Antiangiogenic therapy inhibits human neuroblastoma growth.
BACKGROUND
Angiogenesis plays a crucial role in the progression and metastasis of malignant solid tumors. In many types of cancer, including neuroblastoma, high tumor vascularity correlates with poor outcome. Recently, a number of angiogenic inhibitors have been identified that had antitumor activity in preclinical studies.


METHODS
To investigate the effect of the antiangiogenic agent TNP-470 on neuroblastoma tumor growth, we treated nude mice with TNP-470 after they were inoculated subcutaneously with 5 x 10(6) cells from the MYCN-amplified, human neuroblastoma cell line NBL-W-N.


RESULTS
TNP-470 did not significantly affect tumor growth when it was administered to mice with large tumors (>600 mm3). However, when TNP-470 was administered in the setting of microscopic disease 12 hr following tumor cell inoculation, treated mice had a significantly improved tumor-free survival at 12 weeks (P < 0.001), and overall survival at 45 weeks (P < 0.001), compared to control animals.


CONCLUSIONS
Our studies suggest that TNP-470 treatment may be most effective if it is administered in the setting of microscopic disease. We speculate that TNP-470 may inhibit neuroblastoma growth in children if treatment is initiated following intensive multimodality therapy, when residual disease is minimal.
Katzenstein
H M
HM
Robert H. Lurie Comprehensive Cancer Center, Northwestern University Medical School and Children's Memorial Hospital, Chicago, Illinois 60614, USA.
Salwen
H R
HR
Nguyen
N N
NN
Meitar
D
D
Cohn
S L
SL
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D002455:Cell Division; D003510:Cyclohexanes; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D009447:Neuroblastoma / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D012717:Sesquiterpenes / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured / Q000637:transplantation; D023041:Xenograft Model Antitumor Assays
D020533:Angiogenesis Inhibitors; D003510:Cyclohexanes; D012717:Sesquiterpenes; D000077609:O-(Chloroacetylcarbamoyl)fumagillol