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Gene Therapy for Brain Tumors: Regression of Experimental Gliomas by Adenovirus-Mediated Gene Transfer in vivo
The therapeutic efficacy of adenovirus-mediated herpes simplex virus thymidine kinase (HSV-tk) gene transduction of rat C6glioma cells followed by ganciclovir (GCV) administration was studied in tumors generated in the brains of nude mice. C6glioma cells were efficiently transduced in vitro by a rep...
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| Published in: | Proceedings of the National Academy of Sciences - PNAS 1994-04, Vol.91 (8), p.3054-3057 |
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| cited_by | cdi_FETCH-LOGICAL-c641t-eef69430f00bed5197a3443a44d3a73c2b6486ea19dc398a16051460788424043 |
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| container_end_page | 3057 |
| container_issue | 8 |
| container_start_page | 3054 |
| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Chen, S H Shine, H D Goodman, J C Grossman, R G Woo, S L |
| description | The therapeutic efficacy of adenovirus-mediated herpes simplex virus thymidine kinase (HSV-tk) gene transduction of rat C6glioma cells followed by ganciclovir (GCV) administration was studied in tumors generated in the brains of nude mice. C6glioma cells were efficiently transduced in vitro by a replicative-defective recombinant adenovirus carrying the HSV-tk gene (ADV/RSV-tk) that rendered them sensitive to GCV in a dose-dependent manner. Tumors were generated by stereotaxic intracerebral injection of 1 x 104C6cells in nude mice. After 8 days of tumor growth, 3 x 108ADV/RSV-tk viral particles were injected into the tumors and the mice subsequently were treated with GCV for 6 days. Tumor size in untreated and treated animals was compared 20 days after tumor implantation. The mean cross-sectional area of the tumors in the treated animals was 23-fold smaller than in control animals and the tumor volume was reduced by >500-fold. These results demonstrate that the recombinant adenoviral vector can function as an efficient gene delivery vehicle for the treatment of gliomas by in vivo gene therapy. |
| doi_str_mv | 10.1073/pnas.91.8.3054 |
| format | article |
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C6glioma cells were efficiently transduced in vitro by a replicative-defective recombinant adenovirus carrying the HSV-tk gene (ADV/RSV-tk) that rendered them sensitive to GCV in a dose-dependent manner. Tumors were generated by stereotaxic intracerebral injection of 1 x 104C6cells in nude mice. After 8 days of tumor growth, 3 x 108ADV/RSV-tk viral particles were injected into the tumors and the mice subsequently were treated with GCV for 6 days. Tumor size in untreated and treated animals was compared 20 days after tumor implantation. The mean cross-sectional area of the tumors in the treated animals was 23-fold smaller than in control animals and the tumor volume was reduced by >500-fold. These results demonstrate that the recombinant adenoviral vector can function as an efficient gene delivery vehicle for the treatment of gliomas by in vivo gene therapy.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.91.8.3054</identifier><identifier>PMID: 8159705</identifier><identifier>CODEN: PNASA6</identifier><language>eng</language><publisher>Washington, DC: National Academy of Sciences of the United States of America</publisher><subject>Adenoviridae - genetics ; adenovirus ; Adenoviruses ; Animals ; Antineoplastic agents ; Biological and medical sciences ; Biotechnology ; Brain ; Brain Neoplasms - therapy ; Cell lines ; Cells ; Fundamental and applied biological sciences. Psychology ; Ganciclovir - pharmacology ; Gene therapy ; General aspects ; Genes ; Genetic Therapy - methods ; Genetic Vectors ; Genetics ; Glioma ; Glioma - therapy ; Health. Pharmaceutical industry ; Herpes viruses ; Industrial applications and implications. Economical aspects ; Injections ; Kidney cells ; Medical sciences ; Mice ; Mice, Nude ; Neurons ; Pharmacology. Drug treatments ; Rodents ; Therapy ; Thymidine Kinase - genetics ; Transduction, Genetic ; Tumors</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 1994-04, Vol.91 (8), p.3054-3057</ispartof><rights>Copyright 1994 The National Academy of Sciences of the United States of America</rights><rights>1994 INIST-CNRS</rights><rights>Copyright National Academy of Sciences Apr 12, 1994</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c641t-eef69430f00bed5197a3443a44d3a73c2b6486ea19dc398a16051460788424043</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/91/8.