1996 Fiscal Year Final Research Report Summary
BASIC STUDIES FOR DEVELOPMENT OF GENE THERAPY OF STOMATITIS
| Project/Area Number |
07807183
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Surgical dentistry
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| Research Institution | TOKYO MEDICAL AND DENTAL UNIVERSITY |
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Principal Investigator |
KAMATA Nobuyuki TOKYO MEDICAL AND DENTAL UNIVERSITY,FACULTY OF DENTISTRY,ASSISTANT PROFESSOR, 歯学部, 助手 (70242211)
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| Co-Investigator(Kenkyū-buntansha) |
TACHIKAWA Noriko TOKYO MEDICAL AND DENTAL UNIVERSITY,FACULTY OF DENTISTRY,ASSISTANT PROFESSOR, 歯学部, 助手 (70236537)
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| Project Period (FY) |
1995 – 1996
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| Keywords | GENE THERAPY / STOMATITIS / ORAL CANCER / ANTISENSE / ADENOVIRUS / TRANFECTION |
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| Research Abstract |
To investigate the mechanism and develop new therapy for the stomatitis, we conducted to examine the possibility of the introduction of genes or antisense genes for cytekines into oral mucous, locally.
The introduction of expression plasmid carrying beta-Galactosidase gene using liposome resulted the detectable enzyme activity in cultured human oral squamous cell carcinomas and nomal oral epitherial cells.
But the introduction using adenovirus vectors containing LacZ gene resulted in the expression of this enzyme in almost 100% cells in culture.
We also found that the elevated expression of I-CAM1 protein by stimulation of TPA,INF-beta, and TNF-gamma, was inhibited by treatment of 20 mer antisense DNA for I-CAM1 in cultured squamous cell carcinoma cell lines.
Next we tried to express the introduced gene in vivo. Injection of expression plasmids with liposome into mouse tongue did not show enough expression of introduced genes. Also, injection of antisense DNA did not show the detectable inhibition of TNF-gamma-stimulated expression of I-CAM1 protein. However, injection of adenovirus vectors into transplanted tumors in nude mouse showed locally expressed gene products. This suggested the possibility of the local gene therapy in stomatitis. And using this system, we found that the over-expression of PKC-eta, which is a PKC isozyme characteristically found in epitherial cells, inhibited the growth of squamous cell carcinoma cell lines but not fibroblasts with TPA treatment. These results suggested the Possibility of gene therapy of oral cancer and stomatitis.
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