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Fertil Steril ; 105(2): 529-38, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26616441

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. DESIGN: Heterologous leiomyoma mouse model. SETTING: University-affiliated infertility center. ANIMAL(S): Ovariectomized and hormone-replaced nude mice (n = 16) who received human leiomyoma fragment transplantation. INTERVENTION(S): 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. MAIN OUTCOME MEASURE(S): 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. RESULT(S): 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. CONCLUSION(S): 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.


Subject(s)
Angiogenesis Inhibitors/pharmacology , Apoptosis/drug effects , Cell Proliferation/drug effects , Leiomyoma/drug therapy , Neovascularization, Pathologic , Poly I-C/pharmacology , Polyethyleneimine/pharmacology , Uterine Neoplasms/drug therapy , Adult , Animals , Disease Models, Animal , Estrogen Replacement Therapy , Female , Humans , Ki-67 Antigen/metabolism , Leiomyoma/blood supply , Leiomyoma/genetics , Leiomyoma/metabolism , Leiomyoma/pathology , Mice, Nude , Middle Aged , Ovariectomy , Platelet Endothelial Cell Adhesion Molecule-1/metabolism , Time Factors , Tumor Burden/drug effects , Tumor Cells, Cultured , Uterine Neoplasms/blood supply , Uterine Neoplasms/genetics , Uterine Neoplasms/metabolism , Uterine Neoplasms/pathology , Xenograft Model Antitumor Assays
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