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/2364380$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/2364380$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793,58238,58471</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=4221393$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8159705$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, S H</creatorcontrib><creatorcontrib>Shine, H D</creatorcontrib><creatorcontrib>Goodman, J C</creatorcontrib><creatorcontrib>Grossman, R G</creatorcontrib><creatorcontrib>Woo, S L</creatorcontrib><title>Gene Therapy for Brain Tumors: Regression of Experimental Gliomas by Adenovirus-Mediated Gene Transfer in vivo</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>The therapeutic efficacy of adenovirus-mediated herpes simplex virus thymidine kinase (HSV-tk) gene transduction of rat C6glioma cells followed by ganciclovir (GCV) administration was studied in tumors generated in the brains of nude mice. C6glioma cells were efficiently transduced in vitro by a replicative-defective recombinant adenovirus carrying the HSV-tk gene (ADV/RSV-tk) that rendered them sensitive to GCV in a dose-dependent manner. Tumors were generated by stereotaxic intracerebral injection of 1 x 104C6cells in nude mice. After 8 days of tumor growth, 3 x 108ADV/RSV-tk viral particles were injected into the tumors and the mice subsequently were treated with GCV for 6 days. Tumor size in untreated and treated animals was compared 20 days after tumor implantation. The mean cross-sectional area of the tumors in the treated animals was 23-fold smaller than in control animals and the tumor volume was reduced by >500-fold. These results demonstrate that the recombinant adenoviral vector can function as an efficient gene delivery vehicle for the treatment of gliomas by in vivo gene therapy.</description><subject>Adenoviridae - genetics</subject><subject>adenovirus</subject><subject>Adenoviruses</subject><subject>Animals</subject><subject>Antineoplastic agents</subject><subject>Biological and medical sciences</subject><subject>Biotechnology</subject><subject>Brain</subject><subject>Brain Neoplasms - therapy</subject><subject>Cell lines</subject><subject>Cells</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Ganciclovir - pharmacology</subject><subject>Gene therapy</subject><subject>General aspects</subject><subject>Genes</subject><subject>Genetic Therapy - methods</subject><subject>Genetic Vectors</subject><subject>Genetics</subject><subject>Glioma</subject><subject>Glioma - therapy</subject><subject>Health. Pharmaceutical industry</subject><subject>Herpes viruses</subject><subject>Industrial applications and implications. Economical aspects</subject><subject>Injections</subject><subject>Kidney cells</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Neurons</subject><subject>Pharmacology. Drug treatments</subject><subject>Rodents</subject><subject>Therapy</subject><subject>Thymidine Kinase - genetics</subject><subject>Transduction, Genetic</subject><subject>Tumors</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1994</creationdate><recordtype>article</recordtype><recordid>eNqFkkGP0zAQhSMEWroLV04gWQhxSxnHjmMjLstqKUiLkFA5W24y2XWV2sVOqu2_X0ctUUFIe_LhfTNv5nmy7BWFOYWKfdg6E-eKzuWcQcmfZDMKiuaCK3iazQCKKpe84M-z8xjXAKBKCWfZmaSlqqCcZW6BDsnyDoPZ7knrA_kcjHVkOWx8iB_JT7wNGKP1jviWXN9vMdgNut50ZNFZvzGRrPbkskHndzYMMf-OjTU9NuTQOBgXWwwktdzZnX-RPWtNF_Hl8b3Ifn25Xl59zW9-LL5dXd7kteC0zxFboTiDFmCFTUlVZRjnzHDeMFOxulgJLgUaqpqaKWmogJJyAZUclwXOLrJPh77bYbXBpk4TB9PpbRrehL32xuq_FWfv9K3fac5KylL5-2N58L8HjL3e2Fhj1xmHfoi6EpxzEPxRkCqZOKoeB4UsJJWj9dt_wLUfgkth6QIoEyUraILmB6gOPsaA7bQZBT2ehR7PQiuqpR7PIhW8Oc1jwo93kPR3R93E2nRt-rbaxgnjRTJVp7mM7f-ok41uh67r8b4_8fsvmPTXB30dex8moGApUwnsAR9f4LU</recordid><startdate>19940412</startdate><enddate>19940412</enddate><creator>Chen, S H</creator><creator>Shine, H D</creator><creator>Goodman, J C</creator><creator>Grossman, R G</creator><creator>Woo, S L</creator><general>National Academy of Sciences of the United States of America</general><general>National Acad Sciences</general><general>National Academy of Sciences</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>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7QO</scope><scope>7T3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>19940412</creationdate><title>Gene Therapy for Brain Tumors: Regression of Experimental Gliomas by Adenovirus-Mediated Gene Transfer in vivo</title><author>Chen, S H ; Shine, H D ; Goodman, J C ; Grossman, R G ; Woo, S