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KAKEN_16K07125seika.pdf
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In vivoエレクトロポレーションを用いた新規マウス脳腫瘍モデルの開発
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In vivo エレクトロポレーション オ モチイタ シンキ マウス ノウシュヨウ モデル ノ カイハツ
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In vivo erekutoroporēshon o mochiita shinki mausu nōshuyō moderu no kaihatsu
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Development of novel mouse brain tumor model using in vivo electroporation and piggyBac system
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大西, 伸幸
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オオニシ, ノブユキ
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Ōnishi, Nobuyuki
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慶應義塾大学・医学部 (信濃町) ・訪問研究員
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Research team head
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科研費研究者番号 : 40534540
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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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効果的な治療法が確立されていない悪性脳腫瘍の分子基盤解明を目的に、マウス脳に直接がん遺伝子を導入して脳腫瘍を作製するin vivo発がんモデルの構築を目的とした。具体的には、ゲノム上に存在するトランスポゾン配列に目的配列を組み込むpiggyBacシステムとin vivoエレクトロポレーション法を組み合わせ、マウス脳内の神経幹細胞にがん遺伝子を導入したところ、高い細胞密度で周囲の脳実質に浸潤性に増殖し、不均質で悪性度の高い脳腫瘍を作製することができた。本モデルで作製した脳腫瘍で詳細な解析を行うことで、ヒト脳腫瘍の発がんおよび悪性化過程における分子基盤を明らかにしたいと考えている。
Glioblastoma multiforme (GBM), is one of the most malignant brain tumors, has highly-proliferative and invasive characters. To understand these malignant characters of GBM, an appropriate carcinogenesis model is required. Loss of INK4A/ARF and stimulation of common signal transduction pathways involving RAS are frequently found in GBM. Previously, we have established a stable mouse models of brain tumors, transplanting the genetically modified neural stem cells NSCs). Recently, for the purpose of reproducing a clinical tumor initiating process, we are developing a novel mouse model of brain tumors by gene transfer into mouse brain directly. Using in vivo electroporation and piggyBac system, transduction of activated-H-RAS and shInk4a/Arf into NSCs in mouse brain, efficiently formed highly proliferative, invasive and heterogeneous brain tumors. Based on these findings, we propose this in vivo carcinogenesis technique is efficient method to generate appropriate mouse brain tumor models.
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研究種目 : 基盤研究 (C) (一般)
研究期間 : 2016~2018
課題番号 : 16K07125
研究分野 : 腫瘍生物学
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