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Molecular association of functioning stroma with carcinoma cells in the ovary

Research Project

Project/Area Number 19K16778
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 50010:Tumor biology-related
Research InstitutionOita University

Principal Investigator

Yano Mitsutake  大分大学, 医学部, 助教 (70817064)

Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords腫瘍間質 / 機能性間質 / KRAS / 卵巣癌 / 中腎様腺癌
Outline of Research at the Start

卵巣癌における癌上皮と、機能性間質をはじめとした腫瘍間質の、遺伝子解析や免疫組織化学を行い、両者の共通性や差異を明らかにする。それによって腫瘍間質の起源や役割を明らかにし、治療標的となる可能性を模索する。

Outline of Final Research Achievements

We identified 14 cases of ovarian cancer with functioning stroma. Seven cases were endometrioid carcinoma and seven cases were clear cell carcinoma. Carcinoma cells and functioning stromal tissue were isolated by laser microdissection, and genetic analysis (KRAS, ARID1A, PIK3CA, PTEN, FOXL2) was performed. The same gene mutation KRAS (E31K) was found in the whole tumor, carcinoma cells, and functioning stroma in only one case, suggesting that both may have a common cellular origin.

Academic Significance and Societal Importance of the Research Achievements

これまでに卵巣癌の腫瘍間質,特にホルモン産生能を伴う機能性間質に着目した研究はわずかしかなかった.我々は,機能性間質を伴う卵巣癌を14例同定して,手術前後の血清エストロゲン値やFSH値の変化から,卵巣腫瘍のエストロゲン産生能とフィードバック機構を確認した.また1例のみであったが卵巣癌上皮と機能性間質に同一のKRAS遺伝子変異がみられ,両者が同一の細胞由来である可能性を見出した.従来から使用されている化学療法は癌細胞自体を標的とするものが多いが,本研究が発信した腫瘍間質の遺伝子変異やその由来の仮説は,腫瘍間質や癌微小環境を標的とする治療開発の一助になると考えられる.

Report

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

    (28 results)

All 2023 2022 2021 2020 2019

All Journal Article (14 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 14 results,  Open Access: 10 results) Presentation (13 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results) Book (1 results)

  • [Journal Article] Vulvar neuroendocrine carcinoma that is independent of merkel cell polyomavirus and human papillomavirus suggests endometrial cancer recurrence: a case report2022

    • Author(s)
      Hirakawa Tomoko、Yano Mitsutake、Nishida Haruto、Sato Shimpei、Nasu Kaei
    • Journal Title

      BMC Endocrine Disorders

      Volume: 22 Issue: 1 Pages: 81-81

    • DOI

      10.1186/s12902-022-00987-8

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Molecular Characterization of Metanephric Adenoma, Epithelial Wilms Tumor, and Overlap Lesions: An Integrated Whole-exome and Transcriptome Sequencing Analysis2022

    • Author(s)
      Pan Chin-Chen、Tseng Chih-En、Kuroda Naoto、Yano Mitsutake、Yasuda Masanori、Nagashima Yoji、Yeh Yi-Chen、Wang Yu-Chao、Chang Yen-Hwa、Epstein Jonathan I.
    • Journal Title

      Applied Immunohistochemistry & Molecular Morphology

      Volume: 30 Issue: 4 Pages: 257-263

    • DOI

      10.1097/pai.0000000000000996

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Pathological processes and pretreatment cytologic diagnosis of neuroendocrine carcinoma of the endometrium: addendum report of the Kansai Clinical Oncology Group/Intergroup study in Japan2021

    • Author(s)
      Matsumoto Harunobu、Nasu Kaei、Shikama Ayumi、Shiozaki Takaya、Futagami Masayuki、Kai Kentaro、Mori Taisuke、Yano Mitsutake、Yamada Takashi、Teramoto Norihiro
    • Journal Title

      Medical Molecular Morphology

      Volume: - Issue: 3 Pages: 237-244

    • DOI

      10.1007/s00795-021-00288-4

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] A multi‐ethnic analysis of immune‐related gene expression signatures in patients with ovarian clear cell carcinoma2021

