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Tumor-Selective Gene Expression in a Hepatic Metastasis Model after Locoregional Delivery of a Replication-Competent Retrovirus Vector
Purpose: Replication-competent retrovirus (RCR) vectors have been shown to achieve highly efficient and tumor-restricted replicative spread and gene transfer in vivo after direct intratumoral injection in a variety of primary cancer models. In this setting, the intrinsic inability of retroviruses to...
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| Published in: | Clinical cancer research 2006-12, Vol.12 (23), p.7108-7116 |
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| container_end_page | 7116 |
| container_issue | 23 |
| container_start_page | 7108 |
| container_title | Clinical cancer research |
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| creator | HIRAOKA, Kei KIMURA, Takahiro LOGG, Christopher R KASAHARA, Noriyuki |
| description | Purpose: Replication-competent retrovirus (RCR) vectors have been shown to achieve highly efficient and tumor-restricted replicative
spread and gene transfer in vivo after direct intratumoral injection in a variety of primary cancer models. In this setting, the intrinsic inability of retroviruses
to infect postmitotic normal cells, combined with their unique ability to persist through stable integration, allow further
transduction of ectopic tumor foci as the infected cancer cells migrate. However, i.v. delivery of RCR vectors has never been
tested previously, particularly in an immunocompetent tumor model.
Experimental Design: We combined optical imaging, flow cytometry, and molecular analysis to monitor RCR vector spread after administration via
locoregional infusion in a hepatic metastasis model of colorectal cancer.
Results: Robust RCR replication was first confirmed in both human WiDr and murine CT26 colorectal cancer cells in vitro , with transduction levels reaching >90% in |
| doi_str_mv | 10.1158/1078-0432.CCR-06-1452 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8207453</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>68218250</sourcerecordid><originalsourceid>FETCH-LOGICAL-c570t-ce694d933e55cb25c43bcaf4162cc0e88181ccee676928adee87a6a83eaaef53</originalsourceid><addsrcrecordid>eNqFkl2L1DAUhoso7of-BCU3Cl50zUfTZG4EqeuuMIuwDt6GzJnTmUja1KQd3T-wv9uUGV29EgIJOc_75hzeFMULRi8Yk_oto0qXtBL8omluS1qXrJL8UXHKpFSl4LV8nM-_mZPiLKVvlLKK0eppccJUprWQp8X9aupCLL-gRxjdHskV9kgufw4RU3KhJ64nllzjYEcH5AZHm_JyidyEDXpi2xEjWQYIEbcZt558QJ994h0JbVbe4uAdZHHoyyZ0A47Yj_l2jGHv4pTI1_xuiM-KJ631CZ8f9_Ni9fFy1VyXy89Xn5r3yxKkomMJWC-qzUIIlBLWXEIl1mDbitUcgKLWTDMAxFrVC67tBlErW1st0FpspTgv3h1sh2nd4QZyL9F6M0TX2XhngnXm30rvdmYb9kZzqiopssHro0EM3ydMo-lcAvTe9himZGrNmeaS_hdkCy2VVLOjPIAQQ0oR2z_dMGrmpM2coplTNDlpQ2szJ511L_8e5UF1jDYDr46ATWB9G20PLj1wM1PRmXtz4HZuu_vhIhrIJMb8AdBG2BnGDRdGMarFLzf2w_0</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>19857573</pqid></control><display><type>article</type><title>Tumor-Selective Gene Expression in a Hepatic Metastasis Model after Locoregional Delivery of a Replication-Competent Retrovirus Vector</title><source>Freely Accessible Science Journals</source><creator>HIRAOKA, Kei ; KIMURA, Takahiro ; LOGG, Christopher R ; KASAHARA, Noriyuki</creator><creatorcontrib>HIRAOKA, Kei ; KIMURA, Takahiro ; LOGG, Christopher R ; KASAHARA, Noriyuki</creatorcontrib><description>Purpose: Replication-competent retrovirus (RCR) vectors have been shown to achieve highly efficient and tumor-restricted replicative
spread and gene transfer in vivo after direct intratumoral injection in a variety of primary cancer models. In this setting, the intrinsic inability of retroviruses
to infect postmitotic normal cells, combined with their unique ability to persist through stable integration, allow further
transduction of ectopic tumor foci as the infected cancer cells migrate. However, i.v. delivery of RCR vectors has never been
tested previously, particularly in an immunocompetent tumor model.
Experimental Design: We combined optical imaging, flow cytometry, and molecular analysis to monitor RCR vector spread after administration via
locoregional infusion in a hepatic metastasis model of colorectal cancer.
