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Liver angiogenesis as a risk factor for hepatocellularcarcinoma development in hepatitis C virus cirrhotic patients

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World Journal of Gastroenterology 2007年第37期13卷 5009-5014页

作者： Roberto Mazzanti Luca Messerini Camilla E Comin Lorenzo Fedeli Nathalie Gannè-Carrie michel beaugrand Dipartimento di Medicina Interna Sezione di Oncologia Medica Centro di Eccellenza DENOthe Azienda Ospedaliero-Universitaria Careggi Istituto Toscano Tumori Università degli Studi di Firenze Florence Italy Dipartimento di Patologia Umana ed Oncologia Istituto Toscano Tumori Università degli Studi di Firenze Florence Italy Nathalie Gannè-Carrie Michel Beaugrand Service d'Hepato-Gastroenterologie Hopital Jean Verdier Assistance Publique-Hopitaux de Paris et UFR SMBH-Universite Paris XIII Bondy France Nathalie Gannè-Carrie Michel Beaugrand Service d’Hepato-Gastroenterologie Hopital Jean Verdier Assistance Publique-Hopitaux de Paris et UFR SMBH-Universite Paris XIII Bondy France

AIM： To evaluate the predictive value of hepatocyte proliferation and hepatic angiogenesis for the occurrence of Hepatocellular carcinoma （HCC） in hepatitis C virus （HCV） cirrhotic patients.METHODS： One hundred-five patients （69 males, 36 females; age range, 51-90 year; median 66 year） with biopsy proven HCV cirrhosis were prospectively monitored for HCC occurrence for a median time of 64 too. Angiogenesis was assessed by using microvessel density （MVD）, hepatocyte turnover by MIB1 and PCNA indexes at inclusion in liver biopsies.RESULTS： Forty six patients （43.8%） developed HCC after a median time of 55 （6-120） mo while 59 （56.2%） did not. Patients were divided into two groups according to the median value of each index. The difference between patients with low （median MVD = 3; range 0-20） and high （median MVD = 7; range 1-24） MVD was statist（caUy s（gn（ficant （χ^2= 22.06; P 〈 0.0001） wh（ch was not the case for MIB1 or PCNA （MIB-I： χ^2 = 1.41; P = 0.2351; PCNA： χ^2 = 1.27; P = 0.2589）. The median MVD was higher in patients who developed HCC than in those who did not. HOe-free interval was significantly longer in patients with the MVD ≤ 4 （P = 0.0006）. No relationship was found between MIB1 or PCNA and MVD （MIB-1 r^2 = 0.00007116, P = 0.9281; PCNA： P =0.001950; P = 0.6692）. MVD only was able to predict the occurrence of HCC in these patients. Among other known risk factors for HCC, only male sex was statistically associated with an increased risk. CONCLUSION： Liver angiogenesis has a role for in HCV- related liver carcinogenesis and for defining patients at higher risk.

关键词： Liver cancer Hepatitis C virus Angiogenesis Proliferating cell nuclear antigen

Chemokine system polymorphisms, survival and hepatocellular carcinoma occurrence in patients with hepatitis C virus-related cirrhosis

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World Journal of Gastroenterology 2008年第5期14卷 713-719页

作者： Pierre Nahon Angela Sutton Pierre Rufat Chantal Simon Jean-Claude Trinchet Liliane Gattegno michel beaugrand Nathalie Charnaux Department of Hepatology Jean Verdier Hospital (AP-HP) Bondy 93140 France Department of Biochemistry Jean Verdier Hospital (AP-HP) Bondy 93140 France Department of Public Health Pitié-Salpetrière Hospital (AP-HP) Paris 75013 France

AIM： To explore the influence of polymorphisms in genes encoding for the chemokines Stromal cell-Derived Factor-1 （SDF-1）/CXCL12 and Monocyte Chemotactic Protein-1 （MCP-1）/CCL2, or for the chemokine receptor CCR5 on the risks of liver-related death and hepatocellular carcinoma （HCC） occurrence in hepatitis C virus （HCV）-infected patients. METHODS： SDF-1 3＇A, MCP-1 （-2518） and CCRS-△32 polymorphisms, SDF-1α, Regulated upon Activation Normal T cells Expressed and Secreted （RANTES）/CCL5 and MCP-1 serum levels were determined in 120 HCV- infected patients, included at time of cirrhosis diagnosis and prospectively followed-up. RESULTS： During follow-up, 23/120 （19.1%） patients died and 47/120 （39.1%） developed HCC. Carriers and noncarriers of each genetic marker had similar baseline characteristics estimating the severity of liver disease. The occurrence of death or HCC during follow-up was similar among carriers and noncarriers of each polymorphism. There was no association between the carriage of mutated alleles and chemokine serum levels and the latter were not associated with the risks of death or HCC. CONCLUSION： This study suggests the lack of association of SDF-1 3＇A, MCP-1 （-2518）, CCRS-△32 polymorphisms with death and HCC occurrence in cirrhotic HCV-infected patients.

