Antitumor efficacy of viral therapy using genetically engineered Newcastle disease virus [NDV(F3aa)-GFP] for peritoneally disseminated gastric cancer Journal Article

   

Authors:	Song, K. Y.; Wong, J.; Gonzalez, L.; Sheng, G.; Zamarin, D.; Fong, Y.
Article Title:	Antitumor efficacy of viral therapy using genetically engineered Newcastle disease virus [NDV(F3aa)-GFP] for peritoneally disseminated gastric cancer
Abstract:	Peritoneal dissemination is a common and fatal clinical manifestation of gastric cancer with few effective therapies available. Natural Newcastle disease virus (NDV) has been shown to be an effective oncolytic agent, and recent advances now allow genetic manipulation of this virus to improve cancer killing and safety. This study was designed to investigate the effectiveness of a genetically engineered NDV in the treatment of peritoneally disseminated gastric carcinoma. NDV mutant virus containing a modified F cleavage site and insertion of enhanced green fluorescent protein (GFP), NDV(F3aa)-GFP, was tested in vitro against human gastric cancer cells by standard cytotoxicity at different multiplicities of infection. To test NDV(F3aa)-GFP in vivo in a peritoneal carcinomatosis gastric tumor model, MKN-74 human gastric cancer cells were injected intraperitoneally (IP) in severe combined immunodeficient mice. Mice were treated with NDV (F3aa)-GFP either once or multiple times after tumor challenge. Effective killing of MKN-74 cells by NDV (F3aa)-GFP was found in vitro. This cancer killing was dose-related and correlated with viral replication. GFP expression was a good marker of infection. The virus was also effective as an antitumor therapy in a peritoneal cancer model that simulates clinical disease. Half the animals treated with virus had no evidence of disease. Genetically engineered NDV [NDV(F3aa)-GFP] administered IP is an effective antitumor therapy against peritoneal carcinomatosis from human gastric cancer in a xenograft model, without significant toxicity. These data provide further rationale for clinical trials involving NDV for peritoneal carcinomatosis from gastric cancer. © Springer-Verlag 2010.
Keywords:	human cell; disseminated cancer; nonhuman; mouse; animals; mice; peritoneal neoplasms; animal experiment; animal model; cytotoxicity; mice, scid; cell line, tumor; cancer model; cancer therapy; mice, inbred c57bl; cancer inhibition; genetic engineering; cancer cell; oncolytic virus; oncolytic virotherapy; stomach cancer; green fluorescent proteins; virus replication; neoplasm transplantation; carcinomatous peritonitis; stomach carcinoma; stomach neoplasms; cell killing; stomach tumor; newcastle disease virus; enhanced green fluorescent protein; newcastle disease paramyxovirus; peritoneum; oncolysis; peritoneal carcinomatosis
Journal Title:	Journal of Molecular Medicine
Volume:	88
Issue:	6
ISSN:	0946-2716
Publisher:	Springer
Date Published:	2010-06-01
Start Page:	589
End Page:	596
Language:	English
DOI:	10.1007/s00109-010-0605-6
PUBMED:	20393691
PROVIDER:	scopus
PMCID:	PMC3269811
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-77954565093&partnerID=40&md5=9d4d717d8e936c20b662a5bf95b5bb3d
Notes:	--- - "Cited By (since 1996): 2" - "Export Date: 20 April 2011" - "CODEN: JMLME" - "Source: Scopus"

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