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The aim of this study was to investigate the molecular mechanism that enhances the sensitivity to 5-FU treated with 5-Aza-CdR via thymidine phosphorylase (TP). Materials and Methods: The sensitivity to drugs was determined on several cancer cell lines by the MTT assay. Protein and mRNA levels were examined by immunoblot and RT-PCR, respectively. Gene silencing, binding of Sp1 to DNA and methylation of DNA was performed by siRNA, ChIP assay and sodium bisulfate genomic sequencing, respectively. Results: Sp1-binding sites in the TP promoter were methylated in epidermoid carcinoma. 5-Aza-CdR demethylated Sp1-binding sites and enhanced sensitivity to 5-FU. 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5-Aza-2-deoxycytidine enhances thesensitivity of 5-fluorouracil by demethylation of the thymidine phosphorylase promoter
http://hdl.handle.net/10232/00031492
http://hdl.handle.net/10232/00031492c7db7588-4d2c-4196-bca8-508cd68b4759
名前 / ファイル | ライセンス | アクション |
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Item type | 学位論文 / Thesis or Dissertation(1) | |||||
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公開日 | 2020-10-27 | |||||
タイトル | ||||||
タイトル | 5-Aza-2-deoxycytidine enhances thesensitivity of 5-fluorouracil by demethylation of the thymidine phosphorylase promoter | |||||
別言語のタイトル | ||||||
その他のタイトル | 5-Aza-2-deoxycytidineはthymidine phosphorylaseの脱メチル化を介して5-fluorouracilの | |||||
著者 |
西澤, 由紀彦
× 西澤, 由紀彦 |
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著者よみ | ||||||
姓名 | ニシザワ, ユキヒコ | |||||
別言語の著者 | ||||||
姓名 | NISHIZAWA, Yukihiko | |||||
言語 | ||||||
言語 | eng | |||||
キーワード | ||||||
主題言語 | en | |||||
主題Scheme | Other | |||||
主題 | 5-fluorouracil | |||||
キーワード | ||||||
主題言語 | en | |||||
主題Scheme | Other | |||||
主題 | 5-aza-2-deoxycytidine | |||||
キーワード | ||||||
主題言語 | en | |||||
主題Scheme | Other | |||||
主題 | thymidine phosphorylase | |||||
キーワード | ||||||
主題言語 | en | |||||
主題Scheme | Other | |||||
主題 | methylation | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||
資源タイプ | doctoral thesis | |||||
アクセス権 | ||||||
アクセス権 | open access | |||||
アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||
要約(Abstract) | ||||||
内容記述タイプ | Other | |||||
内容記述 | Background/Aim: 5-Aza-2-deoxycytidine (5-Aza-CdR) enhances the sensitivity to 5-fluorouracil (5-FU), but the molecular mechanism is not fully understood. The aim of this study was to investigate the molecular mechanism that enhances the sensitivity to 5-FU treated with 5-Aza-CdR via thymidine phosphorylase (TP). Materials and Methods: The sensitivity to drugs was determined on several cancer cell lines by the MTT assay. Protein and mRNA levels were examined by immunoblot and RT-PCR, respectively. Gene silencing, binding of Sp1 to DNA and methylation of DNA was performed by siRNA, ChIP assay and sodium bisulfate genomic sequencing, respectively. Results: Sp1-binding sites in the TP promoter were methylated in epidermoid carcinoma. 5-Aza-CdR demethylated Sp1-binding sites and enhanced sensitivity to 5-FU. Conclusion: Demethylation of Sp1-binding sites by 5-Aza-CdR was a key factor enhancing 5-FU sensitivity, which may enable more effective treatments for cancer patients with the combination of 5-Aza-CdR and 5-FU. | |||||
要約(Abstract) | ||||||
内容記述タイプ | Other | |||||
内容記述 | YUKIHIKO NISHIZAWA, RYUJI IKEDA, MASATATSU YAMAMOTO, KOHICHI KAWAHARA, YOSHINARI SHINSATO, KENTARO MINAMI, MINA NITTA, HIDEYUKI TERAZONO, SHIN-ICHI AKIYAMA, TATSUHIKO FURUKAWA and YASUO TAKEDA 5-Aza-2-deoxycytidine Enhances the Sensitivity of 5-Fluorouracil by Demethylation of the Thymidine Phosphorylase Promoter Anticancer Research, 2019, 39(8) p.4129-4136 DOI: https://doi.org/10.21873/anticanres.13571 |
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作成日 | ||||||
日付 | 2020-10-08 | |||||
出版タイプ | ||||||
出版タイプ | VoR | |||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
NDC | ||||||
主題Scheme | NDC | |||||
主題 | 490 | |||||
ファイル(説明) | ||||||
内容記述タイプ | Other | |||||
内容記述 | 博士論文全文 | |||||
ファイル(説明) | ||||||
内容記述タイプ | Other | |||||
内容記述 | 博士論文要旨 | |||||
ファイル(説明) | ||||||
内容記述タイプ | Other | |||||
内容記述 | 最終試験結果の要旨 | |||||
ファイル(説明) | ||||||
内容記述タイプ | Other | |||||
内容記述 | 論文審査の要旨 | |||||
公開者・出版者 | ||||||
出版者 | International Institute of Anticancer Research | |||||
公開者・出版者 | ||||||
出版者 | 鹿児島大学 | |||||
公開者よみ | ||||||
公開者よみ | カゴシマ ダイガク | |||||
公開者別名 | ||||||
公開者別名 | Kagoshima University | |||||
備考 | ||||||
備考 | 【指導教員:武田泰生】 | |||||
date.appl | ||||||
【学位申請日】2020-08-05 | ||||||
学位名 | ||||||
学位名 | 博士(医学)Doctor of Philosophy in Medical Science | |||||
学位授与機関 | ||||||
学位授与機関識別子Scheme | kakenhi | |||||
学位授与機関識別子 | 17701 | |||||
学位授与機関名 | 鹿児島大学 | |||||
学位授与年月日 | ||||||
学位授与年月日 | 2020-10-16 | |||||
学位授与番号 | ||||||
学位授与番号 | 乙総論第40号 |