2005 Fiscal Year Final Research Report Summary
The effect of simultaneous transfection of HGF gene-plasmid and NFκB-decoy using ultrasound exposure with contrast agent in a rat kidney allograft model
| Project/Area Number |
15390499
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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 |
Urology
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| Research Institution | Osaka Medical College |
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Principal Investigator |
AZUMA Haruhito Osaka Medical College, Faculty of Medicine, Assistant Professor, 医学部, 講師 (40231914)
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| Co-Investigator(Kenkyū-buntansha) |
KATSUOKA Yoji Osaka Medical College, Faculty of Medicine, Professor, 医学部, 教授 (10051757)
TAKAHARA Shiro Osaka Medical College, Faculty of Medicine, Professor, 医学部, 寄付講座教授 (70179547)
MORISHITA Ryuiti Osaka Medical College, Faculty of Medicine, Professor, 医学部, 寄付講座教授 (40291439)
TOMITA Naruya Osaka Medical College, Faculty of Medicine, Assistant Professor, 医学部, 助教授 (70314432)
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| Project Period (FY) |
2003 – 2005
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| Keywords | NFκB / decoy / Optison / Hepatocyte Growth Factor / kidney transplantation |
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| Research Abstract |
We have previously demonstrated that in the mechanism of development of chronic allograft nephropathy (CAN), a decreased number of functioning glomeruli due to ischemic-reperfusion injury during renal transplantation as well as acute graft rejection are highly involved ; and activation of nuclear factor kappaB (NFκB) and enhancement of expression of adhesion molecules and cytokine production, mediated by such a factor, constitute important factors in that process. Together with Morishita, Tomita and others, we previously developed "NFκB-decoy", decoy cis-elements oligo deoxyribonucleic acid against NFκB, which modulates expression of inflammatory cytokines and adhesion molecules, and transfected them into kidney transplants in a rat kidney transplantation model for acute rejection using ultrasound exposure with an echocardiographic contrast agent (Gene Ther.2003 Mar ; 10(5):415-25). In the present study, based on the results from our investigation for causes of the failure to induce pe
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rmanent graft survival, we considered the possibility that the renal tubules may directly be impaired by echocardiographic contrast agent, Optison, and ultrasound exposure, and conducted experiments to reduce such adverse effects. In order to induce permanent graft survival by simultaneously suppressing acute graft rejection and tissue damage caused by ultrasound exposure with Optison, as well as reducing ischemic-reperfusion injury during renal transplantation, we developed a plasmid of the gene for hepatocyte growth factor (HGF), which provides protection against renal tubule damage, and transfected it and NFκB-decoy into the donor kidney. (We previously described the inhibitory effect of HGF on renal tubule damage. See Azuma, et al. : J.Am Soc Nephrol ; Tanaka et al. : Am J Transplant.) The present data obtained in the rat kidney transplantation model for acute rejection have shown a significantly prolonged graft survival for animals receiving simultaneous transfection of HGF gene-plasmid and NFκB-decoy, compared with the control transfected with the decoy alone. Unfortunately the treatment failed to induce permanent graft survival, but we will further investigate development of a kidney transplantation method for permanent graft survival. Less
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Research Products
(24 results)
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[Journal Article] Effect of Smad7 Expression on Metastasis of Mouse Mammary Carcinoma JygMC(A) Cells2005
Author(s)
Haruhito Azuma, Shogo Ehata, Hideyo Miyazaki, Tetsuro Watabe, Osamu Maruyama, Takeshi Imamura, Takeshi Sakamoto, Satoshi Kiyama, Yuko Kiyama, Takanobu Ubai, Teruo Inamoto, Shiro Takahara, Yuko Itoh, Yoshinori Otsuki, Yoji Katsuoka, Kohei Miyazono, Shigeo Horie
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Journal Title
Journal of the National Cancer Institute 97-23
Pages: 1734-1746
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Selective cancer cell apoptosis induced by FTY720; evidence for a Bcl-dependent pathway and impairment in ERK activity.2003
Author(s)
Azuma H, Horie S, Muto S, Otsuki Y, Matsumoto K, Morimoto J, Gotoh R, Okuyama A, Suzuki S, Katsuoka Y, Takahara S.
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Journal Title
Anticancer Res. 23・4
Pages: 3183-93
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Gamma-aminobutyric acid as a promoting factor of cancer metastasis; induction of matrix metalloproteinase production is potentially its underlying mechanism.2003
Author(s)
Azuma H, Inamoto T, Sakamoto T, Kiyama S, Ubai T, Shinohara Y, Maemura K, Tsuji M, Segaw N, Masuda H, Takahara K, Katsunka Y, Watanahe M.
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Journal Title
Cancer Res. 63・23
Pages: 8090-6
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Gamma-aminobutyric acid as a promoting factor of cancer metastasis ; induction of matrix metalloproteinase production is potentially its underlying mechanism.2003
Author(s)
Azuma H, Inamoto T, Sakamoto T, Kiyama S, Ubai T, Shinohara Y, Maemura K, Tsuji M, Segaw N, Masuda H, Takahara K, Katsuoka Y, Watanabe M.
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Journal Title
Cancer Res. 63-23
Pages: 8090-8096
Description
「研究成果報告書概要(欧文)」より
