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An Efficacy of polyphenols for Il13Ra2-positive advanced pancreatic cancer

Research Project

Project/Area Number 18K07332
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 50020:Tumor diagnostics and therapeutics-related
Research InstitutionJuntendo University

Principal Investigator

FUJISAWA Toshio  順天堂大学, 医学部, 先任准教授 (50627346)

Co-Investigator(Kenkyū-buntansha) 伊佐山 浩通  順天堂大学, 医学部, 教授 (70376458)
Project Period (FY) 2018-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
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)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsIL-13Ra2 / 膵癌 / EUS-FNA / 緑茶ポリフェノール / 浸潤・転移 / 予後 / 抗癌剤効果予測 / バイオマーカー / IL-13Rα2 / 浸潤 / 転移 / Gemcitabine / 化学療法 / ポリフェノール / 膵臓癌 / gemcitabine / 予測因子 / 浸潤転移 / 動物モデル / epigenetics / エピジェネティクス / 神経浸潤 / IL-13 receptor alpha2 / Histone修飾 / HDAC inhibitor
Outline of Final Research Achievements

Since only about 20% of patients with pancreatic cancer can undergo surgery, we investigated whether the expression of IL-13Ra2 could be evaluated using biopsy specimens obtained by EUS-FNA when pancreatic cancer is diagnosed. In more than 90% of cases, the expression was consistent when compared with surgical specimens, and the expression of IL-13Ra2 was also evaluable in EUS-FNA. When EUS-FNA samples were used to compare the low and high expression groups of IL-13Ra2 in 132 new pancreatic cancer patients, progression-free survival and overall survival were significantly shorter in the low expression group. Furthermore, we found that IL-13Ra2 attenuated the effect of gemcitabine and was involved in the metabolic pathway of gemcitabine and the growth of tumor blood vessels. In addition, animal studies have shown that small molecules containing green tea polyphenols can be used to suppress the expression of IL-13Ra2 and improve the prognosis of IL-13Ra2-positive pancreatic cancer.

Academic Significance and Societal Importance of the Research Achievements

前回の科研費を用いた研究で、IL-13Ra2が膵癌の進展を促進し予後を悪化させることを見出したが、今回の研究ではIL-13Ra2が予後を悪化させるメカニズムを詳細に検討した。更に膵癌診断時に用いるEUS-FNA検体を用いてIL-13Ra2の発現が評価できることが分かったため、予後や化学療法の効果判定のバイオマーカーや治療のターゲットとして活用しうる。今後はIL-13Ra2による治療法の選択やIL-13Ra2を抑制することによる化学療法の効果改善を評価していく予定である。膵癌は未だ最難治癌であり、IL-13Ra2の治療応用が膵癌の予後の改善に貢献すると確信している。

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

    (18 results)

All 2023 2022 2021 2020 Other

All Int'l Joint Research (4 results) Journal Article (5 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 5 results,  Open Access: 5 results) Presentation (8 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results) Remarks (1 results)

  • [Int'l Joint Research] Food and Drug Administration(米国)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] US Food and Drug Administration(米国)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] Food and Drug Administration(米国)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] Food and Drug Administrations(米国)

    • Related Report
      2018 Research-status Report
  • [Journal Article] Clinical Practice Guidelines for Pancreatic Cancer 2022 from the Japan Pancreas Society: a synopsis2023

    • Author(s)
      Takuji Okusaka, Masafumi Nakamura, Masahiro Yoshida, Masayuki Kitano, Yoshinori Ito, Nobumasa Mizuno, Keiji Hanada, Masato Ozaka, Chigusa Morizane, Yoshifumi Takeyama, Toshio Fujisawa et. al
    • Journal Title

      International Journal of Clinical Oncology

      Volume: 28 Issue: 4 Pages: 493-511

    • DOI

      10.1007/s10147-023-02317-x

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pancreatic Adenocarcinoma With Strong Expression of Interleukin-13 Receptor α2 Shows a Poor Response to Gemcitabine-Based Chemotherapy.2022

    • Author(s)
      Tomishima K, Fujisawa T, Fukumura Y, Ushio M, Fukuma T, Takahashi S, Takasaki Y, Suzuki A, Ito K, Ishii S, Yao T, Nagahara A, Isayama H.
    • Journal Title