    • Author(s)
      Heong Valerie、Tan Tuan Z、Miwa Maiko、Ye Jieru、Lim Diana、Herrington C Simon、Iida Yasushi、Yano Mitsutake、Yasuda Masanori、Ngoi Natalie YL、Wong SB Justin、Okamoto Aikou、Gourley Charlie、Hasegawa Kosei、Tan David SP、Huang Ruby YJ
    • Journal Title

      The Journal of Pathology

      Volume: 255 Issue: 3 Pages: 285-295

    • DOI

      10.1002/path.5769

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Role of repressed microRNAs in endometriosis.2021

    • Author(s)
      Kaei Nasu, Yoko Aoyagi, Ruofei Zhu, Mamiko Okamoto, Mitsutake Yano, Kentaro Kai, Yasuhi Kawano.
    • Journal Title

      Med Mol Morphol.

      Volume: 55 Issue: 1 Pages: 1-7

    • DOI

      10.1007/s00795-021-00303-8

    • Related Report
      2021 Research-status 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
      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] Pembrolizumab and Radiotherapy for Platinum-refractory Recurrent Uterine Carcinosarcoma With an Abscopal Effect: A Case Report2020

    • Author(s)
      YANO MITSUTAKE、ASO SAKI、SATO MIHO、AOYAGI YOKO、MATSUMOTO HARUNOBU、NASU KAEI
    • Journal Title

      Anticancer Research

      Volume: 40 Issue: 7 Pages: 4131-4135

    • DOI

      10.21873/anticanres.14412

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Uterine tumor resembling ovarian sex-cord tumor (UTROSCT) with sarcomatous features without recurrence after extended radical surgery2020

    • Author(s)
      Sato Miho、Yano Mitsutake、Sato Shimpei、Aoyagi Yoko、Aso Saki、Matsumoto Harunobu、Yamamoto Ichiro、Nasu Kaei
    • Journal Title

      Medicine

      Volume: 99 Issue: 11 Pages: e19166-e19166

    • DOI

      10.1097/md.0000000000019166

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed
  • [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
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Molecular association of functioning stroma with carcinoma cells in the ovary: A preliminary study2019

    • Author(s)
      Narikiyo Mika、Yano Mitsutake、Kamada Kouichi、Katoh Tomomi、Ito Kozue、Shuto Masayo、Kayano Hidekazu、Yasuda Masanori
    • Journal Title

      Oncology Letters

      Volume: 17(3) Pages: 3562-3568

    • DOI

      10.3892/ol.2019.9992

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Coexistence of endometrial mesonephric-like adenocarcinoma and endometrioid carcinoma suggests a M?llerian duct lineage: a case report2019

    • Author(s)
      Yano Mitsutake、Shintani Daisuke、Katoh Tomomi、Hamada Mei、Ito Kozue、Kozawa Eito、Hasegawa Kosei、Yasuda Masanori
    • Journal Title

      Diagnostic Pathology

      Volume: 14 Issue: 1 Pages: 54-54

    • DOI

      10.1186/s13000-019-0830-4

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A unique uterine cervical “teratocarcinosarcoma”: a case report2019

    • Author(s)
      Ito Kozue、Yano Mitsutake、Ogasawara Aiko、Miwa Maiko、Kozawa Eito、Yasuda Masanori
    • Journal Title

      Diagnostic Pathology

      Volume: 14 Issue: 1 Pages: 122-122

    • DOI

      10.1186/s13000-019-0890-5

    • Related Report
      2019 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
  • [Presentation] The lymphocyte activation gene-3 (LAG-3) protein expression in tumor-infiltrating lymphocytes is associated with a poor prognosis of ovarian clear cell carcinoma2023

    • Author(s)
      Sumika Zaitsu, Mitsutake Yano, Sawako Adachi, Maiko Miwa, Tomomi Katoh, Yasushi Kawano, Masanori Yasuda
    • Organizer
      ESMO Gynaecological Cancers Congress 2023
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] PD-L1 expression following neoadjuvant chemotherapy is upregulated and serves as a prognostic factor in patients with advanced high-grade serous ovarian carcinoma2023

