| Migratory neural stem cells for improved thymidine kinase-based gene therapy of malignant gliomas. | |
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MedLine Citation:
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PMID: 15670759 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Gene therapy of glioma based on viral delivery of herpes simplex virus type I thymidine kinase (HSV-TK) has failed in the clinic because of low transduction efficacy. To circumvent this problem, this study evaluated highly migratory HSV-TK-transduced neural stem cells (NSC) for their ability to kill untransduced glioma cells by a gap junction-mediated bystander effect. The admixture of HSV-TK-transduced NSC to U87MG and LN-18 human malignant glioma cell lines at ratios of 1:10 or 1:1 eliminated more than 50% or 90% of glioma cells in the presence of ganciclovir (25 microM). Glioma cell cytotoxicity required cell-cell contact. Similarly, tumor cell cytotoxicity was observed in two of three primary glioblastoma cell cultures, and the presence of this bystander effect correlated with the expression of connexin 43 in the untransduced glioma target cells. In conclusion, we delineate a role for migratory HSV-transfected NSC to eliminate glioma cells purely by means of the bystander effect. |
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Authors:
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Martin Uhl; Markus Weiler; Wolfgang Wick; Andreas H Jacobs; Michael Weller; Ulrich Herrlinger |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Biochemical and biophysical research communications Volume: 328 ISSN: 0006-291X ISO Abbreviation: Biochem. Biophys. Res. Commun. Publication Date: 2005 Mar |
Date Detail:
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Created Date: 2005-01-26 Completed Date: 2005-03-28 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0372516 Medline TA: Biochem Biophys Res Commun Country: United States |
Other Details:
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Languages: eng Pagination: 125-9 Citation Subset: IM |
Affiliation:
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Department of General Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Hoppe-Seyler-Str. 3, D-72076 Tübingen, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Bystander Effect
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physiology* Cell Line, Tumor Cell Movement / physiology Gap Junctions / physiology Gene Therapy / methods* Glioma / drug therapy* Humans Neurons / enzymology*, secretion*, transplantation Stem Cell Transplantation / methods* Thymidine Kinase / genetics, secretion, therapeutic use* Treatment Outcome Viral Proteins / genetics, secretion, therapeutic use* |
| Chemical | |
Reg. No./Substance:
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0/Viral Proteins; EC 2.7.1.-/thymidine kinase, Canid herpesvirus 1; EC 2.7.1.21/Thymidine Kinase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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