L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c641t-eef69430f00bed5197a3443a44d3a73c2b6486ea19dc398a16051460788424043</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1994</creationdate><topic>Adenoviridae - genetics</topic><topic>adenovirus</topic><topic>Adenoviruses</topic><topic>Animals</topic><topic>Antineoplastic agents</topic><topic>Biological and medical sciences</topic><topic>Biotechnology</topic><topic>Brain</topic><topic>Brain Neoplasms - therapy</topic><topic>Cell lines</topic><topic>Cells</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Ganciclovir - pharmacology</topic><topic>Gene therapy</topic><topic>General aspects</topic><topic>Genes</topic><topic>Genetic Therapy - methods</topic><topic>Genetic Vectors</topic><topic>Genetics</topic><topic>Glioma</topic><topic>Glioma - therapy</topic><topic>Health. Pharmaceutical industry</topic><topic>Herpes viruses</topic><topic>Industrial applications and implications. Economical aspects</topic><topic>Injections</topic><topic>Kidney cells</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Neurons</topic><topic>Pharmacology. Drug treatments</topic><topic>Rodents</topic><topic>Therapy</topic><topic>Thymidine Kinase - genetics</topic><topic>Transduction, Genetic</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, S H</creatorcontrib><creatorcontrib>Shine, H D</creatorcontrib><creatorcontrib>Goodman, J C</creatorcontrib><creatorcontrib>Grossman, R G</creatorcontrib><creatorcontrib>Woo, S L</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>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>Biotechnology Research Abstracts</collection><collection>Human Genome Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, S H</au><au>Shine, H D</au><au>Goodman, J C</au><au>Grossman, R G</au><au>Woo, S L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Gene Therapy for Brain Tumors: Regression of Experimental Gliomas by Adenovirus-Mediated Gene Transfer in vivo</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>1994-04-12</date><risdate>1994</risdate><volume>91</volume><issue>8</issue><spage>3054</spage><epage>3057</epage><pages>3054-3057</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><coden>PNASA6</coden><abstract>The therapeutic efficacy of adenovirus-mediated herpes simplex virus thymidine kinase (HSV-tk) gene transduction of rat C6glioma cells followed by ganciclovir (GCV) administration was studied in tumors generated in the brains of nude mice. C6glioma cells were efficiently transduced in vitro by a replicative-defective recombinant adenovirus carrying the HSV-tk gene (ADV/RSV-tk) that rendered them sensitive to GCV in a dose-dependent manner. Tumors were generated by stereotaxic intracerebral injection of 1 x 104C6cells in nude mice. After 8 days of tumor growth, 3 x 108ADV/RSV-tk viral particles were injected into the tumors and the mice subsequently were treated with GCV for 6 days. Tumor size in untreated and treated animals was compared 20 days after tumor implantation. The mean cross-sectional area of the tumors in the treated animals was 23-fold smaller than in control animals and the tumor volume was reduced by >500-fold. These results demonstrate that the recombinant adenoviral vector can function as an efficient gene delivery vehicle for the treatment of gliomas by in vivo gene therapy.</abstract><cop>Washington, DC</cop><pub>National Academy of Sciences of the United States of America</pub><pmid>8159705</pmid><doi>10.1073/pnas.91.8.3054</doi><tpages>4</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Proceedings of the National Academy of Sciences - PNAS, 1994-04, Vol.91 (8), p.3054-3057 |
| issn | 0027-8424 1091-6490 |
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| source | PMC (PubMed Central); JSTOR Archival Journals and Primary Sources Collection |
| subjects | Adenoviridae - genetics adenovirus Adenoviruses Animals Antineoplastic agents Biological and medical sciences Biotechnology Brain Brain Neoplasms - therapy Cell lines Cells Fundamental and applied biological sciences. Psychology Ganciclovir - pharmacology Gene therapy General aspects Genes Genetic Therapy - methods Genetic Vectors Genetics Glioma Glioma - therapy Health. Pharmaceutical industry Herpes viruses Industrial applications and implications. Economical aspects Injections Kidney cells Medical sciences Mice Mice, Nude Neurons Pharmacology. Drug treatments Rodents Therapy Thymidine Kinase - genetics Transduction, Genetic Tumors |
| title | Gene Therapy for Brain Tumors: Regression of Experimental Gliomas by Adenovirus-Mediated Gene Transfer in vivo |
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