Results: Robust RCR replication was first confirmed in both human WiDr and murine CT26 colorectal cancer cells in vitro , with transduction levels reaching >90% in <12 days after virus inoculation at multiplicities of infection of 0.01 to 0.1.
In vivo , infusion of RCR supernatant into the portal circulation resulted in progressive and significant transduction of multifocal
intrahepatic CT26 tumors in syngeneic mice, averaging about 30% but with up to 60% transduction in some tumors within 4 weeks.
However, immunohistochemistry and quantitative PCR analysis showed no evidence of RCR spread to adjacent normal liver or to
any other normal tissues.
Conclusions: Our results thus show that locoregional infusion of RCR vectors can be used to deliver therapeutic genes selectively to tumor
cells in the liver while sparing normal hepatocytes and without dissemination to extrahepatic normal tissues.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>DOI: 10.1158/1078-0432.CCR-06-1452</identifier><identifier>PMID: 17145835</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Adenoviridae - genetics ; Animals ; Antineoplastic agents ; Biological and medical sciences ; Catheterization - methods ; Cell Line, Tumor ; colon cancer ; Colorectal Neoplasms - genetics ; Colorectal Neoplasms - therapy ; Colorectal Neoplasms - virology ; Disease Models, Animal ; Female ; Gastroenterology. Liver. Pancreas. Abdomen ; Gene Expression Profiling ; gene therapy ; Genetic Therapy - methods ; Genetic Vectors - administration & dosage ; Genetic Vectors - genetics ; Humans ; Infusions, Intralesional ; liver metastasis ; Liver Neoplasms, Experimental - genetics ; Liver Neoplasms, Experimental - secondary ; Liver Neoplasms, Experimental - therapy ; Liver. Biliary tract. Portal circulation. Exocrine pancreas ; Medical sciences ; Mice ; Mice, Nude ; molecular imaging ; oncolytic virotherapy ; Pharmacology. Drug treatments ; Predictive Value of Tests ; retrovirus ; Reverse Transcriptase Polymerase Chain Reaction - methods ; Transfection ; Transplantation, Heterologous ; Tumors ; Virus Replication ; Xenograft Model Antitumor Assays</subject><ispartof>Clinical cancer research, 2006-12, Vol.12 (23), p.7108-7116</ispartof><rights>2007 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c570t-ce694d933e55cb25c43bcaf4162cc0e88181ccee676928adee87a6a83eaaef53</citedby><cites>FETCH-LOGICAL-c570t-ce694d933e55cb25c43bcaf4162cc0e88181ccee676928adee87a6a83eaaef53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18353405$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17145835$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>HIRAOKA, Kei</creatorcontrib><creatorcontrib>KIMURA, Takahiro</creatorcontrib><creatorcontrib>LOGG, Christopher R</creatorcontrib><creatorcontrib>KASAHARA, Noriyuki</creatorcontrib><title>Tumor-Selective Gene Expression in a Hepatic Metastasis Model after Locoregional Delivery of a Replication-Competent Retrovirus Vector</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>Purpose: Replication-competent retrovirus (RCR) vectors have been shown to achieve highly efficient and tumor-restricted replicative
spread and gene transfer in vivo after direct intratumoral injection in a variety of primary cancer models. In this setting, the intrinsic inability of retroviruses
to infect postmitotic normal cells, combined with their unique ability to persist through stable integration, allow further
transduction of ectopic tumor foci as the infected cancer cells migrate. However, i.v. delivery of RCR vectors has never been
tested previously, particularly in an immunocompetent tumor model.
Experimental Design: We combined optical imaging, flow cytometry, and molecular analysis to monitor RCR vector spread after administration via
locoregional infusion in a hepatic metastasis model of colorectal cancer.
Results: Robust RCR replication was first confirmed in both human WiDr and murine CT26 colorectal cancer cells in vitro , with transduction levels reaching >90% in <12 days after virus inoculation at multiplicities of infection of 0.01 to 0.1.
In vivo , infusion of RCR supernatant into the portal circulation resulted in progressive and significant transduction of multifocal
intrahepatic CT26 tumors in syngeneic mice, averaging about 30% but with up to 60% transduction in some tumors within 4 weeks.
However, immunohistochemistry and quantitative PCR analysis showed no evidence of RCR spread to adjacent normal liver or to
any other normal tissues.
