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Epigenetic alterations related to efficacy of neoadjuvant therapy before esophagectomy

Research Project

Project/Area Number 15K10124
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Digestive surgery
Research InstitutionNational Center for Global Health and Medicine

Principal Investigator

Yamada Kazuhiko  国立研究開発法人国立国際医療研究センター, その他部局等, 医長 (70401081)

Co-Investigator(Kenkyū-buntansha) 河村 由紀  国立研究開発法人国立国際医療研究センター, その他, 消化器病態生理研究室長 (10392391)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords癌 / 食道扁平上皮癌 / 化学放射線療法
Outline of Final Research Achievements

Esophageal squamous cell carcinoma (ESCC) is an aggressive form of cancer. Surgery and combined therapies, such as chemotherapy, radiotherapy, or synchronous chemoradiotherapy, have significantly developed in the past several years. To improve the survival rate of ESCC, identifying new markers to predict efficacy of preoperative chemotherapy and/or irradiation is urgently needed. The aim of this study is to identify differences in gene expression and epigenetic alterations between between responders and non-responders who have received neoadjuvant chemotherapy or chemoradiotherapy before esophagectomy for ESCC. We performed integrative transcriptomics by RNA sequencing and methylome sequencing by methyl-DNA immunoprecipitation (MeDIP) analysis. We found genes whose expression levels were different between responders and non-responders; however, there was no difference in their DNA methylation levels between responders and non-responders.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (48 results)

All 2018 2017 2016 2015

All Journal Article (14 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 14 results,  Open Access: 6 results,  Acknowledgement Compliant: 2 results) Presentation (28 results) (of which Int'l Joint Research: 14 results) Book (6 results)

  • [Journal Article] Expression of the desmosome-related molecule periplakin is associated with advanced stage and poor prognosis of esophageal squamous cell carcinoma.2018

    • Author(s)
      Yamada K, Hagiwara T, Inazuka F, Sezaki T, Igari T, Yokoi C, Nohara K, Yamashita S, Dohi T, Kawamura YI.
    • Journal Title

      Transl Cancer Res

      Volume: 7 Pages: 79-87

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] DNA Hypermethylation and silencing of PITX1 correlated with advanced stage and poor postoperative prognosis of esophageal squamous cell carcinoma2017

    • Author(s)
      Otsubo T, Yamada K, Hagiwara T, Oshima K, Iida K, Nishikata K, Toyoda T, Igari T, Nohara K, Yamashita S, Hattori M, Dohi T and Kawamura YI.
    • Journal Title

      Ongotarget

      Volume: 8 Issue: 48 Pages: 84434-84448

    • DOI

      10.18632/oncotarget.21375

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Long-term outcome of esophagectomy for primary malignant melanoma of the esophagus: a single-institute retrospective analysis.2016

    • Author(s)
      Harada K, Mine S, Yamada K, Shigaki H, Oya S, Baba H, Watanabe M
    • Journal Title

      Disease of Esophagus

      Volume: 29 Pages: 314-319

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Fatty acids in a high-fat diet potentially induce gastric parietal-cell damage and metaplasia in mice2016

    • Author(s)
      Hirata, Y. Sezaki, T. Tamura-Nakano, M. Oyama, C. Hagiwara, T. Ishikawa, T. Fukuda, S. Yamada, K. Higuchi, K. Dohi, T. Kawamura, Y. I.
    • Journal Title

      J Gastroenterol

      Volume: - Issue: 8 Pages: 889-903

    • DOI

      10.1007/s00535-016-1291-0

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Telomere Visualization in Tissue Sections Using Pyrrole-Imidazole Polyamide Probes.2016

    • Author(s)
      Sasaki, A., Ide, S., Kawamoto, Y., Bando, T., Murata, Y., Shimura, M., Yamada, K., Hirata, A., Nokihara, K., Hirata, T., Sugiyama, H., Maeshima, K.
    • Journal Title

      Scientific Reports

      Volume: 6 Issue: 1 Pages: 29261-29261

    • DOI

      10.1038/srep29261

    • NAID

      120005774690

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 【イラストで学ぶ消化器外科再建法のすべて】 食道 胃管再建 細径胃管2016

    • Author(s)
      山田 和彦, 野原 京子, 相馬 大介, 山下 智
    • Journal Title

      外科

      Volume: 78 Pages: 1262-1265

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Aberrant DNA hypermethylation reduces the expression of the desmosome-related molecule periplakin in esophageal squamous cell carcinoma2015

