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Targeting annexin A4 to counteract chemoresistance in Gynecologic Cancer

Research Project

Project/Area Number 22591854
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionOsaka University

Principal Investigator

ENOMOTO Takayuki  大阪大学, 大学院・医学系研究科, 招へい教授 (90283754)

Co-Investigator(Kenkyū-buntansha) FUJITA Masami  大阪大学, 大学院・医学系研究科, 講師 (60303963)
YOSHINO Kiyoshi  大阪大学, 大学院・医学系研究科, 講師 (90362730)
UEDA Yutaka  大阪大学, 大学院・医学系研究科, 助教 (10346215)
KIMURA Toshihiro  大阪大学, 大学院・医学系研究科, 助教 (90584524)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords婦人科腫瘍学 / 子宮体癌 / 卵巣癌 / AnnexinA4 / 蛋白質 / トランスポーター
Research Abstract

In this report, we investigated the mechanism of platinum resistance induced by Anx A4 in endometrial carcinoma cells (HEC1 cells) which had low level expression of Anx A4. In HEC1 cells, forced expression of Anx A4 resulted in chemoresistance to Cisplatin or Carboplatin in vitro and in vivo. Most importantly, after exposure to Cisplatin or Carboplatin, Anx A4 changed localization from the cytoplasm to the cellular membrane and Anx A4 and ATP7A co-localized to the cellular membrane. Our results indicate that enhanced expression of Anx A4 confers platinum resistance by promoting efflux of platinum drugs via ATP7A.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (35 results)

All 2013 2012 2011 Other

All Journal Article (17 results) (of which Peer Reviewed: 17 results) Presentation (18 results)

  • [Journal Article] Salvage chemotherapy for recurrent or persistent clear cell carcinoma of the ovary: a single-institution experience for a series of 20 patients2013

    • Author(s)
      Yoshino K, Enomoto T, Fujita M, Ueda Y, Kimura T, Kobayashi E, Tsutsui T, Kimura T
    • Journal Title

      Int J Clin Oncol

      Volume: 18 Issue: 1 Pages: 148-53

    • DOI

      10.1007/s10147-011-0357-5

    • NAID

      10031176248

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Plasma nlembrane proteonlics identifies bone marrow stromal antigen 2 as a potential therapeutic target in endometrial cancer2013

    • Author(s)
      Yokoyama T, Enomoto T, Serada S, Morimoto A, Matsuzaki S, Ueda Y, Yoshino K, Fujita M, Kyo S, Iwahori K, Fujimoto M, Kimura T, Naka T
    • Journal Title

      Int J Cancer

      Volume: 132(2) Issue: 2 Pages: 472-84

    • DOI

      10.1002/ijc.27679

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] nvestigating the relative efficacies of combination chemotherapy of paclitaxel/carboplatin, with or without anthracycline, for endometrial carcinoma2012

    • Author(s)
      Fujiwara K, Egawa-Takata T, Ueda Y, Kimura T, Yoshino K, Fujita M, Miyatake T, Kamiura S, Enomoto T, Kimura T
    • Journal Title

      Arch Gyn Ob

      Volume: 285 Issue: 5 Pages: 1447-53

    • DOI

      10.1007/s00404-011-2154-9

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Salvage chemotherapy for ovarian carcinoma recurring during or after consolidation chemotherapy with paclitaxel2011

    • Author(s)
      Miyoshi Y, Ueda Y, Morimoto A, Yokoyama T, Matsuzaki S, Kobayashi E, Kimura T, Yoshino K, Fujita M, Enomoto T, Kimura T
    • Journal Title

      Anticanc R

      Volume: 31 Pages: 4613-17

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] HB-EGF and PDGF Mediate Reciprocal Interactions of Carcinoma Cells with Cancer-associated Fibroblasts to Support Progression of Uterine Cervical Cancers2011

    • Author(s)
      Murata T, Mizushima H, Ichino Chinen I, Moribe H, Yagi S, Robert M Hoffman, Kimura T, Yoshino K, Ueda Y, Enomoto T, Mekada E
    • Journal Title

      Cancer Research

      Volume: 71 Pages: 6633-42

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Targeting SRC in Mucinous Ovarian Carcinoma2011

