2002 Fiscal Year Final Research Report Summary
ESTABLISHMENT AND APPLIANCE OF NEWLY GENE THERAPY FOR INHIBITION OF MULTIDRUG RESISTANCE
| Project/Area Number |
13557158
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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 |
病態科学系歯学(含放射線系歯学)
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| Research Institution | Kyushu University |
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Principal Investigator |
ISHIBASHI Hiroaki KYUSHU UNIVERSITY, GRADUATE SCHOOL OF DENTAL SCIENCE, ASS PROF, 大学院・歯学研究院, 助手 (90254630)
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| Co-Investigator(Kenkyū-buntansha) |
SUGIURA Tuyoshi KYUSHU UNIVERSITY, GRADUATE SCHOOL OF DENTAL SCIENCE, ASS PROF, 歯学部附属病院, 助手 (40322292)
SHIRASUNA Kenemitsu KYUSHU UNIVERSITY, GRADUATE SCHOOL OF DENTAL SCIENCE, PROF, 大学院・歯学研究院, 教授 (30093420)
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| Project Period (FY) |
2001 – 2002
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| Keywords | ANTITUMORAL RAGENT / GENETHERAPY / NEOPLASMS |
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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 prompter 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 TNF α. This Sp1 decoy introduction into tumor cells may be a novel and useful therapeutic tool for induction of tumor domancy 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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Research Products
(10 results)
