| 1 | A novel animal model for in vivo study of liver cancer metastasis显示文摘AIM:To establish an animal model with human hepatocyte-repopulated liver for the study of liver cancer metastasis.METHODS:Cell transplantation into mouse livers was conducted using alpha-fetoprotein(AFP)-producing hu-man gastric cancer cells(h-GCCs) and h-hepatocytes as donor cells in a transgenic mouse line expressing urokinase-type plasminogen activator(uPA) driven by the albumin enhancer/promoter crossed with a severe combined immunodeficient(SCID) mouse line(uPA/SCID mice).Host mice were divided into two groups(A and B).Group A mice were transplanted with h-GCCs alone,and group B mice were transplanted with h-GCCs and h-hepatocytes together.The replacement index(RI),which is the ratio of transplanted h-GCCs and h-hepatocytes that occupy the examined area of a histological section,was estimated by measuring h-AFP and h-albumin concentrations in sera,respectively,as well as by immunohistochemical analyses of h-AFP and human cytokeratin 18 in histological sections.RESULTS:The h-GCCs successfully engrafted,repopulated,and colonized the livers of mice in group A(RI = 22.0% ± 2.6%).These mice had moderately differentiated adenocarcinomatous lesions with disrupted glandular structures,which is a characteristics feature of gastric cancers.The serum h-AFP level reached 211.0 ± 142.2 g/mL(range,7.1-324.2 g/mL).In group B mice,the h-GCCs and h-hepatocytes independently engrafted,repopulated the host liver,and developed colonies(RI = 12.0% ± 6.8% and 66.0% ± 12.3%,respectively).h-GCC colonies also showed typical adenocarcinomatous glandular structures around the h-hepatocyte-colonies.These mice survived for the full 56 day-study and did not exhibit any metastasis of h-GCCs in the extrahepatic regions during the observational period.The mice with an h-hepatocyte-repopulated liver possessed metastasized h-GCCs and therefore could be a useful humanized liver animal model for studying liver cancer metastasis in vivo.CONCLUSION:A novel animal model of human liver cancer metastasis was established using the uPA/SCID mouse line.This model could be useful for in vivo testing of anti-cancer drugs and for studying the mechanisms of human liver cancer metastasis. | Shinsuke Fujiwara Hikaru Fujioka Chise Tateno Ken Taniguchi Masahiro Ito Hiroshi Ohishi Rie Utoh Hiromi Ishibashi Takashi Kanematsu Katsutoshi Yoshizato | 2012 | World Journal of Gastroenterology2012，18，29： | 6 |
| 2 | Effects on coagulation factor production following primary hepatomitogen-induced direct hyperplasia显示文摘AIM:To investigate the molecular mechanisms involved in coagulation factor expression and/or function during direct hyperplasia(DH) -mediated liver regeneration.METHODS:Direct hyperplasia-mediated liver regeneration was induced in female C57BL/6 mice by administering 1,4-bis[2-(3,5-dichloropyridyloxy) ] benzene(TCPOBOP) ,a representative hepatomitogen.Mice were weighed and sacrificed at various time points [Day 0(D0:prior to injection) ,3 h,D1,D2,D3,and D10] after TCPOBOP administration to obtain liver and blood samples.Using the RNA samples extracted from the liver,a comprehensive analysis was performed on the hepatic gene expression profiling of coagulation-related factors by real-time RT-PCR(fibrinogen,prothrombin,factors Ⅴ,Ⅶ,Ⅷ,Ⅸ,Ⅹ,Ⅺ,Ⅻ,XⅢβ,plasminogen,antithrombin,protein C,protein S,ADAMTS13,and VWF) .The corresponding plasma levels of coagulation factors(fibrinogen,prothrombin,factors Ⅴ,Ⅶ,Ⅷ,Ⅸ,Ⅹ,Ⅺ,Ⅻ,XⅢ,and VWF) were also analyzed and compared with their mRNA levels.RESULTS:Gavage administration of TCPOBOP(3 mg/kg body weight) resulted in a marked and gradual increase in the weight of the mouse livers relative to the total body weight to 220% by D10 relative to the D0(control) ratios.At the peak of liver regeneration(D1 and D2) ,the gene expression levels for most of the coagulationrelated factors(fibrinogen,prothrombin,factors Ⅴ,Ⅶ,Ⅷ,Ⅸ,Ⅺ,Ⅻ,XⅢβ,plasminogen,antithrombin,protein C,ADAMTS13,VWF) were found to be downregulated in a time-dependent manner,and gradually recovered by D10 to the basal levels.Only mRNA levels of factor Ⅹ and protein S failed to show any decrease during the regenerative phase.As for the plasma levels,5 clotting factors(prothrombin,factors Ⅷ,Ⅸ,Ⅺ,and Ⅻ) demonstrated a significant decrease(P < 0.05) during the regeneration phase compared with D0.Among these 5 factors,factor Ⅸ and factor Ⅺ showed the most dramatic decline in their activities by about 50% at D2 compared to the basal levels,and these reductions in plasma activity for both factors were consistent with our RT-PCR findings.In contrast,the plasma activities of the other coagulation factors(fibrinogen,factors Ⅴ,Ⅶ,XⅢ,and VWF) were not significantly reduced,despite the reduction in the liver mRNA levels.Unlike the other factors,FX showed a temporal increase in its plasma activity,with significant increases(P < 0.05) detected at D1.CONCLUSION:Investigating the coagulation cascade protein profiles during liver regeneration by DH may help to better understand the basic biology of the liver under normal and pathological conditions. | Kohei Tatsumi Kazuo Ohashi Sanae Taminishi Soichi Takagi Rie Utoh Akira Yoshioka Midori Shima Teruo Okano | 2009 | World Journal of Gastroenterology2009，15，42： | 5 |
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