    • Author(s)
      Otsubo T, Hagiwara T, Tamura-Nakano M, Sezaki T, Miyake O, Hinohara C, Shimizu T, Yamada K, Dohi T, Kawamura YI.
    • Journal Title

      Cancer Medicine

      Volume: 4 Issue: 3 Pages: 415-425

    • DOI

      10.1002/cam4.369

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Intussusception causing postoperative intestinal obstruction following free jejunum transfer in adults: two case reports and review of the literature.2015

    • Author(s)
      Matsumoto A, Watanabe M, Shigaki H, Okumura Y, Nishida K, Mine S, Yamada K, Yanaga K, Sano T.
    • Journal Title

      Surg Case Rep

      Volume: 1 Issue: 1

    • DOI

      10.1186/s40792-015-0028-2

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Oesophageal cancer with an aberrant right subclavian artery accompanied by a thoracic duct anomaly.2015

    • Author(s)
      Oya S, Mine S, Watanabe M, Yamada K.
    • Journal Title

      Eur J Cardiothorac Surg

      Volume: 48 Issue: 3 Pages: e55-e57

    • DOI

      10.1093/ejcts/ezv224

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Salvage Esophagectomy After Definitive Chemoradiotherapy for Patients with Esophageal Squamous Cell Carcinoma: Who Really Benefits from this High-Risk Surgery?2015

    • Author(s)
      Watanabe M, Mine S, Nishida K, Yamada K, Shigaki H, Matsumoto A, Sano T.
    • Journal Title

      Ann Surg Oncol.

      Volume: 22 Issue: 13 Pages: 4438-44

    • DOI

      10.1245/s10434-015-4556-6

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Long-term outcome of esophagectomy for primary malignant melanoma of the esophagus: a single-institute retrospective analysis.2015

    • Author(s)
      Harada K, Mine S, Yamada K, Shigaki H, Oya S, Baba H, Watanabe M.
    • Journal Title

      Dis Esophagus.

      Volume: Epub Issue: 4 Pages: 314-319

    • DOI

      10.1111/dote.12331

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] 重度心合併症を有する食道切除術の管理2015

    • Author(s)
      荒武 俊伍, 山田 和彦, 新里 陽, 望月 理玄, 橋本 政典, 矢野 秀朗
    • Journal Title

      日本臨床外科学会雑誌

      Volume: 76 Pages: 1272-1276

    • NAID

      130005116718

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] 【食道手術-合併症対処の各施設の工夫-】 術中・術後合併症の予防と対処 当施設の工夫 反回神経麻痺 臨床解剖の理解と合併症の対応2015

    • Author(s)
      山田 和彦, 山田 純, 藤谷 順子, 山内 典恵, 田山 二朗, 峯 真司
    • Journal Title

      手術

      Volume: 69 Pages: 1043-1052

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] 画像を診る 鑑別診断のポイント 胃悪性リンパ腫 胃癌との鑑別が必要な代表的疾患2015

    • Author(s)
      横井 千寿, 山田 和彦, 猪狩 亨
    • Journal Title

      消化器の臨床

      Volume: 18 Pages: 630-632

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Presentation] 食道切除後の腸瘻抜去におけるプレアルブミン値の有用性について2017

    • Author(s)
      山田和彦、野原京子、相馬大介、山下智、大橋恵理、月永暁裕、藤谷順子、岡本竜哉、橋本政典、矢野秀朗
    • Organizer
      日本静脈経腸栄養学会総会
    • Place of Presentation
      岡山
    • Year and Date
      2017-02-23
    • Related Report
      2016 Research-status Report
  • [Presentation] DNA hypermethylation of PITX1 correlated with poor prognosis of esophageal squamous cell carcinoma.2017

    • Author(s)
      Yamada K, Otsubo T, Hagiwara T, Oshima K, Iida K, Nishikata K, Toyoda T, Igari T, Nohara K, Soma D, Kataoka A, Yamashita S, Hattori M, Dohi T, Kawamura YI.
    • Organizer
      The 28th Annual Meeting of the European Society for Diseases of the Esophagus (ESDE)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Expression of the desmosome-related periplakin is associated with advanced stage of esophageal squamous cell carcinoma.2017

