2023 Fiscal Year Final Research Report
Basic Study on Tumor Suppression Effects of Read-Through Therapy in Familial Colorectal Adenomatosis
| Project/Area Number |
20K07684
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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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| Review Section |
Basic Section 50020:Tumor diagnostics and therapeutics-related
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| Research Institution | Juntendo University |
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Principal Investigator |
Arai Masami 順天堂大学, 大学院医学研究科, 教授 (20232027)
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| Co-Investigator(Kenkyū-buntansha) |
柿沼 志津子 国立研究開発法人量子科学技術研究開発機構, 放射線医学総合研究所, 副所長(任常) (20392219)
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| Project Period (FY) |
2020-04-01 – 2024-03-31
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| Keywords | ナンセンス変異 / リードスルー療法 / マクロライド系抗生剤 / 家族性大腸腺腫症 / 遺伝性腫瘍 / APC遺伝子 |
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| Outline of Final Research Achievements |
Macrolide antibiotics induce read-through of pathogenic nonsense mutations. We conducted the following investigation to determine whether this mechanism leads to a tumor suppressive effect on hereditary tumors using a mouse model of familial adenomatous polyposis.
Using female C3B6F1ApcMin/+ mice, we analyzed four groups: three groups were continuously administered with different concentrations of macrolide antibiotics (low, medium, and high) in drinking water from 3 weeks of age, and an untreated group as a control. As a result, although the duration of treatment was limited, macrolide antibiotics reduced the number of cancers and suppressed the malignant transformation of adenomas into carcinomas. It was also revealed that highest-dose administration reduced altered the intestinal flora and had limited tumor suppressive effects.
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| Free Research Field |
腫瘍診断および治療学関連
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| Academic Significance and Societal Importance of the Research Achievements |
遺伝性腫瘍には、がん発症リスク軽減のマネジメントとしてリスク低減手術や計画的なサーベイランスがある。しかし、大腸を全摘するなど手術侵襲は大きく、また臓器を喪失することによる有害事象も生じうる。また、期間限定的ではあっても手術の時期を遅らせることができれば受験期などへの影響を抑えることも期待でき、その社会的な意義は大きい。また有望なリードスルー化合物も見出されており、創薬にも繋がる可能性をもつ。
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