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Study to overcome the inherent chemoresistance of ovarian clear cell adenocarcinoma based on the functional analyses of ANXA4 molecular subtypes

Research Project

Project/Area Number 25462602
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Obstetrics and gynecology
Research InstitutionYokohama City University

Principal Investigator

MIYAGI Etsuko  横浜市立大学, 医学(系)研究科(研究院), 教授 (40275053)

Co-Investigator(Kenkyū-buntansha) MIYAGI Yohei  地方独立行政法人神奈川県立がんセンター(臨床研究所), がん分子病態学部, 総括部長 (00254194)
YAMADA Roppei  地方独立行政法人神奈川県立がんセンター(臨床研究所), がん生物学部, 技幹 (30404974)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords卵巣がん / パクリタキセル / ANXA4 / 卵巣明細胞腺癌 / パクリタキセル耐性 / annexinA4 / 卵巣明細胞腺がん / 卵巣癌 / 浸潤 / 転移 / アネキシンA4
Outline of Final Research Achievements

Clear cell adenocarcinoma (CCA) is the frequent histologic subtype of the epithelial ovarian cancer in Japanese population. Because it shows resistance to chemotherapy resulted in poor prognosis, the improvement of the treatment is really needed. The group of the principal investigator of this research found annexin A4 (ANXA4) as a highly enriched protein in CCA. Although ANXA4 has been known as a protein involved in chemoresistance in other types of cancers, precise mechanisms of the resistance is still unclear.
The present study disclosed that there are two different molecular types of ANXA4, and each type is involved in Paclitaxel and Carboplatin resistance respectively, which are usually used in ovarian cancer chemotherapy. We further demonstrated a possibility that the chaperon-mediated autophagy through LAMP-2 protein could be involved in the chemoresistance mechanism.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (23 results)

All 2016 2015 2014 2013

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

  • [Journal Article] High-level secretion of tissue factor-rich extracellular vesicles from ovarian cancer cells mediated by filamin-A and protease-activated receptors2016

    • Author(s)
      Koizume S, Ito S, Yoshioka Y, Kanayama T, Nakamura Y, Yoshihara M, Yamada R, Ochiya T, Ruf W, Miyagi E, Hirahara F, Miyagi Y
    • Journal Title

      Thromb Haemost

      Volume: 115 Issue: 02 Pages: 299-310

    • DOI

      10.1160/th15-03-0213

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Phase II study of concurrent chemoradiotherapy with weekly cisplatin and paclitaxel in patients with locally advanced uterine cervical cancer: The JACCRO GY-01 trial.2016

    • Author(s)
      Umayahara K, Takekuma M, Hirashima Y, Noda SE, Ohno T, Miyagi E, Hirahara F, Hirata E, Kondo E, Tabata T, Nagai Y, Aoki Y, Wakatsuki M, Takeuchi M, Toita T, Takeshima N, Takizawa K.
    • Journal Title

      Gynecol Oncol.

      Volume: 140 Issue: 2 Pages: 253-258

    • DOI

      10.1016/j.ygyno.2015.12.008

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Aberrant Expression of the Cell Polarity Regulator aPKCλ/ι is Associated With Disease Progression in Cer2016

    • Author(s)
      Mizushima T, Asai-Sato M, Akimoto K, Nagashima Y, Taguri M, Sasaki K, Nakaya MA, Asano R, Tokinaga A, Kiyono T, Hirahara F, Ohno S, Miyagi E.
    • Journal Title

      Int J Gynecol Pathol.

      Volume: 35 Issue: 2 Pages: 106-17

    • DOI

      10.1097/pgp.0000000000000228

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Aberrant expression of erythropoietin in uterine leiomyoma: implications in tumor growth2015

    • Author(s)
      Ryoko Asano, Mikiko Asai-Sato, Yohei Miyagi, Taichi Mizushima, Makiko Koyama-Sato, Yoji Nagashima, Masataka Taguri, Hideya Sakakibara, Fumiki Hirahara, Etsuko Miyagi
    • Journal Title

      American Journal of Obstetrics and Gynecology

      Volume: 212 Issue: 2 Pages: 1-9

    • DOI

      10.1016/j.ajog.2015.02.016

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Radiation Therapy for Para-Aortic Lymph Node Metastasis from Uterine Cervical Cance2015

    • Author(s)
      Hata M,Miyagi E,Koike I,Numazaki R,Asai-Sato M,Kasuya T,Kaizu H,Mukai Y,Hirahara F,Inoue T
    • Journal Title

      Anticancer Res

      Volume: 35 Pages: 4849-4854

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Three-year questionnaire survey on human papillomavirus vaccination targeting new female college students2015

    • Author(s)
      Sukegawa A, Ohshige K, Arai S, Sakanashi K, Usui M, Hirahara F, Miyagi E
    • Journal Title

      J Obstet Gynaecol Res

      Volume: 41 Issue: 1 Pages: 99-106

    • DOI

      10.1111/jog.12500

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Postoperative radiation therapy for extramammary Paget's disease2015

    • Author(s)
      Hata M, Koike I, Wada H, Miyagi E, Kasuya T, Kaizu H, Mukai Y, Inoue T
    • Journal Title

      Br J Dermatology

      Volume: 172 Issue: 4 Pages: 1014-1020

    • DOI

      10.1111/bjd.13357

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lipid starvation and hypoxia synergistically activate ICAM1 and multiple genes in an Sp1-dependent manner to promote the growth of ovarian cancer2015

    • Author(s)
      Koizume S, Ito S, Nakamura Y et al.
    • Journal Title

      Mol Cancer

      Volume: 14 Issue: 1 Pages: 77-77

    • DOI

      10.1186/s12943-015-0351-z

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Increasing trends in cervical cancer mortality among young Japanese women below the age of 50 years: an analysis using the Kanagawa population-based Cancer Registry, 1975-2012.2015

    • Author(s)
      Motoki Y, Mizushima S, Taguri M, Takahashi K, Asano R, Kato H, Asai-Sato M, Katayama K, Okamoto N, Hirahara F, Miyagi E.
    • Journal Title

      Cancer Epidemiol

      Volume: 39 Issue: 5 Pages: 700-706

    • DOI

      10.1016/j.canep.2015.08.001

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Attitudes toward cervical cancer screening among women receiving human papillomavirus vaccination in a university-hospital-based community: Interim 2-year follow-up results2014

    • Author(s)
      Miyagi E, Sukegawa A, Motoki Y, Kaneko T, Maruyama Y, Asai-Sato M, Numazaki R, Mizushima S, Hirahara F
    • Journal Title

      J Obstet Gynaecol Res

      Volume: 40 Issue: 4 Pages: 1105-1113

    • DOI

      10.1111/jog.12288

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Amino acid profile index for early detection of endometrial cancer: verification as a novel diagnostic marker2014

    • Author(s)
      Ihata Y, Miyagi E, Numazaki R, Muramatsu T, Imaizumi A, Yamamoto H, Yamakado M, Okamoto N, Hirahara F
    • Journal Title

      Int J Clin Oncol

      Volume: 19 Issue: 2 Pages: 364-372

    • DOI

      10.1007/s10147-013-0565-2

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Annexin A4 is involved in proliferation, chemoresistance and migration and invasion in ovarian clear cell adenocarcinoma cells.2013

    • Author(s)
      Mogami T, Yokota N, Asai-sato M, Yamada R, Koizume S, Sakuma Y, Yoshihara M, Nakamura Y, Takano Y, Hirahara F, Miyagi Y, and Miyagi E.
    • Journal Title

      PLOS ONE

      Volume: 8 Issue: 11 Pages: 1-8

    • DOI

      10.1371/journal.pone.0080359

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Secretome-based identification of TFPI2, a novel serum biomarker for detection of ovarian clear cell adenocarcinoma.2013

    • Author(s)
      Arakawa N, Miyagi E, Nomura A, Morita E, Ino Y, Ohtake N, Miyagi Y, Hirahara F, Hirano H.
    • Journal Title

