title: Changes in growth factor levels after thermal ablation in a murine model of colorectal liver metastases.
abstract: OBJECTIVE
  This study examines changes in the expression of growth factors following thermal ablation (TA) of selected colorectal cancer (CRC) liver metastases.
  
  
  METHODS
  Using mice with established CRC liver metastases, two tumours in each animal were thermally ablated. Liver and tumour tissues were collected at various time-points (days 0, 1, 2, 3, 5 and 7) following TA treatment from the ablation site and from sites distant from ablated tumour. Changes in growth factor expression (epidermal growth factor [EGF], vascular endothelial growth factor [VEGF], hepatocyte growth factor [HGF] and transforming growth factor-β[TGF-β]) in comparison with baseline levels (non-ablated) were assessed by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry.
  
  
  RESULTS
  Baseline TGF-β and VEGF levels in the liver parenchyma of tumour-bearing mice were significantly higher than levels in naive liver parenchyma. Levels of VEGF and HGF decreased after TA treatment in all tissues. Levels of EGF decreased in ablated and distant tumour tissues, but displayed a tendency to increase in liver tissue. Levels of TGF-β also decreased during the first 2 days following TA, but later increased in liver and tumour tissues distant from the ablation site to a level that reached significance in tumour tissue at day 7 (P < 0.001). Decreases in growth factor levels were also observed in animals that underwent laparotomy without TA treatment, which indicates that these decreases were caused by the experimental procedure.
  
  
  CONCLUSIONS
  Tumour induces upregulation of TGF-β and VEGF in liver parenchyma. Growth factors decreased after TA, but this appears to be the result of the experimental procedure rather than the TA itself. However, TA resulted in increased levels of TGF-β, which may contribute to tumour recurrence.
authors.affiliation: Department of Surgery, University of Melbourne, Austin Hospital, Heidelberg, Vic, Australia. tfifis@unimelb.edu.au
authors.forename: Theodora
authors.initials: T
authors.lastname: Fifis
authors.forename: Caterina
authors.initials: C
authors.lastname: Malcontenti-Wilson
authors.forename: Jason
authors.initials: J
authors.lastname: Amijoyo
authors.forename: Beatrice
authors.initials: B
authors.lastname: Anggono
authors.forename: Vijayaragavan
authors.initials: V
authors.lastname: Muralidharan
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Nikfarjam
authors.forename: Christopher
authors.initials: C
authors.lastname: Christophi
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D004815:Epidermal Growth Factor / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D053685:Laser Therapy; D008113:Liver Neoplasms / Q000378:metabolism / Q000556:secondary / Q000601:surgery*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C553307:HGF protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D004815:Epidermal Growth Factor; D017228:Hepatocyte Growth Factor