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Development of novel antitumor agents to defunctionalize of HIF-1 and reduce of side effects in ovarian clear cell carcinoma

Research Project

Project/Area Number 16K11157
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

MIYAZAWA Masaki  東海大学, 医学部, 客員講師 (30624572)

Research Collaborator MIYAZAWA Mariko  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords卵巣明細胞癌 / HIF-1 / Silibinin / 休眠療法 / シリビニン / 抗腫瘍薬 / 抗腫瘍効果 / 明細胞腺癌 / HDACs / 副作用軽減
Outline of Final Research Achievements

We have been studying for the development of novel antitumor agents through the defunctionalization of HIF-1 in ovarian clear cell carcinoma, which is a kind of refractory ovarian cancer. Among them, we focused on Silibinin(SLB), which is an extract of the milk thistle of the family Asteraceae. We showed that SLB administration significantly reduces the proto-oncogenes EIF4E and RPS6 RNA in some clear cell carcinoma cell lines. To sum up, SLB defunctionalizes HIF-1 by suppressing HIF-1α protein synthesis.

Academic Significance and Societal Importance of the Research Achievements

今回着目したHIF-1の非機能化させたSilibinin(SLB)は既に、ドイツにおいてレガロンと呼ばれる肝機能障害の治療薬として長年使用されてきたこと、さらに重篤な副作用が認められないことから、本薬剤の抗腫瘍効果が明らかになったことで、より患者のQOL改善に寄与できるものと思われた。またSLBは肝機能障害の抑制の観点から、既存の抗癌剤との組み合わせによる副作用を軽減させることも期待できる。また経口剤での内服が可能であることから、入院治療せず在宅での治療も可能であり、この点からもQOLの改善ができることから、今後臨床応用を視野にさらに十分な検討を重ねていきたいと考えている。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (17 results)

All 2019 2018 2017 2016

All Journal Article (10 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 10 results,  Open Access: 7 results) Presentation (7 results)

  • [Journal Article] Association of the hypoxia-inducible factor-1α (HIF-1α) gene polymorphisms with prognosis in ovarian clear cell carcinoma2019

    • Author(s)
      Suzuki Hiroyuki、Yano Mitsutake、Miyazawa Mariko、Miyazawa Masaki、Ogane Naoki、Hasegawa Kosei、Tsuda Hitoshi、Yoshida Masayuki、Okagaki Ryugo、Ishihara Osamu、Yasuda Masanori
    • Journal Title

      Journal of Ovarian Research

      Volume: 12 Issue: 1 Pages: 7-7

    • DOI

      10.1186/s13048-019-0481-9

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Impact of TP53 immunohistochemistry on the histological grading system for endometrial endometrioid carcinoma2019

    • Author(s)
      Yano Mitsutake、Ito Kozue、Yabuno Akira、Ogane Naoki、Katoh Tomomi、Miyazawa Mariko、Miyazawa Masaki、Hasegawa Kosei、Narahara Hisashi、Yasuda Masanori
    • Journal Title

      Modern Pathology

      Volume: 印刷中 Issue: 7 Pages: 1023-1031

    • DOI

      10.1038/s41379-019-0220-1

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinicopathological correlation of ARID1A status with HDAC6 and its related factors in ovarian clear cell carcinoma2019

    • Author(s)
      Yano Mitsutake、Katoh Tomomi、Miyazawa Mariko、Miyazawa Masaki、Ogane Naoki、Miwa Maiko、Hasegawa Kosei、Narahara Hisashi、Yasuda Masanori
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 2397-2397

    • DOI

      10.1038/s41598-019-38653-0

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] UPLC-MS/MS based diagnostics for epithelial ovarian cancer using fully sialylated C4-binding protein2018

    • Author(s)
      Tanabe Kazuhiro、Matsuo Koji、Miyazawa Masaki、Hayashi Masaru、Ikeda Masae、Shida Masako、Hirasawa Takeshi、Sho Ryuichiro、Mikami Mikio
    • Journal Title

      Biomedical Chromatography

      Volume: 32 Issue: 5

    • DOI

      10.1002/bmc.4180

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Fully sialylated alpha-chain of complement 4-binding protein (A2160): a novel prognostic marker for epithelial ovarian carcinoma2018

    • Author(s)
      Matsuo Koji、Tanabe Kazuhiro、Ikeda Masae、Shibata Takeo、Kajiwara Hiroshi、Miyazawa Masaki、Miyazawa Mariko、Hayashi Masaru、Shida Masako、Hirasawa Takeshi、Roman Lynda D.、Mikami Mikio
    • Journal Title

      Archives of Gynecology and Obstetrics

      Volume: 297 Issue: 3 Pages: 749-756

    • DOI

      10.1007/s00404-018-4658-z

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Association of histone deacetylase expression with histology and prognosis of ovarian cancer2018

    • Author(s)
      Yano Mitsutake、Yasuda Masanori、Sakaki Mika、Nagata Koji、Fujino Takashi、Arai Eiichi、Hasebe Takahiro、Miyazawa Masaki、Miyazawa Mariko、Ogane Naoki、Hasegawa Kosei、Narahara Hisashi
    • Journal Title

      Oncology Letters

      Volume: 15 Issue: 3 Pages: 3524

    • DOI

      10.3892/ol.2018.7726

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Enhanced expression of hydroxylated ceramide in well-differentiated endometrial adenocarcinoma.2017

    • Author(s)
      Tajima T, Miyazawa M, Hayashi M, Asai S, Ikeda M, Shida M, Hirasawa T, Iwamori M, Mikami M.
    • Journal Title

      Oncol Lett.

