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How is the histological subtype of the ovarian carcinoma associated with hypoxia-related factors in terms of its chemotherapeutic resistance

Research Project

Project/Area Number 18K06997
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 49020:Human pathology-related
Research InstitutionSaitama Medical University

Principal Investigator

Yasuda Masanori  埼玉医科大学, 医学部, 教授 (50242508)

Co-Investigator(Kenkyū-buntansha) 矢野 光剛  大分大学, 医学部, 助教 (70817064)
長谷川 幸清  埼玉医科大学, 医学部, 教授 (30534193)
宮澤 昌樹  東海大学, 医学部, 客員講師 (30624572)
宮澤 麻里子  東海大学, 医学部, 特定研究員 (80637091)
Project Period (FY) 2018-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords卵巣明細胞癌(OVCCC) / 高異型度漿液性癌 / 低酸素誘導因子(HIF) / ヒストン脱アセチル化酵素(HDAC) / ARID1A / Silibinin / 卵巣癌 / 低酸素 / HIF-1α / ヒストン脱アセチル化酵素 / 卵巣明細胞癌 / 卵巣漿液性癌 / 低酸素誘導因子 / PD-L1 / silibinin
Outline of Final Research Achievements

In ovarian clear cell carcinomas (OVCCC), the single-nucleotide polymorphism (C1772T) of hypoxia inducible factor (HIF)-1α is more frequent than in healthy population as well as other carcinomas, but the single-nucleotide polymorphism does not affect its protein expression and the prognosis. Immunohistochemical expression of HIF-1α and its regulator histone deacetylase (HDAC) 6 do not correlate with prognosis in OVCCC patients without ARID1A mutation, but with ARID1A mutation significantly reduced survival time. It was supposed that in OVCCC HIF-1α and HDAC6 could be prognostic factors and therapeutic targets along with ARID1A as a biomarker.
Following these summaries shown in the report 15K08355, ///

Academic Significance and Societal Importance of the Research Achievements

我々の一連の研究においては,「卵巣明細胞癌(OVCCC)の低酸素関連因子の発現」に着目し,化学療法抵抗性との関わりから有望とされる標的因子の解明に取り組んできた。卵巣癌の薬物治療においては,昨今,BRCA遺伝子異常をもつ高異型度漿液性癌に対してのpoly-ADP ribose polymerase(PARP)阻害薬の意義が最も大きな話題となっているが,免疫チェックポイント阻害薬なども明細胞癌には有効性があまり注目されていないのが実情である。治療の個別化は今やいずれの悪性腫瘍においても必須の概念であり,がんパネル検査から発掘される新治療薬とも並行して,社会的なニーズに応えていく必要がある。

Report

(6 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (14 results)

All 2023 2022 2021 2020 2019

All Journal Article (10 results) (of which Peer Reviewed: 10 results,  Open Access: 9 results) Presentation (4 results) (of which Int'l Joint Research: 3 results)

  • [Journal Article] Immunohistochemical and molecular analysis of an α-fetoprotein-producing cervical adenocarcinoma with clear cell morphology.2023

    • Author(s)
      Kuriyama S, Yano M, Kusaba T, Zaitsu S, Nishida H, Yasuda M, Nasu K.
    • Journal Title

      Med Mol Morphol.

      Volume: 56 Issue: 1 Pages: 20-27

    • DOI

      10.1007/s00795-022-00336-7

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Co-clinical study of [fam-] trastuzumab deruxtecan (DS8201a) in patient-derived xenograft models of uterine carcinosarcoma and its association with clinical efficacy.2023

    • Author(s)
      Yagishita S, Nishikawa T, Yoshida H, Shintani D, Sato S, Miwa M, Suzuki M, Yasuda M, Ogitani Y, Jikoh T, Yonemori K, Hasegawa K, Hamada A.
    • Journal Title

      Clin Cancer Res.

      Volume: CCR-22

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Diagnostic utility of a conventional MRI-based analysis and texture analysis for discriminating between ovarian thecoma-fibroma groups and ovarian granulosa cell tumors.2022

    • Author(s)
      Nagawa K, Kishigami T, Yokoyama F, Murakami S, Yasugi T, Takaki Y, Inoue K, Tsuchihashi S, Seki S, Okada Y, Baba Y, Hasegawa K, Yasuda M, Kozawa E.
    • Journal Title

      J Ovarian Res.

