title: Enhanced cancer therapy with the combination of EGFR and VEGFR-2 targeting in an orthotopic glioblastoma model.
abstract: Using an orthotopic glioblastoma model, we investigated the activity of the combination of monoclonal antibody DC101 against vascular endothelial growth factor receptor-2 (VEGFR-2) and monoclonal antibody C225 against epidermal growth factor receptor (EGFR). Nude mice bearing intracerebral glioblastoma xenografts were administered either DC101 or C225, or the combination via intraperitoneal (i.p.) injection. Histopathological analysis of solid tumor volume, microvessel density, tumor cell proliferation and apoptosis were performed. In the DC101-treated group, solid tumor volume and microvessel density were reduced by 59.7% and 64%, respectively. The tumor cell proliferation level was reduced by 53.2% and tumor cell apoptosis was increased by 66.7% but there was enhanced tumor cell invasiveness. C225 alone reduced the invasiveness of tumor tissue, but had no effect on solid tumor growth, microvessel density, tumor cell proliferation or apoptosis. The combination cancer therapy with C225 and DC101 enhanced tumor treatment with reduced tumor volume, microvessel density, tumor cell proliferation level, and increased cancer cell apoptosis, while decreasing tumor cell invasiveness.
authors.affiliation: Neurosurgical Department of Affiliated Zhongshan Hospital, Xiamen University, People's Republic of China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Diao
authors.forename: Xin-Hua
authors.initials: XH
authors.lastname: Tian
authors.forename: Yan-Lin
authors.initials: YL
authors.lastname: Huang
authors.forename: Lu-Kui
authors.initials: LK
authors.lastname: Chen
authors.forename: Xiao-Ning
authors.initials: XN
authors.lastname: Lin
authors.forename: Zai-Wang
authors.initials: ZW
authors.lastname: Zhuang
mesh_terms: D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001932:Brain Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D000068818:Cetuximab; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005260:Female; D005909:Glioblastoma / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000473:pathology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors*; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C511761:DC101 monoclonal antibody; D066246:ErbB Receptors; D040301:Vascular Endothelial Growth Factor Receptor-2; D000068818:Cetuximab