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Development of molecular targeted therapy by the inhibition of MET-PAI-1 pathway for the prevention of thrombosis in cancer patients

Research Project

Project/Area Number 26462509
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

TOYOSHIMA Masafumi  東北大学, 大学病院, 講師 (70451581)

Co-Investigator(Kenkyū-buntansha) 北谷 和之  東北大学, 東北メディカル・メガバンク機構, 助教 (40539235)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords卵巣明細胞腺癌 / 血栓症 / 遺伝子解析 / PAI-1 / c-MET / 阻害剤 / c-MET / 卵巣明細胞腺がん / PAT-1
Outline of Final Research Achievements

For the purpose of preventing thrombosis in cancer patients, we investigated the effectiveness of MET-PAI-1 pathway inhibition in ovarian cancer. No significant differences were observed between several ovarian cancer tissue types by PAI-1 measurement in the blood by the ELISA method. In in vitro experiments, the addition of the PAI-1 inhibitor TM5275 inhibited the proliferation of ovarian cancer cell line ES-2 by G2 / M arrest. In addition, these phonotypes were confirmed in PAI-1 knockdown by siRNA. There was a significant difference in PAI-1 expression level between clear cell adenocarcinoma and serous adenocarcinoma by immunohistochemical staining of ovarian cancer patients’ sample. Furthermore, gene copy number analysis of ovarian clear cell adenocarcinoma was performed, and we found that the copy number of gene X, which is known to be involved in the coagulation system, was higher in DVT onset cases.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (34 results)

All 2017 2016 2015 2014 2013

All Journal Article (11 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 10 results,  Open Access: 5 results,  Acknowledgement Compliant: 5 results) Presentation (23 results) (of which Int'l Joint Research: 4 results,  Invited: 1 results)

  • [Journal Article] Leptomeningeal metastasis from gynecologic cancers diagnosed by brain MRI2017

    • Author(s)
      Toyoshima M* (*corresponding author), Tsuji K, Shigeta S, Tokunaga H, Ito K, Watanabe Y, Yoshinaga K, Otsuki T, Niikura H, Yaegashi N
    • Journal Title

      Clinical Imaging

      Volume: 41 Pages: 42-47

    • DOI

      10.1016/j.clinimag.2016.09.013

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] ASGO 4th International Workshop on Gynecologic Oncology2017

    • Author(s)
      Shibuya Y, Toyoshima M* (*corresponding author), Yaegashi N
    • Journal Title

      J Gynecol Onco

      Volume: 28(2) Issue: 1

    • DOI

      10.3802/jgo.2017.28.e24

    • Related Report
      2016 Annual Research Report
    • Acknowledgement Compliant
  • [Journal Article] Steroid Sulfatase Inhibitor Reduces Proliferation of Ishikawa Endometrial Cancer Cells in Co-Culture Systems2016

    • Author(s)
      Nishimoto M, Toyoshima M* (*corresponding author), Shiga N, Utsunomiya H,Tsuji K, Suzuki F, Nagase S, Suzuki T, Sasano H, Ito K, Yaegashi N
    • Journal Title

      OJEMD

      Volume: 6 Issue: 09 Pages: 193-204

    • DOI

      10.4236/ojemd.2016.69025

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Cytokeratin 7-positive/cytokeratin 20-negative cecal adenocarcinoma metastatic to the uterine cervix: a case report2016

    • Author(s)
      Toyoshima M* (*corresponding author), Momono Y, Makino H, Kudo T, Oka N, Sakurada J, Suzuki H, Kodama H, Yoshinaga K
    • Journal Title

      World Journal of Surgical Oncology

      Volume: - Issue: 1

    • DOI

      10.1186/s12957-016-0774-z

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ceramide limits phosphatidylinositol-3-kinase C2β-controlled cell motility in ovarian cancer: potential of ceramide as a metastasis-suppressor lipid2015

