Document Detail

Evaluation of prodrugs ability to induce effective ablation of cells transduced with viral thymidine kinase gene.
MedLine Citation:
PMID:  8917361     Owner:  NLM     Status:  MEDLINE    
Transduction of the herpes simplex virus thymidine kinase (HSV-tk) gene into tumor cells followed by treatment with prodrugs is one of the most promising approaches for gene therapy in cancer. The choice of prodrugs is important in order to obtain maximum anticancer effects with minimum adverse reactions. We retrovirally transduced the HSV-tk gene into murine and rat hepatocellular carcinoma (HCC) cells, and investigated their sensitivity to ganciclovir and acyclovir. Retrovirally-mediated HSV-tk transduction did not affect cell proliferation, but led to both ganciclovir- and acyclovir-dependent cytotoxicity in the HCC cells. Ganciclovir exhibited much stronger cytotoxicity on HSV-tk transduced cells than acyclovir. Importantly, HSV-tk transduced cells were completely abrogated at a ganciclovir concentration which was lower than the minimum plasma level achieved in the clinical usage of ganciclovir. Furthermore, HSV-tk transduced cells induced stronger killing of neighboring untransduced cells in the presence of ganciclovir than acyclovir. Ganciclovir may be preferable to acyclovir in the HSV-tk transduction system.
S Kuriyama; T Nakatani; K Masui; T Sakamoto; K Tominaga; M Yoshikawa; H Fukui; K Ikenaka; T Tsujii
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Anticancer research     Volume:  16     ISSN:  0250-7005     ISO Abbreviation:  Anticancer Res.     Publication Date:    1996 Sep-Oct
Date Detail:
Created Date:  1996-12-18     Completed Date:  1996-12-18     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8102988     Medline TA:  Anticancer Res     Country:  GREECE    
Other Details:
Languages:  eng     Pagination:  2623-8     Citation Subset:  IM    
Third Department of Internal Medicine, Nara Medical University, Japan.
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MeSH Terms
Acyclovir / pharmacology*
Antiviral Agents / pharmacology*
Cell Division / drug effects
Dose-Response Relationship, Drug
Ganciclovir / pharmacology*
Genes, Viral / drug effects,  genetics*
Liver Neoplasms, Experimental / genetics,  pathology,  therapy
Prodrugs / pharmacology*
Simplexvirus / genetics*
Thymidine Kinase / genetics*
Reg. No./Substance:
0/Antiviral Agents; 0/Prodrugs; 59277-89-3/Acyclovir; 82410-32-0/Ganciclovir; EC Kinase

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