    • Author(s)
      Yamada K, Kawamura YI, Hagiwara T, Inazuka F, Sezaki T, Dohi T, Nohara K, Soma D, Yamashita S, Edamoto Y, Yano H, Hashimoto M, Kokudo N.
    • Organizer
      The 15th World Congress of the OESO
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 食道扁平上皮癌におけるメチル化分析から得られたKallikrein-related peptidase 13 (KLK13) の発現と臨床病理学的検討2017

    • Author(s)
      山田和彦、河村由紀、萩原輝記、大坪武史、中野(田村)美和、土肥多惠子、野原京子、相馬大介、山下智、枝元良広、矢野秀朗、橋本政典.
    • Organizer
      第25回日本消化器関連学会週間(JDDW2017)
    • Related Report
      2017 Annual Research Report
  • [Presentation] The utility of 11C-4DST PET compared of 18F-FDG PET in esophageal cancer.2016

    • Author(s)
      Yamada K, Minamimoto R, Hotta M, Nohara K, Soma D, Yamashita S, Yokomizo Y, Yokoi C, Igari T
    • Organizer
      ヨーロッパ食道学会
    • Place of Presentation
      ミュンヘン
    • Year and Date
      2016-12-01
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] PRS27 is downregulated in esophageal squamous cell carcinoma in association with aberrant DNA hypermethylation.2016

    • Author(s)
      Sugimoto T, Hagiwara T, Yamada K, Oyama C, Tamura-Nakano M, Nohara K, Soma D, Yamashita S, Shiba D, Igari T, Yokoi C, Dohi T, Kawamura Y.
    • Organizer
      ヨーロッパ食道学会
    • Place of Presentation
      ミュンヘン
    • Year and Date
      2016-12-01
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 食道癌における縦隔との連続性を意識した頸部郭清.2016

    • Author(s)
      山田 和彦, 野原 京子, 相馬 大介, 山下 智, 横溝 悠里子, 枝元 良広, 徳原 真, 矢野 秀朗, 橋本 政典
    • Organizer
      日本臨床外科学会総会
    • Place of Presentation
      東京
    • Year and Date
      2016-11-24
    • Related Report
      2016 Research-status Report
  • [Presentation] 食道癌手術に対するチーム医療の介入による短期成績2016

    • Author(s)
      山田 和彦, 野原 京子, 相馬 大介, 山下 智, 横溝 悠里子, 大橋 恵里, 岡本 竜哉, 前原 康宏, 橋本 政典.
    • Organizer
      国立病医会
    • Place of Presentation
      沖縄
    • Year and Date
      2016-11-11
    • Related Report
      2016 Research-status Report
  • [Presentation] Expression of the desmosome-related molecule periplakin in esophageal squamous cell carcinoma2016

    • Author(s)
      Yamada K and Kawamura YI.
    • Organizer
      国際食道学会
    • Place of Presentation
      シンガポール
    • Year and Date
      2016-09-19
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Perioperative nutritional support of palliative esophageal bypass surgery.2016

    • Author(s)
      Nakamura M, Yamada K, Nohara K, Yamada J, Yamashita S
    • Organizer
      国際食道学会
    • Place of Presentation
      シンガポール
    • Year and Date
      2016-09-19
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Salvage lymphadenectomy for lymph node recurrence after definitive chemo-radiotherapy.2016

    • Author(s)
      Harino T, Yamada K, Nohara K, Yamashita S, Yamada J, Igari T.
    • Organizer
      国際食道学会
    • Place of Presentation
      シンガポール
    • Year and Date
      2016-09-19
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] ncidence of tachycardia after esophageal cancer surgery in the cases with using β1-selective βblockade2016

    • Author(s)
      Henmi K, Yamada J, Nohara K, Yamashita S, Yamada K.
    • Organizer
      国際食道学会
    • Place of Presentation
      シンガポール
    • Year and Date
      2016-09-19
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Postoperative Delirium in Patients after esophagectomy.2016

    • Author(s)
      Yamashita S, Yamada K, Nohara K, Yamada J, Okamoto T, Henmi K, Tokuhara M, Edamoto Y, Hashimoto M, Yano H
    • Organizer
      国際食道学会
    • Place of Presentation
      シンガポール
    • Year and Date
      2016-09-19
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Integrative analysis of methylome and transcriptome detected loss of Rh type C-glycoprotein in esophageal squamous cell carcinoma.2016

