Antitumor activity of an hTERT promoter-regulated tumor-selective oncolytic adenovirus in human hepatocellular carcinoma
AIM: To construct a tumor-selective replicationcompetent adenovirus (RCAd), SG300, using a modified promoter of human telomerase reverse transcriptase (hTERT). METHODS: The antitumor efficacy of SG300 in hepatocellular carcinoma was assessed in vitro and in vivo. In vitro cell viability by MTT assay...
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Veröffentlicht in: | World journal of gastroenterology : WJG 2006-12, Vol.12 (47), p.7613-7620 |
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creator | Su, Chang-Qing Wang, Xing-Hua Chen, Jie Liu, Yong-Jing Wang, Wei-Guo Li, Lin-Fang Wu, Meng-Chao Qian, Qi-Jun |
description | AIM: To construct a tumor-selective replicationcompetent adenovirus (RCAd), SG300, using a modified promoter of human telomerase reverse transcriptase (hTERT).
METHODS: The antitumor efficacy of SG300 in hepatocellular carcinoma was assessed in vitro and in vivo. In vitro cell viability by MTT assay was used to assess the tumor-selective oncolysis and safety features of SG300, and in vivo antitumor activity of SG300 was assessed in established hepatocellular carcinoma models in nude mice.
RESULTS: SG300 could lyse hepatocellular carcinoma cells at a low multiplicity of infection (MOI), but could not affect growth of normal cells even at a high MOI. Both in Hep3B and SMMC-7721 xenograft models of hepatocellular carcinoma, SG300 had an obvious antitumor effect, resulting in a decrease in tumor volume. Its selective oncolysis to tumor cells and safety to normal cells was also superior to that of ONYX-015. Pathological examination of tumor specimens showed that SG300 replicated selectively in cancer cells and resulted in apoptosis and necrosis of cancer cells.
CONCLUSION: hTERT promoter-regulated replicative adenovirus SG300 has a better cancer-selective replication-competent ability, and can specifically kill a wide range of cancer cells with positive telomerase activity, and thus has better potential for targeting therapy of hepatocellular carcinoma. |
doi_str_mv | 10.3748/wjg.v12.i47.7613 |
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METHODS: The antitumor efficacy of SG300 in hepatocellular carcinoma was assessed in vitro and in vivo. In vitro cell viability by MTT assay was used to assess the tumor-selective oncolysis and safety features of SG300, and in vivo antitumor activity of SG300 was assessed in established hepatocellular carcinoma models in nude mice.
RESULTS: SG300 could lyse hepatocellular carcinoma cells at a low multiplicity of infection (MOI), but could not affect growth of normal cells even at a high MOI. Both in Hep3B and SMMC-7721 xenograft models of hepatocellular carcinoma, SG300 had an obvious antitumor effect, resulting in a decrease in tumor volume. Its selective oncolysis to tumor cells and safety to normal cells was also superior to that of ONYX-015. Pathological examination of tumor specimens showed that SG300 replicated selectively in cancer cells and resulted in apoptosis and necrosis of cancer cells.