      J. Proteome Res.

      Volume: 12(10) Issue: 10 Pages: 4340-4350

    • DOI

      10.1021/pr400282j

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Radiation therapy for pelvic lymph node metastasis from uterine cervical cancer2013

    • Author(s)
      Hata M, Koike I, Miyagi E, Numazaki R, Asai-Sato M, Kasuya T, Kaizu H, Matsui T, Hirahara F, Inoue T
    • Journal Title

      Gynecol Oncol

      Volume: 131 Issue: 1 Pages: 99-102

    • DOI

      10.1016/j.ygyno.2013.07.085

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] 日本の子宮頸がん予防の将来を考える~横浜・神奈川子宮頸がん予防プロジェクトから見えてきた意識と行動の課題~2015

    • Author(s)
      宮城悦子
    • Organizer
      第34回神奈川県臨床細胞学会学術集会
    • Place of Presentation
      相模原南メディカルセンター(神奈川県相模原市)
    • Year and Date
      2015-10-03
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] International comparison of background to the success or failure of HPV vaccination programmes2015

    • Author(s)
      Konnno R, Miyagi E, Hanley S
    • Organizer
      HPV2015 (30th International Papillomavirus Conference & Clinical Workshop)
    • Place of Presentation
      Lisbon (Portugal)
    • Year and Date
      2015-09-17
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The long and winding road to explore ovarian cancer biomarkers2014

    • Author(s)
      Miyagi E
    • Organizer
      International Symposium for Life Design and Engineering 2014
    • Place of Presentation
      Pacifico Yokohama (神奈川県横浜市)
    • Related Report
      2013 Research-status Report
  • [Presentation] Women against cervical cancer in Japan; Local activities in Yokohama City2013

    • Author(s)
      Miyagi E, Motoki Y, Sato MA, Sukegawa A, Numazaki R, Iwata M, Mizushima S, Ohshige K, Nakayama H, Kato H, Hirahara F
    • Organizer
      EUROGIN2013
    • Place of Presentation
      Florence, Italy
    • Related Report
      2013 Research-status Report
  • [Presentation] Trends in incidence of cervical cancer from 1985 to 2009 in Kanagawa, Japan2013

    • Author(s)
      Motoki Y, Mizushima S, Kaneko T, Kato H, Sato AM, Numazaki R, Okamoto N, Hirahara F, Miyagi E
    • Organizer
      EUROGIN2013
    • Place of Presentation
      Florence, Italy
    • Related Report
      2013 Research-status Report
  • [Presentation] Inhibition of synergistic ICAM1 induction suppresses growth of ovarian clear cell carcinoma2013

    • Author(s)
      Koizume S, Itoh S, Yoshihara M, Nakamura Y, Miyagi E, Hirahara F, Takano Y, Miyagi Y
    • Organizer
      72nd Annual Meeting of the Japanese Cancer Association
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Related Report
      2013 Research-status Report
  • [Presentation] Increase of cervical cancer risk among young Japanese women; Analyses of Kanagawa cancer registry data 1985-20112013

    • Author(s)
      Motoki Y, Kaneko T, Mizushima S, Asai-Sato M, Numazaki R, Kato H, Okamoto N, Hirahara F, Miyagi E
    • Organizer
      The 3rd Biennial Meeting of ASGO/The 55th Meeting of JSGO
    • Place of Presentation
      ウェスティン都ホテル京都(京都府京都市)
    • Related Report
      2013 Research-status Report
  • [Presentation] How can we overcome adverse reactions in HPV vaccination in Japan?2013

    • Author(s)
      Miyagi E
    • Organizer
      The 3rd Biennial Meeting of ASGO/The 55th Meeting of JSGO
    • Place of Presentation
      ウェスティン都ホテル京都(京都府京都市)
    • Related Report
      2013 Research-status Report
  • [Book] がん化学療法クリティカルポイント対応マニュアル2013

    • Author(s)
      監修・編集 宮城悦子
    • Total Pages
      337
    • Publisher
      株式会社じほう
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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