    • Author(s)
      Kitatani K, Usui T, Sriraman S, Toyoshima M, Ishibashi M, Shigeta S, Nagase S, Sakamoto M, Hannun Y, Torchilin V, Okazaki T, Ogiso H, Yaegashi N
    • Journal Title

      Oncogene

      Volume: - Issue: 21 Pages: 2801-2812

    • DOI

      10.1038/onc.2015.330

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Transferrin facilitates the formation of DNA double-strand breaks via transferrin receptor 1:the possible involvement of transferrin in carcinogenesis of high-grade serous ovarian cancer.2015

    • Author(s)
      Shigeta S, Toyoshima M* (*corresponding author), Ishibashi M, Usui T, Kitatani K*, Yaegashi N
    • Journal Title

      Oncogene

      Volume: - Issue: 27 Pages: 3577-3586

    • DOI

      10.1038/onc.2015.425

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Inhibition of plasminogen activator inhibitor-1 is a potential therapeutic strategy in ovarian cancer.2015

    • Author(s)
      Mashiko S, Kitatani K, Toyoshima M, Ichimura A, Dan T, Usui T, Ishibashi M, Shigeta S, Nagase S, Miyata T, Yaegashi N
    • Journal Title

      Cancer Biology & Therapy

      Volume: 16 Issue: 2 Pages: 253-260

    • DOI

      10.1080/15384047.2014.1001271

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Solitary uterine metastasis of invasive lobular carcinoma after adjuvant endocrine therapy: a case report.2015

    • Author(s)
      Toyoshima M, Iwahashi H, Shima T, Hayasaka A, Kudo T, Makino H, Igeta S, Matsuura R, Ishigaki N, Akagi K, Sakurada J, Suzuki H, Yoshinaga K
    • Journal Title

      Journal of Medical Case Reports

      Volume: 9 Issue: 1 Pages: 47-47

    • DOI

      10.1186/s13256-014-0511-6

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Paclitaxel-carboplatin for advanced or recurrent carcinosarcoma of the uterus: the Japan Uterine Sarcoma Group and Tohoku Gynecologic Cancer Unit Study2014

    • Author(s)
      Tadao Takano,Takeo Otsuki,Hideki Tokunaga,Masafumi Toyoshima,Hiroki Utsunomiya,Satoru Nagase,Hitoshi Niikura,Kiyoshi Ito,Nobuo Yaegashi,Hidekazu Yamada,Toru Tase,Masahiro Kagabu,Tadahiro Shoji,Toru Sugiyama,Naoki Sato,Toshio Fujimoto,Yukihiro Terada, Junzo Kigawa,et al
    • Journal Title

      Int J Clin Oncol.

      Volume: accepted Issue: 6 Pages: 1052-1058

    • DOI

      10.1007/s10147-013-0658-y

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Outcomes of Abdominal Radical Trachelectomy: Results of a Multicenter Prospective Cohort Study in a Tohoku Gynecologic Cancer Unit.2014

    • Author(s)
      Tokunaga H, Watanabe Y, Niikura H, Nagase S, Toyoshima M, Shiro R, Yoshihito Yokoyama Y, Mizunuma H, Ohta T, Nishiyama H, Watanabe T, Sato N, Sugiyama T, Takano T, Takahashi F, Yaegashi N
    • Journal Title

      International Journal of Clinical Oncology

      Volume: in press Issue: 4 Pages: 776-780

    • DOI

      10.1007/s10147-014-0763-6

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Feasibility study of gemcitabine plus docetaxel in advanced or recurrent uterine leiomyosarcoma and undifferentiated endometrial sarcoma in Japan2013

    • Author(s)
      Takano T, Niikura H, Ito K, Nagase S, Utsunomiya H, Otsuki T, Toyoshima M, Tokunaga H, Kaiho-Sakuma M, Shiga N, Nagai T, Tanaka S, Otsuki A, Kurosawa H, Shigeta S, Yamaguchi T, Yaegashi N.
    • Journal Title

      International Journal of Clinical Oncology.