    • Author(s)
      Matsuo K, Enomoto T
    • Journal Title

      Clin Cancer Res

      Volume: 17 Pages: 5367-78

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Chemotherapy for endometrial carcinoma (GOGO-EM1study):TEC(paclitaxel, epirubicin and carboplatin) is an effective remission-induction and adjuvant therapy2011

    • Author(s)
      Egawa-Takata T, Ueda Y, Fujita M, Yoshino K, Enomoto T
    • Journal Title

      Cancer Chemother Pharmacol

      Volume: 68 Issue: 6 Pages: 1603-10

    • DOI

      10.1007/s00280-011-1638-4

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Recurrent endometrial carcinoma:Prognosis for patients with recurrence within six to twelve months is worse relative at 12 months or later2011

    • Author(s)
      Miyake T, Ueda Y, Egawa-Takata T, Matsuzaki S, Yokoyama T, Miyoshi Y, Kimura T, Yoshino K, Fujita M, Yamasaki M, Enomoto T, Kimura T
    • Journal Title

      Am J Obstet Gynecol

      Volume: 204

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Questionnaire survey of the current status of radical trachelectomy in Japan2011

    • Author(s)
      Sato S, Enomoto T
    • Journal Title

      Int J Clin Oncol

      Volume: 16 Issue: 2 Pages: 141-4

    • DOI

      10.1007/s10147-010-0146-6

    • NAID

      10029366477

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Salvage chemotherapy for ovarian carcinoma recurring during or after of onsolidation chemotherapy with paclitaxel2011

    • Author(s)
      Miyoshi Y, Ueda Y, Morimoto A, Yokoyama T, Matsuzaki s, Kobayashi E, Kimura T, Yoshino K, Fujita M, Enomoto T, Kimura T
    • Journal Title

      Anticancer Res

      Volume: 31 Pages: 4613-4613

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Salvage chemotherapy for recurrent or persistent clear cell carcinoma of the ovary : a single-institution experience for a series of 20 patients2011

    • Author(s)
      Yoshino K, Enomoto T, Fujita M Ueda Y, Kimura T, Kobayashi E, Tsutsui T, Kimura T
    • Journal Title

      Int J Clin Oncol

      Volume: (印刷中)

    • NAID

      10031176248

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Investigating the relative efficacies of combination chemotherapy of paclitaxel/carboplatin, with or without anthracycline, for endometrial carcinoma2011

    • Author(s)
      Fujiwara K, Egawa-Takata T, Ueda Y, Kimura T, Yoshino K, Fujita M, Miyatake T, Ohta Y, Kamiura S, Enomoto T, Kimura T
    • Journal Title

      Arch Gynecol Obstet

      Volume: (印刷中)

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] HB-EGF and PDGF mediate reciprocal interactions of carcinoma cells with cancer-associated fibroblasts to support progression of uterine cervical cancers2011

    • Author(s)
      Murata T, Mizushima H, Chinen I, Moribe H, Yagi S, Hoffman RM, Kimura T, Yoshino K, Ueda Y, Enomoto T, Mekada E
    • Journal Title

      Cancer Res

      Volume: 71 Pages: 6633-6633

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Targeting SRC in mucinous ovarian carcinoma2011

    • Author(s)
      Matsuo K, Nishimura M, Bottsford-Miller JN, Huang J, Komurov K, Armaiz-Pena GN, Shahzad MM, Stone RL, Roh JW, Sanguino AM, Lu C, Im DD, Rosenshien NB, Sakakibara A, Nagano T, Yamasaki M, Enomoto T, Kimura T, Ram PT, Schmeler KM, Gallick GE, Wong KK, Frumovitz M, Sood AK
    • Journal Title

      Clin Cancer Res

      Volume: 17 Pages: 5367-5367

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chemotherapy for endometrial carcinoma (GOGO-EM1 study) : TEC (paclitaxel, epirubicin, and carboplatin) is an effective remission-induction and adjuvant therapy2011

    • Author(s)
      Egawa-Takata T, Ueda Y, Kuragaki C, Miyake T, Miyatake T, Fujita M, Yoshino K, Nakashima R, Okazawa M, Tsutsui T, Morishige K, Kimura T, Yamasaki M, Nishizaki T, Nagamatsu M, Ito K, Asada M, Ogita K, Wakimoto A, Yamamoto T, Nishio Y, Enomoto T
    • Journal Title

