title: The effects of sorafenib on liver regeneration in a model of partial hepatectomy.
abstract: BACKGROUND
  Sorafenib is currently approved for advanced hepatocellular carcinoma (HCC) and is presently being studied as an adjuvant treatment for HCC following resection. The effects of sorafenib on liver regeneration have not been clearly defined. Our objective was to identify the effects of sorafenib on liver regeneration in a murine partial hepatectomy (PH) model.
  
  
  METHODS
  We performed PH in C57Bl/6 mice treated with a range of sorafenib doses with assessments at several time points. Liver sinusoidal endothelial cells (LSEC) and hepatocyte DNA synthesis and proliferation were assessed with 5-bromo-2'-deoxyuridine (BrdU) and Ki67 by flow cytometry and immunohistochemistry.
  
  
  RESULTS
  Treatment with sorafenib did not result in any deaths following PH. When we measured BrdU uptake to assess DNA synthesis, there was a statistically significant increase at 48 h post-PH for nonfibrotic LSEC following treatment with 60 mg/kg of sorafenib. However, BrdU and Ki67 staining among LSEC and hepatocytes was not significantly affected by sorafenib at any of the other doses or time points. BrdU and Ki67 flow cytometry data correlated with immunohistochemistry findings and postoperative liver weights.
  
  
  CONCLUSIONS
  In a murine PH model, sorafenib did not alter the repair response of normal or fibrotic livers following PH as measured by changes in liver weight, DNA synthesis, and cellular proliferation. These findings suggest sorafenib administered following hepatic resection does not impair liver regeneration.
authors.affiliation: Department of Medicine, Roger Williams Medical Center, Providence, Rhode Island 02908, USA.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Kurniali
authors.forename: Katie
authors.initials: K
authors.lastname: O'Gara
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Wang
authors.forename: Li Juan
authors.initials: LJ
authors.lastname: Wang
authors.forename: Ponnandai
authors.initials: P
authors.lastname: Somasundar
authors.forename: Vincent
authors.initials: V
authors.lastname: Falanga
authors.forename: N Joseph
authors.initials: NJ
authors.lastname: Espat
authors.forename: Steven C
authors.initials: SC
authors.lastname: Katz
mesh_terms: D000818:Animals; D001557:Benzenesulfonates / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000601:surgery; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006498:Hepatectomy / Q000379:methods*; D022781:Hepatocytes / Q000187:drug effects / Q000502:physiology; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000601:surgery; D008113:Liver Neoplasms / Q000188:drug therapy / Q000601:surgery; D008115:Liver Regeneration / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D000077157:Sorafenib
chemical_list: D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib