| Project/Area Number |
04557090
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| Research Category |
Grant-in-Aid for Developmental Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
外科・放射線系歯学
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| Research Institution | The University of TOKUSHIMA |
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Principal Investigator |
MAGAYAMA Masaru The University of TOKUSHIMA,School of Dentistry, Professor, 歯学部, 教授 (30022867)
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| Co-Investigator(Kenkyū-buntansha) |
MORISHITA Hideaki Mochida Phamaceutical Company, Bio-science Institute, バイオサイエンス研究所, 主幹
HAYASHI Eiji The University of TOKUSHIMA,School of Dentistry, Research Associates, 歯学部, 助手 (50173000)
RIKIMARU Koichi The University of TOKUSHIMA,School of Dentistry, Associate Professor, 歯学部, 助教授 (40220800)
森下 英明 持田製薬(株), バイオサイエンス研究所, 主幹
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| Project Period (FY) |
1992 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥16,800,000 (Direct Cost: ¥16,800,000)
Fiscal Year 1994: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1993: ¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 1992: ¥9,900,000 (Direct Cost: ¥9,900,000)
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| Keywords | Oral Cnacer / Squamous Cell Carcinoma / EGF Receptor / p53 / Cadherin / Monoclonal Antidody / 遺伝子診断 / 分子細胞生物学 |
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| Research Abstract |
In order that the gene diagnosis technique may be introduced into the field of oral cancer, we attempted to find out the biological features of squamous cell carcinoma, which is the majority of oral cancers.
1)The frequency of mutations in p53 tumor-suppressor gene was studied by the method of polymerase chain reaction followed by single-strand conformation polymorphism (PCR-SSCP) . The assay revealed that overall 63% of oral squamous cell carcinomas carried the mutated p53 gene within the regions of exon 5 to 8, suggesting that the mutation of p53 gene is the most frequent gene alteration occurred in oral squamous cell carcinoma. In order to clear the relationship between the gene mutation and the detectability of its protein in immuno-histochemistry, we injected the tumor cells, of which the patterns of p53 gene mutation were well characterized, into SCID mice and made tumors on animals, and then cross sections were prepared and stained with anti-p53 protein antibodies. The detection
… More
of p53 protein in the cross sections was correlated with the type of gene mutations, mis-sense mutation, suggesting the limitation of immuno-histochemistry to detect the p53 gene mutations.
2)We investigated the gene amplification of erbB-1 and its expression. Out of four cell lines, which were newly established from the oral squamous cell carcinoma patients, only one carried the amplified gene, as was consistent with our previous observation. Interestingly we noticed that some cell lines expressed unexpectedly large number of EGF receptor on the surface. The kinetic analysis of EGF receptor revealed that these cells showed delayd pattern of the protein degradation.
3)We investigated the effects of EGF administration on the formation of lung metastases of EGF receptor-hyperproducing squamous cell carcinoma cells in SCID mice. The results suggested that EGF administered somatically did not exert the obvious effects on the formation of metastases.
4)We studied the patterns of the protein secretion from the normal epithelial cells and squamous cell carcinoma cells, and compared the differences of them using a hybridoma technique. As results, two monoclonal antibodies were obtained, one of which recognized the protein that secreted by cancer cells rather than normal cells and another one recognized the protein decreased in secretion in caner cells. These findings suggest the possibility to know the novel characteristics of oral squamous cell carcinoma after the molecular cloning of these proteins was accomplished successfullyaccomplished. Less
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