    • Author(s)
      Shiba D, Yamada K, Nohara K, yamada J, Yamashita S, Yokoi C, Igari T, Hagiwara T, Dohi T, Kawamura Y.
    • Organizer
      国際食道学会
    • Place of Presentation
      シンガポール
    • Year and Date
      2016-09-19
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] デスモゾーム関連分子であるperiplakinの発現は予後不良因子になる DNAメチル化と免疫染色での検討.2016

    • Author(s)
      山田 和彦, 河村 由紀, 萩原 輝記, 土肥 多恵子, 猪狩 亨, 山田 純, 野原 京子, 山下 智, 橋本 政典, 矢野 秀朗
    • Organizer
      日本消化器外科学会総会
    • Place of Presentation
      徳島
    • Year and Date
      2016-07-14
    • Related Report
      2016 Research-status Report
  • [Presentation] 食道癌における血液および毛髪でのCDDP濃度に関する検討.2016

    • Author(s)
      山田 和彦, 志村 まり, 山田 純, 野原 京子, 山下 智, 横井 千寿, 猪狩 亨, 橋本 政典, 矢野 秀朗, 飯田 豊
    • Organizer
      日本食道学会総会
    • Place of Presentation
      東京
    • Year and Date
      2016-07-04
    • Related Report
      2016 Research-status Report
  • [Presentation] 食道癌における網羅的メチル化解析より見出されたデスモソーム関連分子periplakinと臨床病理学的検討.2016

    • Author(s)
      山田 和彦, 河村 由紀, 山田 純, 野原 京子, 山下 智, 萩原 輝記, 大坪 武史, 中野 美和[田村], 瀬崎 拓人, 土肥 多恵子, 枝元 良広, 徳原 真, 橋本 政典, 矢野 秀朗.
    • Organizer
      日本外科学会総会
    • Place of Presentation
      大阪
    • Year and Date
      2016-04-14
    • Related Report
      2016 Research-status Report
  • [Presentation] 食道胃接合部癌におけるメチル化分析から得られたデスモソーム関連分子periplakinの意義2016

    • Author(s)
      山田 和彦、河村 由紀、萩原 輝記、平田 有基、土肥 多恵子、山田 純、野原 京子、山下 智、横井 千寿、小島 康志、橋本 政典
    • Organizer
      日本胃癌学会総会
    • Place of Presentation
      別府国際コンベンションセンター、大分
    • Year and Date
      2016-03-17
    • Related Report
      2015 Research-status Report
  • [Presentation] 食道癌切除後周術期におけるインスリン積極的導入の影響2016

    • Author(s)
      山田 和彦, 山田 純, 岡本 竜哉, 金森 功次, 野原 京子, 山下 智, 橋本 政典, 矢野 秀朗, 峯 真司, 渡邊 雅之
    • Organizer
      日本静脈経腸栄養学会
    • Place of Presentation
      福岡国際会議場 福岡
    • Year and Date
      2016-02-26
    • Related Report
      2015 Research-status Report
  • [Presentation] Conventional continuous insulin infusion therapy of perioperative management after esophagectomy.2016

    • Author(s)
      Yamada K, Nohara K, Soma D, Yamashita S, Okamoto T.
    • Organizer
      24th UEG
    • Place of Presentation
      ウィーン
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 食道癌のメチロームおよびトランスクリプトーム統合解析により見出されたホメオボックス遺伝子の発現低下2015

    • Author(s)
      河村 由紀、大坪 武史、山田 和彦、萩原 輝記、大島 健志朗、飯田 慶、西方 公郎、豊田 哲郎、猪狩 亨、山田 純、野原 京子、服部 正平、土肥 多惠子
    • Organizer
      日本生化学会大会
    • Place of Presentation
      神戸国際展示場、兵庫
    • Year and Date
      2015-12-02
    • Related Report
      2015 Research-status Report
  • [Presentation] Perioperative management of esophagectomy with liver disease2015

    • Author(s)
      K. Yamada, J. Yamada, K. Nohara, S. Yamashita, S. Mine, M. Watanabe, H. Yano, M. Hashimoto
    • Organizer
      European Society for Disease of the Esophagus
    • Place of Presentation
      ストックホルム スウェーデン
    • Year and Date
      2015-11-05
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 食道扁平上皮癌のメチロームおよびトランスクリプトーム統合解析により見出されたデスモソーム関連分子periplakinの発現低下2015