      Pancreas

      Volume: 51 Issue: 9 Pages: 1133-1139

    • DOI

      10.1097/mpa.0000000000002151

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] IL-13Rα2 Is a Biomarker of Diagnosis and Therapeutic Response in Human Pancreatic Cancer2021

    • Author(s)
      Fujisawa T, Joshi BH, Takahashi S, Takasaki Y, Suzuki A, Ito K, Ochiai K, Tomishima K, Ishii S, Puri RK, Isayama H.
    • Journal Title

      Diagnostics

      Volume: 11 Issue: 7 Pages: 1140-1140

    • DOI

      10.3390/diagnostics11071140

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A Novel Role of Interleukin 13 Receptor alpha2 in Perineural Invasion and Its Association With Poor Prognosis of Patients With Pancreatic Ductal Adenocarcinoma2020

    • Author(s)
      Toshio Fujisawa, Takeshi Shimamura, Kaku Goto, Ryo Nakagawa, Ryosuke Muroyama, Yoshinori Ino, Hajime Horiuchi, Itaru Endo, Shin Maeda, Yasushi Harihara, Atsushi Nakajima,, Nobuyuki Matsuhashi, Naoya Kato, Hiroyuki Isayama, Ankit Puri, Akiko Suzuki, Ian Bellayr, Pamela Leland, Bharat H Joshi, Raj K Puri
    • Journal Title

      Cancers

      Volume: 12 Issue: 5 Pages: 1294-1294

    • DOI

      10.3390/cancers12051294

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Immunotherapy for Pancreatic Cancer2020

    • Author(s)
      Toshio Fujisawa, Hiroyuki Isayama
    • Journal Title

      Juntendo Medical Journal

      Volume: 66 Issue: 3 Pages: 238-244

    • DOI

      10.14789/jmj.2020.66.JMJ20-LN02

    • NAID

      130007867030

    • ISSN
      2187-9737, 2188-2126
    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 膵癌抗癌剤治療におけるIL-13 receptorα2 発現による効果予測と感受性低下機序の解明2023

    • Author(s)
      藤澤聡郎, 冨嶋享, 伊佐山浩通.
    • Organizer
      第109回日本消化器病学会総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 膵癌の化学療法選択においてIL-13 receptorα2発現の示す意義.2022

    • Author(s)
      冨嶋 享
    • Organizer
      U45消化器疾患 イノベーションカンファレンス ~サイエンスでつながる次世代の会~
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 癌精巣抗原IL-13Rα2の膵癌における役割と分子標的治療法の開発.2022

    • Author(s)
      藤澤 聡郎
    • Organizer
      第6回がんブレインストーミング研究会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 膵癌EUS-FNA検体で評価し得たIL-13 receptor&alpha2発現と化学療法効果について.2022

    • Author(s)
      冨嶋享, 藤澤聡郎, 伊佐山浩通, 福村由紀.
    • Organizer
      第103回日本消化器内視鏡学会総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 膵癌の化学療法選択においてIL-13 receptorα2発現の示す意義.2022

    • Author(s)
      冨嶋享, 藤澤聡郎, 伊佐山浩通.
    • Organizer
      第108回日本消化器病学会総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] PANCREATIC ADENOCARCINOMA WITH STRONG EXPRESSION OF IL-13RA2 SHOWS A POOR RESPONSE TO GEMCITABINE-BASED CHEMOTHERAPY.2022

    • Author(s)
      Ko Tomishima, Toshio Fujisawa, Hiroyuki Isayama
    • Organizer
      United-European Gastrointestinal Week
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 膵癌EUS-FNA検体で評価し得たIL-13 receptor a2発現と化学療法効果について2022

    • Author(s)
      冨嶋 享、藤澤 聡郎、伊佐山 浩通、福村 由紀
    • Organizer
      第103回 日本消化器内視鏡学会総会
    • Related Report
      2021 Research-status Report
  • [Presentation] 膵癌の化学療法の選択においてIL-13 receptor a2発現の示す意義2022

    • Author(s)
      冨嶋 享、藤澤 聡郎、伊佐山 浩通
    • Organizer
      第108回 日本消化器病学会総会
    • Related Report
      2021 Research-status Report
  • [Remarks] Dr. Puri's site

    • URL

      https://www.linkedin.com/in/raj-puri-m-d-ph-d-19383430

    • Related Report
      2020 Research-status Report

URL: 

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

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