Prolonged survival of mice with multiple liver metastases of human colon cancer by intravenous administration of replicable E1B-55K-deleted adenovirus with E1A expressed by CEA promoter
Liver is the most preferential site for metastasis of colon cancer. We, in the present study, constructed a self-replicable adenovirus in which E1A is driven by a CEA promoter and E1B-55K is deleted from the E1B region (AdCEAp/Rep) and examined its effects on multiple metastases of a human colon can...
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| Veröffentlicht in: | Molecular therapy 2004-12, Vol.10 (6), p.1043-1050 |
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| creator | Sagawa, Tamotsu Takahashi, Minoru Sato, Tsutomu Sato, Yasushi Lu, Yue Sumiyoshi, Tetsuya Yamada, Yasuyuki Iyama, Satoshi Fukaura, Junki Sasaki, Katsunori Hamada, Hirofumi Miyanishi, Koji Takayama, Tetsuji Kato, Junji Niitsu, Yoshiro |
| description | Liver is the most preferential site for metastasis of colon cancer. We, in the present study, constructed a self-replicable adenovirus in which E1A is driven by a CEA promoter and E1B-55K is deleted from the E1B region (AdCEAp/Rep) and examined its effects on multiple metastases of a human colon cancer cell in a mouse xenograft model. We first showed effective replication of the virus in various CEA-producing human colon cancer cells (M7609, HT-29) and subsequent lysis of the infected cells in vitro. We then demonstrated that a single intratumoral injection of the virus (1 x 10(8) PFU/100 microl) induced a complete regression of subcutaneous tumors (M7609) inoculated into nude mice. Further, we demonstrated that systemic administration of the virus (1 x 10(8) PFU/100 microl) through the tail vein to nude mice, which 1 week prior had been inoculated with tumor cells (colon carcinoma cell line HT-29) via the spleen and showed apparent multiple metastases in the liver, effectively suppressed the metastasis formation. The mean survival time of the treated mice was significantly longer than that of the controls. Thus, the systemic administration of AdCEAp/Rep was considered to be effective on multiple liver metastases of CEA-positive colon cancer in a xenograft model. |
| doi_str_mv | 10.1016/j.ymthe.2004.08.023 |
| format | Article |
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We, in the present study, constructed a self-replicable adenovirus in which E1A is driven by a CEA promoter and E1B-55K is deleted from the E1B region (AdCEAp/Rep) and examined its effects on multiple metastases of a human colon cancer cell in a mouse xenograft model. We first showed effective replication of the virus in various CEA-producing human colon cancer cells (M7609, HT-29) and subsequent lysis of the infected cells in vitro. We then demonstrated that a single intratumoral injection of the virus (1 x 10(8) PFU/100 microl) induced a complete regression of subcutaneous tumors (M7609) inoculated into nude mice. Further, we demonstrated that systemic administration of the virus (1 x 10(8) PFU/100 microl) through the tail vein to nude mice, which 1 week prior had been inoculated with tumor cells (colon carcinoma cell line HT-29) via the spleen and showed apparent multiple metastases in the liver, effectively suppressed the metastasis formation. The mean survival time of the treated mice was significantly longer than that of the controls. Thus, the systemic administration of AdCEAp/Rep was considered to be effective on multiple liver metastases of CEA-positive colon cancer in a xenograft model.