| Project/Area Number |
10470428
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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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 |
SAKAI Eiki Graduate School, Tokyo Medical and Dental University, Research Associate, 大学院・医歯学総合研究科, 助手 (60292976)
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| Co-Investigator(Kenkyū-buntansha) |
KURABAYASI Toru Graduate School, Tokyo Medical and Dental University, Lecturer, 大学院・医歯学総合研究科, 講師 (60178093)
MIURA Masahiko Graduate School, Tokyo Medical and Dental University, Associate Professor, 大学院・医歯学総合研究科, 助教授 (10272600)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥13,100,000 (Direct Cost: ¥13,100,000)
Fiscal Year 2000: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1999: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1998: ¥7,300,000 (Direct Cost: ¥7,300,000)
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| Keywords | p53 / oral squamous cell carcinoma / 4-1BBL / adenovirus vector / 口腔扁平上皮癌細胞株 / アポトーシス関連遺伝子 / p53癌抑制遺伝子 / CDDP / Hela細胞 / DNA ladderig法 / differential display法 / 抗腫瘍剤 / アポトーシス / p53遺伝子 / tunnel法 / DNAladdering法 |
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| Research Abstract |
To achive the successful transduction of the CD80 gene into oral SCC, we produced a recombinant adenovirus in which human CD80 cDNA was cloned in the E1-deficient Advector. We infected these tumor cell lines with CD80-Ad and cell surface expression of CD80 was determined by flow cytometry after 48 hr. Efficient and high levels of cell surface expression was observed in oral SCC cell lines. This results demonstrate that the use of adenovirus vector enables the transduction of a molecule into oral SCC cell lines.
We examined the effect of gene-transduction with murine 4-1 BB ligand (CD137L), which is one of the tumor necrosis facter (TNF) families. 4-1 BBL costimulatory signals preferentially induce CD8+ T cell proliferation and IFN-γ production. Administration of mAb against 4-1 BB eradicated established several murine tumors. We transduced of 4-1 BB ligand (CD137L) into a murine squamous cell carcinoma. Introduction of the 4-1 BBL gene efficiently elicited anti-tumor immune responses in syngenic mice. Our results suggested that introduction of 4-1 BBL may induce efficient T cell immune responses against tumors.
Surgically resected oral SCCs (n=37) were investigated by immunohistochemistry and 29 cases were positive for p53. Forty three samples diagnosed as leukoplakia with epithelial dysplasia in the oral cavity were subjected to immunohistochemical staining of p53 protein. Among these lesions, 12 were developed into SCC during the clinical observation. Nine out of above 12 lesions showed p53 positive staining even before malignant transformation to SCC.It was suggested that the immunohistochenical analysis of p53 protein is suggested to be a useful diagnostic procedure for oral Leukoplakia which probably develop future into SCC.
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