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KAKEN_16K11154seika.pdf
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エピゲノム異常を標的とした子宮内膜癌の新たな診断・治療法の探索
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Kana |
エピゲノム イジョウ オ ヒョウテキ ト シタ シキュウ ナイマクガン ノ アラタナ シンダン・チリョウホウ ノ タンサク
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Epigenomu ijō o hyōteki to shita shikyū naimakugan no aratana shindan chiryōhō no tansaku
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The study of novel diagnosis and treatment for endometrial cancer targeting aberrant DNA methylation
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阪埜, 浩司
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バンノ, コウジ
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Banno, Kōji
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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 : 70265875
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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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(1)腫瘍部において異常高メチル化を認める子宮内膜癌患者と認めない子宮内膜癌患者の末梢血DNAにおける遺伝子プロモーター領域のメチル化をゲノムワイドに比較した結果、Differentially Methylated CpG (DMC) およびDifferentially Methylated Region (DMR)としてmiR-663aを同定した。(2) プロゲスチン製剤および2型糖尿病薬を併用することにより、子宮内膜癌細胞に対し殺細胞効果が認められることをin vitroおよびin vivo実験にて明らかにした。
(1) Based on genome-wide bisulfite sequencing, peripheral blood cells(PBCs) DNA in M-H cases had significant hypermethylation in the miR-663a promoter region, compared to U cases (meth. Diff. > 25%, q-value < 0.01). Consistent with this methylation status, miR-663a expression was lower in M-H PBCs than in U PBCs. DNMTs expression levels in M-H endometrial cancer were higher than those in U endometrial cancer. (2) Metformin had a dose-dependent anticancer effect on endometrial cancer cell lines. Moreover, the combined treatment also caused lower cell viability.The microarray analysis indicated that EDN2 expression was upregulated in cells subject to the combined treatment. EDN2 expression was upregulated in each cell line upon treatment with a demethylating agent.
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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 : 16K11154
研究分野 : 婦人科腫瘍学
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