title: Treatment of endometriosis with a VEGF-targeted conditionally replicative adenovirus.
abstract: OBJECTIVE
  To evaluate a vascular endothelial growth factor (VEGF)-targeted gene therapy for the treatment of endometriosis.
  
  
  METHODS
  Analysis of the VEGF gene expression and promoter activity in ectopic and eutopic endometrium. Evaluation of the specific replication and cell-killing effect of a VEGF-targeted adenovirus (Ad5VEGFE1) in endometriotic cells.
  
  
  METHODS
  Four patients who underwent hysterectomy for benign disease, 30 women with moderate superficial, and 30 women with deep infiltrating endometriosis.
  
  
  METHODS
  Immunostaining and gene expression of VEGF was examined in eutopic endometrium, endometriotic lesions, and normal peritoneum. The VEGF promoter activity was evaluated in eutopic endometrium and endometriotic lesions. A VEGF-targeted conditionally replicative adenovirus (Ad5VEGFE1) was evaluated regarding specific viral replication in endometriosis cells and induction of apoptosis. The biodistribution of the VEGF-targeted conditionally replicative adenovirus was examined in a mouse model.
  
  
  RESULTS
  The VEGF gene was highly expressed in ectopic endometrium compared with eutopic endometrium and normal peritoneum. The VEGF promoter was active in endometriotic cells. Ad5VEGFE1 showed efficient viral replication and induction of apoptosis in purified primary endometriotic cells and demonstrated a similar lower targeting to the liver and the uterus in a mouse model.
  
  
  CONCLUSIONS
  Ad5VEGFE1 is a promising candidate for treating endometriosis and holds potential for clinical testing.
authors.affiliation: Department of Obstetrics and Gynecology, University of Düsseldorf Medical Center, Düsseldorf, Germany. rein@med.uni-duesseldorf.de
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Rein
authors.forename: Torsten
authors.initials: T
authors.lastname: Schmidt
authors.forename: Gerd
authors.initials: G
authors.lastname: Bauerschmitz
authors.forename: Monika
authors.initials: M
authors.lastname: Hampl
authors.forename: Ines M
authors.initials: IM
authors.lastname: Beyer
authors.forename: Arasen A V
authors.initials: AA
authors.lastname: Paupoo
authors.forename: David T
authors.initials: DT
authors.lastname: Curiel
authors.forename: Martina
authors.initials: M
authors.lastname: Breidenbach
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D017209:Apoptosis; D004195:Disease Models, Animal; D004715:Endometriosis / Q000473:pathology / Q000628:therapy* / Q000821:virology; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: D042461:Vascular Endothelial Growth Factor A