title: Multimutated herpes simplex virus g207 is a potent inhibitor of angiogenesis.
abstract: 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.
authors.affiliation: Institute of Medical Virology, Center of Hygiene, Paul-Ehrlich Str. 40, Frankfurt am Main D-60596, Germany. Cinatl@em.uni-frankfurt.de
authors.forename: Jindrich
authors.initials: J
authors.lastname: Cinatl
authors.forename: Martin
authors.initials: M
authors.lastname: Michaelis
authors.forename: Pablo Hernáiz
authors.initials: PH
authors.lastname: Driever
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Cinatl
authors.forename: Jan
authors.initials: J
authors.lastname: Hrabeta
authors.forename: Tatyana
authors.initials: T
authors.lastname: Suhan
authors.forename: Hans Wilhelm
authors.initials: HW
authors.lastname: Doerr
authors.forename: Jens-Uwe
authors.initials: JU
authors.lastname: Vogel
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003588:Cytopathogenic Effect, Viral; D004591:Electrophoresis, Polyacrylamide Gel; D042783:Endothelial Cells / Q000821:virology*; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D046529:Microscopy, Electron, Transmission; D009154:Mutation; D009389:Neovascularization, Pathologic / Q000821:virology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012208:Rhabdomyosarcoma / Q000821:virology; D018139:Simplexvirus / Q000235:genetics / Q000502:physiology*; D014471:Umbilical Veins; D014779:Virus Replication / Q000502:physiology
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