      Volume: 15 Issue: 1 Pages: 65-65

    • DOI

      10.1186/s13048-022-00989-z

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinicopathological features and programmed death-ligand 1 immunohistochemical expression in a multicenter cohort of uterine and ovarian melanomas: a retrospective study in Japan (KCOG-G1701s).2022

    • Author(s)
      Yano M, Nasu K, Yasuda M, Katoh T, Kagabu M, Kobara H, Matsuura M, Tokuyama O, Yamawaki T, Wakahashi S, Noguchi T, Mizuno K, Shitsukawa K, Onohara Y, Nakabori T, Miyasaka A, Nakao T, Matsunaga T, Kunimi Y, Sakurai M, Uchiyama A, Itoh R, Ohike N, Hirakawa T, Watanabe T, Nishino K, Motohashi T, Ito K.
    • Journal Title

      Melanoma Res.

      Volume: 32 Issue: 3 Pages: 150-158

    • DOI

      10.1097/cmr.0000000000000811

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Up-regulation of HDAC6 Results in Poor Prognosis and Chemoresistance in Patients With Advanced Ovarian High-grade Serous Carcinoma2021

    • Author(s)
      YANO MITSUTAKE、MIYAZAWA MARIKO、OGANE NAOKI、OGASAWARA AIKO、HASEGAWA KOSEI、NARAHARA HISASHI、YASUDA MASANORI
    • Journal Title

      Anticancer Research

      Volume: 41 Issue: 3 Pages: 1647-1654

    • DOI

      10.21873/anticanres.14927

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Uterine intravenous leiomyomatosis with an isolated large metastasis to the right atrium: a case report2020

    • Author(s)
      Yano Mitsutake、Katoh Tomomi、Nakajima Yoshie、Iwanaga Shiro、Kin Rei、Kozawa Eito、Yasuda Masanori
    • Journal Title

      Diagnostic Pathology

      Volume: 15 Issue: 1 Pages: 4-4

    • DOI

      10.1186/s13000-019-0913-2

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hypoxia-inducible Factor-1α Suppression in Ovarian Clear-cell Carcinoma Cells by Silibinin Administration2020

    • Author(s)
      MIYAZAWA MARIKO、YASUDA MASANORI、MIYAZAWA MASAKI、OGANE NAOKI、KATOH TOMOMI、YANO MITSUTAKE、HIRASAWA TAKESHI、MIKAMI MIKIO、ISHIMOTO HITOSHI
    • Journal Title

      Anticancer Research

      Volume: 40 Issue: 12 Pages: 6791-6798

    • DOI

      10.21873/anticanres.14702

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tumor-to-tumor metastasis from appendiceal adenocarcinoma to an ovarian mature teratoma, mimicking malignant transformation of a teratoma: a case report2019

    • Author(s)
      Yano Mitsutake、Katoh Tomomi、Hamaguchi Tetsuya、Kozawa Eito、Hamada Mei、Nagata Koji、Yasuda Masanori
    • Journal Title

      Diagnostic Pathology

      Volume: 14 Issue: 1 Pages: 88-88

    • DOI

      10.1186/s13000-019-0865-6

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [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
      2019 Research-status 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 Research-status Report
    • Peer Reviewed
  • [Presentation] Distinct Clinicopathological Features of Endometrial Mesonephric-like Adenocarcinoma2020

    • Author(s)
      Yano M, Katoh T, Yabuno A, Ogane N, Ito K, Miyazawa M, Miyazawa M, Hasegawa K, Narahara H, Yasuda M
    • Organizer
      USCAP 109th AnnualMeeting 2020
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Clinicopathological correlation of ARID1A status with HDAC6 and its related factors in ovarian clear cell carcinoma2019

    • Author(s)
      Mitsutake Yano, Tomomi Katoh, Mariko Miyazawa, Masaki Miyazawa, Naoki Ogane, Maiko Miwa, Kosei Hasegawa, Hisashi Narahara, Masanori Yasuda
    • Organizer
      北米病理学会USCAP
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 卵巣明細胞癌におけるARID1AとHDAC6の相関2019

    • Author(s)
      矢野光剛,伊藤梢絵,三輪真唯子,加藤智美,宮澤麻里子,宮澤昌樹,大金直樹,長谷川幸清,楢原久司,安田政実
    • Organizer
      第108回日本病理学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] Stratification of endometrial endometrioid carcinoma with a support of p53 immuhohistochemical status.2019

    • Author(s)
      Mitsutake Yano, Kozue Ito, Akira Yabuno, Tomomi Katoh, Naoki Ogane, Mariko Miyazawa, Masaki Miyazawa, Kosei Hasegawa, Hisashi Narahara, Masanori Yasuda
    • Organizer
      The 108th Annual Meeting of United States and Canadian Academy of Pathology (USCAP)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research

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Published: 2018-04-23   Modified: 2024-01-30  

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