CONCLUSION: hTERT promoter-regulated replicative adenovirus SG300 has a better cancer-selective replication-competent ability, and can specifically kill a wide range of cancer cells with positive telomerase activity, and thus has better potential for targeting therapy of hepatocellular carcinoma.</description><identifier>ISSN: 1007-9327</identifier><identifier>EISSN: 2219-2840</identifier><identifier>DOI: 10.3748/wjg.v12.i47.7613</identifier><identifier>PMID: 17171789</identifier><language>eng</language><publisher>United States: Laboratory of Viral and Gene Therapy, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China</publisher><subject>Adenoviridae - genetics ; Animals ; Carcinoma, Hepatocellular - pathology ; Carcinoma, Hepatocellular - therapy ; Cell Line, Tumor ; Humans ; Liver Cancer ; Liver Neoplasms - pathology ; Liver Neoplasms - therapy ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Oncolytic Virotherapy - methods ; Oncolytic Viruses - genetics ; Promoter Regions, Genetic ; Telomerase - genetics ; Xenograft Model Antitumor Assays ; 抗癌活性 ; 溶癌作用 ; 癌细胞 ; 腺病毒</subject><ispartof>World journal of gastroenterology : WJG, 2006-12, Vol.12 (47), p.7613-7620</ispartof><rights>Copyright © Wanfang Data Co. Ltd. All Rights Reserved.</rights><rights>2006 Baishideng Publishing Group Co., Limited. All rights reserved. 2006</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c450t-1c5b240dd238edd75d4031047cc425ec8ce3e9039ae3c69d10fb60dd17c47103</citedby><cites>FETCH-LOGICAL-c450t-1c5b240dd238edd75d4031047cc425ec8ce3e9039ae3c69d10fb60dd17c47103</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://image.cqvip.com/vip1000/qk/84123X/84123X.jpg</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4088042/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4088042/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27903,27904,53769,53771</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17171789$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Su, Chang-Qing</creatorcontrib><creatorcontrib>Wang, Xing-Hua</creatorcontrib><creatorcontrib>Chen, Jie</creatorcontrib><creatorcontrib>Liu, Yong-Jing</creatorcontrib><creatorcontrib>Wang, Wei-Guo</creatorcontrib><creatorcontrib>Li, Lin-Fang</creatorcontrib><creatorcontrib>Wu, Meng-Chao</creatorcontrib><creatorcontrib>Qian, Qi-Jun</creatorcontrib><title>Antitumor activity of an hTERT promoter-regulated tumor-selective oncolytic adenovirus in human hepatocellular carcinoma</title><title>World journal of gastroenterology : WJG</title><addtitle>World Journal of Gastroenterology</addtitle><description>AIM: To construct a tumor-selective replicationcompetent adenovirus (RCAd), SG300, using a modified promoter of human telomerase reverse transcriptase (hTERT).
METHODS: The antitumor efficacy of SG300 in hepatocellular carcinoma was assessed in vitro and in vivo. In vitro cell viability by MTT assay was used to assess the tumor-selective oncolysis and safety features of SG300, and in vivo antitumor activity of SG300 was assessed in established hepatocellular carcinoma models in nude mice.
RESULTS: SG300 could lyse hepatocellular carcinoma cells at a low multiplicity of infection (MOI), but could not affect growth of normal cells even at a high MOI. Both in Hep3B and SMMC-7721 xenograft models of hepatocellular carcinoma, SG300 had an obvious antitumor effect, resulting in a decrease in tumor volume. Its selective oncolysis to tumor cells and safety to normal cells was also superior to that of ONYX-015. Pathological examination of tumor specimens showed that SG300 replicated selectively in cancer cells and resulted in apoptosis and necrosis of cancer cells.
