title: First in-mouse development and application of a surgically relevant xenograft model of ovarian carcinoma.
abstract: OBJECTIVE
  Preclinical models of epithelial ovarian cancer have not been exploited to evaluate the clinical standard combination therapy of surgical debulking with follow-up chemotherapy. As surgery is critical to patient survival, here we establish a combined surgical/chemotherapy xenograft model of epithelial ovarian cancer and demonstrate its translational relevance.
  
  
  METHODS
  SKOV-3luc+ ovary cancer cells were injected topically into the ovaries of immunodeficient mice. Disease development and effect of clinical standard treatment including hysterectomy, bilateral salpingoophorectomy and removal of metastasis with follow up chemotherapy (carboplatin 12 mg/kg + paclitaxel 15 mg/kg) was evaluated by clinical parameters. Tumor burden was quantified by bioluminescence imaging (BLI).
  
  
  RESULTS
  The xenograft ovarian tumors developed were poorly differentiated and multicystic and the disease disseminated into the peritoneal cavity. When compared to the controls with a mean survival time of 4.9 weeks, mice treated with surgery and chemotherapy, surgery or chemotherapy demonstrated significantly improved mean survival of 16.1 weeks (p = 0.0008), 12.7 weeks (p = 0.0008), or 10.4 weeks (p = 0.008), respectively.
  
  
  CONCLUSIONS
  Combined surgical intervention and adjuvant chemotherapy was demonstrated for the first time in an orthotopic xenograft model of ovarian cancer. Similar to observation in human studies the combined approach resulted in the longest medial survival time, advocating application of this strategy in future preclinical therapeutic development for this disease.
authors.affiliation: Department of Obstetrics and Gynecology, Haukeland University Hospital, Bergen, Norway; Department of Clinical Science, University of Bergen, Bergen, Norway.
authors.forename: Oystein
authors.initials: O
authors.lastname: Helland
authors.affiliation: KinN Therapeutics, Bergen, Norway.
authors.forename: Mihaela
authors.initials: M
authors.lastname: Popa
authors.affiliation: The Gade Laboratory for Pathology, Department of Clinical Medicine, University of Bergen, Bergen, Norway; Department of Pathology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Olav K
authors.initials: OK
authors.lastname: Vintermyr
authors.affiliation: The Gade Laboratory for Pathology, Department of Clinical Medicine, University of Bergen, Bergen, Norway; Department of Pathology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Anders
authors.initials: A
authors.lastname: Molven
authors.affiliation: Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway.
authors.forename: Bjørn Tore
authors.initials: BT
authors.lastname: Gjertsen
authors.affiliation: Department of Obstetrics and Gynecology, Haukeland University Hospital, Bergen, Norway; Department of Clinical Science, University of Bergen, Bergen, Norway.
authors.forename: Line
authors.initials: L
authors.lastname: Bjørge
authors.affiliation: Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway.
authors.forename: Emmet
authors.initials: E
authors.lastname: McCormack
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D045744:Cell Line, Tumor; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy / Q000473:pathology / Q000601:surgery; D004273:DNA, Neoplasm / Q000235:genetics; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008156:Luciferases / Q000378:metabolism; D008163:Luminescent Measurements; D051379:Mice; D018895:Microsatellite Repeats / Q000235:genetics; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000601:surgery*; D023041:Xenograft Model Antitumor Assays
chemical_list: D004273:DNA, Neoplasm; D008156:Luciferases