Concomitant tumour resistance in patients with osteosarcoma. A clue to a new therapeutic strategy.
Concomitant tumour resistance (CTR) is a unique phenomenon in which animals harbouring large primary tumours are resistant to the growth of smaller metastatic tumours by systemic angiogenic suppression. To examine this clinically, in ten patients with osteosarcoma, we investigated the effects of removal of the primary tumour on the development of pulmonary metastases, the systemic angiogenesis-inducing ability and the serum levels of several angiogenesis modulators. We found that removal of the primary tumour significantly elevated systemic angiogenesis-inducing ability in five patients who had post-operative recurrence of the tumour. Post-operative elevation of the angiogenesis-induced ability was suppressed by the addition of an angiogenic inhibitor, endostatin. Also, primary removal of the tumour decreased the serum levels of vascular endothelial growth factor and endostatin. These findings suggest, for the first time, the presence of CTR in patients with osteosarcoma for whom post-operative antiangiogenic therapy may be used to prevent the post-operative progression of micrometastases.
Kaya
M
M
Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, Sapporo 060-8543, Hokkaido, Japan.
Wada
T
T
Nagoya
S
S
Kawaguchi
S
S
Isu
K
K
Yamashita
T
T
D000293:Adolescent; D000818:Animals; D001859:Bone Neoplasms / Q000097:blood / Q000601:surgery*; D002648:Child; D043169:Endostatins / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000098:blood supply / Q000556:secondary*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000209:etiology* / Q000517:prevention & control; D012516:Osteosarcoma / Q000097:blood / Q000556:secondary / Q000601:surgery*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
D043169:Endostatins; D042461:Vascular Endothelial Growth Factor A