Angiostatic treatment of neuroblastoma.
The growth of solid tumours has been shown to be dependent on new blood vessel formation, i.e. angiogenesis. Several steps in the metastatic process have also been found to be angiogenesis dependent. The mediators of tumour angiogenesis are now being elucidated, and angiostatic agents have been developed. Some of these agents are currently undergoing clinical trials. In addition to inhibition of angiogenesis, two other clinical applications of angiogenetic research in tumour diseases are monitoring of disease activity by analyses of circulating angiogenic peptides and prediction of a poor outcome by tumour microvascular counts. Neuroblastomas grow quickly, are highly vascularised and metastasise early and hence inhibition of angiogenesis--angiostatic therapy--may be indicated in this disease. The effects of treatment with the angiostatic agent TNP-470 in an experimental model results in a significant reduction of the tumour growth rate, reduced microvascular counts and a reduced fraction of viable tumour cells compared to controls. TNP-470 as single therapy has an objective tumoristatic effect in our neuroblastoma model. Angiostatic treatment of neuroblastoma is a new and theoretically promising treatment modality that merits clinical investigations. The feasibility of assessing disease activity by repeated determinations of the levels of circulating angiogenic peptides should also be determined, as well as the use of microvascular counts to predict a poor outcome.
Wassberg
E
E
Department of Human Anatomy, University of Uppsala, Sweden.
Christofferson
R
R
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003510:Cyclohexanes; D006801:Humans; D007150:Immunohistochemistry; D008854:Microscopy, Electron; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000378:metabolism; D009447:Neuroblastoma / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D011379:Prognosis; D051381:Rats; D012717:Sesquiterpenes / Q000494:pharmacology / Q000627:therapeutic use*
D000903:Antibiotics, Antineoplastic; D003510:Cyclohexanes; D012717:Sesquiterpenes; D000077609:O-(Chloroacetylcarbamoyl)fumagillol