    • Author(s)
      Mitsutake Yano, Tomomi Katoh, Mariko Miyazawa, Aiko Ogasawara, Kosei Hasegawa, Yasushi Kawano, Masanori Yasuda
    • Organizer
      ESMO Gynaecological Cancers Congress 2023
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 子宮体部Mesonephric-like Adenocarcinomaは類内膜癌と混同される傾向があり,頻繁なKRAS変異を伴う2022

    • Author(s)
      矢野 光剛, 藪野 彰, 長谷川 幸清, 河野 康志, 安田 政実
    • Organizer
      第74回日本産科婦人科学会学術講演会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 子宮体部Mesonephric-like Adenocarcinomaは類内膜癌と混同される傾向がある2022

    • Author(s)
      矢野 光剛, 加藤 智美, 藪野 彰, 大金 直樹, 宮澤 麻里子, 宮澤 昌樹, 長谷川 幸清, 河野 康志, 安田 政実
    • Organizer
      第111回日本病理学会総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 卵巣明細胞癌におけるlymphocyte activation gene-3発現の臨床的意義2022

    • Author(s)
      財津 純可, 矢野 光剛, 足立 佐和子, 三輪 真唯子, 加藤 智美, 河野 康志, 安田 政実
    • Organizer
      第37回日本生殖免疫学会総会・学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 卵巣明細胞癌におけるLymphocyte activation gene3の予後予測因子としての意義2022

    • Author(s)
      財津 純可, 矢野 光剛, 足立 佐和子, 三輪 真唯子, 河野 康志, 安田 政実
    • Organizer
      第64回日本婦人科腫瘍学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 再発腟悪性黒色腫に対するニボルマブ+イピリムマブ併用療法の使用経験2021

    • Author(s)
      矢野光剛
    • Organizer
      第36回日本生殖免疫学会学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] Histone Deacetylase 6を基軸とした卵巣明細胞癌の治療標的の同定および治療薬の開発2021

    • Author(s)
      矢野光剛
    • Organizer
      第63回日本婦人科腫瘍学会学術講演会(高得点演題)
    • Related Report
      2021 Research-status Report
  • [Presentation] 卵巣成熟奇形腫に悪性リンパ腫が併存した一例2021

    • Author(s)
      矢野光剛
    • Organizer
      第53回日本婦人科病理学会学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] Aggressive angiomyxomaに対して腫瘍切除後にアロマターゼ阻害剤を使用した1例2021

    • Author(s)
      矢野光剛
    • Organizer
      第53回日本臨床分子形態学会学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] 扁平上皮病変を考える-どこからLSILとして拾うか・どこからHSIL とするべきか-2020

    • Author(s)
      矢野光剛
    • Organizer
      第59回日本臨床細胞学会秋期大会シンポジウム1
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] 子宮体部Mesonephric-like Adenocarcinomaの同定と他組織型との臨床病理学的特徴の比較2020

    • Author(s)
      矢野光剛
    • Organizer
      第52回日本臨床分子形態学会総会シンポジウム2
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] A unique uterine cervical cancer: Carcinosarcoma with teratomatous features2019

    • Author(s)
      Mitsutake Yano, Masanori Yasuda, Maiko Miwa, Aiko Ogasawara, Hisashi Narahara
    • Organizer
      第71回日本産科婦人科学会学術講演会
    • Related Report
      2019 Research-status Report
  • [Book] 産婦人科の実際 2021年11月臨時増刊号【図解 分子メカニズムから理解する婦人科がんの薬物療法】臓器横断的な考え方を要する婦人科悪性腫瘍 悪性黒色腫2021

    • Author(s)
      矢野光剛, 奈須家栄
    • Total Pages
      7
    • Publisher
      金原出版
    • Related Report
      2021 Research-status Report

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Published: 2019-04-18   Modified: 2024-01-30  

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