirrhosis prior to hepatocellular carcinoma occurrence

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World Journal of Gastroenterology 2009年第3期15卷 300-309页

作者： frédérique Caillot Céline derambure Paulette Bioulac-Sage Arnaud franois Michel Scotte Odile Goria Martine Hiron Maryvonne daveau Jean-Philippe Salier inserm unité 905 and institut fédératif de recherches multidisciplinaires sur les peptides Faculté de Médecine-Pharmacie76183 RouenFrance Service d'Anatomie Pathologique Centre Hospitalier Universitaireand Inserm U88933000 BordeauxFrance département Pathologie Centre Hospitalier Universitaire76183 RouenFrance Service de Chirurgie Générale et digestive Centre Hospitalier Universitaire76183 RouenFrance Service d'Hépato-gastro-entérologie Centre Hospitalier Universitaire76183 RouenFrance

AIM： To search for transcription dysregulation that could （1） differentiate hepatocellular carcinoma （HCC）-free from HCC-related cirrhosis （2） differentiate HCC-free cirrhosis related to HCV from that related to alcohol intake. METHOdS： Using microarray analysis, we compared transcript levels in HCC-free cirrhosis （alcoholism： 7; hepatitis C： 7）, HCC-associated cirrhosis （alcoholism： 10; hepatitis C： 10） and eight control livers. The identified transcripts were validated by qRT-PCR in an independent cohort of 45 samples （20 HCC-free cirrhosis; 15 HCC-associated cirrhosis and 10 control livers）. We also confirmed our results by ***： In HCC-free livers, we identified 70transcripts which differentiated between alcoholicrelated-cirrhosis, HCV-related cirrhosis and control livers. They mainly corresponded to down-regulation. dysregulation of Signal Transduction and Activator of Transcription-3 （STAT-3） was found along with related changes in STAT-3 targets which occurred in an etiology-dependent fashion in HCC-free cirrhosis. In contrast, in HCC, such transcription dysregulations were not observed. CONCLUSION： We report that transcriptional dysregulations exist in HCC-free cirrhosis, are transiently observed prior to detectable HCC onset and may be appear like markers from cirrhosis to HCC transition.

关键词： Liver Pathology Alcoholism Hepatitis Cvirus Gene expression Carcinogenesis

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