Svensson Asa, Bäckman Ulrika, Fuchs Dieter, Christofferson Rolf, Azarbayjani Faranak
Department of Medical Cell Biology, Children's Hospital, Uppsala University, Sweden.
Anticancer Res. 2007 Nov-Dec;27(6B):3883-9.
High risk neuroblastoma (NB) patients have an overall five-year survival of approximately 50%, indicating the need for new treatment strategies, such as angiogenesis inhibition.
The angiogenesis inhibitor TNP-470 (30 mg/kg, every other day, subcutaneously) was given to nude mice with subcutaneous human neuroblastoma xenografts. The plasma concentrations of the angiogenesis stimulators, i.e. vascular endothelial growth factor A (VEGF-A), fibroblast growth factor 2 (FGF-2) and hepatocyte growth factor (HGF), were assayed longitudinally. Angiogenesis, proliferation and apoptosis were quantified on tumor tissue slides.
Upon treatment with TNP-470, angiogenesis was significantly inhibited by the reduction of length and surface area of vessels per tumor volume, without having significant effect on tumor growth, tumor cell proliferation or apoptosis. Plasma concentrations of VEGF-A per tumor volume were significantly increased upon treatment.
Angiogenesis inhibition must reach a threshold before significant tumor cell apoptosis and a reduction of the tumor growth rate occur.
高危神经母细胞瘤（NB）患者的总体五年生存率约为50%，这表明需要新的治疗策略，如血管生成抑制。
将血管生成抑制剂TNP-470（30mg/kg，每隔一天皮下注射）给予皮下接种人神经母细胞瘤异种移植物的裸鼠。纵向检测血管生成刺激因子，即血管内皮生长因子A（VEGF-A）、成纤维细胞生长因子2（FGF-2）和肝细胞生长因子（HGF）的血浆浓度。对肿瘤组织切片上的血管生成、增殖和凋亡进行定量分析。
用TNP-470治疗后，每肿瘤体积的血管长度和表面积减少，血管生成受到显著抑制，但对肿瘤生长、肿瘤细胞增殖或凋亡无显著影响。治疗后每肿瘤体积的VEGF-A血浆浓度显著升高。
在显著的肿瘤细胞凋亡和肿瘤生长速率降低发生之前，血管生成抑制必须达到一个阈值。
