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Elucidating the mechanism of resistance to chemotherapy in gynecologic cancer based on intratumor heterogeneity

Research Project

Project/Area Number 15K15598
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Obstetrics and gynecology
Research InstitutionNiigata University

Principal Investigator

Enomoto Takayuki  新潟大学, 医歯学系, 教授 (90283754)

Co-Investigator(Kenkyū-buntansha) 吉原 弘祐  新潟大学, 医歯学系, 助教 (40547535)
加嶋 克則  新潟大学, 医歯学総合病院, 特任教授 (50345500)
関根 正幸  新潟大学, 医歯学系, 准教授 (70345502)
石黒 竜也  新潟大学, 医歯学総合病院, 助教 (80625690)
Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywordsintratumor heterogeneity / cancer genome / spheroid / Intratumor heterogeneity
Outline of Final Research Achievements

In this study, we generated total 11 spheroid cultures derived from gynecologic cancers. Before genomic analyses for spheroid cultures, we focused on Sex-determining region Y-box 2 (SOX2), which is an essential factor involved in the self-renewal and pluripotency of embryonic stem cells, to clarify the significance of SOX2 expression in endometrial cancer. SOX2 overexpression regulated the expression of cyclin-dependent kinase inhibitor 1A (CDKN1A), and SOX2 specifically bound to p21 promoter DNA in endometrial cancer cell lines expressing SOX2. Expressions of SOX2 in endometrial cancer patients were significantly correlated with histological grade and poor prognosis. Moreover, low p21 together with high SOX2 expressions in advanced endometrial cancer patients were associated with the most unfavorable outcomes of patients. These results indicated that simultaneous measurement of SOX2 and p21 expression in endometrial cancer patients may be a useful biomarker for patient prognosis.

Report

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

    (22 results)

All 2017 2016 2015

All Journal Article (14 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 14 results,  Acknowledgement Compliant: 2 results,  Open Access: 5 results) Presentation (8 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results)

  • [Journal Article] Establishment and characterization of an in vitro model of ovarian cancer stem-like cells with an enhanced proliferative capacity2016

    • Author(s)
      Ishiguro T, Sato A, Ohata H, Ikarashi Y, Takahashi R, Ochiya T, Yoshida M, Tsuda H, Onda T, Kato T, Kasamatsu T, Enomoto T, Tanaka K, Nakagama H, Okamoto K.
    • Journal Title

      Cancer Research

      Volume: 76 Issue: 1 Pages: 150

    • DOI

      10.1158/0008-5472.can-15-0361

    • Related Report
      2016 Annual Research Report 2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] The randomized phase 3 trial of irinotecan plus cisplatin compared with paclitaxel plus carboplatin as first line chemotherapy for ovarian clear cell carcinoma: JGOG3017/GCIG Trial.2016

    • Author(s)
      Sugiyama T, Okamoto A, Enomoto T, Hamano T, Aotani E, Terao Y, Suzuki N, Mikami M, Yaegashi N, Kato K, Yoshikawa H, Yokoyama Y, Tanabe H, Nishino K, Nomura H, Kim JW, Kim BG, Pignata S, Alexandre J, Green J, Isonishi S, Terauchi F, Fujiwara K, Aoki D.
    • Journal Title

      J Clin Oncol

      Volume: 34 Issue: 24 Pages: 2881-2887

    • DOI

      10.1200/jco.2016.66.9010

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Single-dose intra- arterial neoadjuvant chemotherapy while waiting for radical hysterectomy for stage IB-IIB cervical cancer.2016

    • Author(s)
      Yoshino K, Hosoi A, Osuga K, Enomoto T, Ueda Y, Sawada K, Mabuchi S, Kobayashi E, Matsuo K, Kimura T.
    • Journal Title

      Mol Clin Oncol.

      Volume: 4 Issue: 6 Pages: 1068-1072

    • DOI

      10.3892/mco.2016.846

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Association of Low-Dose Aspirin and Survival of Women With Endometrial Cancer.2016

    • Author(s)
      Matsuo K, Cahoon SS, Yoshihara K, Shida M, Kakuda M, Adachi S, Moeini A, Machida H, Garcia-Sayre J, Ueda Y, Enomoto T, et al.
    • Journal Title

      Obstet Gynecol.