    • Author(s)
      河村 由紀、大坪 武史、山田 和彦、猪狩 亨、土肥 多惠子
    • Organizer
      日本癌学会総会
    • Place of Presentation
      名古屋国際会議場、名古屋
    • Year and Date
      2015-10-09
    • Related Report
      2015 Research-status Report
  • [Presentation] 消化器外科領域における医療安全の状況2015

    • Author(s)
      山田 和彦, 山田 純, 野原 京子, 山下 智, 矢野 秀朗, 橋本 政典, 六ツ見 しのぶ, 廣井 透雄, 蓑和田 滋, 岡本 竜哉
    • Organizer
      国立病院総合医学会総会
    • Place of Presentation
      ロイトン札幌 札幌
    • Year and Date
      2015-10-01
    • Related Report
      2015 Research-status Report
  • [Presentation] Survey and reporting system for patient safety at Gastrointestinal Surgical ward in Japan2015

    • Author(s)
      K. Yamada, C. Yokoi, M. Takamoto, T. Fukaya, K. Doi, S. Mutsumi, Y. Hiroi, S. Minowada
    • Organizer
      International Association of Risk Management Medicine
    • Place of Presentation
      ウィーン オーストリア
    • Year and Date
      2015-09-28
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 食道扁平上皮癌でのデスモソーム関連分子periplakinとDNAメチル化異常について2015

    • Author(s)
      山田 和彦、河村 由紀、萩原 輝記、大坪 武史、中野(田村) 美和、瀬崎 拓人、土肥 多恵子、枝元 良広、橋本 政典、矢野 秀朗
    • Organizer
      日本消化器外科学会総会
    • Place of Presentation
      アクトシティ浜松、静岡
    • Year and Date
      2015-07-17
    • Related Report
      2015 Research-status Report
  • [Presentation] 根治的化学放射線療法後の高度狭窄、瘻孔に対する食道バイパス手術の成績2015

    • Author(s)
      山田 和彦, 山田 純, 望月 理玄, 山田 玲央, 橋本 政典, 矢野 秀朗, 志垣 博信, 峯 真司, 渡邊 雅之, 瀬戸 泰之
    • Organizer
      日本食道学会総会
    • Place of Presentation
      パシフィコ横浜 横浜
    • Year and Date
      2015-07-02
    • Related Report
      2015 Research-status Report
  • [Presentation] Integrative analysis of DNA methylome and transcriptome detected loss of a desmosome protein in esophageal squamous cell carcinoma2015

    • Author(s)
      Yuki I. Kawamura, Takeshi Otsubo, Teruki Hagiwara, Miwa Tamura-Nakano, Takuhito Sezaki, Oki Miyake, Toru Igari, Kazuhiko Yamada, Taeko Dohi
    • Organizer
      Digestive Disease Week Annual Meeting
    • Place of Presentation
      Washington DC, USA
    • Year and Date
      2015-05-16
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Book] がん研スタイル 癌の標準手術 食道癌2016

    • Author(s)
      山田和彦
    • Total Pages
      214
    • Publisher
      メジカルビュー社
    • Related Report
      2016 Research-status Report
  • [Book] がん研スタイル 癌の標準手術 食道癌 再建胃管癌の手術2016

    • Author(s)
      山田和彦
    • Total Pages
      214
    • Publisher
      メジカルビュー社
    • Related Report
      2016 Research-status Report
  • [Book] がん研スタイル 癌の標準手術 食道癌 頸部郭清2016

    • Author(s)
      山田和彦
    • Total Pages
      214
    • Publisher
      メジカルビュー社
    • Related Report
      2016 Research-status Report
  • [Book] がん研スタイル 癌の標準手術 食道癌 経裂孔的下部食道切除2016

    • Author(s)
      山田和彦
    • Publisher
      メジカルビュー社
    • Related Report
      2015 Research-status Report
  • [Book] がん研スタイル 癌の標準手術 食道癌 再建胃管癌の手術2015

    • Author(s)
      山田和彦
    • Publisher
      メジカルビュー社
    • Related Report
      2015 Research-status Report
  • [Book] がん研スタイル 癌の標準手術 食道癌 頸部郭清2015

    • Author(s)
      山田和彦
    • Publisher
      メジカルビュー社
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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