Synergistic antitumor effects of transarterial viroembolization for multifocal hepatocellular carcinoma in rats

Oncolytic virotherapy is a promising strategy for safe and effective treatment of malignancy. We have reported previously that recombinant vesicular stomatitis virus (VSV) vectors are effective oncolytic agents that can be safely administered via the hepatic artery in immunocompetent rats to treat m...

Full description

Saved in:
Bibliographic Details
Published in:Hepatology (Baltimore, Md.) Md.), 2008-12, Vol.48 (6), p.1864-1873
Main Authors: Altomonte, Jennifer, Braren, Rickmer, Schulz, Stephan, Marozin, Sabrina, Rummeny, Ernst J., Schmid, Roland M., Ebert, Oliver
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Biological and medical sciences
Carcinoma, Hepatocellular - pathology
Carcinoma, Hepatocellular - therapy
Carcinoma, Hepatocellular - virology
Cell Line, Tumor
Combined Modality Therapy
Disease Models, Animal
Embolization, Therapeutic - methods
Gastroenterology. Liver. Pancreas. Abdomen
Hepatic Artery
Liver Neoplasms - pathology
Liver Neoplasms - therapy
Liver Neoplasms - virology
Liver. Biliary tract. Portal circulation. Exocrine pancreas
Male
Medical sciences
Microspheres
Oncolytic Virotherapy - methods
Platelet Endothelial Cell Adhesion Molecule-1 - metabolism
Rats
Rats, Inbred BUF
Starch
Tumors
Vesiculovirus - genetics
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Oncolytic virotherapy is a promising strategy for safe and effective treatment of malignancy. We have reported previously that recombinant vesicular stomatitis virus (VSV) vectors are effective oncolytic agents that can be safely administered via the hepatic artery in immunocompetent rats to treat multifocal hepatocellular carcinoma (HCC), resulting in tumor necrosis and prolonged survival. Though the results were encouraging, complete tumor regression was not observed, which led us to explore alternative approaches to further enhance the efficacy of VSV treatment. Transarterial embolization techniques have been shown to improve the efficiency and tumor selectivity of anticancer treatments. Degradable starch microspheres (DSM) are one such embolic agent that provides transient embolization of the therapeautic agent before being degraded by serum amylases. Here we demonstrate via dynamic contrast‐enhanced magnetic resonance imaging that in our rat model of multifocal HCC, DSM injection into the hepatic artery results in a substantial reduction in tumor perfusion of systemically applied contrast agent. VSV, when administered in combination with DSM, results in enhanced tumor necrosis and synergistically prolongs survival when compared with VSV or DSM monotherapy. Conclusion: This regimen of viroembolization represents an innovative therapeutic modality that can augment the future development of transarterial oncolytic virus therapy for patients with advanced HCC. (HEPATOLOGY 2008;48:1864‐1873.)
ISSN:0270-9139
1527-3350
DOI:10.1002/hep.22546