|
|
|
题名
|
作者
|
年代
|
出处
|
被引量
|
| 1 | m TOR signaling in liver regeneration: Rapamycin combined with growth factor treatment显示文摘AIM: To investigate the effects of mammalian target of rapamycin(mT OR) inhibition on liver regeneration and autophagy in a surgical resection model.METHODS: C57BL/6 mice were subjected to a 70% partial hepatectomy(PH) and treated intraperitoneally every 24 h with a combination of the m TOR inhibitor rapamycin(2.5 mg/kg per day) and the steroid dexamethasone(2.0 mg/kg per day) in phosphate bufferedsaline(PBS) or with PBS alone as vehicle control. In the immunosuppressant group, part of the group was treated subcutaneously 4 h prior to and 24 h after PH with a combination of human recombinant interleukin 6(IL-6; 500 μg/kg per day) and hepatocyte growth factor(HGF; 100 μg/kg per day) in PBS. Animals were sacrificed 2, 3 or 5 d after PH and liver tissue and blood were collected for further analysis. Immunohistochemical staining for 5-Bromo-2'-deoxyuridine(Brd U) was used to quantify hepatocyte proliferation. Western blotting was used to detect hepatic microtubule-associated protein 1 light chain 3(LC3)-Ⅱ protein expression as a marker for autophagy. Hepatic gene expression levels of proliferation-, inflammation- and angiogenesisrelated genes were examined by real-time reverse transcription-polymerase chain reaction and serum bilirubin and transaminase levels were analyzed at the clinical chemical core facility of the Erasmus MC-University Medical Center.RESULTS: m TOR inhibition significantly suppressed regeneration, shown by decreased hepatocyte proliferation(2% vs 12% Brd U positive hepatocyte nuclei at day 2, P < 0.01; 0.8% vs 1.4% at day 5, P = 0.02) and liver weight reconstitution(63% vs 76% of initial total liver weight at day 3, P = 0.04), and furthermore increased serum transaminase levels(aspartate aminotransferase 641 U/L vs 185 U/L at day 2, P = 0.02). Expression of the autophagy marker LC3-Ⅱ, which was reduced during normal liver regeneration, increased after mT OR inhibition(46% increase at day 2, P = 0.04). Hepatic gene expression showed an increased inflammation-related response [tumor necrosis factor(TNF)-α 3.2-fold upregulation at day 2, P = 0.03; IL-1Ra 6.0-fold upregulation at day 2 and 42.3-fold upregulation at day 5, P < 0.01] and a reduced expression of cell cycle progression and angiogenesis-related factors(HGF 40% reduction at day 2; vascular endothelial growth factor receptor 2 50% reduction at days 2 and 5; angiopoietin 1 60% reduction at day 2, all P ≤ 0.01). Treatmentwith the regeneration stimulating cytokine IL-6 and growth factor HGF could overcome the inhibitory effect on liver weight(75% of initial total liver weight at day 3, P = 0.02 vs immunosuppression alone and P = 0.90 vs controls) and partially reversed gene expression changes caused by rapamycin(TNF-α and IL-1Ra levels at day 2 were restored to control levels). However, no significant changes in hepatocyte proliferation, serum injury markers or autophagy were found.CONCLUSION: mT OR inhibition severely impairs liver regeneration and increases autophagy after PH. These effects are partly reversed by stimulation of the IL-6 and HGF pathways. | Suomi MG Fouraschen Petra E de Ruiter Jaap Kwekkeboom Ron WF de Bruin Geert Kazemier Herold J Metselaar Hugo W Tilanus Luc JW van der Laan Jeroen de Jonge | 2013 | World Journal of Transplantation2013，3，3： | 6 |
| 2 | Increased incidence of early de novo cancer in liver graft recipients treated with cyclosporine: An association with C显示文摘 | Angela S. W. Tjon Jerome Sint Nicolaas Jaap Kwekkeboom Robert A. de Man Geert Kazemier Hugo W. Tilanus Bettina E. Hansen Luc J. W. van der Laan Thanyalak Tha‐In Herold J. Metselaar | 2010 | Liver Transpl2010，，7： | 2 |
