Angiogenesis can be reduced without significant reduction of tumor growth.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
Angiogenesis inhibition must reach a threshold before significant tumor cell apoptosis and a reduction of the tumor growth rate occur.
Svensson
Asa
A
Department of Medical Cell Biology, Children's Hospital, Uppsala University, Sweden.
Bäckman
Ulrika
U
Fuchs
Dieter
D
Christofferson
Rolf
R
Azarbayjani
Faranak
F
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D003510:Cyclohexanes / Q000494:pharmacology*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D009447:Neuroblastoma / Q000097:blood / Q000098:blood supply* / Q000188:drug therapy* / Q000473:pathology; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D012717:Sesquiterpenes / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D023041:Xenograft Model Antitumor Assays
D020533:Angiogenesis Inhibitors; D003510:Cyclohexanes; D012717:Sesquiterpenes; D042461:Vascular Endothelial Growth Factor A; D000077609:O-(Chloroacetylcarbamoyl)fumagillol