      Cancer Chemother Pharmacol

      Volume: 68 Pages: 1603-1603

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Recurrent endometrial carcinoma : prognosis for patients with recurrence within 6 to 12 months is worse relative to those relapsing at 12 months or later2011

    • Author(s)
      Miyake T, Ueda Y, Egawa-Takata T, Matsuzaki S, Yokoyama T, Miyoshi Y, Kimura T, Yoshino K, Fujita M, Yamasaki M, Enomoto T, Kimura T
    • Journal Title

      Am J Obstet Gynecol

      Volume: 204 Pages: 535-535

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Questionnaire survey of the current status of radical trachelectomy in Japan2011

    • Author(s)
      Sato S, Aoki D, Kobayashi H, Saito T, Nishimura R, Nagano T, Yaegashi N, Enomoto T, Kigawa J
    • Journal Title

      Int J Clin Oncol

      Volume: 16 Pages: 141-141

    • NAID

      10029366477

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] 卵巣明細胞腺癌において特異的に高発現している Annexin A4 は抗癌剤の多剤耐性因子である2012

    • Author(s)
      松崎慎哉、 森本晶子、横山拓平、小林栄仁、木村敏啓、上田豊、吉野潔、藤田征巳、榎本隆之、木村正、仲哲治
    • Organizer
      第53回日本婦人科腫瘍学会学術講演会
    • Place of Presentation
      岡山
    • Year and Date
      2012-11-23
    • Related Report
      2012 Final Research Report
  • [Presentation] 卵巣明細胞腺癌において特異的に高発現している Annexin A4は抗癌剤の多剤耐性因子である2012

    • Author(s)
      松崎慎哉、 森本晶子、横山拓平、小林栄仁 木村敏啓、上田豊、吉野潔、藤田征巳、榎本隆之、木村正、仲哲治
    • Organizer
      第53回日本婦人科腫瘍学会学術講演会
    • Place of Presentation
      東京
    • Year and Date
      2012-07-19
    • Related Report
      2012 Final Research Report
  • [Presentation] 子宮内膜癌の新規標的分子の探索、2012

    • Author(s)
      横山拓平、 榎本隆之、世良田聡、森本晶子、松崎慎哉、小林栄仁、木村敏啓、上田豊、吉野潔、藤田征巳、仲哲治
    • Organizer
      日本婦人科がん分子的研究会
    • Place of Presentation
      日光
    • Year and Date
      2012-06-22
    • Related Report
      2012 Final Research Report
  • [Presentation] 抗癌剤抵抗性である卵巣明細胞腺癌に対して Annexin A4 は治療ターゲットとなりうるか?2012

    • Author(s)
      松崎慎哉、 森本晶子、横山拓平、小林栄仁、木村敏啓、上田豊、吉野潔、藤田征巳、榎本隆之、木村正、仲哲治
    • Organizer
      第64回日本産科婦人科学会学術講演会
    • Place of Presentation
      神戸
    • Year and Date
      2012-04-14
    • Related Report
      2012 Final Research Report
  • [Presentation] Quantitative proteomic analysis of cell-surface membrane proteins: Biomarker discovery in endometrial cancer2012

    • Author(s)
      Yokoyama T, Enomoto T, Serada S, Matsuzaki S, Kimura T, Ueda Y, Fujita M, Yoshino K, Kim A, Fujimoto M, Kimura T, Naka T
    • Organizer
      American Association for Cancer Research 102nd Annual Meeting
    • Place of Presentation
      U.S.A
    • Year and Date
      2012-04-06
    • Related Report
      2012 Final Research Report
  • [Presentation] Annexin A4 induces chemoresistance for multiple drugs in ovarian clear cell carcinoma2012

    • Author(s)
      Morimoto A, Enomoto T, Serada S, Matsuzaki S, Yokoyama T, Kimura T, Ueda Y, Yoshino K, Fujita M, Fujimoto M, Kimura T, Naka T
    • Organizer
      American Association for Cancer Research Annual Meeting 2012
    • Place of Presentation
      Chicago
    • Year and Date
      2012-04-03
    • Related Report
      2012 Final Research Report
  • [Presentation] 子宮内膜癌における Annexin A4 の発現とプラチナ系抗癌剤耐性の機序解明2011

