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This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Roboz, G. J. Articles by Rafii, S. Search for Related Content PubMed PubMed Citation Articles by Roboz, G. J. Articles by Rafii, S. Related Collections Hemostasis, Thrombosis, and Vascular Biology Neoplasia Apoptosis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 August 2000, Vol. 96, No. 4, pp. 1525-1530 NEOPLASIA Arsenic trioxide induces dose- and time-dependent apoptosis of endothelium and may exert an antileukemic effect via inhibition of angiogenesis Gail J. Roboz, Sergio Dias, George Lam, William J. Lane, Steven L. Soignet, Raymond P. Warrell Jr, and Shahin Rafii From the Division of Hematology and Oncology, Weill Medical College of Cornell University, New York, NY; Memorial Sloan Kettering Cancer Center, New York, NY. Arsenic trioxide (As2O3) has recently been used successfully in the treatment of acute promyelocytic leukemia and has been shown to induce partial differentiation and apoptosis of leukemic cells in vitro. However, the mechanism by which As2O3 exerts its antileukemic effect remains uncertain. Emerging data suggest that the endothelium and angiogenesis play a seminal role in the proliferation of liquid tumors, such as leukemia. We have shown that activated endothelial cells release cytokines that may stimulate leukemic cell growth. Leukemic cells, in turn, can release endothelial growth factors, such as vascular endothelial growth factor (VEGF). On the basis of these observations, we hypothesized that As2O3 may interrupt a reciprocal loop between leukemic cells and the endothelium by direct action on both cell types. We have shown that treatment of proliferating layers of human umbilical vein endothelial cells (HUVECs) with a variety of concentrations of As2O3 results in a reproducible dose- and time-dependent sequence of events marked by change to an activated morphology, up-regulation of endothelial cell adhesion markers, and apoptosis. Also, treatment with As2O3 caused inhibition of VEGF production in the leukemic cell line HEL. Finally, incubation of HUVECs with As2O3 prevented capillary tubule and branch formation in an in vitro endothelial cell-differentiation assay. In conclusion, we believe that As2O3 interrupts a reciprocal stimulatory loop between leukemic cells and endothelial cells by causing apoptosis of both cell types and by inhibiting leukemic cell VEGF production. © 2000 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: P. Kumar, Q. Gao, Y. Ning, Z. Wang, P. H. Krebsbach, and P. J. Polverini Arsenic trioxide enhances the therapeutic efficacy of radiation treatment of oral squamous carcinoma while protecting bone Mol. Cancer Ther., July 1, 2008; 7(7): 2060 - 2069. [Abstract] [Full Text] [PDF] W. C. Prozialeck, J. R. Edwards, D. W. Nebert, J. M. Woods, A. Barchowsky, and W. D. Atchison The Vascular System as a Target of Metal Toxicity Toxicol. Sci., April 1, 2008; 102(2): 207 - 218. [Abstract] [Full Text] [PDF] A. Hines-Peralta, V. Sukhatme, M. Regan, S. Signoretti, Z.-j. Liu, and S. N. 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