</description><identifier>ISSN: 1525-0016</identifier><identifier>EISSN: 1525-0024</identifier><identifier>DOI: 10.1016/j.ymthe.2004.08.023</identifier><identifier>PMID: 15564136</identifier><language>eng</language><publisher>United States: Elsevier Limited</publisher><subject>Adenoviridae - genetics ; Adenoviridae - physiology ; Adenovirus E1A Proteins - genetics ; Adenovirus E1A Proteins - metabolism ; Adenovirus E1B Proteins - deficiency ; Adenovirus E1B Proteins - genetics ; Adenoviruses ; Animals ; Cancer therapies ; Carcinoembryonic Antigen - analysis ; Carcinoembryonic Antigen - biosynthesis ; Carcinoembryonic Antigen - genetics ; Colonic Neoplasms - genetics ; Colonic Neoplasms - pathology ; Colonic Neoplasms - therapy ; Colorectal cancer ; Cytotoxicity ; Disease Models, Animal ; Female ; Gene Deletion ; Gene therapy ; Genetic Therapy ; Hepatocytes - metabolism ; Humans ; Infections ; Infusions, Intravenous ; Liver ; Liver Neoplasms - genetics ; Liver Neoplasms - pathology ; Liver Neoplasms - secondary ; Liver Neoplasms - therapy ; Medical prognosis ; Medical research ; Metastasis ; Mice ; Neoplasm Transplantation ; Promoter Regions, Genetic - genetics ; Skin Neoplasms - genetics ; Skin Neoplasms - pathology ; Skin Neoplasms - secondary ; Skin Neoplasms - therapy ; Survival Rate ; Time Factors ; Tumor Cells, Cultured ; Tumors ; Virus Replication</subject><ispartof>Molecular therapy, 2004-12, Vol.10 (6), p.1043-1050</ispartof><rights>Copyright Nature Publishing Group Dec 2004</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c376t-ae127256a20874c6ad0160ff32a042c312b1b6bccae8e493b3971dac131d85ef3</citedby><cites>FETCH-LOGICAL-c376t-ae127256a20874c6ad0160ff32a042c312b1b6bccae8e493b3971dac131d85ef3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15564136$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sagawa, Tamotsu</creatorcontrib><creatorcontrib>Takahashi, Minoru</creatorcontrib><creatorcontrib>Sato, Tsutomu</creatorcontrib><creatorcontrib>Sato, Yasushi</creatorcontrib><creatorcontrib>Lu, Yue</creatorcontrib><creatorcontrib>Sumiyoshi, Tetsuya</creatorcontrib><creatorcontrib>Yamada, Yasuyuki</creatorcontrib><creatorcontrib>Iyama, Satoshi</creatorcontrib><creatorcontrib>Fukaura, Junki</creatorcontrib><creatorcontrib>Sasaki, Katsunori</creatorcontrib><creatorcontrib>Hamada, Hirofumi</creatorcontrib><creatorcontrib>Miyanishi, Koji</creatorcontrib><creatorcontrib>Takayama, Tetsuji</creatorcontrib><creatorcontrib>Kato, Junji</creatorcontrib><creatorcontrib>Niitsu, Yoshiro</creatorcontrib><title>Prolonged survival of mice with multiple liver metastases of human colon cancer by intravenous administration of replicable E1B-55K-deleted adenovirus with E1A expressed by CEA promoter</title><title>Molecular therapy</title><addtitle>Mol Ther</addtitle><description>Liver is the most preferential site for metastasis of colon cancer. We, in the present study, constructed a self-replicable adenovirus in which E1A is driven by a CEA promoter and E1B-55K is deleted from the E1B region (AdCEAp/Rep) and examined its effects on multiple metastases of a human colon cancer cell in a mouse xenograft model. We first showed effective replication of the virus in various CEA-producing human colon cancer cells (M7609, HT-29) and subsequent lysis of the infected cells in vitro. We then demonstrated that a single intratumoral injection of the virus (1 x 10(8) PFU/100 microl) induced a complete regression of subcutaneous tumors (M7609) inoculated into nude mice. Further, we demonstrated that systemic administration of the virus (1 x 10(8) PFU/100 microl) through the tail vein to nude mice, which 1 week prior had been inoculated with tumor cells (colon carcinoma cell line HT-29) via the spleen and showed apparent multiple metastases in the liver, effectively suppressed the metastasis formation. The mean survival time of the treated mice was significantly longer than that of the controls. Thus, the systemic administration of AdCEAp/Rep was considered to be effective on multiple liver metastases of CEA-positive colon cancer in a xenograft model.