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Investigation of the role myeloid-derived suppressor cells (MDSC) in the maternal-fetal tolerance and pregnancy-complicated female cancer progression.

Research Project

Project/Area Number 15H02564
Research Category

Grant-in-Aid for Scientific Research (A)

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

Principal Investigator

Kimura Tadashi  大阪大学, 医学系研究科, 教授 (90240845)

Co-Investigator(Kenkyū-buntansha) 馬淵 誠士  大阪大学, 医学系研究科, 助教 (00452441)
遠藤 誠之  大阪大学, 医学系研究科, 講師 (30644794)
熊澤 惠一  大阪大学, 医学系研究科, 助教 (90444546)
Research Collaborator Matsumoto Yuri  
Takahashi Ryoko  
Sasano Tomoyuki  
Kuroda Hiromasa  
Kozasa Katsumi  
Yokoi Eriko  
Komura Naoko  
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥41,470,000 (Direct Cost: ¥31,900,000、Indirect Cost: ¥9,570,000)
Fiscal Year 2017: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000)
Fiscal Year 2016: ¥15,080,000 (Direct Cost: ¥11,600,000、Indirect Cost: ¥3,480,000)
Fiscal Year 2015: ¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000)
KeywordsMDSC / エストロゲン / 妊娠 / 子宮頸癌 / 流産 / 造血幹細胞 / MDSC制御 / 婦人科癌 / 妊娠高血圧症候群 / 新規治療
Outline of Final Research Achievements

We have investigated the impact of estradiol (E2) in the induction of MDSC as well as the roles of E2-induced MDSC in maternal-fetal tolerance or cervical cancer progression during pregnancy. We have found that E2 enhanced the proliferation of bone marrow (BM) cells, and stimulated the differentiation of BM cells into MDSC. We also found that increased E2 level during pregnancy is involved in the maternal-fetal tolerance as well as cervical cancer progression, which read to the enhanced progression of cervical/breast cancers during pregnancy. Finally we identified a novel agent PM01183, which exhibits strong inhibitory effects on MDSCs. We are conducting clinical researches to verify these preclinical findings in human.

Report

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

    (28 results)

All 2017 2016 2015

All Journal Article (12 results) (of which Peer Reviewed: 12 results,  Open Access: 12 results,  Acknowledgement Compliant: 2 results) Presentation (12 results) (of which Int'l Joint Research: 4 results,  Invited: 1 results) Book (4 results)

  • [Journal Article] Comparison of clinical utility between neutrophil count and neutrophil?lymphocyte ratio in patients with ovarian cancer: a single institutional experience and a literature review2017

    • Author(s)
      Komura Naoko、Mabuchi Seiji、Yokoi Eriko、Kozasa Katsumi、Kuroda Hiromasa、Sasano Tomoyuki、Matsumoto Yuri、Kimura Tadashi
    • Journal Title

      Int J Clin Oncol

      Volume: 23 Issue: 1 Pages: 104-113

    • DOI

      10.1007/s10147-017-1180-4

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] PM01183 inhibits myeloid-derived suppressor cells in vitro and in vivo2017

    • Author(s)
      Kuroda Hiromasa、Mabuchi Seiji、Kozasa Katsumi、Yokoi Eriko、Matsumoto Yuri、Komura Naoko、Kawano Mahiru、Hashimoto Kae、Sawada Kenjiro、Kimura Tadashi
    • Journal Title

      Immunotherapy

      Volume: 9 Issue: 10 Pages: 805-817

    • DOI

      10.2217/imt-2017-0046

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 腫瘍随伴性白血球増多を伴う子宮頸癌 ~発症のメカニズムの解明と個別化治療の開発~2017

    • Author(s)
      馬淵誠士
    • Journal Title

      日本産科婦人科学会雑誌

      Volume: 69 Pages: 1527-1537

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The significance of tumor-associated neutrophil density in uterine cervical cancer treated with definitive radiotherapy.2017

    • Author(s)
      Matsumoto Y, Mabuchi S, Kozasa K, Kuroda H, Sasano T, Yokoi E, Komura N, Sawada K, Kimura T.
    • Journal Title

      Gynecol Oncol

      Volume: 印刷中

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The significance of pretreatment thrombocytosis and its association with neutrophilia in patients with in surgically-treated endometrial cancer patients.2017

