title: Contrast-enhanced ultrasound (CEUS) detects effects of vascular disrupting therapy in an experimental model of gastric cancer.
abstract: OBJECTIVE
  To assess the effects of vascular-disrupting agent (VDA)-based therapy including monitoring of therapeutic efficacy with contrast-enhanced ultrasound (CEUS) in a gastric cancer model.
  
  
  METHODS
  Gastric cancer cell lines and endothelial cells were used. Effects of the VDA ASA404 on cells were determined by MTT assays and Western blotting in vitro. Therapeutic efficacy of ASA404 was assessed in vivo in a subcutaneous mouse model in combination with paclitaxel. CEUS with TIC (time intensity curve) analyses was employed to measure tumor perfusion. Finally, tumor tissue was harvested and processed for histological work-up.
  
  
  RESULTS
  In vitro, ASA404 impaired growth of ECs upon stimulation with conditioned media from gastric cancer cells. No direct effects on tumor cells were observed. In vivo treatment with ASA404 in combination with paclitaxel led to significant decrease of tumor microvascularization as determined by CEUS. Furthermore, combination of ASA404 with paclitaxel showed a significant inhibition of tumor growth which was paralleled by strong reduction of tumor cell proliferation and vessel area.
  
  
  CONCLUSIONS
  VDA-based therapy in combination with paclitaxel, and therapy monitoring by CEUS, appears to be a promising strategy for gastric cancer.
authors.affiliation: Department of Surgery, University Regensburg Medical Center, Regensburg, Germany.
authors.forename: Sven A
authors.initials: SA
authors.lastname: Lang
authors.affiliation: Department of Surgery, University Regensburg Medical Center, Regensburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Moser
authors.affiliation: Department of Surgery, University Regensburg Medical Center, Regensburg, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Gehmert
authors.affiliation: Department of Surgery, University Regensburg Medical Center, Regensburg, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Pfister
authors.affiliation: Department of Surgery, University Regensburg Medical Center, Regensburg, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Hackl
authors.affiliation: Department of Surgery, University Regensburg Medical Center, Regensburg, Germany.
authors.forename: Andreas A
authors.initials: AA
authors.lastname: Schnitzbauer
authors.affiliation: Department of Radiology, University Regensburg Medical Center, Regensburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Stroszczynski
authors.affiliation: Department of Surgery, University Regensburg Medical Center, Regensburg, Germany.
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Schlitt
authors.affiliation: Department of Surgery, University Regensburg Medical Center, Regensburg, Germany.
authors.forename: Edward K
authors.initials: EK
authors.lastname: Geissler
authors.affiliation: Department of Radiology, University Regensburg Medical Center, Regensburg, Germany.
authors.forename: Ernst M
authors.initials: EM
authors.lastname: Jung
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003287:Contrast Media; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging / Q000188:drug therapy; D011897:Random Allocation; D013274:Stomach Neoplasms / Q000098:blood supply* / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D018084:Ultrasonography, Interventional / Q000379:methods*; D044004:Xanthones / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D003287:Contrast Media; D044004:Xanthones; C066668:vadimezan