关键词： Chemokine Polymorphism Cirrhosis Hepatocarcinoma Hepatitis C virus

Effect of sustained virological response on long-term clinical outcome in 113 patients with compensated hepatitis C-related cirrhosis treated by interferon alpha and ribavirin

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World Journal of Gastroenterology 2007年第42期13卷 5648-5653页

作者： Roland El Braks Nathalie Ganne-Carrié Hélène Fontaine Jacques Paries Véronique Grando-Lemaire michel beaugrand Stanislas Pol Jean-Claude Trinchet Department of Hepatology Hopital Jean Verdier (AP-HP) and UPRES EA 3409 (University Paris 13) Bondy 93140 France Department of Hepatology Hopital Cochin (AP-HP) and University Paris 5 Paris 75014 France Department of Public Health Jean Verdier Hospital (AP-HP) and UPRES EA 3409 (University Paris 13) Bondy 93140 France

AIM： To assess the long-term clinical benefit of sustained virological response （SVR） in patients with hepatitis C virus （HCV） cirrhosis treated by antiviral therapy using mostly ribavirin plus interferon either standard or ***： One hundred and thirteen patients with uncomplicated HCV biopsy-proven cirrhosis, treated by at least one course of antiviral treatment ≥ 3 mo and followed ≥ 30 mo were included. The occurrence of clinical events [hepatocellular carcinoma （HCC）, decompensation and death] was compared in SVR and non SVR ***： Seventy eight patients received bitherapy and 63 had repeat treatments. SVR was achieved in 37 patients （33%）. During a mean follow-up of 7.7 years, clinical events occurred more frequently in non SVR than in SVR patients, with a significant difference for HCC （24/76 vs 1/37, P = 0.01）. No SVR patient died while 20/76 non-SVR did （P = 0.002）, mainly in relation to HCC （45%）.CONCLUSION： In patients with HCV-related cirrhosis, $VR is associated with a significant decrease in the incidence of HCC and mortality during a follow-up period of 7.7 years. This result is a strong argument to perform and repeat antiviral treatments in patients with compensated cirrhosis.

关键词： Hepatitis C Cirrhosis Interferon alpha

Liver insulin-like growth factor 2 methylation in hepatitis C virus cirrhosis and further occurrence of hepatocellular carcinoma

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World Journal of Gastroenterology 2008年第35期14卷 5419-5427页

作者： Philippe Couvert Alain Carrié Jacques Pariès Jenny Vaysse Audrey Miroglio Antoine Kerjean Pierre Nahon Jamel Chelly Jean-Claude Trinchet michel beaugrand Nathalie Ganne-Carrié INSERM U551 Dyslipopro-teinemia and Atherosclerosis Research UnitParis F-75013France Université Paris6 UMR S551Paris F-75013France AP-HP Groupe hospitalier Pitié SalpétrièreService de Biochimie endocrinienne et OncologiqueParis F-75013France Department of Public health Jean Verdier HospitalAP-HPBondy 93140France Department of Biochemistry Jean Verdier HospitalAP-HPBondy 93140France Cochin Institut-INSERM-CNRS-University Paris 5-CHU Cochin Paris 75014France Department of Hepato-Gastroenterology Jean Verdier HospitalAP-HPBondy 93140France UPRES EA3409 University Paris 13Paris F-75651France

AIM: To assess the predictive value of the insulinlike growth factor 2 (Igf2) methylation profile for the occurrence of Hepatocellular Carcinoma (HCC) in hepatitis C (HCV) cirrhosis. METHODS: Patients with: (1) biopsy-proven compensated HCV cirrhosis; (2) available baseline frozen liver sample; (3) absence of detectable HCC; (4) regular screening for HCC; (5) informed consent for genetic analysis were studied. After DNA extraction from liver samples and bisulfite treatment, unbiased PCR and DHPLC analysis were performed for methylation analysis at the Igf2 locus. The predictive value of the Igf2 methylation profile for HCC wasassessed by Kaplan-Meier and Cox methods. RESULTS: Among 94 included patients, 20 developed an HCC during follow-up (6.9 ± 3.2 years). The methylation profile was hypomethylated, intermediate and hypermethylated in 13, 64 and 17 cases, respectively. In univariate analysis, two baseline parameters were associated with the occurrence of HCC: age (P = 0.01) and prothrombin (P = 0.04). The test of linear tendency between the three ordered levels of Igf2 methylation and probability of HCC occurrence was significant (Log Rank, P = 0.043; Breslow, P = 0.037; Tarone-Ware, P = 0.039). CONCLUSION: These results suggest that hypomethylation at the Igf2 locus in the liver could be predictive for HCC occurrence in HCV cirrhosis.