      Volume: 128 Issue: 1 Pages: 127-37

    • DOI

      10.1097/aog.0000000000001491

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Allelic Imbalance in Regulation of ANRIL through Chromatin Interaction at 9p21 Endometriosis Risk Locus.2016

    • Author(s)
      Nakaoka H, Gurumurthy A, Hayano T, Ahmadloo S, Omer WH, Yoshihara K, Yamamoto A, Kurose K, Enomoto T, Akira S, Hosomichi K,, Inoue I.
    • Journal Title

      PLoS Genet.

      Volume: 1 Issue: 4 Pages: 1-23

    • DOI

      10.1371/journal.pgen.1005893

    • Related Report
      2016 Annual Research Report 2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Establishment of a Novel Histopathological Classification of High-Grade Serous Ovarian Carcinoma Correlated with Prognostically Distinct Gene Expression Subtypes.2016

    • Author(s)
      Murakami R, Matsumura N, Mandai M, Yoshihara K, Tanabe H, Nakai H, Yamanoi K, Abiko K, Yoshioka Y, Hamanishi J, Yamaguchi K, Baba T, Koshiyama M, Enomoto T, Okamoto A, Murphy SK, Mori S, Mikami Y, Minamiguchi S, Konishi I
    • Journal Title

      Am J Pathol.

      Volume: 186 Issue: 5 Pages: 1103-13

    • DOI

      10.1016/j.ajpath.2015.12.029

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Mothers' attitudes in Japan regarding cervical cancer screening correlates with intention to recommend cervical cancer screening for daughters.2016

    • Author(s)
      Egawa-Takata T, Ueda Y, Tanaka Y, Morimoto A, Kubota S, Yagi A, Terai Y, Ohmichi M, Ichimura T, Sumi T, Murata H, Okada H, Nakai H, Mandai M, Yoshino K, Kimura T, Saito J, Kudo R, Sekine M, Enomoto T, Horikoshi Y, Takagi T, Shimura K.
    • Journal Title

      Int J Clin Oncol.

      Volume: 21 Issue: 5 Pages: 962-968

    • DOI

      10.1007/s10147-016-0970-4

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Similar protein expression profiles of ovarian and endometrial high-grade serous carcinomas.2016

    • Author(s)
      Hiramatsu K, Yoshino K, Serada S, Yoshihara K, Hori Y, Fujimoto M, Matsuzaki S, Egawa-Takata T, Kobayashi E, Ueda Y, Morii E, Enomoto T, Naka T, Kimura T.
    • Journal Title

      Br J Cancer.

      Volume: 114(5) Issue: 5 Pages: 554-561

    • DOI

      10.1038/bjc.2016.27

    • Related Report
      2016 Annual Research Report 2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] A phase II study of postoperative concurrent carboplatin and paclitaxel combined with intensity-modulated pelvic radiotherapy followed by consolidation chemotherapy in surgically treated cervical cancer patients with positive pelvic lymph nodes.2016

    • Author(s)
      Mabuchi S, Isohashi F, Yokoi T, Takemura M, Yoshino K, Shiki Y, Ito K, Enomoto T, Ogawa K, Kimura T.
    • Journal Title

      Gynecol Oncol.

      Volume: 141 Pages: 240-6

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Venous thromboembolism, interleukin-6 and survival outcomes in patients with advanced ovarian clear cell carcinoma.2015

    • Author(s)
      Matsuo K, Hasegawa K, Yoshino K, Murakami R, Hisamatsu T, Stone RL, Previs RA, Hansen JM, Ikeda Y, Miyara A, Hiramatsu K, Enomoto T, Fujiwara K, Matsumura N, Konishi I, Roman LD, Gabra H, Fotopoulou C, Sood AK.
    • Journal Title

      Eur J Cancer

      Volume: 51(14) Pages: 1978-88

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Survival outcome of stage I ovarian clear cell carcinoma with lympho-vascular space invasion.2015

    • Author(s)
      Matsuo K, Yoshino K, Hasegawa K, Murakami R, Ikeda Y, Adachi S, Hiramatsu K, Yokoyama T, Nishimura M, Sheridan TB, Enomoto T, Fujiwara K, Matsumura N, Konishi I, Fotopoulou C, Roman LD, Sood AK.
    • Journal Title

      Gynecol Oncol.

