Newly Gene Therapy Targeting Inhibition of the Tumor Angiogenesis Using Decoy System
| Project/Area Number |
16390539
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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 |
Pathobiological dentistry/Dental radiology
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
ISHIBASHI Hiroaki KYUSHU UNIVERSITY, SCHOOL OF DENTAL SCIENCE, ASS PROF, 歯学研究院, 講師 (90254630)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAGAWA Kazunori KYUSHU UNIVERSITY, SCHOOL OF DENTAL SCIENCE, ASS PROF, 医学研究院, 講師 (50217668)
SHIRASUNA Kanemitu KYUSHU UNIVERSITY, SCHOOL OF DENTAL SCIENCE, PROF, 歯学研究院, 教授 (30093420)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥14,100,000 (Direct Cost: ¥14,100,000)
Fiscal Year 2006: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2005: ¥4,800,000 (Direct Cost: ¥4,800,000)
Fiscal Year 2004: ¥5,900,000 (Direct Cost: ¥5,900,000)
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| Keywords | Oral cancer / Angiogenesis / Gene therapy / 悪性新生物 |
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| Research Abstract |
The development of newly capillary networks from the normal microvasculature of the surrounding tissue has thought to play a critical role for the growth of the solid tumors. Tumor cells influence the angiogenesis by stimulation of endothelial cells with producing several angiogenic factors. Among them, vascular endothelial growth factor (VEGF) is one of the most potent angiogenic factors, and endothelial cell specific mitogen. Several previous studies suggested that inhibition of VEGF using antisense oligodeoxynucleotides or neutralizing antibodies against VEGF suppressed tumor growth in various in vivo and in vitro models. VEGF is well known to be hypoxia-inducible, and has been recently reported to be synthesized by stimulation with tumor necrosis factor α (TNFα) via binding of transcription factor Sp1 to the VEGF promoter. We hypothesized that transfection into the tumor cells nucleus of the synthetic double stranded DNA including consensus sequence of binding site of the Sp1 as cis-trans element decoy could block the binding of Sp1 to the VEGF promoter gene. Transfection of wild type Sp1 decoy, but mutant type decoy, revealed prominent inhibitory effects of VEGF synthesis of cultured human carcinoma cells stimulated by TNFα. This Sp1 decoy introduction into tumor cells may be a novel and useful therapeutic tool for induction of tumor dormancy by its inhibitory effect on VEGF synthesis. In addition, the transfer of the Sp1 decoy would be more effective for regulating tumor growth and invasion than that of antisense oligonucleotide, since not all angiogenic factors but also growth and invasion related factors expression modulated by Sp1 could be simultaneously suppressed.
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Report
(4 results)
Research Products
(12 results)
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[Journal Article] Expression of tumor-associated RCASI and its possible involvement in immune evasion in oral squamous cell carcinoma2006
Author(s)
Toyoshima, T., Nakamura, S., Kumamaru, W., Kawamura, E., Ishibashi, H., et al.
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Journal Title
J Oral Pathol Med 3
Pages: 361-368
Related Report
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