title: The effect of sorafenib on liver regeneration and angiogenesis after partial hepatectomy in rats.
abstract: BACKGROUND
  Liver regeneration is vital for the survival of patients submitted to extensive liver resection as a treatment of hepatocellular carcinoma (HCC). Sorafenib is a multikinase inhibitor of angiogenesis and cell division, both of which are integral components of liver regeneration. We investigated the effect of preoperative treatment with sorafenib, a drug used for the treatment of HCC, on liver regeneration and angiogenesis in healthy rats, after two-thirds partial hepatectomy (PH2/3).
  
  
  METHODS
  In total 48 Wistar rats received intragastric injections of sorafenib (30 mg/kg/d) or vehicle, underwent PH2/3, and were sacrificed at 48, 96 or 168 hours after that. The regenerative index of the liver remnant was studied, as well as the mitotic index. DNA synthesis and angiogenesis were estimated by immunohistochemistry for the Ki-67 and CD34 antigens, respectively.
  
  
  RESULTS
  Sorafenib reduced significantly the regenerative index at all time points but not the mitotic index at 48, 96 or 168 hours. Deoxyribonucleic acid (DNA) synthesis and angiogenesis were not affected significantly either.
  
  
  CONCLUSIONS
  Sorafenib, when administered preoperatively, reduces incompletely and transiently the regeneration of the liver after PH2/3 in rats. This could mean that sorafenib can be used as neoadjuvant treatment of patients with HCC prior to liver resection, but further experimental and clinical studies are needed to establish the safety of this treatment. Hippokratia 2015; 19 (3): 249-255.
authors.affiliation: 5 Surgical Department, Aristotle University of Thessaloniki, Hippokratio General Hospital, Thessaloniki, Greece.
authors.forename: K
authors.initials: K
authors.lastname: Kiroplastis
authors.affiliation: Division of Transplantation, Department of Surgery, Aristotle University of Thessaloniki, Hippokratio General Hospital, Thessaloniki, Greece.
authors.forename: I
authors.initials: I
authors.lastname: Fouzas
authors.affiliation: Department of Pathology, Hippokratio General Hospital, Thessaloniki, Greece.
authors.forename: E
authors.initials: E
authors.lastname: Katsiki
authors.affiliation: Department of Pathology, Hippokratio General Hospital, Thessaloniki, Greece.
authors.forename: K
authors.initials: K
authors.lastname: Patsiaoura
authors.affiliation: Division of Transplantation, Department of Surgery, Aristotle University of Thessaloniki, Hippokratio General Hospital, Thessaloniki, Greece.
authors.forename: M
authors.initials: M
authors.lastname: Daoudaki
authors.affiliation: School of Veterinary Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: A
authors.initials: A
authors.lastname: Komninou
authors.affiliation: Division of Transplantation, Department of Surgery, Aristotle University of Thessaloniki, Hippokratio General Hospital, Thessaloniki, Greece.
authors.forename: E
authors.initials: E
authors.lastname: Xolongitas
authors.affiliation: Division of Transplantation, Department of Surgery, Aristotle University of Thessaloniki, Hippokratio General Hospital, Thessaloniki, Greece.
authors.forename: E
authors.initials: E
authors.lastname: Katsika
authors.affiliation: Department of Histology Embryology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: K
authors.initials: K
authors.lastname: Kaidoglou
authors.affiliation: Division of Transplantation, Department of Surgery, Aristotle University of Thessaloniki, Hippokratio General Hospital, Thessaloniki, Greece.
authors.forename: V
authors.initials: V
authors.lastname: Papanikolaou
keywords: Sorafenib; angiogenesis; hepatocellular carcinoma; liver regeneration; liver transplantation; partial hepatectomy