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Basic research of PARP inhibitor effects for chemotherapy induced mucositis

Research Project

Project/Area Number 20K10196
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 57060:Surgical dentistry-related
Research InstitutionTsurumi Junior College

Principal Investigator

Fujihara Hisako  鶴見大学短期大学部, 歯科衛生科, 教授 (80396746)

Co-Investigator(Kenkyū-buntansha) 熊谷 賢一  東京大学, 医学部附属病院, 助教 (10518129)
川口 浩司  鶴見大学, 歯学部, 准教授 (50277951)
濱田 良樹  鶴見大学, 歯学部, 教授 (70247336)
大島 朋子  鶴見大学, 歯学部, 教授 (50233101)
伊藤 由美  鶴見大学, 歯学部附属病院, 講師 (00176372)
Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
KeywordsPARP阻害剤 / CDDP / 抗腫瘍薬誘発障害 / 菌叢解析 / 化学療法誘発粘膜炎 / 腸管免疫応答
Outline of Research at the Start

本研究では、抗腫瘍薬のシスプラチンと分子標的薬のPARP阻害剤をマウスへ投与し、悪性腫瘍への影響ならびに全身へ及ぼす影響について、特に消化管粘膜(口腔と腸管)と菌叢(口腔と腸管)への影響を検証する。
先行実験ならびに、口腔がん細胞へのシスプラチンとPARP阻害剤の相乗効果を踏まえて、PARP阻害剤には癌治療効果と副作用抑制効果の双方があると仮説を立てている。
従って本研究では、PARP阻害剤の消化管粘膜と腸管細菌叢に対する役割という観点から、抗腫瘍薬誘発粘膜障害のメカニズム解明を目指す。最終的には粘膜免疫応答の破綻によって発症する疾患の予防法開発の一助となることを目指す。

Outline of Final Research Achievements

In this study, the systemic effects of the anti-tumour drug CDDP and the molecularly targeted drug PARP inhibitor on mice were examined. Mice were randomly divided into four groups: CDDP, PARP inhibitor, combination, and control group. Cisplatin and the PARP inhibitor were administered by intraperitoneal injection. At 1 month, weight significantly decreased in the CDDP and combination groups but recovered by months 3 and 6. Survival analysis indicated a significant decrease in the CDDP group by day 40. Regarding the gastrointestinal mucosa, no significant differences were observed between the control and PARP inhibitor groups. The CDDP group showed significant shortening of villi compared to the control and PARP inhibitor groups. The combination group did not exhibit significant villi shortening compared to the CDDP group and showed no significant difference from the control group. These findings suggest that the PARP inhibitor may mitigate the intestinal damage caused by cisplatin.

Academic Significance and Societal Importance of the Research Achievements

本研究において、PARP阻害剤を併用することによって、以前から報告されているCDDPの抗腫瘍効果の増強効果だけでなく、CDDPによる副作用軽減の両方を期待できることが示唆される結果が得られた。従って、さらに分子生物学的なメカニズム解明のための研究意義が生じるだけでなく、消化管症状を誘発させる他の抗腫瘍薬においても同様の検証を行う学術的意義が発生する。それにより抗腫瘍薬誘発消化管粘膜障害ならびに粘膜免疫応答の破綻によって発症する疾患のメカニズム解明につながる可能性が期待でき、当該疾患発症の予防法や治療法の新たな展開につながる社会的意義がある。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (1 results)

All 2022

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results)

  • [Journal Article] Possible Action of Olaparib for Preventing Invasion of Oral Squamous Cell Carcinoma In Vitro and In Vivo2022

    • Author(s)
      Nakamura Nanami、Fujihara Hisako、Kawaguchi Koji、Yamada Hiroyuki、Nakayama Ryoko、Yasukawa Masaaki、Kishi Yuta、Hamada Yoshiki、Masutani Mitsuko
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 23 Issue: 5 Pages: 2527-2527

    • DOI

      10.3390/ijms23052527

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access

URL: 

Published: 2020-04-28   Modified: 2025-01-30  

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