CONCLUSION: hTERT promoter-regulated replicative adenovirus SG300 has a better cancer-selective replication-competent ability, and can specifically kill a wide range of cancer cells with positive telomerase activity, and thus has better potential for targeting therapy of hepatocellular carcinoma.</description><subject>Adenoviridae - genetics</subject><subject>Animals</subject><subject>Carcinoma, Hepatocellular - pathology</subject><subject>Carcinoma, Hepatocellular - therapy</subject><subject>Cell Line, Tumor</subject><subject>Humans</subject><subject>Liver Cancer</subject><subject>Liver Neoplasms - pathology</subject><subject>Liver Neoplasms - therapy</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Nude</subject><subject>Oncolytic Virotherapy - methods</subject><subject>Oncolytic Viruses - genetics</subject><subject>Promoter Regions, Genetic</subject><subject>Telomerase - genetics</subject><subject>Xenograft Model Antitumor Assays</subject><subject>抗癌活性</subject><subject>溶癌作用</subject><subject>癌细胞</subject><subject>腺病毒</subject><issn>1007-9327</issn><issn>2219-2840</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkUuP0zAUhSMEYsrAnhWyEGKXcv1InGyQRqPhIY2EhLq3XOcmdUnsju106L_HoRUPeeGFz_l87j1F8ZrCmkvRfHjcD-sjZWsr5FrWlD8pVozRtmSNgKfFigLIsuVMXhUvYtwDMM4r9ry4onI5Tbsqft64ZNM8-UC0SfZo04n4nmhHdpu77xtyCH7yCUMZcJhHnbAjv9VlxBEXAxLvjB9PyRqiO3T-aMMcic2AeVoweNDJGxzHbA_E6GCs85N-WTzr9Rjx1eW-Ljaf7ja3X8r7b5-_3t7cl0ZUkEpqqi0T0HWMN9h1suoEcApCGiNYhaYxyLEF3mrkpm47Cv22znIqjZAU-HXx8Yw9zNsJO4MuBT2qQ7CTDifltVX_vzi7U4M_KgFNA4JlwLsz4FG7XrtB7f0cXE6s8vIZQC0kQJNl7y__BP8wY0xqsnGZWjv0c1R1wyoqqzYL4Sw0wccYsP-ThYJaSl24KpeqcqlqKTVb3vw7w1_DpcUseHth7rwbHmxOudXmR29HVIxXVdvWwH8BkpSt-Q</recordid><startdate>20061221</startdate><enddate>20061221</enddate><creator>Su, Chang-Qing</creator><creator>Wang, Xing-Hua</creator><creator>Chen, Jie</creator><creator>Liu, Yong-Jing</creator><creator>Wang, Wei-Guo</creator><creator>Li, Lin-Fang</creator><creator>Wu, Meng-Chao</creator><creator>Qian, Qi-Jun</creator><general>Laboratory of Viral and Gene Therapy, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China</general><general>Jiangsu Key Laboratory for Molecular and Medical Biotechnology, Life Science College, Nanjing Normal University, Nanjing 210097, Jiangsu Province, China%Changhai Hospital, Second Military Medical University, Shanghai 200438, China%Laboratory of Viral and Gene Therapy, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China%Laboratory of Viral and Gene Therapy, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China</general><general>Xinyuan Institute of Medicine and Biotechnology,College of Life Science, Zhejiang Sci-Tech University, Hangzhou 310018, Zhejiang Province, China</general><general>Baishideng Publishing Group Co., Limited</general><scope>2RA</scope><scope>92L</scope><scope>CQIGP</scope><scope>W91</scope><scope>~WA</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><scope>2B.</scope><scope>4A8</scope><scope>92I</scope><scope>93N</scope><scope>PSX</scope><scope>TCJ</scope><scope>5PM</scope></search><sort><creationdate>20061221</creationdate><title>Antitumor activity of an hTERT promoter-regulated tumor-selective oncolytic adenovirus in human hepatocellular carcinoma</title><author>Su, Chang-Qing ; Wang, Xing-Hua ; Chen, Jie ; Liu, Yong-Jing ; Wang, Wei-Guo ; Li, Lin-Fang ; Wu, Meng-Chao ; Qian, Qi-Jun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c450t-1c5b240dd238edd75d4031047cc425ec8ce3e9039ae3c69d10fb60dd17c47103</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Adenoviridae - genetics</topic><topic>Animals</topic><topic>Carcinoma, Hepatocellular - pathology</topic><topic>Carcinoma, Hepatocellular - therapy</topic><topic>Cell Line, Tumor</topic><topic>Humans</topic><topic>Liver Cancer</topic><topic>Liver Neoplasms - pathology</topic><topic>Liver Neoplasms - therapy</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Nude</topic><topic>Oncolytic Virotherapy - methods</topic><topic>Oncolytic Viruses - genetics</topic><topic>Promoter Regions, Genetic</topic><topic>Telomerase - genetics</topic><topic>Xenograft Model Antitumor