      Volume: - Issue: 5 Pages: 897-905

    • DOI

      10.1007/s10147-013-0627-5

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Presentation] 卵巣癌における c-Mycと合成致死作用を持つ 治療標的分子の探索2017

    • Author(s)
      湊 純子、豊島将文、北谷 和之、重田 昌吾、石橋 ますみ、八重樫 伸生
    • Organizer
      第5回婦人科がんバイオマーカー研究会学術集会
    • Place of Presentation
      大阪医科大学 本部北キャンパス(大阪府高槻市)
    • Year and Date
      2017-02-25
    • Related Report
      2016 Annual Research Report
  • [Presentation] 卵巣がんに対するセラミドナノリポソーム製剤の抗腫瘍作用2017

    • Author(s)
      張 雪薇、北谷和之、豊島将文、石橋ますみ、臼井利典、湊 純子、重田昌吾、Mark Kester、八重樫伸生
    • Organizer
      第5回婦人科がんバイオマーカー研究会学術集会
    • Place of Presentation
      大阪医科大学 本部北キャンパス(大阪府高槻市)
    • Year and Date
      2017-02-25
    • Related Report
      2016 Annual Research Report
  • [Presentation] 卵巣がん転移制御へのセラミド合成酵素 2 の関与2017

    • Author(s)
      北谷和之、張雪薇、臼井利典、豊島将文、重田昌吾、石橋ますみ、湊純子、小木曽英夫、岡崎俊朗、八重樫伸生
    • Organizer
      第5回婦人科がんバイオマーカー研究会学術集会
    • Place of Presentation
      大阪医科大学 本部北キャンパス(大阪府高槻市)
    • Year and Date
      2017-02-25
    • Related Report
      2016 Annual Research Report
  • [Presentation] フローサイトメトリーを利用した腹水細胞診断法のパイロットスタディ2016

    • Author(s)
      徳永英樹、岡本聡、渡部洋、重田昌吾、辻圭太、海法道子、豊島将文、新倉仁、八重樫伸生
    • Organizer
      第55回日本臨床細胞学会秋期大会
    • Place of Presentation
      別府国際コンベンションセンターB-Con Plaza(大分県別府市)
    • Year and Date
      2016-11-18
    • Related Report
      2016 Annual Research Report
  • [Presentation] 子宮体癌のセンチネルリンパ節生検における捺印細胞診の診断精度についての検討2016

    • Author(s)
      佐藤いずみ、岡本聡、新倉仁、重田昌吾、橋本千明、辻圭太、徳永英樹、豊島将文、三浦弘守、渡部みか、八重樫伸生
    • Organizer
      第55回日本臨床細胞学会秋期大会
    • Place of Presentation
      別府国際コンベンションセンターB-Con Plaza(大分県別府市)
    • Year and Date
      2016-11-18
    • Related Report
      2016 Annual Research Report
  • [Presentation] セラミドナノリポソーム製剤によるネクロプト―シスの誘導2016

    • Author(s)
      張 雪薇、北谷 和之、豊島 将文、石橋 ますみ、臼井 利典、湊 純子、重田 昌吾、Mark Kester、八重樫 伸生
    • Organizer
      第9回セラミド研究会 学術集会
    • Place of Presentation
      東京ユビキタス協創広場CANVAS(東京都中央区)
    • Year and Date
      2016-10-27
    • Related Report
      2016 Annual Research Report
  • [Presentation] セラミドナノリポソームはネクロプトーシスを誘導する薬剤である2016

    • Author(s)
      張雪薇、豊島将文、石橋ますみ、臼井利典、湊純子、重田昌吾、Mark Kester,北谷和之、八重樫伸生
    • Organizer
      第89回日本生化学会
    • Place of Presentation
      仙台国際センター(宮城県仙台市)
    • Year and Date
      2016-09-27
    • Related Report
      2016 Annual Research Report
  • [Presentation] Involvement of the receptor tyrosine kinase TIE-1 in the platinum-resistance of ovarian cancer cells2016

