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KAKEN_15K19349seika.pdf
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Download
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:111.7 KB
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HTS技術による消化器がん幹細胞を標的とした個別化医療開発
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HTS ギジュツ ニ ヨル ショウカキガン カンサイボウ オ ヒョウテキ ト シタ コベツカ イリョウ カイハツ
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HTS gijutsu ni yoru shokakigan kansaibo o hyoteki to shita kobetsuka iryo kaihatsu
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High- throughput screening for personalized medicine targeting gastrointestinal cancer stem cell.
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高野, 愛
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タカノ, アイ
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Takano, Ai
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慶應義塾大学・医学部・研究員
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Research team head
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科研費研究者番号 : 50647584
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佐藤, 俊朗
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サトウ, トシロウ
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Sato, Toshiro
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慶應義塾大学・医学部・特任准教授
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Research team member
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科研費研究者番号 : 70365245
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股野, 麻未
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マタノ, マミ
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Matano, Mami
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慶應義塾大学・医学部・研究員
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Research team member
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科研費研究者番号 : 20439889
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2017
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科学研究費補助金研究成果報告書
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2016
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ヒト消化器がん(大腸, 胃, 肝臓, 膵臓)患者から採取した生検組織からがんオルガノイドを樹立し, 最適化した培養環境下において大量培養することに成功した。また遺伝子操作技術を用いて蛍光蛋白レポーターLgr5遺伝子座位へのノックインによりがん幹細胞の可視化に成功し, この技術を利用して, 樹立した消化器がん幹細胞の可視化を行った。これらの樹立したがんオルガノイドを用いてHTSを行った。可視化した消化器がんオルガノイドに対し, 360種類のPKI libraryを用い, HTSを行った結果, 各消化器がん細胞及びがん幹細胞に効果を有する薬剤がいくつか得られた。
We have established gastrointestinal cancer organoids from the patient. As a result, we succeeded in isolating 4 kinds of tumor organoids including colorectal, gastric , liver, and pancreatic cancer from patient. It was possible to continuously and long-term culture of each of the human gastrointestinal cancer organoids by optimizing the culture condition based on the orgnoid culture protocol. We also have been successful knocked-in reporter to LGR5 locus of intestinal organoids using genome editing. Each gastrointestinal cancer organoids derived from patients became culture in 384-well plate. Furthermore, we have established tumor organoids ; based High-throughput drug screen system. Image analysis was performed with 360 drugs on tumor organoids using High Contents Analyzer. Our results suggest that our established HTS for tumor organids will be apply to genetic mutation based drug discovery and personalized medicine.
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研究種目 : 若手研究(B)
研究期間 : 2015～2016
課題番号 : 15K19349
研究分野 : 下部消化管学
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