Oncolytic HSV exerts direct antiangiogenic activity in ovarian carcinoma.

Détails

ID Serval
serval:BIB_ECECF1B0ADF6
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Oncolytic HSV exerts direct antiangiogenic activity in ovarian carcinoma.
Périodique
Human Gene Therapy
Auteur⸱e⸱s
Benencia F., Courreges M.C., Conejo-García J.R., Buckanovich R.J., Zhang L., Carroll R.H., Morgan M.A., Coukos G.
ISSN
1043-0342 (Print)
ISSN-L
1043-0342
Statut éditorial
Publié
Date de publication
2005
Volume
16
Numéro
6
Pages
765-778
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.Publication Status: ppublish
Résumé
In the present study, we investigated the ability of replication-restricted herpes simplex virus (HSV) 1716 lacking ICP34.5 to infect endothelium and disrupt tumor vasculature. HSV-1716 efficiently infected and killed mouse endothelial cell lines H5V and MS1 cells, as well as human umbilical vein endothelial cells in vitro. Capillary tube formation by endothelial cells was inhibited by HSV-1716 in vitro and in vivo. Following intratumoral administration of oncolytic HSV-1716, HSV-glycoproteins could be detected in CD31-positive tumor vascular endothelium by immunostaining. Viral DNA was recovered from highly purified microdissected tumor vascular endothelium. Furthermore, endothelium of tumors treated with HSV-1716 exhibited expression of tissue factor, a marker of endothelial damage. Importantly, HSV antigen and DNA were also detected in endothelium distant from foci of active tumor infection. After intravascular inoculation of HSV-1716, viral glycoproteins were detected in association to tumor endothelium, but not vascular endothelium of different organs. Purified tumor endothelial cells showed high proliferative capability and were susceptible to HSV-1716 infection and killing ex vivo while endothelium from normal organs was not. We conclude that oncolytic HSV-1716 exerts direct antiangiogenic effects, which may contribute to the overall therapeutic efficacy of the virus.
Mots-clé
Angiogenesis Inhibitors/genetics, Angiogenesis Inhibitors/pharmacology, Animals, Carcinoma/genetics, Carcinoma/therapy, Cells, Cultured, Endothelial Cells/drug effects, Endothelial Cells/pathology, Endothelium, Vascular/drug effects, Endothelium, Vascular/pathology, Female, Genetic Vectors/pharmacology, Humans, Mice, Ovarian Neoplasms/genetics, Ovarian Neoplasms/therapy, Simplexvirus/genetics, Tumor Cells, Cultured, Vascular Endothelial Growth Factor A/genetics
Pubmed
Web of science
Création de la notice
14/10/2014 11:43
Dernière modification de la notice
20/08/2019 16:14
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