| Project/Area Number |
15390389
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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 |
Digestive surgery
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| Research Institution | The University of Tokyo |
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Principal Investigator |
YANAGIE Hironobu The University of Tokyo, RCAST, Project, associate professor, 先端科学技術研究センター・科学技術振興特任(常勤形態)(特任助教授) (30212278)
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| Co-Investigator(Kenkyū-buntansha) |
TANI Kenzaburo Kyushu University, Dept. of Molecular Genetics, Medical Institute of Bioregulation, Professor, 生態防御医学研究所, 教授 (00183864)
MARUYAMA Kazuo Teikyo University, Dept. of Pharmaceutical Science, Professor, 薬学部, 教授 (30130040)
KONO Kenji Osaka Meteroporitan University, Dept. of Engeneering, Professor, 大学院・工学研究科, 教授 (90215187)
TAMAI Ikumi Tokyo Science University, Dept. of Pharmacy, Professor, 薬学部, 教授 (20155237)
KOYAMA Yoshiyuki Otsuma Women's University, Faculty of Home Economics, Professor, 家政学部, 教授 (00162090)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥14,800,000 (Direct Cost: ¥14,800,000)
Fiscal Year 2004: ¥7,100,000 (Direct Cost: ¥7,100,000)
Fiscal Year 2003: ¥7,700,000 (Direct Cost: ¥7,700,000)
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| Keywords | Polyethyleneimine / anionic PEG complex / JTS-1 / Drug Delivery System / Gene Therapy / Multidrug resistant gene / Targeting / Drug Delivery System / JTS-1 / DNAマクロアレイ / トランスポーター / JTS-1、4 DDS |
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| Research Abstract |
We develop polyion complex with DNA and polycation for gene delivery systems. Polyethyleneimine was selected for polycation that have protonsponde effect on transfection to cancer cells. Polyethylene-glycol binding carboxyl chain was also used for coating the cationic charged DNA/polycation complex. To increase the transfection efficacy, we also examined pH sensitive peptide, JTS-1 that constructed with analysis of Influenza virus. Polyethyleneimine and DNA complex showed 1 × 10^9 IU/mg luciferase activity. In case of coating the DNA/polyion complex with PEG-C, the luciferase activity was increase to 3 × 10^9 IU/mg, because of the compaction and incresent of stability with addition of PEG-C to complex, so the transfection efficacy was increased. When addition of JTS-1 to the DNA/polyethyleneimine/lactose-binding PEG-C complex, it is easily to escape the lysis of lysosome and transfect the DNA to cytoplasm, and 6 × 10^9 IU/mg luciferase activity was obtained. Increasing of transfection efficacy of β-gal gene by intratumor injection of β-gal DNA plasmid/Polyethyleneimine/lactose-binding PEG-C/JTS-1 complex on gastric cancer tumor bearing mice model.
According to the analysis of DNA microarray with ancer cell lines that were sensitive or resistant to Oxaliplatin or Cisplatin, Tubrin specific Chaperon E gene and CBP/P300-interacting transactivator (CITED2) gene were increased on Oxaliplatin or Cisplatin resistant cancer cells.
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