This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Morioka, H. Articles by Hornicek, F. J. Search for Related Content PubMed PubMed Citation Articles by Morioka, H. Articles by Hornicek, F. J.

Antiangiogenesis Treatment Combined with Chemotherapy Produces Chondrosarcoma Necrosis¹

Orthopedic Research Laboratories [H. M., L. W., L. S., F. J. H.] and Department of Pathology [G. P. N.], Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; Bio-Technology General, Rehovot, Israel [T. V.]; and PharmaMar USA, Cambridge, Massachusetts 02149 [G. T. F.]

A combination therapy protocol using a marine chemotherapeutic and anantiangiogenic molecule was tested in a mouse tumor xenograftmodel 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.

This article has been cited by other articles:

				J. Fayette, I. R. Coquard, L. Alberti, D. Ranchere, H. Boyle, and J.-Y. Blay ET-743: A Novel Agent with Activity in Soft Tissue Sarcomas Oncologist, November 1, 2005; 10(10): 827 - 832. [Abstract] [Full Text] [PDF]

				G. Li, L. Tian, J.-m. Hou, Z.-y. Ding, Q.-m. He, P. Feng, Y.-j. Wen, F. Xiao, B. Yao, R. Zhang, et al. Improved Therapeutic Effectiveness by Combining Recombinant CXC Chemokine Ligand 10 with Cisplatin in Solid Tumors Clin. Cancer Res., June 1, 2005; 11(11): 4217 - 4224. [Abstract] [Full Text] [PDF]

				S. Emanuel, R. H. Gruninger, A. Fuentes-Pesquera, P. J. Connolly, J. A. Seamon, S. Hazel, R. Tominovich, B. Hollister, C. Napier, M. R. D'Andrea, et al. A Vascular Endothelial Growth Factor Receptor-2 Kinase Inhibitor Potentiates the Activity of the Conventional Chemotherapeutic Agents Paclitaxel and Doxorubicin in Tumor Xenograft Models Mol. Pharmacol., September 1, 2004; 66(3): 635 - 647. [Abstract] [Full Text] [PDF]

				S. J. Kim, H. Uehara, S. Yazici, R. R. Langley, J. He, R. Tsan, D. Fan, J. J. Killion, and I. J. Fidler Simultaneous Blockade of Platelet-Derived Growth Factor-Receptor and Epidermal Growth Factor-Receptor Signaling and Systemic Administration of Paclitaxel as Therapy for Human Prostate Cancer Metastasis in Bone of Nude Mice Cancer Res., June 15, 2004; 64(12): 4201 - 4208. [Abstract] [Full Text] [PDF]