title: Heterogeneous sensitivity of hepatocellular carcinoma to sorafenib revealed by the short-term culture of tumor fragments.
abstract: OBJECTIVE
  Sorafenib is currently the only medical treatment with proven efficacy against hepatocellular carcinoma (HCC). HCC cell lines display heterogeneous sensitivity to sorafenib, but little is known about the sensitivity of clinical tumors. We aimed to examine this aspect.
  
  
  METHODS
  Using experimental tumors generated in nude mice, we set up a technique for short-term culture of HCC fragments. We applied this technique to six human HCC samples obtained from surgical resection.
  
  
  RESULTS
  HCC fragments in culture retain their morphology and viability for at least 48 h, permitting an in vitro analysis of the effect of sorafenib on the Extracellular signal-regulated kinase (ERK) cascade. HCC exhibit heterogeneous individual responses, ranging from potent inhibition to paradoxical activation of this oncogenic cascade.
  
  
  CONCLUSIONS
  Our observations highlight the heterogeneous sensitivity of HCC to sorafenib, and point to the potential interest of short-term culture of tumor fragments for personalizing the medical treatment of HCC.
authors.affiliation: Inserm U1088, University of Picardie Jules Verne, Amiens, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Godin
authors.forename: Sebastien
authors.initials: S
authors.lastname: Dupont
authors.forename: Zakaria
authors.initials: Z
authors.lastname: Ezzoukhry
authors.forename: Christophe
authors.initials: C
authors.lastname: Louandre
authors.forename: Denis
authors.initials: D
authors.lastname: Chatelain
authors.forename: Lucie
authors.initials: L
authors.lastname: Henaut
authors.forename: Charles
authors.initials: C
authors.lastname: Sabbagh
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Regimbeau
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Maziere
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Barbare
authors.forename: Bruno
authors.initials: B
authors.lastname: Chauffert
authors.forename: Antoine
authors.initials: A
authors.lastname: Galmiche
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D015151:Immunoblotting; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D010671:Phenylurea Compounds / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D000077157:Sorafenib; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3