    • Author(s)
      Ishibashi M, Toyoshima M, Zhang X, Minato J, Shigeta S, Kitatani K, Yaegashi N
    • Organizer
      Marsha Rikin the 11th Ovarian Cancer Research Symposium
    • Place of Presentation
      ワシントン大学(Seattle, USA)
    • Year and Date
      2016-09-12
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] セラミドナノリポソームによる新しい細胞死ネクロプトーシス2016

    • Author(s)
      張雪薇、北谷和之、石橋ますみ、湊純子、豊島将文、八重樫伸生
    • Organizer
      第15回日本婦人がん分子標的研究会
    • Place of Presentation
      ホテルニューオータニ札幌(北海道札幌市)
    • Year and Date
      2016-08-20
    • Related Report
      2016 Annual Research Report
  • [Presentation] セラミド合成酵素による癌転移制御2016

    • Author(s)
      北谷和之,張雪薇,臼井利典,豊島将文,重田昌吾,Mahy Egiz,湊 純子,石橋ますみ,小木曽英夫, 岡崎俊朗,八重樫伸生
    • Organizer
      第58回日本脂質生化学会
    • Place of Presentation
      秋田キャッスルホテル(秋田市)
    • Year and Date
      2016-06-10
    • Related Report
      2016 Annual Research Report
  • [Presentation] 卵巣がん細胞に対するセラミド卵巣がん細胞に対するセラミドナノリポソームの抗腫瘍効果-ネクロプト-シスの誘導-2016

    • Author(s)
      張 雪薇, 豊島 将文, 石橋 ますみ, 臼井 利典, 湊 純子, 重田 昌吾, Mark Kester, 北谷 和之, 八重樫伸生
    • Organizer
      第58回日本脂質生化学会
    • Place of Presentation
      秋田キャッスルホテル(秋田市)
    • Year and Date
      2016-06-09
    • Related Report
      2016 Annual Research Report
  • [Presentation] 子宮頸癌のセンチネルリンパ節生検における捺印細胞診の診断精度についての検討2016

    • Author(s)
      佐藤いずみ、岡本聡、新倉仁、橋本千明、徳永英樹、豊島将文、三浦弘守、渡部みか、渡部洋、八重樫伸生
    • Organizer
      第57回日本臨床細胞学会総会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-05-29
    • Related Report
      2016 Annual Research Report
  • [Presentation] Casein kinase I epsilon is a novel molecular target for c-Myc driven ovarian cancers2016

    • Author(s)
      Toyoshima M, Kitatani K, Shigeta S, Ishibashi M, Hasegawa-Minato J, Yaegashi N
    • Organizer
      第68回日本産科婦人科学会学術総会
    • Place of Presentation
      東京国際フォーラム(東京都千代田区)
    • Year and Date
      2016-04-22
    • Related Report
      2016 Annual Research Report
  • [Presentation] Transferrin is involved in the carcinogenesis of high-grade serous ovarian cancer by facilitating the DNA double-strand breaks via transferrin receptor 1 in fallopian tube.2016

    • Author(s)
      Shigeta S, Toyoshima M, Kitatani K, Ishibashi M, Minato J, Yaegashi N
    • Organizer
      第68回日本産科婦人科学会学術総会
    • Place of Presentation
      東京国際フォーラム(東京都千代田区)
    • Year and Date
      2016-04-22
    • Related Report
      2016 Annual Research Report
  • [Presentation] Furin, a pro-protein convertase, is a novel molecular target for c-Myc-driven ovarian cancers2016

    • Author(s)
      Minato J, Toyoshima M, Kitatani K, Shigeta S, Ishibashi M, Yaegashi N
    • Organizer
      The 13th International Congress of Human Genetics
    • Place of Presentation
      京都国際会館(京都市)
    • Year and Date
      2016-04-05
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Transferrin in follicular fluid can facilitate DNA double-strand breaks to fallopian tube epithelium: possible involvement of transferrin in the carcinogenesis of high-grade serous ovarian cancer.2016