    • Author(s)
      松崎慎哉、榎本隆之、金雅子、横山拓平、森本晶子、三好ゆかり、 木村敏啓、 上田豊、吉野潔、藤田征巳、木村正
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Year and Date
      2011-10-04
    • Related Report
      2012 Final Research Report
  • [Presentation] 子宮内膜癌におけるAnnexin A4の発現とプラチナ系抗癌剤耐性の機序解明2011

    • Author(s)
      松崎慎哉
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場(愛知)
    • Year and Date
      2011-10-04
    • Related Report
      2011 Annual Research Report
  • [Presentation] Annexin A4は既知の薬剤トランスポーターを介して卵巣明細胞腺癌のプラチナ系薬剤耐性に関与する2011

    • Author(s)
      金雅子
    • Organizer
      第63回日本産科婦人科学会学術講演会
    • Place of Presentation
      大阪国際会議場(大阪)
    • Year and Date
      2011-08-30
    • Related Report
      2011 Annual Research Report
  • [Presentation] 子宮内膜癌の新規標的分子の探索2011

    • Author(s)
      横山拓平
    • Organizer
      第63回日本産科婦人科学会学術講演会
    • Place of Presentation
      大阪国際会議場(大阪)
    • Year and Date
      2011-08-30
    • Related Report
      2011 Annual Research Report
  • [Presentation] Annexin A4 は既知の薬剤トランスポーターを介して卵巣明細胞腺癌のプラチナ系薬剤耐性に関与する2011

    • Author(s)
      金雅子、世良田聡、 榎本隆之、仲哲治
    • Organizer
      第63回日本産科婦人科学会学術講演会
    • Place of Presentation
      大阪
    • Year and Date
      2011-08-29
    • Related Report
      2012 Final Research Report
  • [Presentation] 子宮内膜癌における Annexin A4 の発現とプラチナ系抗癌剤耐性の機序解明2011

    • Author(s)
      松崎慎哉、榎本隆之、金雅子、横山拓平、森本晶子、三好ゆかり、 木村敏啓、 上田豊、吉野潔、藤田征巳、木村正
    • Organizer
      第63回日本産科婦人科学会学術講演会
    • Place of Presentation
      大阪
    • Year and Date
      2011-08-29
    • Related Report
      2012 Final Research Report
  • [Presentation] 子宮内膜癌におけるAnnexin A4の発現とプラチナ系抗癌剤耐性の機序解明2011

    • Author(s)
      松崎慎哉
    • Organizer
      第63回日本産科婦人科学会学術講演会
    • Place of Presentation
      大阪国際会議場(大阪)
    • Year and Date
      2011-08-29
    • Related Report
      2011 Annual Research Report
  • [Presentation] Quantitative proteomic analysis of cell-surface membrane proteins : Biomarker discovery in endometrial cancer2011

    • Author(s)
      横山拓平
    • Organizer
      American Association Cancer Research
    • Place of Presentation
      アメリカ合衆国
    • Year and Date
      2011-04-06
    • Related Report
      2011 Annual Research Report
  • [Presentation] Annexin A4 induces chemoresistance for multiple drugs in ovarian clear cell carcinoma

    • Author(s)
      Morimoto, A.
    • Organizer
      American Association for Cancer Research Annual meeting 2012
    • Place of Presentation
      Chicago, U.S.A.
    • Related Report
      2012 Annual Research Report
  • [Presentation] 抗癌剤抵抗性である卵巣明細胞腺癌に対してAnnexin A4は治療ターゲットとなりうるか?

    • Author(s)
      松崎慎哉
    • Organizer
      第64回日本産科婦人科学会学術講演会
    • Place of Presentation
      神戸
    • Related Report
      2012 Annual Research Report
  • [Presentation] 卵巣明細胞腺癌において特異的に高発現しているAnnexin A4は抗癌剤の多剤耐性因子である

    • Author(s)
      松崎慎哉
    • Organizer
      第52回日本婦人科腫瘍学会学術講演会
    • Place of Presentation
      東京
    • Related Report
      2012 Annual Research Report
  • [Presentation] 卵巣明細胞腺癌において特異的に高発現しているAnnexin A4は抗癌剤の多剤耐性因子である

    • Author(s)
      松崎慎哉
    • Organizer
      第53回日本婦人科腫瘍学会学術講演会
    • Place of Presentation
      岡山
    • Related Report
      2012 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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