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KAKEN_25460422seika.pdf
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Title |
Title |
腎細胞癌の分子標的薬による治療効果の病理学的解析と耐性機構の解明
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Kana |
ジンサイボウガン ノ ブンシ ヒョウテキヤク ニ ヨル チリョウ コウカ ノ ビョウリガクテキ カイセキ ト タイセイ キコウ ノ カイメイ
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Jinsaibogan no bunshi hyotekiyaku ni yoru chiryo koka no byorigakuteki kaiseki to taisei kiko no kaimei
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Analysis of effect and resistance of molecular-targeted therapy in renal cell carcinoma
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三上, 修治
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ミカミ, シュウジ
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Mikami, Shuji
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慶應義塾大学・医学部・講師
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Research team head
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科研費研究者番号 : 20338180
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小坂, 威雄
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コサカ, タケオ
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Kosaka, Takeo
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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 : 30445407
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水野, 隆一
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ミズノ, リュウイチ
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Mizuno, Ryuichi
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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 : 60383824
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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 |
本研究は腎細胞癌の分子標的治療効果の解析・耐性機構を解明するために行われた。腎細胞癌では腫瘍壊死因子(TNF-α)および癌幹細胞マーカーCD44発現が原発巣の進展度, 遠隔転移, 不良予後と相関した。TNF-αはE-cadherin発現を抑制, MMP9, CD44発現を亢進させることで遊走・浸潤を促進した(EMTおよび癌幹細胞の誘導)。分子標的薬スニチニブ治療を行った場合, CD44高発現が治療抵抗性と関連していた。また, スニチニブ治療後の転移性腎細胞癌組織は未治療癌組織に比べCD44が高発現していた。TNF-αはEMTおよび癌幹細胞を誘導により腎細胞癌の進展・治療抵抗性に関与していると考えられる。
This study was performed to clarify the significance of TNF-α and CD44 in clear cell renal cell carcinomas (ccRCCs). Co-upregulation of TNF-α and CD44 was associated with primary tumor stage, distant metastasis, and poor prognosis. TNF-α enhanced migration and invasion of ccRCC cells together with down-regulation of E-cadherin expression and up-regulation of matrix MMP9 and CD44 expression. Among ccRCC patients treated with sunitinib for metastatic disease, high CD44 expression was associated with poor treatment outcome. Importantly, residual carcinoma cells in the sunitinib-treated metastatic ccRCCs were strongly positive for CD44, and the CD44 expression was significantly higher in the tumors from the sunitinib-treated patients than in those from untreated ones. Our data show that TNF-α plays an important role in progression of ccRCCs by inducing EMT and CD44 expression, and suggest that CD44 induced by TNF-α may be involved in the resistance to the sunitinib treatment.
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研究種目 : 基盤研究(C)(一般)
研究期間 : 2013~2015
課題番号 : 25460422
研究分野 : 病理学
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