Assays</topic><topic>抗癌活性</topic><topic>溶癌作用</topic><topic>癌细胞</topic><topic>腺病毒</topic><toplevel>online_resources</toplevel><creatorcontrib>Su, Chang-Qing</creatorcontrib><creatorcontrib>Wang, Xing-Hua</creatorcontrib><creatorcontrib>Chen, Jie</creatorcontrib><creatorcontrib>Liu, Yong-Jing</creatorcontrib><creatorcontrib>Wang, Wei-Guo</creatorcontrib><creatorcontrib>Li, Lin-Fang</creatorcontrib><creatorcontrib>Wu, Meng-Chao</creatorcontrib><creatorcontrib>Qian, Qi-Jun</creatorcontrib><collection>中文科技期刊数据库</collection><collection>中文科技期刊数据库-CALIS站点</collection><collection>中文科技期刊数据库-7.0平台</collection><collection>中文科技期刊数据库-医药卫生</collection><collection>中文科技期刊数据库- 镜像站点</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><collection>Wanfang Data Journals - Hong Kong</collection><collection>WANFANG Data Centre</collection><collection>Wanfang Data Journals</collection><collection>万方数据期刊 - 香港版</collection><collection>China Online Journals (COJ)</collection><collection>China Online Journals (COJ)</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>World journal of gastroenterology : WJG</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Su, Chang-Qing</au><au>Wang, Xing-Hua</au><au>Chen, Jie</au><au>Liu, Yong-Jing</au><au>Wang, Wei-Guo</au><au>Li, Lin-Fang</au><au>Wu, Meng-Chao</au><au>Qian, Qi-Jun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Antitumor activity of an hTERT promoter-regulated tumor-selective oncolytic adenovirus in human hepatocellular carcinoma</atitle><jtitle>World journal of gastroenterology : WJG</jtitle><addtitle>World Journal of Gastroenterology</addtitle><date>2006-12-21</date><risdate>2006</risdate><volume>12</volume><issue>47</issue><spage>7613</spage><epage>7620</epage><pages>7613-7620</pages><issn>1007-9327</issn><eissn>2219-2840</eissn><abstract>AIM: To construct a tumor-selective replicationcompetent adenovirus (RCAd), SG300, using a modified promoter of human telomerase reverse transcriptase (hTERT).
METHODS: The antitumor efficacy of SG300 in hepatocellular carcinoma was assessed in vitro and in vivo. In vitro cell viability by MTT assay was used to assess the tumor-selective oncolysis and safety features of SG300, and in vivo antitumor activity of SG300 was assessed in established hepatocellular carcinoma models in nude mice.
RESULTS: SG300 could lyse hepatocellular carcinoma cells at a low multiplicity of infection (MOI), but could not affect growth of normal cells even at a high MOI. Both in Hep3B and SMMC-7721 xenograft models of hepatocellular carcinoma, SG300 had an obvious antitumor effect, resulting in a decrease in tumor volume. Its selective oncolysis to tumor cells and safety to normal cells was also superior to that of ONYX-015. Pathological examination of tumor specimens showed that SG300 replicated selectively in cancer cells and resulted in apoptosis and necrosis of cancer cells.
CONCLUSION: hTERT promoter-regulated replicative adenovirus SG300 has a better cancer-selective replication-competent ability, and can specifically kill a wide range of cancer cells with positive telomerase activity, and thus has better potential for targeting therapy of hepatocellular carcinoma.</abstract><cop>United States</cop><pub>Laboratory of Viral and Gene Therapy, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China</pub><pmid>17171789</pmid><doi>10.3748/wjg.v12.i47.7613</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adenoviridae - genetics Animals Carcinoma, Hepatocellular - pathology Carcinoma, Hepatocellular - therapy Cell Line, Tumor Humans Liver Cancer Liver Neoplasms - pathology Liver Neoplasms - therapy Mice Mice, Inbred BALB C Mice, Nude Oncolytic Virotherapy - methods Oncolytic Viruses - genetics Promoter Regions, Genetic Telomerase - genetics Xenograft Model Antitumor Assays 抗癌活性 溶癌作用 癌细胞 腺病毒 |
title | Antitumor activity of an hTERT promoter-regulated tumor-selective oncolytic adenovirus in human hepatocellular carcinoma |
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