1,721,006 research outputs found
Development and engineering of lymphatic endothelial cells: Clinical implications
No full textStudies on the lymphatic endothelium have been hampered by the difficulty to identify lymphatic endothelial cells (LECs) and to distinguish them from blood vascular endothelial cells (BECs). The situation was greatly improved by the identification of molecules with high specificity for LECs. A great deal of progress in the field of lymphangiogenesis research has been due to the detection of lymphangiogenic growth factors and their receptors, and there is growing evidence that these molecules are also involved in tumor-induced lymphangiogenesis and lymphatic dissemination of tumor cells. There is a considerable spectrum of congenital and acquired lymphedema-lymphangiodysplasia syndromes ranging from primary aplasia, hypoplasia and hyperplasia to secondary (acquired) obstructive, obliterative and surgical hindrance of lymph drainage. Consequently, there are a number of clinical applications for therapeutics that either inhibit or induce lymphangiogenesis. Although natural lymphatic regeneration is mostly very efficient, engineering of LECs may be useful in cases of lymphatic aplasia or hypoplasia. To achieve these goals, studies on the embryonic development and differentiation of LECs will reveal the key regulatory factors that need to be targeted
Arginine deiminase and other antiangiogenic agents inhibit unfavorable neuroblastoma growth: potentiation by irradiation
Get PDFIn spite of aggressive therapy, children suffering from neuroblastoma have a poor prognosis. Therapeutic failure is most often observed in neuroblastomas with unfavorable features, including amplification/over-expression of the N-myc oncogene, rapid growth, effective angiogenesis and/or the tendency to metastasize. Here, we have used cultured human neuroblastoma cells with such features and we have examined whether antiangiogenic agents alone or in combination with tumor irradiation inhibit their angiogenesis and growth in vivo. We report that antiangiogenic agents (arginine deiminase, SUS416 and DC 101) inhibit in vivo growth of neuroblastomas with unfavorable properties and that these effects are potentiated by simultaneous irradiation. Combination of either agent with irradiation leads to a reduction in the absolute number of tumor vessels and of perfused tumor vessels. Combination of arginine deiminase or DC101 with irradiation does not increase tumor hypoxia. Our data demonstrate for the first time that arginine deiminase suppresses the growth of unfavorable experimental neuroblastomas and that this effect is potentiated by irradiation. We suggest that antiangiogenesis alone or in combination with established therapeutic regimen may improve the outcome of unfavorable neuroblastomas in a clinical setting. (C) 2003 Wiley-Liss, Inc
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