title: Sunitinib treatment reduces tumor growth and limits changes in microvascular properties after minor surgical intervention in an in vivo model of secondary breast cancer growth in bone.
abstract: OBJECTIVE
  Surgical interventions can alter the balance between pro- and anti-angiogenic growth factors and thereby modulate tumor growth. Since the microcirculatory properties of tumors underlie organ-specific differences, the microhemodynamic characteristics of bone metastasis have not yet been fully described. Angiogenesis inhibitors are increasingly being used to treat advanced stages of cancer. We hypothesized that the anti-angiogenic drug sunitinib abrogates alterations in microvascular properties following a minor surgical intervention in an in vivo model of secondary breast cancer growth in the bone.
  
  
  METHODS
  Intravital microscopy was performed over 25 days using a xenograft model of breast cancer tumor growth in the bone to determine changes in microvascular properties during sunitinib treatment. Mastectomy was performed on day 5 to evaluate the effect of a minor surgical trauma on tumor growth and microvascular properties.
  
  
  RESULTS
  Anti-angiogenic therapy resulted in reduced tumor growth, decreased vascular density, and increased vascular diameters. Blood flow velocity remained constant while microvascular permeability temporarily increased after the surgical intervention.
  
  
  CONCLUSIONS
  Administration of sunitinib reduced tumor growth and altered microcirculatory properties in a time-dependent manner. The observed dramatic increase in microvascular permeability after the surgical intervention may have implications for local tumor growth, and metastatic dissemination. J. Surg. Oncol. 2016;113:515-521. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Trauma, Hand, and Reconstructive Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.|Department of Orthopaedics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Malte
authors.initials: M
authors.lastname: Schroeder
authors.affiliation: Department of Trauma, Hand, and Reconstructive Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.|Department of Orthopaedics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Lennart
authors.initials: L
authors.lastname: Viezens
authors.affiliation: Department of Oncology and Hematology With The Sections Pneumonology and Bone Marrow Transplantation, Hubertus Wald Tumor Center, University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Wellbrock
authors.affiliation: Department of Oncology and Hematology With The Sections Pneumonology and Bone Marrow Transplantation, Hubertus Wald Tumor Center, University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Walter
authors.initials: W
authors.lastname: Fiedler
authors.affiliation: Department of Orthopaedics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Rüther
authors.affiliation: Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Germany.|Medicum Eppendorf, Hamburg, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Algenstaedt
authors.affiliation: Department of Orthopaedics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.|OrthoCentrum Hamburg, Parkklinik Manhagen, Hamburg, Germany.
authors.forename: Nils
authors.initials: N
authors.lastname: Hansen-Algenstaedt
authors.affiliation: Department of Orthopaedics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.|Department of Spine Surgery, Klinikum Bad Bramstedt, Bad Bramstedt, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Schaefer
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001859:Bone Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000556:secondary*; D001943:Breast Neoplasms / Q000098:blood supply / Q000473:pathology* / Q000601:surgery*; D005260:Female; D007211:Indoles / Q000627:therapeutic use*; D051379:Mice; D016513:Mice, SCID; D008833:Microcirculation; D011758:Pyrroles / Q000627:therapeutic use*; D000077210:Sunitinib; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib
keywords: angiogenesis; bone metastasis; breast cancer; intravital microscopy; surgery