Conclusions: Our results thus show that locoregional infusion of RCR vectors can be used to deliver therapeutic genes selectively to tumor
cells in the liver while sparing normal hepatocytes and without dissemination to extrahepatic normal tissues.</description><subject>Adenoviridae - genetics</subject><subject>Animals</subject><subject>Antineoplastic agents</subject><subject>Biological and medical sciences</subject><subject>Catheterization - methods</subject><subject>Cell Line, Tumor</subject><subject>colon cancer</subject><subject>Colorectal Neoplasms - genetics</subject><subject>Colorectal Neoplasms - therapy</subject><subject>Colorectal Neoplasms - virology</subject><subject>Disease Models, Animal</subject><subject>Female</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Gene Expression Profiling</subject><subject>gene therapy</subject><subject>Genetic Therapy - methods</subject><subject>Genetic Vectors - administration & dosage</subject><subject>Genetic Vectors - genetics</subject><subject>Humans</subject><subject>Infusions, Intralesional</subject><subject>liver metastasis</subject><subject>Liver Neoplasms, Experimental - genetics</subject><subject>Liver Neoplasms, Experimental - secondary</subject><subject>Liver Neoplasms, Experimental - therapy</subject><subject>Liver. Biliary tract. Portal circulation. Exocrine pancreas</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>molecular imaging</subject><subject>oncolytic virotherapy</subject><subject>Pharmacology. Drug treatments</subject><subject>Predictive Value of Tests</subject><subject>retrovirus</subject><subject>Reverse Transcriptase Polymerase Chain Reaction - methods</subject><subject>Transfection</subject><subject>Transplantation, Heterologous</subject><subject>Tumors</subject><subject>Virus Replication</subject><subject>Xenograft Model Antitumor Assays</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><recordid>eNqFkl2L1DAUhoso7of-BCU3Cl50zUfTZG4EqeuuMIuwDt6GzJnTmUja1KQd3T-wv9uUGV29EgIJOc_75hzeFMULRi8Yk_oto0qXtBL8omluS1qXrJL8UXHKpFSl4LV8nM-_mZPiLKVvlLKK0eppccJUprWQp8X9aupCLL-gRxjdHskV9kgufw4RU3KhJ64nllzjYEcH5AZHm_JyidyEDXpi2xEjWQYIEbcZt558QJ994h0JbVbe4uAdZHHoyyZ0A47Yj_l2jGHv4pTI1_xuiM-KJ631CZ8f9_Ni9fFy1VyXy89Xn5r3yxKkomMJWC-qzUIIlBLWXEIl1mDbitUcgKLWTDMAxFrVC67tBlErW1st0FpspTgv3h1sh2nd4QZyL9F6M0TX2XhngnXm30rvdmYb9kZzqiopssHro0EM3ydMo-lcAvTe9himZGrNmeaS_hdkCy2VVLOjPIAQQ0oR2z_dMGrmpM2coplTNDlpQ2szJ511L_8e5UF1jDYDr46ATWB9G20PLj1wM1PRmXtz4HZuu_vhIhrIJMb8AdBG2BnGDRdGMarFLzf2w_0</recordid><startdate>20061201</startdate><enddate>20061201</enddate><creator>HIRAOKA, Kei</creator><creator>KIMURA, Takahiro</creator><creator>LOGG, Christopher R</creator><creator>KASAHARA, Noriyuki</creator><general>American Association for Cancer Research</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>7QO</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20061201</creationdate><title>Tumor-Selective Gene Expression in a Hepatic Metastasis Model after Locoregional Delivery of a Replication-Competent Retrovirus Vector</title><author>HIRAOKA, Kei ; KIMURA, Takahiro ; LOGG, Christopher R ; KASAHARA, Noriyuki</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c570t-ce694d933e55cb25c43bcaf4162cc0e88181ccee676928adee87a6a83eaaef53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Adenoviridae - genetics</topic><topic>Animals</topic><topic>Antineoplastic agents</topic><topic>Biological and medical sciences</topic><topic>Catheterization - methods</topic><topic>Cell Line, Tumor</topic><topic>colon cancer</topic><topic>Colorectal Neoplasms - genetics</topic><topic>Colorectal Neoplasms - therapy</topic><topic>Colorectal Neoplasms - virology</topic><topic>Disease Models, Animal</topic><topic>Female</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Gene Expression Profiling</topic><topic>gene therapy</topic><topic>Genetic Therapy - methods</topic><topic>Genetic Vectors - administration & dosage</topic><topic>Genetic Vectors - genetics</topic><topic>Humans</topic><topic>Infusions, Intralesional</topic><topic>liver metastasis</topic><topic>Liver Neoplasms, Experimental - genetics</topic><topic>Liver Neoplasms, Experimental - secondary</topic><topic>Liver Neoplasms, Experimental - therapy</topic><topic>Liver. Biliary tract. Portal circulation. Exocrine pancreas</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>molecular imaging</topic><topic>oncolytic virotherapy</topic><topic>Pharmacology. Drug