      Volume: 136(2) Pages: 198-204

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Novel kinase fusion transcripts found in endometrial cancer.2015

    • Author(s)
      Tamura R, Yoshihara K, Yamawaki K, Suda K, Ishiguro T, Adachi S, Okuda S, Inoue I, Verhaak RG, Enomoto T.
    • Journal Title

      Sci Rep.

      Volume: 5 Issue: 1 Pages: 18657-18657

    • DOI

      10.1038/srep18657

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] CpG ODN potentiates the anti-tumor activity of anti-BST2 antibody.2015

    • Author(s)
      Hiramatsu, K., Serada, S., Kobiyama, K., Nakagawa, S., Morimoto, A., Matsuzaki, S., Ueda,Y., Fujimoto, M., Yoshino, K., Ishii, K., Enomoto, T., Kimura, T., Naka, T.
    • Journal Title

      Cancer Science

      Volume: 106(10) Issue: 10 Pages: 474-82

    • DOI

      10.1111/cas.12738

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of novel exonic mobile element insertions in epithelial ovarian cancers.2015

    • Author(s)
      Hayano,T., Yamada,S., Hosomichi,K., Nakaoka,H., Yoshihara,K., Adachi.S. Kashima,K., Tanaka, K and Enomoto,T.& Inoue,I.
    • Journal Title

      Human Genome Variation

      Volume: 2 Issue: 1 Pages: 15030-15030

    • DOI

      10.1038/hgv.2015.30

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Presentation] The significance of activated PI3K/AKT pathway in FGFR3-TACC3 fusion positive cervical cancer2017

    • Author(s)
      田村 亮、吉原 弘祐、森 裕太郎、山脇 芳、須田 一暁、石黒 竜也、榎本 隆之
    • Organizer
      American Association of Cancer Research Annual Meeting 2017
    • Place of Presentation
      Washington DC,USA
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Identificat of therapeutically targetable FGFR-fusion genes in cervical cancer through RNA sequencing2017

    • Author(s)
      田村 亮、吉原 弘祐、石黒 竜也、榎本 隆之
    • Organizer
      第69回日本産科婦人科学会学術講演会
    • Place of Presentation
      広島県立総合体育館 外(広島県広島市)
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 婦人科領域における分子標的治療の現況と将来2016

    • Author(s)
      榎本 隆之
    • Organizer
      第42回日本臨床細胞学会近畿連合会
    • Place of Presentation
      ナレッジキャピタルコンベンションセンター(大阪府大阪市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] 妊娠と子宮頸がん2016

    • Author(s)
      榎本 隆之
    • Organizer
      第43回日本産婦人科医会学術集会
    • Place of Presentation
      万国津梁館(沖縄県名護市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] 子宮頸がんについての最近の話題2016

    • Author(s)
      榎本 隆之
    • Organizer
      第4回新潟市医師会総会 第51回新潟市医師会臨床懇話会総会
    • Place of Presentation
      新潟東映ホテル(新潟県新潟市)
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 子宮体がんにおける幹細胞因子Sox2発現の意義2016

    • Author(s)
      森 裕太郎、山脇 芳、石黒 竜也、吉原 弘祐、榎本 隆之
    • Organizer
      第15回日本婦人科がん分子標的研究会
    • Place of Presentation
      ニューオータニイン札幌(北海道札幌市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] A proteomic analysis demonstrates similar expression pattern between ovarian and endometrial high-grade serous carcinoma beyond an organ2015

    • Author(s)
      Kosuke Hiramatsu, Kiyoshi Yoshino, Satoshi Serada, Kosuke Yoshihara, Minoru Fujimoto, Yutaka Ueda, Eiichi Morii, Takayuki Enomoto, Tetsuji Naka, Tadashi Kimura
    • Organizer
      24th Asian and Oceanic Congress of Obstetrics and Gynaecology
    • Place of Presentation
      Borneo Convention Centre Kuching (Malaysia)
    • Year and Date
      2015-06-05
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 卵巣および子宮体部のhigh- grade serous carcinoma の類似性の証明2015

    • Author(s)
      平松宏祐、榎本隆之、吉原弘祐、上田豊、吉野潔、森井英一、仲哲治、木村正
    • Organizer
      第67回日本産科婦人科学会学術講演会
    • Place of Presentation
      パシフィコ横浜(神奈川県、横浜市)
    • Year and Date
      2015-04-10
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2018-03-22  

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