Antiangiogenesis treatment combined with chemotherapy produces chondrosarcoma necrosis.
A combination therapy protocol using a marine chemotherapeutic and an antiangiogenic molecule was tested in a mouse tumor xenograft model for the ability to curtail the growth of a human chondrosarcoma (CHSA). Ecteinascidin-743 (ET-743), a marine-derived chemotherapeutic, was effective at slowing the growth of a primary CHSA. Plasminogen-related protein B, which antagonizes various endothelial cell activities, also elicited a significant inhibition of neoplastic growth, albeit with reduced effectiveness. The combination of the two agents resulted in only a modest further repression of tumor growth over that associated with ET-743 treatment alone, as measured by tumor volume (82% versus 76% inhibition, respectively). However, analysis of the extent of tumor necrosis and vascularization of the tumor revealed that the coadministration of the two compounds was clearly more effective, eliciting a 2.5-fold increase in tumor necrosis relative to single-agent treatment. The combination therapy also was most effective at antagonizing tumor-associated microvessel formation, as assessed by CD31 immunostaining, suggesting that combination therapy may hold promise for treating CHSA. Tumor necrosis produced by combination therapy of ET-743 and recombinant plasminogen-related protein B was also significantly greater than that produced by conventional doxorubicin treatment, further corroborating the efficacy of combination therapy.
Morioka
Hideo
H
Orthopedic Research Laboratories, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA.
Weissbach
Lawrence
L
Vogel
Tikva
T
Nielsen
G Petur
GP
Faircloth
Glynn T
GT
Shao
Li
L
Hornicek
Francis J
FJ
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D002455:Cell Division; D002813:Chondrosarcoma / Q000473:pathology*; D004317:Doxorubicin / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008833:Microcirculation; D008875:Middle Aged; D009336:Necrosis; D009368:Neoplasm Transplantation; D010958:Plasminogen / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014407:Tumor Cells, Cultured
D020533:Angiogenesis Inhibitors; C118420:PLGLB1 protein, human; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012333:RNA, Messenger; D011994:Recombinant Proteins; D004317:Doxorubicin; D010958:Plasminogen