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KAKEN_17K15967seika.pdf
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Download
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:120.0 KB
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:Oct 31, 2019 |
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Total downloads since Oct 31, 2019 : 480
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オルガノイド培養を用いた胃癌ライブラリの構築と人工胃癌モデルの開発
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オルガノイド バイヨウ オ モチイタ イガン ライブラリ ノ コウチク ト ジンコウ イガン モデル ノ カイハツ
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Oruganoido baiyō o mochiita igan raiburari no kōchiku to jinkō igan moderu no kaihatsu
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Investigation of the gastric carcinogenesis using gastric tumor organoid library and artifitial cancer organoids.
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南木, 康作
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ナンキ, コウサク
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Nanki, Kōsaku
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慶應義塾大学・医学部 (信濃町)・助教
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Research team head
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科研費研究者番号 : 30571137
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2019
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科学研究費補助金研究成果報告書
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2018
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本研究はオルガノイド技術の応用から胃がんライブラリーを構築し、その分子遺伝学的な解析結果と培養上の形質を比較検討した研究である。形状変化やニッチ要求性は多彩なゲノム・エピゲノム変化によって生じており、胃がんではCDH1とTP53の両変異によって自律的な増殖が生じていることがわかった。両変異をゲノム編集技術で正常胃上皮に導入したところ、自律的増殖の再現に成功した。さらに、線維芽細胞と共移植を行うことにより胃がん細胞をマウスに効率的に移植することに成功した。本研究で明らかとなった胃がんの自律的増殖機構の解明により、胃がんの新規治療法につながることが期待できる。
In this study, we constructed a stomach tumor organoid library using organoid culture technology, and compare its phenotype with each result of molecular genetic analyses. Transformation of its morphology and niche requirement were caused by various genome and epigenomic changes, and it was found that CDH1 and TP53 co-mutations caused autonomous growth in gastric cancer, CDH1 and TP53 mutations cause autonomous growth. For verification, we established CDH1/TP53 co-mutated engineered gastric organoids. The engineered organoids could grow autonomously. Furthermore, we imploved the efficiency of the success rate of xeno-transplantation of gastric cancer organoids to immuno-deficient mice by co-transplantation with fibroblasts. It can be expected to lead to a new treatment for gastric cancer.
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研究種目 : 若手研究(B)
研究期間 : 2017～2018
課題番号 : 17K15967
研究分野 : 消化器内科学
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