Antitumor treatment efficacy by targeting epidermal growth factor receptor and vascular endothelial growth factor receptor-2 in an orthotopic human glioblastoma model
Authors: Tian Xin Hua
Zhuang Zai Wang
Diao Yi
Huang Yan Lin
Lin Xiao Ning
Chen Lu Kui
Journal: Journal of Neuro-Oncology (2011)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: orthotopic intracerebral model; HM55-BGIV-101 tumor line; antitumor effect; angiogenesis; growth
Affiliations: Neurosurgical Department of Affiliated Zhongshan Hospital, Xiamen University, 209 South Hubin Road, Xiamen 361004, China.

Abstract:  Using an orthotopic intracerebral model from our established HM55-BGIV-101 tumor line, we investigated the antitumor effect on the angiogenesis and growth of human glioblastoma after treatment with monoclonal antibody DC101 against the vascular endothelial growth factor receptor-2 and monoclonal antibody C225 against the epidermal growth factor receptor. Nude mice bearing intracerebral glioblastoma xenografts were treated intraperitoneally with DC101 and C225 either alone or in combination. Histopathological analysis of solid tumor volume, satellite tumor number, microvessel density, tumor cell proliferation, and apoptosis was performed. In the DC101-treated group, solid tumor volume and microvessel density were reduced by 59.7 and 64%, respectively; tumor cell proliferative activity was reduced by 53.2% and the apoptotic index (AI) was increased by 66.7%; satellite tumor number was enhanced by 84.4%. C225 alone reduced satellite tumor number by 43.3%, but had no effect on solid tumor volume, microvessel density, tumor cell proliferation, and apoptosis. C225 combined with DC101 not only reduced solid tumor volume, microvessel density, tumor cell proliferative activity, and increased AI, but also reduced satellite tumor number. Inhibition of angiogenesis achieved by DC101 can cause increased tumor cell invasiveness. In our studies this increased tumor cell invasiveness was inhibited simultaneously by C225, which provides a theoretical basis for treatment of glioblastoma by the method of combining drugs with different pharmacological activity. 

Retracted: No

PubPeer comments:
 Figure 1. * Blue boxes: In the EGFR panels, the xenograft and glioblastoma panels appear to overlap * Yellow boxes: In the VEGF panels, the xenograft and glioblastoma panels appear to overlap * Blue boxes: In the VEGFR2 panels, the xenograft and glioblastoma panels appear to overlap ![file] , 
 Figure 6a. * Blue boxes: The control and C225 panels appear to overlap, with a rotation * Red boxes: The C225 and DC101 panels appear to overlap, with a slight rotation * These four panels appear to be the same as those in Figure 5 of an older paper by the same research group, i.e. Yi Diao et al., Journal of Chemotherapy (2010), doi: 10.1179 joc.2010.22.6.407, https: pubpeer.com publications 27BBC842E96A3F679EBDC609781D61 ![file] , 
 Figure 7 * Cyan boxes: The control and C225 panels appear to overlap, with a rotation * Purple boxes: The DC101 and C225+DC101 panels appear to overlap, albeit with a different aspect ratio ![file] * The DC101 and C225+DC101 panels also appear to overlap with those in Figure 6 of the same paper as mentioned in #2, i.e. Yi Diao et al., Journal of Chemotherapy (2010), doi: 10.1179 joc.2010.22.6.407, https: pubpeer.com publications 27BBC842E96A3F679EBDC609781D61 ![file] ,