    • Author(s)
      Takahashi R, Mabuchi S, Kuroda H, Kozasa K, Yokoi E, Matsumoto Y, Kimura T.
    • Journal Title

      Int J Gynecol Cancer

      Volume: 印刷中

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Impact of preoperative leukocyte alteration in surgically-treated early-stage cervical cancer patients with low-risk, intermediate-risk or high-risk factors.2017

    • Author(s)
      Matsumoto Y, Mabuchi S, Kozasa K, Kuroda H, Sasano T, Yokoi E, Sawada K, Kimura T.
    • Journal Title

      Eur J Gynecol Oncol

      Volume: 印刷中

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Soluble Flt-1 Has Cytotoxic Effects on BeWo Choriocarcinoma Cells.2017

    • Author(s)
      Yamashita M, Kumasawa K, Miyake T, Nakamura H, Kimura T.
    • Journal Title

      Reprod Sci

      Volume: 印刷中

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Preclinical Investigations of PM01183 (Lurbinectedin) as a Single Agent or in Combination with Other Anticancer Agents for Clear Cell Carcinoma of the Ovary.2016

    • Author(s)
      Takahashi R, Mabuchi S, Kawano M, Sasano T, Matsumoto Y, Kuroda H, Kozasa K, Hashimoto K, Sawada K, Kimura T.
    • Journal Title

      PLoS One

      Volume: 17;11(3) Issue: 3 Pages: e0151050-e0151050

    • DOI

      10.1371/journal.pone.0151050

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pathophysiology of preeclampsia: an angiogenic imbalance and long-lasting systemic vascular dysfunction.2016

    • Author(s)
      Tomimatsu T, Mimura K, Endo M, Kumasawa K, Kimura T.
    • Journal Title

      Hypertens Res

      Volume: 40(4) Issue: 4 Pages: 305-310

    • DOI

      10.1038/hr.2016.152

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Placenta accreta following hysteroscopic myomectomy.2016

    • Author(s)
      Tanaka M, Matsuzaki S, Matsuzaki S, Kakigano A, Kumasawa K, Ueda Y, Endo M, Kimura T.
    • Journal Title

      Clin Case Rep

      Volume: 4(6) Issue: 6 Pages: 541-544

    • DOI

      10.1002/ccr3.562

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Soluble VEGF receptor 1 (sFLT1) induces non-apoptotic death in ovarian and colorectal cancer cells.2016

    • Author(s)
      Miyake T, Kumasawa K, Sato N, Takiuchi T, Nakamura H, Kimura T.
    • Journal Title

      Sci Rep

      Volume: 6 Issue: 1 Pages: 24853-24853

    • DOI

      10.1038/srep24853

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] The significance of G-CSF expression and myeloid-derived suppressor cells in the chemoresistance of uterine cervical cancer.2015

    • Author(s)
      Kawano M, Mabuchi S, Matsumoto Y, Sasano T, Takahashi R, Kuroda H, Kozasa K, Hashimoto K, Isobe A, Sawada K, Hamasaki T, Morii E, Kimura T.
    • Journal Title

      Scientific Reports

      Volume: 15;5 Issue: 1 Pages: 18217-18217

    • DOI

      10.1038/srep18217

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 平成 28 年度学術奨励賞 受賞講演;腫瘍随伴性白血球増多を伴う子宮頸癌 ~発症のメカニズムの解明と個別化治療の開発~2017

    • Author(s)
      馬淵誠士
    • Organizer
      第69回日本産科婦人科学会学術講演会
    • Place of Presentation
      広島
    • Year and Date
      2017-04-13
    • Related Report
      2016 Annual Research Report
  • [Presentation] 平成28年度学術奨励賞 受賞講演;腫瘍随伴性白血球増多を伴う子宮頸癌 ~発症のメカニズムの解明と個別化治療の開発~2017

    • Author(s)
      馬淵誠士
    • Organizer
      第69回日本産科婦人科学会学術講演会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 婦人科癌に対する血管新生阻害治療:その臨床開発の現状と効果予見のバイオマーカーに関する新知見2017

    • Author(s)
      馬淵誠士
    • Organizer
      第59回日本婦人科腫瘍学会学術講演会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Therapeutic strategy for ovarian clear cell carcinoma.2017