    • Author(s)
      Shogo Shigeta, Masafumi Toyoshima, Kazuyuki Kitatani, Masumi Ishibashi, Toshinori Usui, Junko Minato, Nobuo Yaegashi
    • Organizer
      Society for Reproductive Investigation 63th scientific annual meeting
    • Place of Presentation
      Montreal, Canada
    • Year and Date
      2016-03-16
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 大規模 siRNA スクリーニングを用いた 卵巣がんのシスプラチン抵抗性を 克服する分子標的の検討2016

    • Author(s)
      石橋 ますみ、豊島 将文、Mahy Egiz、張 雪薇、湊 純子、重田 昌吾、北谷 和之、八重樫 伸生
    • Organizer
      第4回婦人科がんバイオマーカー研究会学術集会
    • Place of Presentation
      岐阜大学サテライトキャンパス(岐阜市)
    • Year and Date
      2016-02-27
    • Related Report
      2015 Research-status Report
  • [Presentation] 卵巣がん転移に関わるセラミド生成代謝酵素2016

    • Author(s)
      北谷和之,張雪薇,臼井利典,豊島将文,重田昌吾,石橋ますみ,湊純子, 小木曽英夫, 岡崎俊朗,八重樫伸生
    • Organizer
      第4回婦人科がんバイオマーカー研究会学術集会
    • Place of Presentation
      岐阜大学サテライトキャンパス(岐阜市)
    • Year and Date
      2016-02-27
    • Related Report
      2015 Research-status Report
  • [Presentation] Transferrin facilitates the formation of DNA-double strand breaks via Transferrin receptor 1 in fallopian tube epithelial cells.2015

    • Author(s)
      Shogo Shigeta, Masafumi Toyoshima, Kazuyuki Kitatani, Junko Minato, Masumi Ishibashi, Toshinori Usui, Nobuo Yaegashi
    • Organizer
      AACR special conference Advance in Ovarian Cancer Research
    • Place of Presentation
      Orland, USA
    • Year and Date
      2015-10-17
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 卵巣癌におけるc-mycと合成致死作用を持つ治療標的分子の探索2015

    • Author(s)
      湊純子、豊島将文、北谷和之、重田昌吾、石橋ますみ、臼井利典、八重樫伸生
    • Organizer
      第14回日本婦人科がん分子標的研究会
    • Place of Presentation
      美ヶ原温泉ホテル翔峰(長野県松本市)
    • Year and Date
      2015-07-18
    • Related Report
      2015 Research-status Report
  • [Presentation] 月経血や卵胞液に含まれるトランスフェリンはⅠ型トランスフェリン受容体を介して卵管上皮細胞におけるDNA二重鎖切断を誘導・増幅する2015

    • Author(s)
      重田昌吾・豊島将文・北谷和之・石橋ますみ・八重樫伸生
    • Organizer
      第67回日本産科婦人科学会学術総会
    • 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
  • [Presentation] Transferrin facilitates DNA-double strand breaks via transferrin receptor 1 in human fallopian tube epithelial cells: possible involvement of transferrin in carcinogenesis.2015

    • Author(s)
      Shigeta S, Toyoshima M, Kitatani K, Ishibashi M, Usui T, Yaegashi N
    • Organizer
      Society for Reproductive Investigation 62th scientific annual meeting
    • Place of Presentation
      San Francisco, USA
    • Year and Date
      2015-03-27
    • Related Report
      2014 Research-status Report
  • [Presentation] セラミドによる卵巣がん播種転移制御2015

    • Author(s)
      北谷和之、豊島将文、臼井利典、重田昌吾、石橋ますみ、永瀬智、八重樫伸生
    • Organizer
      第3回婦人科がんバイオマーカー研究会学術集会
    • Place of Presentation
      九州大学医学部百年講堂(福岡市)
    • Year and Date
      2015-02-21
    • Related Report
      2014 Research-status Report
    • Invited

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Published: 2014-04-04   Modified: 2018-03-22  

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