关键词： Liver cancer Cirrhosis Insulin-growth factor 2, DNA methylation

On Some Elliptic Problems in Unbounded Domains

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Chinese Annals of Mathematics,Series B 2018年第3期39卷 597-606页

作者： michel CHIPOT Dedicated to Philippe G. Ciarlet on the occasion of his 80th birthda

The author presents a method allowing to obtain existence of a solution for some elliptic problems set in unbounded domains,and shows exponential rate of convergence of the approximate solution toward the solution.

关键词： Elliptic Exponential convergence Unbounded domains

A new family of carbonaceous cathodes for rechargeable batteries through electronic structure tuning engineering

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National Science Review 2021年第2期8卷 7-8页

作者： michel Armand Centre for Cooperative Research on Alternative Energies Basque Research and Technology Alliance

Electric vehicles(EVs) and grid storage for renewable energies will require batteries in tens of millions of tons, and thus they need to be sustainable. EVs call also for batteries with higher energy density than currently available, and this value is intrinsically limited by the properties of the transition metal oxide(TMO) cathodes [1]. There are two possible strategies to overcome these limitations: i) increase the operating voltage in the >4.4 V range; and ii) attempt to use more than one electron per transition metal [2]. The first strategy faces problems of electrolyte stability limit and oxygen evolution, and thus safety hazards. The second is limited to vanadium and nickel, but using only1.3 electrons for the former,

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Complete Coulomb stress changes induced by the Ms7.6 earthquake in Lancang-Gengma, Yunnan and triggering of aftershocks by dynamic and static stress

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Science China Earth Sciences 2007年第11期50卷 1655-1662页

作者： michel BOUCHON Université Joseph Fourier F38041 Grenoble France

The spatiotemporal evolution patterns of complete Coulomb stress changes caused by 1988 Ms7.6 earthquake in Lancang-Gengma, Yunnan, are calculated and studied. And the triggering problems of Ms7.2 Gengma shock occurring 13 minutes after the main shock and of Ms5.0―6.9 aftershocks within 24 days after the main shock are discussed. The results show that the spatial distribution patterns of complete Coulomb stress changes of the Ms7.6 main shock are strongly asymmetric. The areas of positive dynamic and static Coulomb stress are both coincident well with the strong aftershocks' loca-tions. The Ms7.2 Gengma shock and most of strong aftershocks are subjected to the triggering effect of dynamic and static Coulomb stresses induced by the Ms7.6 Lancang earthquake.

关键词： complete Coulomb stress changes,dynamic and static stress triggering,earthquakes in Yunnan

New Partial Geometric Difference Sets and Partial Geometric Difference Families

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Acta Mathematica Sinica,English Series 2017年第5期33卷 591-606页

作者： Jerod michel School of Mathematical Sciences Zhejiang University Hangzhou 310027 P. R. China

Using Galois rings and Galois fields, we construct several infinite classes of partial geometric difference sets, and partial geometric difference families, with new parameters. Furthermore, these partial geometric difference sets(and partial geometric difference families) correspond to new infinite families of directed strongly regular graphs. We also discuss some of the links between partially balanced designs, 2-adesigns(which were recently coined by Cunsheng Ding in "Codes from Difference Sets"(2015)), and partial geometric designs, and make an investigation into when a 2-adesign is a partial geometric design.

关键词： Partial geometric design cyclotomic class directed strongly regular graph partial geometric difference set partial geometric difference family

Conodont evolution and stratotype sign of carboniferous Tournaisian-Visean boundary in South China

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Science China Earth Sciences 2005年第12期48卷 2131-2141页

作者： michel Coen Louvian University of Belgium B-1348 Louvian-la-Neuve Belgium

A stratotype section, boundary point and conodont sign have been recommended for GSSP of the Tournaisian-Visean boundary, based on studies of sectional sedimentology, conodont facies and phylogeneses in South China. Two areas representing margin and inner of the Yangtzi Plate and three sections of different facies were chosen, i.e. the Longdianshan sec-tion of the platform facies in Liuzhou of Guangxi, the Yudong section of the ramp facies in Shidian of Yunnan and the Pengchong section of the basin facies in Liuzhou of Guangxi. Stratigraphic frameworks of two areas were set up by systematical studies of carbonate facies and cycles. Conodont facies-distribution and paleoecologic conditions were researched on statistics of fossil variation and richness, and a kind of planktonic conodont, gnathodids that were widespread, is chosen to select the sign-fossil from it. Seven conodont pedigrees were supplemented or erected by studies of statistics and transitional forms. Conodont evolution in the Early Carboniferous could be divided into three stages, i.e. the Siphonodella stage, the Gnathodus typicus stage and the Gnathodus bilineatus stage. The transform-surface between the later two stages could be put as the Tournaisian-Visean boundary. Finally, this paper proposes that the Pengchong section can be the stratotype candidate of the Tournaisian-Visean boundary, the boundary point be put at the bottom of bed 58 and the stratotype sign of conodont be the first occurrence of Gnathodus praebilineatus of the Gnathodus semiglaber branch.

关键词： Tournaisian-Visean boundary, global stratotype, conodont evolution.