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KAKEN_16K07149seika.pdf
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新しい網羅的遺伝子解析による食道癌の薬剤、放射線耐性遺伝子の検索とそのメカニズム
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アタラシイ モウラテキ イデンシ カイセキ ニ ヨル ショクドウガン ノ ヤクザイ、ホウシャセン タイセイ イデンシ ノ ケンサク ト ソノ メカニズム
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Atarashii mōrateki idenshi kaiseki ni yoru shokudōgan no yakuzai, hōshasen taisei idenshi no kensaku to sono mekanizumu
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The novel and comprehensive screening of genes resistant to an anticancer drug and radiation in esophageal squamous cell carcinoma
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川久保, 博文
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カワクボ, ヒロフミ
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Kawakubo, Hirofumi
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慶應義塾大学・医学部 (信濃町) ・准教授
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Research team head
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科研費研究者番号 : 20286496
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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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Abstract |
ヒトゲノム上に存在する全ての遺伝子をスクリーニング可能であるトランスポゾンを用いて、食道癌に対するシスプラチン、5-FU、放射線耐性遺伝子の新しい網羅的解析に関する研究において、37種類のシスプラチン耐性遺伝子を発見した。そのうちTRIM16L overexpression細胞株に関してシスプラチン耐性をMTT assayにて検証し、シスプラチンへの耐性を証明した。TRIM16 knockdown細胞株に関してシスプラチンへの耐性が減少することを確認した。TRIM16L overexpression細胞株のマウスxenograftでのシスプラチンに対する耐性をin vivoにて確認した。
Multimodal therapies including surgery, chemotherapy, and radiotherapy are necessary for advanced esophageal cancer. However, patients with resistance to chemo or radiotherapy cannot derive benefit from the therapy but suffer side effects. Therefore, detecting resistant genes and mechanisms is essential for tailoring treatment to improve the prognosis.We used a novel method involving transposons to screen and identify drug-resistant genes and radio-resistant genes. The new gene screening technique was useful for detecting candidate of drug-resistant genes in esophageal squamous cell carcinoma. We identified 37 candidate genes responsible for CDDP resistance in the two cell lines derived from ESCC cells. TRIM16 is one of the candidate of CDDP resistant gene. We confirmed TRIM 16 overexpression cell has CDDP resistant using MTT assay and resistance is decreased by knocking down TRIM 16. We also confirmed TRIM 16 overexpression cell has CDDP resistant in vivo xenograft model.
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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 : 16K07149
研究分野 : 食道癌
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