| Project/Area Number |
09671276
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | TOHOKU UNIVERSITY |
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Principal Investigator |
ISHII Seiichi Tohoku University Hospital, Research Associate, 医学部・附属病院, 助手 (60221066)
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| Co-Investigator(Kenkyū-buntansha) |
ISHII Keiko Tohoku University Hospital, Lecturer, 医学部・附属病院, 講師 (00291253)
TAKAI Yoshihiro Tohoku University Hospital, Associate Professor, 医学部・附属病院, 助教授 (50107653)
FUNATO Tadao Graduate School of Med., Tohoku Univ., Associate Professor, 大学院・医学研究科, 助教授 (70165455)
MIZOI Takayuki Tohoku University Hospital, Research Associate, 医学部・附属病院, 助手 (90271949)
SHIIBA Ken-ichi Graduate School of Med., Tohoku Univ., Associate Professor, 大学院・医学研究科, 助教授 (90196345)
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| Project Period (FY) |
1997 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1999: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1998: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1997: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | gene therapy / ionizing radiation / EGR1 / EGR1 / 大腸願 / 遺伝子治量 / EGRI / 放射線治療 / EGR1プロモーター |
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| Research Abstract |
The purpose of this study was to develop a novel chemo-radio-gene therapy against colorectal cancer using Esherichia coli cytosine deaminase (CD) suicide gene and ionizing radiation-inducible early growth response 1 (EGR1) promoter. The CD converts non-toxic 5-Fluorocytosine (5FC) to 5-Fluorouracil (5FU) that has the anti-tumor activity for human colorectal cancer cells. The ionizing irradiation induces immediate-early genes including the EGR1. Thus, the EGR1 promoter in combination with the CD gene can be used to induce an intense anti-cancer activity in the irradiated field when treated with 5FC. The EGR1-CD vector is expected to be driven by ionizing irradiation to express CD mRNA in mammalian cells. When colorectal carcinoma cells are transfected with the EGR1-CD vector, ionizing irradiation induces CD expression in the transformant cells and 5FC is converted to 5FU that is cytotoxic for colorectal cancer cells. For this purpose, we tried cloning of the EGR1 promoter region and the bacterial CD gene by PCR amplification with the reported primers. The two DNA fragments were further cloned using a cloning kit. The cloned DNA fragments were co-inserted into a plasmid to construct an expression vector for mammalian cells. The investigators could not confirm the activity of EGR1-CD vector in mammalian cells because we have not completed cloning of the two DNA fragments and construction of EGR1-CD plasmid during the research period.
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