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KAKEN_25293178seika.pdf
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Title |
Title |
CD44バリアント陽性胃がん幹細胞を特異的に検出するPET診断の開発
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Kana |
CD44 バリアント ヨウセイ イガン カンサイボウ オ トクイテキ ニ ケンシュツスル PET シンダン ノ カイハツ
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CD44 barianto yosei igan kansaibo o tokuiteki ni kenshutsusuru PET shindan no kaihatsu
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Basic study for the development of PET diagnosis specific for CD44 variant-positive gastric cancer stem like cells
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鈴木, 秀和
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スズキ, ヒデカズ
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Romanization |
Suzuki, Hidekazu
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慶應義塾大学・医学部・教授
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Research team head
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科研費研究者番号 : 70255454
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井上, 浩義
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イノウエ, ヒロヨシ
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Romanization |
Inoue, Hiroyoshi
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慶應義塾大学・医学部・教授
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Research team member
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科研費研究者番号 : 10213175
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村上, 康二
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ムラカミ, コウジ
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Murakami, Koji
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慶應義塾大学・医学部・教授
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Research team member
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科研費研究者番号 : 50200267
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芝田, 晋介
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シバタ, シンスケ
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Shibata, Shinsuke
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慶應義塾大学・医学部・講師
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Research team member
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科研費研究者番号 : 70407089
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佐谷, 秀行
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サヤ, ヒデユキ
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Saya, Hideyuki
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慶應義塾大学・医学部・教授
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Research team member
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科研費研究者番号 : 80264282
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2016
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科学研究費補助金研究成果報告書
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2015
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Abstract |
CD44v9-MKN28はCD44s-MKN28と比し有意に5-FU耐性を示した。Sulfasalazine投与でCD44v9-MKN28でも5-FUでROSが増えGSHが減少した。Hp曝露でCD44v9-MKN28の浸潤能は有意に亢進した。CD44v9-NCI-N87はtrastuzumab耐性を示し, GSH濃度とMnSOD量が上昇した。XenograftのCD44s-MKN28腫瘍は5-FUで縮小したがCD44v9-MKN28は縮小しなかった。5-FU+sulfasalazineではCD44v9-MKN28腫瘍は有意に縮小した。CD44v9-MKN28腫瘍はHp群で有意に増大した。
1) CD44v9-MKN28 cells were more resistant to 5-FU than CD44s-MKN28. With sulfasalazine, 5-FU enhanced ROS and reduced GSH even in CD44v9-MKN28, suggesting an importance of CD44v9 for 5-FU resistance. 2) Hp exposure significantly enhanced migration of CD44v9-MKN28, indicating that CagA accumulation by autophagy inhibition would accelerate tumor infiltration. 3) Trastuzumab significantly enhanced intramitochondrial MnSOD with the increase of GSH in CD44v9-NCI-N87 cells as compared to NCI-N87. 4) In xenografts, although 5-FU reduced tumor volume of CD44s-MKN28, no reduction of CD44v9-MKN28 was shown. With sulfasalazine, 5-FU significantly reduced tumor volume of CD44v9-MKN28, possibly by inhibiting CD44v9-xCT system, suggesting of xCT as a potential target of CD44v9 (+) cancer stem-like cells. (5) Hp infection expanded xenograft tumor of MNK28-CD44v9 compared to non-infected MNK28-CD44v9 or infected MKN28-CD44s, suggesting the high proliferative activity under CagA accumulation.
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研究種目 : 基盤研究(B)(一般)
研究期間 : 2013~2015
課題番号 : 25293178
研究分野 : 消化器内科学
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