title: Vascular disrupting effects of combretastatin A4 phosphate on murine endometriotic lesions.
abstract: OBJECTIVE
  To study the effect of combretastatin A4 phosphate (CA4P) on the vascularization of endometriotic lesions.
  
  
  METHODS
  Intravital microscopic, histologic, and immunohistochemical study.
  
  
  METHODS
  University institute.
  
  
  METHODS
  BALB/c mice.
  
  
  METHODS
  Murine endometriotic lesions were induced by syngeneic transplantation of endometrium into dorsal skinfold chambers. After 6 days, the mice received an intraperitoneal injection of 80 mg/kg CA4P or vehicle.
  
  
  METHODS
  Vascularization of the lesions and the surrounding tissue was analyzed by intravital fluorescence microscopy over 8 days. Lesion morphology, vessel maturation, viability, and proliferation of endometrial glands and stroma were assessed by histology and immunohistochemistry.
  
  
  RESULTS
  All lesions were initially well vascularized, containing immature and mature microvessels. Injection of CA4P induced a selective vessel collapse in the lesions without affecting the surrounding microvasculature. This resulted in a decreased functional capillary density and blood perfusion of CA4P-treated lesions after 2 hours when compared with controls. However, the vascularization of the lesions progressively normalized, and their numbers of proliferating and apoptotic cells did not differ from those of controls.
  
  
  CONCLUSIONS
  This study demonstrates a selective vascular disrupting effect of CA4P on endometriotic lesions, indicating that vascular disrupting agents may be suitable for endometriosis therapy.
authors.affiliation: Institute for Clinical and Experimental Surgery, University of Saarland, Homburg/Saar, Germany.
authors.forename: Dilu
authors.initials: D
authors.lastname: Feng
authors.forename: Michael D
authors.initials: MD
authors.lastname: Menger
authors.forename: Matthias W
authors.initials: MW
authors.lastname: Laschke
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002196:Capillaries / Q000187:drug effects* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D004715:Endometriosis / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D004717:Endometrium / Q000098:blood supply* / Q000187:drug effects* / Q000473:pathology / Q000637:transplantation; D005260:Female; D007274:Injections, Intraperitoneal; D051379:Mice; D008807:Mice, Inbred BALB C; D009389:Neovascularization, Pathologic; D013267:Stilbenes / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors; D014022:Tissue Survival / Q000187:drug effects
chemical_list: D013267:Stilbenes; C058728:fosbretabulin
keywords: Endometriosis; angiogenesis; combretastatin A4 phosphate (CA4P); vascular disrupting agents; vascularization