Document Detail

Cell death of human oral squamous cell carcinoma cell line induced by herpes simplex virus thymidine kinase gene and ganciclovir.
MedLine Citation:
PMID:  14727689     Owner:  NLM     Status:  MEDLINE    
Suicide gene therapy combining herpes simplex virus thymidine kinase gene (HSVtk) and ganciclovir (GCV) is one strategy for the treatment of head and neck squamous cell carcinoma (HNSCC). The purpose of this study is to determine the mechanism of cell death that occurs in suicide gene therapy using HSVtk and GCV and to assess the safety of that therapy. The human oral squamous cell carcinoma cell line SAS was treated with adenovirus vector containing HSVtk gene (AdHSVtk) and GCV in vitro. Morphological changes including chromatin condensation, cell shrinkage, blebbing of cell membrane, and ballooning formations were observed. Changes in the localization of phospholipids in the cell membrane were also observed. The results of flow cytometry showed a maximum of about 65% of cells in the early phase of apoptosis. In addition, DNA fragmentation was investigated using the TUNEL method in vivo. Nude mice (BALB/c AJD(-nu-), aged 4 weeks) were implanted with SAS and treated with AdHSVtk and GCV. Tumor sections were then observed. The treatment group was confirmed to have DNA fragmentation-positive cells. These results suggest that suicide gene therapy using AdHSVtk and GCV led to apoptosis of the oral squamous cell carcinoma cell line.
Masaya Nishikawa; Yasushi Hayashi; Noriyuki Yamamoto; Takafumi Fukui; Hirokazu Fukuhara; Kenji Mitsudo; Iwai Tohnai; Minoru Ueda; Masaaki Mizuno; Jun Yoshida
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Nagoya journal of medical science     Volume:  66     ISSN:  0027-7622     ISO Abbreviation:  Nagoya J Med Sci     Publication Date:  2003 Nov 
Date Detail:
Created Date:  2004-01-19     Completed Date:  2004-02-27     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  0412011     Medline TA:  Nagoya J Med Sci     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  129-37     Citation Subset:  IM    
Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan.
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MeSH Terms
Adenoviridae / genetics
Carcinoma, Squamous Cell / pathology*
Cell Line, Tumor
Cell Membrane / metabolism
Cell Separation
Chromatin / metabolism
DNA Fragmentation
Flow Cytometry
Ganciclovir / therapeutic use*
In Situ Nick-End Labeling
Lipid Bilayers / metabolism
Mice, Inbred BALB C
Mice, Nude
Microscopy, Fluorescence
Mouth Neoplasms / pathology*
Simplexvirus / enzymology*
Thymidine Kinase / genetics*
Reg. No./Substance:
0/Chromatin; 0/Lipid Bilayers; 82410-32-0/Ganciclovir; EC Kinase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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