    • Author(s)
      Seiji Mabuchi
    • Organizer
      The 5th Biennial Meeting of Asian Society of Gynecologic Oncology.
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Targeting infiltrating immune cells in the treatment of uterine cervical cancer : special focus on myeloid derived suppressor cells.2016

    • Author(s)
      Mabuchi, S.
    • Organizer
      102nd Annual Congress of Korean Association of Obstetrics and Gynecology
    • Place of Presentation
      Seoul, Korea
    • Year and Date
      2016-09-23
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Clear cell carcinoma of the ovary (CCC): molecular insights and future therapeutic perspectives.2016

    • Author(s)
      Mabuchi, S.
    • Organizer
      21st Seoul International Symposium
    • Place of Presentation
      Seoul, Korea
    • Year and Date
      2016-09-23
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 「骨髄由来免疫抑制細胞(MDSC)を標的とした癌治療」: 婦人科悪性腫瘍における骨髄由来抑制細胞(MDSC)の重要性2016

    • Author(s)
      馬淵誠士
    • Organizer
      第 34 回 日本ヒト細胞学会学術集会
    • Place of Presentation
      奈良
    • Year and Date
      2016-07-16
    • Related Report
      2016 Annual Research Report
  • [Presentation] Clear cell carcinoma of the ovary: molecular insights and future therapeutic perspectives2016

    • Author(s)
      馬淵 誠士
    • Organizer
      54th Annual Congress of Taiwan Association of Obstetrics and Gynecology
    • Place of Presentation
      台湾 台北市
    • Year and Date
      2016-03-05
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 卵巣明細胞腺癌に対するmTOR阻害治療:開発の現状と課題2015

    • Author(s)
      馬淵 誠士
    • Organizer
      第53回日本癌治療学会学術集会
    • Place of Presentation
      京都
    • Year and Date
      2015-10-30
    • Related Report
      2015 Annual Research Report
  • [Presentation] Clear cell carcinoma of the ovary: molecular insights and future therapeutic perspectives2015

    • Author(s)
      馬淵 誠士
    • Organizer
      第57回日本婦人科腫瘍学会学術講演会
    • Place of Presentation
      盛岡
    • Year and Date
      2015-08-08
    • Related Report
      2015 Annual Research Report
  • [Presentation] 子宮頸癌におけるTumor related leukocytosis(TRL)の意義と、そのメカニズムの解明を目指した基礎研究2015

    • Author(s)
      馬淵 誠士
    • Organizer
      第57回日本婦人科腫瘍学会学術講演会
    • Place of Presentation
      盛岡
    • Year and Date
      2015-08-08
    • Related Report
      2015 Annual Research Report
  • [Presentation] 腫瘍随伴性白血球増多を伴う子宮頸癌 ~発症のメカニズムの解明と個別化治療の開発~2015

    • Author(s)
      馬淵 誠士
    • Organizer
      第67回日本産科婦人科学会学術講演会
    • Place of Presentation
      横浜
    • Year and Date
      2015-04-11
    • Related Report
      2015 Annual Research Report
  • [Book] Management of Metastatic and Recurrent Cervical Cancer.2016

    • Author(s)
      Mabuchi S, Kawano M, Takahashi R, Kuroda H.
    • Publisher
      Handbook of Gynecology, Springer
    • Related Report
      2016 Annual Research Report
  • [Book] Fertility-Sparing Treatment for Early-Stage Cervical Cancer.2016

    • Author(s)
      Kuroda H, Mabuchi S, Kozasa K, Kimura T.
    • Publisher
      Handbook of Gynecology, Springer
    • Related Report
      2016 Annual Research Report
  • [Book] Cervical Cancer: General Overview.2016

    • Author(s)
      Mabuchi S, Kawano M, Matsumoto Y, and Kimura T.
    • Publisher
      Handbook of Gynecology, Springer
    • Related Report
      2016 Annual Research Report
  • [Book] Management of Early-Stage and Locally Advanced Cervical Cancer.2016

    • Author(s)
      Mabuchi S, Kawano M, Sasano T, Kuroda H.
    • Publisher
      Handbook of Gynecology, Springer
    • Related Report
      2016 Annual Research Report

URL: 

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

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