title: Evaluation of the antiproliferative, proapoptotic, and antiangiogenic effects of a double-stranded RNA mimic complexed with polycations in an experimental mouse model of leiomyoma.
abstract: OBJECTIVE
  To assess the antiproliferative, proapoptotic, and antiangiogenic effects of the double-stranded RNA mimic polyinosine-polycytidylic acid (pIC) complexed with polyethylenimine [pIC(PEI)] in xenografted human leiomyomas.
  
  
  METHODS
  Heterologous leiomyoma mouse model.
  
  
  METHODS
  University-affiliated infertility center.
  
  
  METHODS
  Ovariectomized and hormone-replaced nude mice (n = 16) who received human leiomyoma fragment transplantation.
  
  
  METHODS
  Leiomyoma fragments placed in the peritoneum of 5-week-old nude female mice and treated with the vehicle (n = 8) or 0.6 mg/kg [pIC(PEI)] (n = 8) for 4 weeks.
  
  
  METHODS
  The size of the leiomyoma implants, and cellular proliferation (Ki67), vascularization (PECAM), and apoptosis (OH-ends) assessed by quantitative immunohistochemical/immunofluorescent analysis of the recovered implants.
  
  
  RESULTS
  No significant differences were observed in the size of the leiomyoma implants between groups. Vascularization and proliferation were significantly decreased, and apoptosis was increased in the [pIC(PEI)]-treated group versus control.
  
  
  CONCLUSIONS
  We hypothesize that the antiangiogenic and apoptotic effects exerted by [pIC(PEI)] might lead to a decrease in lesion size in this animal model if the compound is administered for longer periods of time. This study provides promising data on [pIC(PEI)] as a potential novel therapeutic agent against human leiomyoma.
authors.affiliation: Instituto Universitario IVI/INCLIVA, Valencia, Spain; Fundación IVI, Universidad de Valencia, Paterna, Spain.
authors.forename: Carmen Maria
authors.initials: CM
authors.lastname: García-Pascual
authors.affiliation: Instituto Universitario IVI/INCLIVA, Valencia, Spain; Fundación IVI, Universidad de Valencia, Paterna, Spain.
authors.forename: Hortensia
authors.initials: H
authors.lastname: Ferrero
authors.affiliation: Departamento de Ginecología, Hospital Universitario y politécnico la Fe, Valencia, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Juarez
authors.affiliation: Instituto Universitario IVI/INCLIVA, Valencia, Spain.
authors.forename: Jessica
authors.initials: J
authors.lastname: Martínez
authors.affiliation: Bioncotech Therapeutics, Paterna, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Villanueva
authors.affiliation: Bioncotech Therapeutics, Paterna, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Pozuelo-Rubio
authors.affiliation: Melanoma Laboratory, Molecular Pathology Programme, Centro Nacional de Investigaciones Oncológicas (Spanish National Cancer Research Centre), Madrid, Spain.
authors.forename: Marisol
authors.initials: M
authors.lastname: Soengas
authors.affiliation: Bioncotech Therapeutics, Paterna, Spain.
authors.forename: Damiá
authors.initials: D
authors.lastname: Tormo
authors.affiliation: Instituto Universitario IVI/INCLIVA, Valencia, Spain; Fundación IVI, Universidad de Valencia, Paterna, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Simón
authors.affiliation: Instituto Universitario IVI/INCLIVA, Valencia, Spain. Electronic address: raulgomgal@gmail.com.
authors.forename: Raúl
authors.initials: R
authors.lastname: Gómez
authors.affiliation: Fundación IVI, Universidad de Valencia, Paterna, Spain; Departamento de Ginecología, Hospital Universitario y politécnico la Fe, Valencia, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Pellicer
mesh_terms: D000328:Adult; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D004195:Disease Models, Animal; D015914:Estrogen Replacement Therapy; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D007889:Leiomyoma / Q000098:blood supply / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008819:Mice, Nude; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D010052:Ovariectomy; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011070:Poly I-C / Q000494:pharmacology*; D011094:Polyethyleneimine / Q000494:pharmacology*; D013997:Time Factors; D047368:Tumor Burden / Q000187:drug effects; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D019394:Ki-67 Antigen; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011094:Polyethyleneimine; D011070:Poly I-C
keywords: Angiogenesis; [pIC(PEI)]; apoptosis; leiomyoma; mouse model