      Volume: 13 Issue: 1 Pages: 45-50

    • DOI

      10.3892/ol.2016.5410

    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Possible role of thymidine phosphorylase in gynecological tumors as an individualized treatment strategy.2016

    • Author(s)
      Shida M, Yasuda M, Fujita M, Miyazawa M, Kajiwara H, Hirasawa T, Ikeda M, Matsui N, Muramatsu T, Mikami M.
    • Journal Title

      Oncol Lett.

      Volume: 12 Issue: 5 Pages: 3215-3223

    • DOI

      10.3892/ol.2016.5082

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Enhanced expression of unique gangliosides with GM2-determinant in human uterine cervical carcinoma-derived cell lines.2016

    • Author(s)
      Tanaka K, Miyazawa M, Mikami M, Aoki D, Kiguchi K, Iwamori M.
    • Journal Title

      Glycoconj J.

      Volume: 33 Issue: 5 Pages: 745-54

    • DOI

      10.1007/s10719-016-9668-0

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Use of epithelial-specific antigen for cytological diagnosis of glandular lesions in the uterine cervix.2016

    • Author(s)
      Matsui N, Kajiwara H, Morishita A, Iida T, Nakazawa K, Miyazawa M, Mikami M, Ogawa T, Nakamura N, Sato S.
    • Journal Title

      Pathol Int.

      Volume: 66(5) Issue: 5 Pages: 305-8

    • DOI

      10.1111/pin.12379

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] SilibininによるHIF-1阻害の検討 卵巣癌化学療法における補助的意義2018

    • Author(s)
      宮澤 麻里子, 安田 政実, 宮澤 昌樹, 矢野 光剛, 加藤 智美, 大金 直樹, 平澤 猛, 松井 成明, 林 優, 三上 幹男
    • Organizer
      第107回日本病理学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 進行卵巣癌におけるHDACの発現と化学療法感受性の相関2018

    • Author(s)
      矢野 光剛, 榊 美佳, 永田 耕治, 藤野 節, 新井 栄一, 長谷部 孝裕, 小笠原 仁子, 宮澤 麻里子, 宮澤 昌樹, 安田 政   実
    • Organizer
      第107回日本病理学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] SilibininによるHIF-1阻害の検討 卵巣癌化学療法における補助的意義2017

    • Author(s)
      宮澤 麻里子, 安田 政実, 平澤 猛, 宮澤 昌樹, 林 優, 加藤 智美, 松井 成明, 梶原 博, 信田 政子, 池田 仁惠, 村松 俊成, 三上 幹男
    • Organizer
      第59回日本婦人科腫瘍学会学術講演会
    • Related Report
      2017 Research-status Report
  • [Presentation] 卵巣癌におけるHDACの免疫組織化学的発現の検討2017

    • Author(s)
      矢野 光剛, 加藤 智美, 長谷川 幸清, 榊 美佳, 永田 耕治, 新井 栄一, 長谷部 孝裕, 宮澤 麻里子, 宮澤 昌樹, 楢原 久司, 安田 政実
    • Organizer
      第59回日本婦人科腫瘍学会学術講演会
    • Related Report
      2017 Research-status Report
  • [Presentation] 卵巣チョコレート嚢胞の癌化Up to date 基礎的知見を臨床に 卵巣チョコレート嚢胞と初期明細胞癌を鑑別する新規糖鎖マーカーの開発2017

    • Author(s)
      林 優, 宮澤 麻里子, 宮澤 昌樹, 飯田 哲士, 池田 仁惠, 信田 政子, 平澤 猛, 三上 幹男
    • Organizer
      第38回日本エンドメトリオーシス学会学術講演会
    • Related Report
      2017 Research-status Report
  • [Presentation] 上皮性卵巣癌におけるComplement C4b-Binding Proteinの発現と新規マーカーの可能性2016

    • Author(s)
      林 優, 藤井 幸子, 宮澤 麻里子, 宮澤 昌樹, 飯田 哲士, 池田 仁惠, 信田 政子, 平澤 猛, 村松 俊成, 三上 幹男
    • Organizer
      第58回日本婦人科腫瘍学会学術講演会
    • Place of Presentation
      米子コンベンションセンター(鳥取県鳥取市)
    • Year and Date
      2016-07-08
    • Related Report
      2016 Research-status Report
  • [Presentation] 卵巣明細胞腺癌におけるHypoxia Inducible Factor-1α遺伝子多型頻度およびexon12 C1772T遺伝子多型が臨床的予後に及ぼす影響2016

    • Author(s)
      鈴木 裕之, 安田 政実, 加藤 智美, 鎌田 孝一, 吉田 正行, 宮澤 昌樹, 岡垣 竜吾, 藤原 恵一, 石原 理
    • Organizer
      第68回日本産科婦人科学会学術講演会
    • Place of Presentation
      東京国際フォーラム(東京都千代田区)
    • Year and Date
      2016-04-21
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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