| Project/Area Number |
17K09380
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 大腸がん肝転移 / 分子標的薬 / 増殖因子 / バイオマーカー / 大腸癌肝転移 / 分子標的治療 |
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| Outline of Final Research Achievements |
The therapeutic effect biomarker and target selection biomarker for IGF neutralization therapy could be indicated by confirming the increase in blood bioactive IGF with the increase of cancer metastatic lesions and the difference in therapeutic effect depending on the expression level of MMP-7 that releases bioactive IGF. However, in both immunodeficient and wild-type mouse models using human pro-form MMP-7 transfected mouse cancer cells, only the pro-form was detected in the serum, suggesting that human MMP-7 was not activated. Although the differences in the molecular structures of human and mouse MMP-7 are small, it was concluded that human MMP-7 cannot be activated in the mouse microenvironment. It was revealed that the activation mechanism of MMP-7, which activates the tightly regulated IGF system, could be also tightly regulated. Our study results show that the more physiological animal model is needed to validate the usefulness of MMP-7 in IGF neutralizing therapy in the future.
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| Academic Significance and Societal Importance of the Research Achievements |
我が国では大腸癌は罹患者数、死亡者数ともに多く、遠隔転移、特に肝転移症例は、根治困難である。大腸癌肝転移において、IGF機構の活性化が重要なことは明らかで、MMP-7が主要なIGF機構活性化分子であることも報告されている。故に、MMP-7はIGF中和療法の対象選択のためのバイオマーカーとなり得るが、今回の我々の検討により、MMP-7の生体内での活性化もIGF活性化機構と同様に厳密に制御されていることが判明した。今後、大腸癌肝転移を促進するIGF活性化メカニズムの解明の一助となり、IGF中和療法の科学的な根拠ならびに、治療対象選択と治療効果判定のバイオマーカー探索研究に大きく貢献する。
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