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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...
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| Published in: | Hepatology (Baltimore, Md.) Md.), 2008-12, Vol.48 (6), p.1864-1873 |
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| container_title | Hepatology (Baltimore, Md.) |
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| creator | Altomonte, Jennifer Braren, Rickmer Schulz, Stephan Marozin, Sabrina Rummeny, Ernst J. Schmid, Roland M. Ebert, Oliver |
| description | 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.) |
| doi_str_mv | 10.1002/hep.22546 |
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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.)</description><identifier>ISSN: 0270-9139</identifier><identifier>EISSN: 1527-3350</identifier><identifier>DOI: 10.1002/hep.22546</identifier><identifier>PMID: 19003878</identifier><identifier>CODEN: HPTLD9</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>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</subject><ispartof>Hepatology (Baltimore, Md.), 2008-12, Vol.48 (6), p.1864-1873</ispartof><rights>Copyright © 2008 American Association for the Study of Liver Diseases</rights><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3886-53fbefe62f8e80199183b9e7e65d5917cb359731aa1c1379085c6ee18f6ac17a3</citedby><cites>FETCH-LOGICAL-c3886-53fbefe62f8e80199183b9e7e65d5917cb359731aa1c1379085c6ee18f6ac17a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fhep.22546$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fhep.22546$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>315,786,790,27957,27958,50923,51032</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20893174$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19003878$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Altomonte, Jennifer</creatorcontrib><creatorcontrib>Braren, Rickmer</creatorcontrib><creatorcontrib>Schulz, Stephan</creatorcontrib><creatorcontrib>Marozin, Sabrina</creatorcontrib><creatorcontrib>Rummeny, Ernst J.</creatorcontrib><creatorcontrib>Schmid, Roland M.</creatorcontrib><creatorcontrib>Ebert, Oliver</creatorcontrib><title>Synergistic antitumor effects of transarterial viroembolization for multifocal hepatocellular carcinoma in rats</title><title>Hepatology (Baltimore, Md.)</title><addtitle>Hepatology</addtitle><description>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.)</description><subject>Animals</subject><subject>Apoptosis</subject><subject>Biological and medical sciences</subject><subject>Carcinoma, Hepatocellular - pathology</subject><subject>Carcinoma, Hepatocellular - therapy</subject><subject>Carcinoma, Hepatocellular - virology</subject><subject>Cell Line, Tumor</subject><subject>Combined Modality Therapy</subject><subject>Disease Models, Animal</subject><subject>Embolization, Therapeutic - methods</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Hepatic Artery</subject><subject>Liver Neoplasms - pathology</subject><subject>Liver Neoplasms - therapy</subject><subject>Liver Neoplasms - virology</subject><subject>Liver. Biliary tract. Portal circulation. Exocrine pancreas</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Microspheres</subject><subject>Oncolytic Virotherapy - methods</subject><subject>Platelet Endothelial Cell Adhesion Molecule-1 - metabolism</subject><subject>Rats</subject><subject>Rats, Inbred BUF</subject><subject>Starch</subject><subject>Tumors</subject><subject>Vesiculovirus - genetics</subject><issn>0270-9139</issn><issn>1527-3350</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><recordid>eNp1kMFOGzEQhq2qqAlpD30B5EsrcVhir3fX9hGhQJCQqNT2vJp1xq3R7jrYXqrw9HVIBCdOc5hP_z_zEfKVswvOWLn8i9uLsqyr5gOZ87qUhRA1-0jmrJSs0FzoGTmN8YExpqtSfSIzrhkTSqo58T93I4Y_LiZnKIzJpWnwgaK1aFKk3tIUYIwQEgYHPX1ywePQ-d49Q3J-pDbTw9QnZ73J-3wKJG-w76ceAjUQjBv9ANSNNECKn8mJhT7il-NckN_Xq19X6-Lu_ub26vKuMEKppqiF7dBiU1qFinGtuRKdRolNvak1l6YTtZaCA3DDhdRM1aZB5Mo2YLgEsSDfD7nb4B8njKkdXNyfBSP6KbaNVpWuRJXB8wNogo8xoG23wQ0Qdi1n7d5um19qX-xm9uwYOnUDbt7Io84MfDsCELMNm9UZF1-5kiktuNyXLg_cP9fj7v3Gdr36caj-D4OTk6g</recordid><startdate>200812</startdate><enddate>200812</enddate><creator>Altomonte, Jennifer</creator><creator>Braren, Rickmer</creator><creator>Schulz, Stephan</creator><creator>Marozin, Sabrina</creator><creator>Rummeny, Ernst J.</creator><creator>Schmid, Roland M.</creator><creator>Ebert, Oliver</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>200812</creationdate><title>Synergistic antitumor effects of transarterial viroembolization for multifocal hepatocellular carcinoma in rats</title><author>Altomonte, Jennifer ; Braren, Rickmer ; Schulz, Stephan ; Marozin, Sabrina ; Rummeny, Ernst J. ; Schmid, Roland M. ; Ebert, Oliver</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3886-53fbefe62f8e80199183b9e7e65d5917cb359731aa1c1379085c6ee18f6ac17a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Animals</topic><topic>Apoptosis</topic><topic>Biological and medical sciences</topic><topic>Carcinoma, Hepatocellular - pathology</topic><topic>Carcinoma, Hepatocellular - therapy</topic><topic>Carcinoma, Hepatocellular - virology</topic><topic>Cell Line, Tumor</topic><topic>Combined Modality Therapy</topic><topic>Disease Models, Animal</topic><topic>Embolization, Therapeutic - methods</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Hepatic Artery</topic><topic>Liver Neoplasms - pathology</topic><topic>Liver Neoplasms - therapy</topic><topic>Liver Neoplasms - virology</topic><topic>Liver. Biliary tract. Portal circulation. Exocrine pancreas</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Microspheres</topic><topic>Oncolytic Virotherapy - methods</topic><topic>Platelet Endothelial Cell Adhesion Molecule-1 - metabolism</topic><topic>Rats</topic><topic>Rats, Inbred BUF</topic><topic>Starch</topic><topic>Tumors</topic><topic>Vesiculovirus - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Altomonte, Jennifer</creatorcontrib><creatorcontrib>Braren, Rickmer</creatorcontrib><creatorcontrib>Schulz, Stephan</creatorcontrib><creatorcontrib>Marozin, Sabrina</creatorcontrib><creatorcontrib>Rummeny, Ernst J.</creatorcontrib><creatorcontrib>Schmid, Roland M.</creatorcontrib><creatorcontrib>Ebert, Oliver</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Hepatology (Baltimore, Md.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Altomonte, Jennifer</au><au>Braren, Rickmer</au><au>Schulz, Stephan</au><au>Marozin, Sabrina</au><au>Rummeny, Ernst J.</au><au>Schmid, Roland M.</au><au>Ebert, Oliver</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synergistic antitumor effects of transarterial viroembolization for multifocal hepatocellular carcinoma in rats</atitle><jtitle>Hepatology (Baltimore, Md.)</jtitle><addtitle>Hepatology</addtitle><date>2008-12</date><risdate>2008</risdate><volume>48</volume><issue>6</issue><spage>1864</spage><epage>1873</epage><pages>1864-1873</pages><issn>0270-9139</issn><eissn>1527-3350</eissn><coden>HPTLD9</coden><notes>fax: (49)‐89‐41402258.</notes><notes>Potential conflict of interest: Nothing to report.</notes><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>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.)</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>19003878</pmid><doi>10.1002/hep.22546</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| 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 |
| title | Synergistic antitumor effects of transarterial viroembolization for multifocal hepatocellular carcinoma in rats |
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