5-Aza-2-deoxycytidineはthymidine phosphorylaseの脱メチル化を介して5-fluorouracilの感受性を高める

• Material Type: 博士論文
• Title: 5-Aza-2-deoxycytidineはthymidine phosphorylaseの脱メチル化を介して5-fluorouracilの感受性を高める
• Author/Editor: 西澤, 由紀彦
• Author Heading: 西澤, 由紀彦 ニシザワ, ユキヒコ
• Publication, Distribution, etc.: International Institute of Anticancer Research
• Alternative Title: 5-Aza-2-deoxycytidine enhances thesensitivity of 5-fluorouracil by demethylation of the thymidine phosphorylase promoter
• Degree grantor/type: 鹿児島大学
• Date Granted: 2020-10-16
• Dissertation Number: 乙総論第40号
• Degree Type: 博士(医学); Doctor of Philosophy in Medical Science
• Text Language Code: eng
• Subject Heading: 5-fluorouracil; 5-aza-2-deoxycytidine; thymidine phosphorylase; methylation
• Target Audience: 一般
• Note (General): 博士論文全文, 博士論文要旨, 最終試験結果の要旨, 論文審査の要旨; 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. 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
• Format (IMT): application/pdf
• Access Restrictions: インターネット公開
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 鹿児島大学 : 鹿児島大学リポジトリ

Table of Contents

Result_Nishizawa_Yukihiko_isk_40 other

Comments_Nishizawa_Yukihiko_isk_40 other

Diss_西澤_由紀彦_ISK40_2020 fulltext

Abstract_西澤_由紀彦_TO_2020 abstract