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Related Collections Hemostasis, Thrombosis, and Vascular Biology Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 December 2002, Vol. 100, No. 13, pp. 4622-4628 NEOPLASIA In vivo administration of vascular endothelial growth factor (VEGF) and its antagonist, soluble neuropilin-1, predicts a role of VEGF in the progression of acute myeloid leukemia in vivo Gunter Schuch, Marcelle Machluf, Georg Bartsch Jr, Masashi Nomi, Henri Richard, Anthony Atala, and Shay Soker From the Department of Urology, Laboratory for Cellular Therapeutics, Children's Hospital, Boston, MA. Recent findings implied that the progression of hematologic malignancies, like that of solid tumors, is dependent on neovascularization. Recent studies on patients with acute myeloid leukemia (AML) showed increased levels of leukocyte-associated vascular endothelial growth factor (VEGF) and neovascularization of the bone marrow. Murine (32D, M1) and human (HEL, U937, and UKE-1) leukemic cell lines and freshly isolated leukemic cells were analyzed for the expression of VEGF and VEGF receptor mRNA. The expression of VEGF and VEGF receptors KDR and neuropilin-1 (NRP-1) was detected in these cells. In a murine chloroma model, delivery of VEGF165 using microencapsulation technology resulted in enhanced tumor growth and vascularization, whereas treatment with a VEGF antagonist soluble NRP-1 (sNRP-1) inhibited tumor angiogenesis and growth. In a systemic leukemia model, survival of mice injected with adenovirus (Ad) encoding for Fc-sNRP-1 (sNRP-1 dimer) was significantly prolonged as compared with mice injected with Ad-LacZ. Further analyses showed a reduction in circulating leukemic cells and infiltration of liver and spleen as well as bone marrow neovascularization and cellularity. Taken together, these results demonstrate that angiogenic factors such as VEGF promote AML progression in vivo. The use of VEGF antagonists as an antiangiogenesis approach offers a potential treatment for AML. Finally, our novel in vivo drug delivery model may be useful for testing the activities of other peptide antiangiogenic factors. © 2002 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. T.-F. Shih, H.-A. Hou, C.-Y. Liu, B.-B. Chen, J.-L. Tang, H.-Y. Chen, S.-Y. Wei, M. Yao, S.-Y. Huang, W.-C. Chou, et al. Bone marrow angiogenesis magnetic resonance imaging in patients with acute myeloid leukemia: peak enhancement ratio is an independent predictor for overall survival Blood, April 2, 2009; 113(14): 3161 - 3167. [Abstract] [Full Text] [PDF] A. Bagri, M. Tessier-Lavigne, and R. J. Watts Neuropilins in Tumor Biology Clin. Cancer Res., March 15, 2009; 15(6): 1860 - 1864. [Abstract] [Full Text] [PDF] S. M. Kornblau, R. Tibes, Y. H. Qiu, W. Chen, H. M. Kantarjian, M. 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