| Project/Area Number |
11557156
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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 | 展開研究 |
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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 |
TAKAHASHI Yuzou Tokyo Medical and Dental University, Graduate school, Assistant Professor, 大学院・医歯学総合研究科, 助教授 (50014329)
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| Co-Investigator(Kenkyū-buntansha) |
YANAGISHITA Masaki Tokyo Medical and Dental University, Graduate school, Professor, 大学院・医歯学総合研究科, 教授 (70132793)
PODYMA KATARZYNA A. 東京医科歯科大学, 大学院・医歯学総合研究科, 教務職員 (90302877)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥9,600,000 (Direct Cost: ¥9,600,000)
Fiscal Year 2001: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2000: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1999: ¥6,100,000 (Direct Cost: ¥6,100,000)
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| Keywords | gene targeting / oral cancer / 扁平上皮癌 / 遺伝子治療 / アデノウイルス |
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| Research Abstract |
The following results were obtained in this project.
1. Establishment of cancer cell lines exhibiting the high ability of attachment to mouse oral tissue.
2. Selection of the targeting gene.
3. Examination of several vectors for efficient gene targeting in vivo.
The adhesion of different cancer cell lines to nude mouse tissues were examined. Some cell lines that found to attach easily to the dorsal area and the mouth (tongue, buccal mucosa) in mice were selected. Next, a model for neck metastasis of oral cancer in nude mice was established. Such model was utilized for targeting the genes related to metastasis.
The attention was focused on CD80, the gene of adhesion molecule that increases antitumor immunoresponse. Furthermore, other genes were investigated. Heparanase, an enzyme degrading heparan sulfate, a major component of extracellular matrices and basement membranes in vessels was a subject of our special interest. High metastatic ability of cancer cells showed to be correlated with the high heparanase expression level. Thus, it is likely that the transduction with antisense heparanase gene may inhibit the metastatic ability of cancer cells. Moreover, ASK1, apoptosis induced gene, was also analyzed.
Several ways of gene transduction in vitro was examined. It was proved that retrovirus vector is not suitable for this purpose. As a result, adenovirus vector and single plasmid were used. After injection of adenovirus vector including target gene into mice, good efficiency could not be obtained. However, single plasmid could be transfected efficiently using electroporation technique. Hereafter, the best way of the gene targeting of oral cancer mouse will be examined further to aplly the "cell targeting system" in gene therapy.
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