title: combination of vascular endothelial growth factor (VEGF) and thymidine phosphorylase (TP) to improve angiogenic gene therapy.
abstract: To improve current angiogenic gene therapy with a vascular endothelial growth factor (VEGF)-encoding plasmid (Baumgartner et al. Circulation 1998; 97: 1114-23 [1]; Kusumanto et al. Fifth Annual Meeting of the American Society of Gene Therapy, Boston, 2002, Abstr. 621 [2]), we have generated a combination plasmid, encoding the VEGF gene and the thymidine phosphorylase (TP, also known as platelet-derived endothelial growth factor (PD-ECGF) or gliostatin (GLS)) gene: phVEGF165-TP.MB. Upon transfection in COS-7 cells both gene products were expressed and functional as shown by Western blots, ELISAs and bioassays. Culture supernatants of COS-7 cells transfected with this plasmid were able to induce endothelial proliferation. In an in vitro angiogenesis assay with recombinant proteins, TP was able to increase VEGF-induced tube formation. The phVEGF165-TP.MB plasmid is therefore a promising candidate for in vivo angiogenesis studies.
authors.affiliation: Department of Medical Oncology, University Hospital Groningen, The Netherlands.
authors.forename: Diane
authors.initials: D
authors.lastname: Bouïs
authors.forename: Mirjam C
authors.initials: MC
authors.lastname: Boelens
authors.forename: Erna
authors.initials: E
authors.lastname: Peters
authors.forename: Pieter
authors.initials: P
authors.lastname: Koolwijk
authors.forename: Gerrie
authors.initials: G
authors.lastname: Stob
authors.forename: Ido P
authors.initials: IP
authors.lastname: Kema
authors.forename: Marco
authors.initials: M
authors.lastname: Klinkenberg
authors.forename: Nanno H
authors.initials: NH
authors.lastname: Mulder
authors.forename: Geke A P
authors.initials: GA
authors.lastname: Hospers
mesh_terms: D000818:Animals; D019556:COS Cells; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000166:cytology; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D013939:Thymidine Phosphorylase / Q000008:administration & dosage* / Q000235:genetics / Q000494:pharmacology; D013941:Thymine / Q000096:biosynthesis; D014162:Transfection; D014471:Umbilical Veins; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage* / Q000235:genetics / Q000494:pharmacology
chemical_list: D017077:Culture Media, Conditioned; D042461:Vascular Endothelial Growth Factor A; D013939:Thymidine Phosphorylase; D013941:Thymine