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KAKEN_24689036seika.pdf
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Title |
Title |
ヒト大腸癌幹細胞の同定と標的治療の確立
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Kana |
ヒト ダイチョウガン カンサイボウ ノ ドウテイ ト ヒョウテキ チリョウ ノ カクリツ
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Hito daichogan kansaibo no dotei to hyoteki chiryo no kakuritsu
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Identification of human colorectal cancer stem cells.
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佐藤, 俊朗
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サトウ, トシロウ
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Romanization |
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 head
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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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Romanization |
Matano, Mami
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Affiliation |
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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高野, 愛
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Kana |
タカノ, アイ
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Romanization |
Takano, Ai
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Affiliation |
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 : 50647584
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2014
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科学研究費補助金研究成果報告書
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2013
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Abstract |
我々は、ヒト大腸上皮細胞よりオルガノイドを樹立し、ゲノム編集技術による遺伝子操作法を確立した。本法により、人工的な遺伝子変異導入による大腸発がんメカニズムの解明に迫った。さらに、ヒト大腸癌幹細胞の同定のため、LGR5遺伝子領域への細胞系譜解析レポーターの遺伝子ノックインに成功した。遺伝子改変オルガノイドは免疫不全マウスへの異種移植により、患者病理組織を反映した大腸癌組織の形成を示した。ゲノム編集技術による自在なヒト大腸上皮細胞の遺伝子操作は大腸発がんメカニズムの解明、遺伝子変異に着目した創薬や患者大腸癌の個別治療応用などの臨床応用が期待できる。
We have established intestinal organoids from human intestinal epithelium and applied genome engineering system to organoids. With this approach, we introduced multiple driver mutations into human intestinal organoids to elucidate the mechanism of colorectal carcinogenesis. Furthermore, we knocked-in reporter to LGR5 locus of intestinal organoids using genome editing. Owing to the genetic silencing of Lgr5 promoter, we are attempting to employ other stem cell genetic markers. We also established xenotransplantation system with engineered organoids or colorectal cancer organoids. The organoids were readily engrafted and form tumor recapitulating clinical colorectal cancer. Our results suggest that engineered organoid system provide new insights into the understanding of human colorectal cancer. The platform will be useful not only to elucidate cell biological mechanism of colorectal cancer stem cells but also to apply genetic mutation based drug discovery and personalized medicine.
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研究種目 : 若手研究(A)
研究期間 : 2012~2013
課題番号 : 24689036
研究分野 : 医歯薬学
科研費の分科・細目 : 内科系臨床医学・消化器内科学
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