treatments</topic><topic>Predictive Value of Tests</topic><topic>retrovirus</topic><topic>Reverse Transcriptase Polymerase Chain Reaction - methods</topic><topic>Transfection</topic><topic>Transplantation, Heterologous</topic><topic>Tumors</topic><topic>Virus Replication</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>HIRAOKA, Kei</creatorcontrib><creatorcontrib>KIMURA, Takahiro</creatorcontrib><creatorcontrib>LOGG, Christopher R</creatorcontrib><creatorcontrib>KASAHARA, Noriyuki</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>Biotechnology Research Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>HIRAOKA, Kei</au><au>KIMURA, Takahiro</au><au>LOGG, Christopher R</au><au>KASAHARA, Noriyuki</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Tumor-Selective Gene Expression in a Hepatic Metastasis Model after Locoregional Delivery of a Replication-Competent Retrovirus Vector</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2006-12-01</date><risdate>2006</risdate><volume>12</volume><issue>23</issue><spage>7108</spage><epage>7116</epage><pages>7108-7116</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><abstract>Purpose: Replication-competent retrovirus (RCR) vectors have been shown to achieve highly efficient and tumor-restricted replicative
spread and gene transfer in vivo after direct intratumoral injection in a variety of primary cancer models. In this setting, the intrinsic inability of retroviruses
to infect postmitotic normal cells, combined with their unique ability to persist through stable integration, allow further
transduction of ectopic tumor foci as the infected cancer cells migrate. However, i.v. delivery of RCR vectors has never been
tested previously, particularly in an immunocompetent tumor model.
Experimental Design: We combined optical imaging, flow cytometry, and molecular analysis to monitor RCR vector spread after administration via
locoregional infusion in a hepatic metastasis model of colorectal cancer.
Results: Robust RCR replication was first confirmed in both human WiDr and murine CT26 colorectal cancer cells in vitro , with transduction levels reaching >90% in <12 days after virus inoculation at multiplicities of infection of 0.01 to 0.1.
In vivo , infusion of RCR supernatant into the portal circulation resulted in progressive and significant transduction of multifocal
intrahepatic CT26 tumors in syngeneic mice, averaging about 30% but with up to 60% transduction in some tumors within 4 weeks.
However, immunohistochemistry and quantitative PCR analysis showed no evidence of RCR spread to adjacent normal liver or to
any other normal tissues.
Conclusions: Our results thus show that locoregional infusion of RCR vectors can be used to deliver therapeutic genes selectively to tumor
cells in the liver while sparing normal hepatocytes and without dissemination to extrahepatic normal tissues.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>17145835</pmid><doi>10.1158/1078-0432.CCR-06-1452</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Clinical cancer research, 2006-12, Vol.12 (23), p.7108-7116 |
| issn | 1078-0432 1557-3265 |
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| source | Freely Accessible Science Journals |
| subjects | Adenoviridae - genetics Animals Antineoplastic agents Biological and medical sciences Catheterization - methods Cell Line, Tumor colon cancer Colorectal Neoplasms - genetics Colorectal Neoplasms - therapy Colorectal Neoplasms - virology Disease Models, Animal Female Gastroenterology. Liver. Pancreas. Abdomen Gene Expression Profiling gene therapy Genetic Therapy - methods Genetic Vectors - administration & dosage Genetic Vectors - genetics Humans Infusions, Intralesional liver metastasis Liver Neoplasms, Experimental - genetics Liver Neoplasms, Experimental - secondary Liver Neoplasms, Experimental - therapy Liver. Biliary tract. Portal circulation. Exocrine pancreas Medical sciences Mice Mice, Nude molecular imaging oncolytic virotherapy Pharmacology. Drug treatments Predictive Value of Tests retrovirus Reverse Transcriptase Polymerase Chain Reaction - methods Transfection Transplantation, Heterologous Tumors Virus Replication Xenograft Model Antitumor Assays |
| title | Tumor-Selective Gene Expression in a Hepatic Metastasis Model after Locoregional Delivery of a Replication-Competent Retrovirus Vector |
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