| 3 | A prospective study on elective umbilical hernia repair in patients with liver cirrhosis and ascites显示文摘 | Hasan H. Eker G.H. van Ramshorst B. de Goede H.W. Tilanus H.J. Metselaar R.A. de Man J.F. Lange G. Kazemier | 2011 | Surgery2011，，3： | 2 |
| 4 | Optical modeling of a-Si:H solar cells with rough inter- faces: Effect of back contact and interface roughness显示文摘 | Zeman M van Swaaij R A C M M Metselaar J W | 2000 | Journal of Applied Physics2000，8811，： | 1 |
| 5 | Combined antiviral activity of interferon-α and RNA interference directed against hepatitis C without affecting vector delivery and gene silencing显示文摘 | Pan Q Henry SD Metselaar HJ | 2009 | J Mol Med2009，87，7： | 1 |
| 6 | Characteri- zation of human liver dendritic cells in liver grafts and per- fusates显示文摘 | Bosma B M Metselaar H J Mancham S | 2006 | Liver Transpl2006，12，3： | 1 |
| 7 | Reaction-rate-limiting steps in carbothermal reduction processes显示文摘 | VAN DIJEN F K METSELAAR R SISKENS C A M | 1985 | J Am Ceram Soc1985，68，1： | 1 |
| 8 | Imaging the Efficacy of Anti-Inflammatory Liposomes in a Rabbit Model of Atherosclerosis by Non-Invasive Imaging显示文摘 | Mark E. Lobatto Claudia Calcagno Josbert M. Metselaar Gert Storm Erik S.G. Stroes Zahi A. Fayad Willem J.M. Mulder | 2012 | Methods in Enzymology2012，，： | 1 |
| 9 | Respiratory epithelial adenomatoid hamartoma in the nasopharynx 显示文摘 | METSELAAR R M STEL H V VAN DER BAAN S | 2005 | J Laryngol Otol2005，119，： | 1 |
| 10 | Liver transplantation and hepatitis C显示文摘 | M. Willems H. Metselaar H. Tilanus S. Schalm R. de Man | 2002 | Transplant International (-)2002，，2： | 1 |
| 11 | Effects of a rehabilitation programme on daily functioning, participation, health-related quality of life, anxiety and depression in liver transplant recipients显示文摘 | B.T.J. Van Ginneken H.J.G. Van Den Berg-emons H.J. Metselaar H.W. Tilanus G. Kazemier H.J. Stam | 2010 | Disability & Rehabilitation2010，，25： | 1 |
| 12 | A New Estimation Method for the Intrinsic Thermal Conductivity of Nonmetallic Compounds:A Case Study for MgSiN2,AIN and β-Si3N4 Ceramics显示文摘 | Bruls R J Hintzen H T Metselaar R | 2005 | Journal of the European Ceramic Socisty2005，25，6： | 1 |
| 13 | Carcothermal production of β'-sialon from alumina,silica and carbon mixture显示文摘 | SOPICKA L M TERPSTRA R A METSELAAR R | 1995 | J Mater Sci1995，30，24： | 1 |
| 14 | Carbothermal production of β′ -sialon from alumina, silica and carbon mixture显示文摘 | SOPICKA-LIZER M TERPSTRA R A METSELAAR R | 1995 | J Mater Sci1995，30，： | 1 |
| 15 | A prospective group sequential study evaluating a new type of fully covered self-expandable metal stent for the treatment of benign biliary strictures (with video)显示文摘 | Jan-Werner Poley Djuna L. Cahen Herold J. Metselaar Henk R. van Buuren Geert Kazemier Casper H.J. van Eijck Jelle Haringsma Ernst J. Kuipers Marco J. Bruno | 2012 | Gastrointestinal Endoscopy2012，，4： | 1 |
| 16 | Thermodynamics of Alon III: Stabilization of Alon with MgO显示文摘 | Willems H X De With G Metselaar R | 1993 | Journal of the European Ceramic Society1993，12，1： | 1 |
| 17 | Carbothermal preparation and characterization of Ca-α′-sialon显示文摘 | VAN RUTTEN J W T TERPSTRA R A VAN METSELAAR R | 1995 | Third Eur Ceram1995，15，6： | 1 |
| 18 | An- titumor activity of liposomal prednisolone phosphate depends on the presence of functional tumor - associated macrophages in tumor tis-sue显示文摘 | BANCIU M METSELAAR J M SCHIFFELERS R M | 2008 | Neoplasia2008，10，2： | 1 |
| 19 | Living donor liver transplantation in HCV-infected patients: improvement of the donor risk-recipient benefit ratio is around the corner显示文摘 | Koning L de Knegt RJ Metselaar HJ | 2014 | Transpl Int2014，27，8： | 1 |
| 20 | Infrared thermometry for early detection of drought stress in chrysanthemum显示文摘 | Blom Zandstra M Metselaar K | 2006 | HortScience2006，41，1： | 1 |
您所在的机构暂未开通此部分的功能，请联系管理员