title: Sustained liver regeneration after portal vein embolization --a human molecular pilot study.
abstract: BACKGROUND
  Portal vein embolization is a treatment option to achieve a sufficient future remnant liver volume for patients with central liver tumours requiring an extended resection with an extensive parenchymal loss. However, molecular mechanisms of this intervention are up to now poorly understood. The objective of this prospective pilot study was the characterization of molecular events leading to late hypertrophy of the non-embolized liver tissue in the human liver.
  
  
  METHODS
  Liver tissue of ten patients was collected before and intraoperatively more than one month after embolization. Investigation of molecular features was performed by pangenomic chips, polymerase chain reaction, immunostaining of proliferation marker Ki-67 and immunofluorescence measurements.
  
  
  RESULTS
  Significantly elevated genes hint towards angiogenesis and signalling by insulin-like growth factor and associated binding proteins. Increased transcript levels of activator protein 1 complex members like c-jun were reflecting potential molecular events of liver growth after embolization. Immunofluorescence data confirmed a predominant upregulation of β-catenin and c-jun (p<0.1) supported by Ki-67 (p<0.05) in the non-embolized liver. In silico analysis of transcriptomic dysplasia and hepatocellular carcinoma data showed divergent signatures compared to embolization.
  
  
  CONCLUSIONS
  Our findings indicate a sustained regeneration after portal vein embolization reflected in hyperplasia and angiogenesis in the human liver and provide novel molecular mechanisms of interlobe crosstalk.
authors.affiliation: Department of General and Vascular Surgery, University Hospital Jena, Erlanger Allee 101, Jena, Germany. Falk.Rauchfuss@med.uni-jena.de
authors.forename: Falk
authors.initials: F
authors.lastname: Rauchfuss
authors.forename: Sandro
authors.initials: S
authors.lastname: Lambeck
authors.forename: Ralf A
authors.initials: RA
authors.lastname: Claus
authors.forename: Janina
authors.initials: J
authors.lastname: Ullmann
authors.forename: Thomas
authors.initials: T
authors.lastname: Schulz
authors.forename: Martina
authors.initials: M
authors.lastname: Weber
authors.forename: Katrin
authors.initials: K
authors.lastname: Katenkamp
authors.forename: Reinhard
authors.initials: R
authors.lastname: Guthke
authors.forename: Michael
authors.initials: M
authors.lastname: Bauer
authors.forename: Utz
authors.initials: U
authors.lastname: Settmacher
mesh_terms: D051700:Activating Transcription Factor 3 / Q000235:genetics; D000368:Aged; D015536:Down-Regulation; D004621:Embolization, Therapeutic; D020869:Gene Expression Profiling; D006801:Humans; D006965:Hyperplasia / Q000235:genetics / Q000378:metabolism; D051798:Inhibitor of Differentiation Protein 1 / Q000235:genetics; D051796:Inhibitor of Differentiation Proteins / Q000235:genetics; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000235:genetics; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000235:genetics; D019394:Ki-67 Antigen / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008113:Liver Neoplasms / Q000628:therapy*; D008115:Liver Regeneration / Q000235:genetics*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics; D018919:Neovascularization, Physiologic / Q000235:genetics; D010865:Pilot Projects; D011169:Portal Vein; D011446:Prospective Studies; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D018808:Transcription Factor AP-1 / Q000235:genetics; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000235:genetics; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D051176:beta Catenin / Q000235:genetics
chemical_list: D051700:Activating Transcription Factor 3; C064269:FOSB protein, human; C497453:ID1 protein, human; D051798:Inhibitor of Differentiation Protein 1; D051796:Inhibitor of Differentiation Proteins; D018970:Insulin-Like Growth Factor Binding Protein 1; D018971:Insulin-Like Growth Factor Binding Protein 2; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D051176:beta Catenin; C075640:ID3 protein, human