title: Soluble vascular endothelial growth factor receptor-1 improves therapeutic efficacy of suicide gene therapy in an angiogenesis-independent manner.
abstract: Abstract Malignant gliomas (MGs) are highly vascularized, aggressive brain cancers carrying a dismal prognosis. Because of their high vascularity, anti-angiogenic therapy is a potential treatment option. Indeed, the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab has demonstrated promising results in clinical trials. Similarly, adenovirus-medicated Herpes simplex virus thymidine kinase and ganciclovir (AdHSV-tk/GCV) suicide gene therapy has established itself in clinical trials as a potential novel therapeutic strategy for MGs. In this study, we demonstrate the feasibility of combining adenovirus-mediated soluble VEGF receptor-1 anti-angiogenic gene therapy with AdHSV-tk/GCV suicide gene therapy to treat experimental MGs. Our results reveal that, apart from inhibiting angiogenesis, other anti-tumor mechanisms, such as reduction of infiltration by tumor-associated macrophages/microglia, may contribute to the improved therapeutic benefit of combination therapy.
authors: 1 Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute, University of Eastern Finland , FI-70211 Kuopio, Finland .
authors: Haritha D
authors: HD
authors: Samaranayake
authors: Jere T
authors: JT
authors: Pikkarainen
authors: Thomas
authors: T
authors: Wirth
authors: Hanna
authors: H
authors: Stedt
authors: Hanna P
authors: HP
authors: Lesch
authors: Galina
authors: G
authors: Dragneva
authors: Taina
authors: T
authors: Vuorio
authors: Ann-Marie
authors: AM
authors: Määttä
authors: Kari
authors: K
authors: Airenne
authors: Seppo
authors: S
authors: Ylä-Herttuala
mesh_terms: D000818:Animals; D017849:Animals, Inbred Strains; D001932:Brain Neoplasms / Q000098:blood supply / Q000628:therapy*; D045744:Cell Line, Tumor; D002470:Cell Survival; D015316:Genetic Therapy; D005910:Glioma / Q000098:blood supply / Q000628:therapy*; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000628:therapy*; D011485:Protein Binding; D051381:Rats; D014161:Transduction, Genetic; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics*
chemical_list: D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1