</description><subject>Adenoviridae - genetics</subject><subject>Adenoviridae - physiology</subject><subject>Adenovirus E1A Proteins - genetics</subject><subject>Adenovirus E1A Proteins - metabolism</subject><subject>Adenovirus E1B Proteins - deficiency</subject><subject>Adenovirus E1B Proteins - genetics</subject><subject>Adenoviruses</subject><subject>Animals</subject><subject>Cancer therapies</subject><subject>Carcinoembryonic Antigen - analysis</subject><subject>Carcinoembryonic Antigen - biosynthesis</subject><subject>Carcinoembryonic Antigen - genetics</subject><subject>Colonic Neoplasms - genetics</subject><subject>Colonic Neoplasms - pathology</subject><subject>Colonic Neoplasms - therapy</subject><subject>Colorectal cancer</subject><subject>Cytotoxicity</subject><subject>Disease Models, Animal</subject><subject>Female</subject><subject>Gene Deletion</subject><subject>Gene therapy</subject><subject>Genetic Therapy</subject><subject>Hepatocytes - metabolism</subject><subject>Humans</subject><subject>Infections</subject><subject>Infusions, Intravenous</subject><subject>Liver</subject><subject>Liver Neoplasms - genetics</subject><subject>Liver Neoplasms - pathology</subject><subject>Liver Neoplasms - secondary</subject><subject>Liver Neoplasms - therapy</subject><subject>Medical prognosis</subject><subject>Medical research</subject><subject>Metastasis</subject><subject>Mice</subject><subject>Neoplasm Transplantation</subject><subject>Promoter Regions, Genetic - genetics</subject><subject>Skin Neoplasms - genetics</subject><subject>Skin Neoplasms - pathology</subject><subject>Skin Neoplasms - secondary</subject><subject>Skin Neoplasms - therapy</subject><subject>Survival Rate</subject><subject>Time Factors</subject><subject>Tumor Cells, Cultured</subject><subject>Tumors</subject><subject>Virus Replication</subject><issn>1525-0016</issn><issn>1525-0024</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNpdkd-K1DAUxoso7rr6BIIEBO9ac5I27VyOw_gHF_RCr0OanjoZkrYmbd15NN_OM7uDghDIIfl93znJl2UvgRfAQb09FqcwH7AQnJcFbwou5KPsGipR5ZyL8vHfGtRV9iylI1VQbdTT7AqqSpUg1XX2-2sc_Tj8wI6lJa5uNZ6NPQvOIvvl5gMLi5_d5JF5t2JkAWeTaGE6Y4clmIHZswOzZrAEtCfmhjmaFYdxScx0wQ0u0cHsCCJNxMk7a1qy3MO7vKo-5x16nGkC05FodZF09733sGV4N0VMiW7JebffsimOYZwxPs-e9MYnfHHZb7Lv7_ffdh_z2y8fPu22t7mVtZpzgyBqUSkjeFOXVpmO_oP3vRSGl8JKEC20qrXWYIPlRrZyU0NnLEjomgp7eZO9efClxj8XTLMOLln03gxIL9SqBk4RbAh8_R94HJc40Gwa6o1oAOq6JEo-UDaOKUXs9RRdMPGkgetzrvqo73PV51w1bzTlSqpXF--lDdj901yClH8A5W2jLQ</recordid><startdate>200412</startdate><enddate>200412</enddate><creator>Sagawa, Tamotsu</creator><creator>Takahashi, Minoru</creator><creator>Sato, Tsutomu</creator><creator>Sato, Yasushi</creator><creator>Lu, Yue</creator><creator>Sumiyoshi, Tetsuya</creator><creator>Yamada, Yasuyuki</creator><creator>Iyama, Satoshi</creator><creator>Fukaura, Junki</creator><creator>Sasaki, Katsunori</creator><creator>Hamada, Hirofumi</creator><creator>Miyanishi, Koji</creator><creator>Takayama, Tetsuji</creator><creator>Kato, Junji</creator><creator>Niitsu, Yoshiro</creator><general>Elsevier Limited</general><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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>200412</creationdate><title>Prolonged survival of mice with multiple liver metastases of human colon cancer by intravenous administration of replicable E1B-55K-deleted adenovirus with E1A expressed by CEA promoter</title><author>Sagawa, Tamotsu ; Takahashi, Minoru ; Sato, Tsutomu ; Sato, Yasushi ; Lu, Yue ; Sumiyoshi, Tetsuya ; Yamada, Yasuyuki ; Iyama, Satoshi ; Fukaura, Junki ; Sasaki, Katsunori ; Hamada, Hirofumi ; Miyanishi, Koji ; Takayama, Tetsuji ; Kato, Junji ; Niitsu, Yoshiro</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c376t-ae127256a20874c6ad0160ff32a042c312b1b6bccae8e493b3971dac131d85ef3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Adenoviridae - 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Academic</collection><jtitle>Molecular therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sagawa, Tamotsu</au><au>Takahashi, Minoru</au><au>Sato, Tsutomu</au><au>Sato, Yasushi</au><au>Lu, Yue</au><au>Sumiyoshi, Tetsuya</au><au>Yamada, Yasuyuki</au><au>Iyama, Satoshi</au><au>Fukaura, Junki</au><au>Sasaki, Katsunori</au><au>Hamada, Hirofumi</au><au>Miyanishi, Koji</au><au>Takayama, Tetsuji</au><au>Kato, Junji</au><au>Niitsu, Yoshiro</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Prolonged survival of mice with multiple liver metastases of human colon cancer by intravenous administration of replicable E1B-55K-deleted adenovirus with E1A expressed by CEA promoter</atitle><jtitle>Molecular therapy</jtitle><addtitle>Mol Ther</addtitle><date>2004-12</date><risdate>2004</risdate><volume>10</volume><issue>6</issue><spage>1043</spage><epage>1050</epage><pages>1043-1050</pages><issn>1525-0016</issn><eissn>1525-0024</eissn><abstract>Liver is the most preferential site for metastasis of colon cancer. We, in the present study, constructed a self-replicable adenovirus in which E1A is driven by a CEA promoter and E1B-55K is deleted from the E1B region (AdCEAp/Rep) and examined its effects on multiple metastases of a human colon cancer cell in a mouse xenograft model. We first showed effective replication of the virus in various CEA-producing human colon cancer cells (M7609, HT-29) and subsequent lysis of the infected cells in vitro. We then demonstrated that a single intratumoral injection of the virus (1 x 10(8) PFU/100 microl) induced a complete regression of subcutaneous tumors (M7609) inoculated into nude mice. Further, we demonstrated that systemic administration of the virus (1 x 10(8) PFU/100 microl) through the tail vein to nude mice, which 1 week prior had been inoculated with tumor cells (colon carcinoma cell line HT-29) via the spleen and showed apparent multiple metastases in the liver, effectively suppressed the metastasis formation. The mean survival time of the treated mice was significantly longer than that of the controls. Thus, the systemic administration of AdCEAp/Rep was considered to be effective on multiple liver metastases of CEA-positive colon cancer in a xenograft model.</abstract><cop>United States</cop><pub>Elsevier Limited</pub><pmid>15564136</pmid><doi>10.1016/j.ymthe.2004.08.023</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Molecular therapy, 2004-12, Vol.10 (6), p.1043-1050 |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Adenoviridae - genetics Adenoviridae - physiology Adenovirus E1A Proteins - genetics Adenovirus E1A Proteins - metabolism Adenovirus E1B Proteins - deficiency Adenovirus E1B Proteins - genetics Adenoviruses Animals Cancer therapies Carcinoembryonic Antigen - analysis Carcinoembryonic Antigen - biosynthesis Carcinoembryonic Antigen - genetics Colonic Neoplasms - genetics Colonic Neoplasms - pathology Colonic Neoplasms - therapy Colorectal cancer Cytotoxicity Disease Models, Animal Female Gene Deletion Gene therapy Genetic Therapy Hepatocytes - metabolism Humans Infections Infusions, Intravenous Liver Liver Neoplasms - genetics Liver Neoplasms - pathology Liver Neoplasms - secondary Liver Neoplasms - therapy Medical prognosis Medical research Metastasis Mice Neoplasm Transplantation Promoter Regions, Genetic - genetics Skin Neoplasms - genetics Skin Neoplasms - pathology Skin Neoplasms - secondary Skin Neoplasms - therapy Survival Rate Time Factors Tumor Cells, Cultured Tumors Virus Replication |
| title | Prolonged survival of mice with multiple liver metastases of human colon cancer by intravenous administration of replicable E1B-55K-deleted adenovirus with E1A expressed by CEA promoter |
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