TY - JOUR A1 - Cinatl, Jindrich A1 - Michaelis, Martin A1 - Hernáiz Drievert, Pablo A1 - Cinatl, Jaroslav A1 - Hrabeta, Jan A1 - Suhan, Tatyana A1 - Doerr, Hans Wilhelm A1 - Vogel, Jens-Uwe T1 - Multimutated herpes simplex virus G207 is a potent inhibitor of angiogenesis T2 - Neoplasia N2 - The mode of the antitumoral activity of multimutated oncolytic herpes simplex virus type 1 G207 has not been fully elucidated yet. Because the antitumoral activity of many drugs involves the inhibition of tumor blood vessel formation, we determined if G207 had an influence on angiogenesis. Monolayers of human umbilical vein endothelial cells and human dermal microvascular endothelial cells, but not human dermal fibroblasts, bronchial epithelial cells, and retinal glial cells, were highly sensitive to the replicative and cytotoxic effects of G207. Moreover, G207 infection caused the destruction of endothelial cell tubes in vitro. In the in vivo Matrigel plug assay in mice, G207 suppressed the formation of perfused vessels. Intratumoral treatment of established human rhabdomyosarcoma xenografts with G207 led to the destruction of tumor vessels and tumor regression. Ultrastructural investigations revealed the presence of viral particles in both tumor and endothelial cells of G207-treated xenografts, but not in adjacent normal tissues. These findings show that G207 may suppress tumor growth, in part, due to inhibition of angiogenesis. KW - Angiogenesis KW - HSV-1 KW - G207 KW - human rhabdomyosarcoma KW - ribonucleotide reductase Y1 - 2004 UR - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/75952 UR - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-759520 SN - 1476-5586 VL - 6 IS - 6 SP - 725 EP - 735 PB - Elsevier CY - Amsterdam ER -