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Tumor microenvironment and gut microbiota in pancreatic cancer

Research Project

Project/Area Number 19K08444
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53010:Gastroenterology-related
Research InstitutionKobe University

Principal Investigator

Masuda Atsuhiro  神戸大学, 医学研究科, 講師 (60512530)

Co-Investigator(Kenkyū-buntansha) 井上 潤  神戸大学, 医学部附属病院, 助教 (50631561)
児玉 裕三  神戸大学, 医学研究科, 教授 (80378687)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords膵癌 / 細菌叢 / 腫瘍免疫 / 細菌 / 腫瘍内免疫細胞 / 予後 / 腸内細菌 / 腸内細菌叢
Outline of Research at the Start

ヒト膵癌切除症例を前向きに収集し、① 腸内細菌叢の構成・多様性と、腫瘍浸潤T細胞の関連性を検討、② 腫瘍浸潤T細胞と関連のある腸内細菌と予後との関連性を検討する。本研究により膵癌の腫瘍免疫における腸内細菌叢との関連性が明らかとなり、膵癌形成の病態解明やプロバイオティクスとしての免疫修飾による治療介入へと発展する可能性が期待される。

Outline of Final Research Achievements

In recent years, it has become clear that bacterial infection is locally observed in pancreatic cancer, suggesting that it plays an important role in pancreatic carcinogenesis and its progression. However, there are still unclear what and how bacterial species are involved in pancreatic carcinogenesis and progression. In this study, we investigated the relationship between the microbiota profile of cancer and the pathological and clinical features using the histopathology of human pancreatic cancer. Compared with normal pancreatic tissue, pancreatic cancer showed a high amplification reaction of 16S rDNA, and analysis by the next-generation sequencer could identify the same bacteria as previously reported. Furthermore, immunostaining of LPS revealed that LPS-positive pancreatic cancer had a poor prognosis and that tumor immunity was suppressed. Currently, we are considering adding in situ hybridization.

Academic Significance and Societal Importance of the Research Achievements

本研究は、膵癌組織中の細菌叢解析を行う事で膵癌の予後や腫瘍内免疫に当たる影響を調査するものである。予後の悪い膵癌の発癌及び進展機構を解明することで、予後改善に向けた病態解明につながる可能性があると考える。事実、細菌の構成成分の一つであるLPS陽性膵癌では予後不良であり、腫瘍免疫が抑制されている事を見出した。今後はさらに詳細に解析を追加し結果の信頼性を高めるとともにプロバイオティクスによる細菌制御法について研究を進め、膵癌の予後改善を目指す。

Report

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

    (24 results)

All 2022 2021 2020 2019

All Journal Article (10 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 10 results,  Open Access: 3 results) Presentation (9 results) Book (5 results)

  • [Journal Article] Comprehensive Analysis of Molecular Biological Characteristics of Pancreatic Ductal Adenocarcinoma Concomitant with Intraductal Papillary Mucinous Neoplasm2022

    • Author(s)
      Masahiro Tsujimae, Atsuhiro Masuda, et al.
    • Journal Title

      Annals of Surgical Oncology

      Volume: in press Issue: 8 Pages: 4935-4936

    • DOI

      10.1245/s10434-022-11785-w

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Estimation of pancreatic fibrosis and prediction of postoperative pancreatic fistula using extracellular volume fraction in multiphasic contrast-enhanced CT2022

    • Author(s)
      Sofue K, Ueshima E, Masuda A, Shirakawa S, Zen Y, Ueno Y, Tsujita Y, Yamaguchi T, Yabe S, Tanaka T, Inomata N, Toyama H, Fukumoto T, Kodama Y, Murakami T.
    • Journal Title

      Eur Radiol.

      Volume: 32(3) Issue: 3 Pages: 1770-1780

    • DOI

      10.1007/s00330-021-08255-4

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Acute pancreatitis in intraductal papillary mucinous neoplasms correlates with pancreatic volume and epithelial subtypes2021

    • Author(s)
      Tanaka T, Masuda A, Sofue K, Toyama H, Shiomi H, Sakai A, Kobayashi T, Tanaka S, Nakano R, Yamada Y, Ashina S, Tsujimae M, Yamakawa K, Abe S, Gonda M, Masuda S, Inomata N, Uemura H, Kohashi S, Nagao K, Kanzawa M, Itoh T, Fukumoto T, Kodama Y.
    • Journal Title

      Pancreatology

      Volume: 21 Issue: 1 Pages: 138-143

    • DOI

      10.1016/j.pan.2020.11.005

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clinical outcome of conservatively managed pancreatic intraductal papillary mucinous neoplasms with mural nodules and main duct dilation2020

    • Author(s)
      Sakai Arata、Masuda Atsuhiro、Eguchi Takaaki、Anami Takahiro、Nishi Katsuhisa、Furumatsu Keisuke、Okabe Yoshihiro、Kakuyama Saori、Sato Yu、Nishioka Chiharu、Sanuki Tsuyoshi、Yagi Yosuke、Kobayashi Takashi、Shiomi Hideyuki、Kodama Yuzo
    • Journal Title

      Journal of Gastroenterology

      Volume: 56 Issue: 3 Pages: 285-292

    • DOI

      10.1007/s00535-020-01739-y

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Evaluation of efficacy of pancreatic juice cytology for risk classification according to international consensus guidelines in patients with intraductal papillary mucinous neoplasm; a retrospective study2019

    • Author(s)
      Yamakawa Kohei、Masuda Atsuhiro、Nakagawa Takashi、Kobayashi Takashi、Tsujimae Masahiro、Ashina Shigeto、Yamada Yasutaka、Tanaka Takeshi、Tanaka Shunta、Nakano Ryota、Sato Yu、Ikegawa Takuya、Kurosawa Manabu、Fujigaki Seiji、Kutsumi Hiromu、Itoh Tomoo、Fukumoto Takumi、Kodama Yuzo
    • Journal Title

      Pancreatology

      Volume: 19 Issue: 3 Pages: 424-428

    • DOI

      10.1016/j.pan.2019.02.013

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Clinical outcomes of ampullary neoplasms in resected margin positive or uncertain cases after endoscopic papillectomy.2019

    • Author(s)
      Sakai A, Tsujimae M, Masuda A, Iemoto T, Ashina S, Yamakawa K, Tanaka T, Tanaka S, Yamada Y, Nakano R, Sato Y, Kurosawa M, Ikegawa T, Fujigaki S, Kobayashi T, Shiomi H, Arisaka Y, Itoh T, Kodama Y.
    • Journal Title

      World J Gastroenterol.

      Volume: 21;25(11) Issue: 11 Pages: 1387-1397

    • DOI

      10.3748/wjg.v25.i11.1387

    • NAID

      120006601542

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Significance of pancreatic calcification on preoperative computed tomography of intraductal papillary mucinous neoplasms2019

    • Author(s)
      Tsujimae Masahiro、Masuda Atsuhiro、Shiomi Hideyuki、Kobayashi Takashi、Sakai Arata、Kutsumi Hiromu、Zen Yoh、Itoh Tomoo、Fukumoto Takumi、Kodama Yuzo
    • Journal Title

      Journal of Gastroenterology and Hepatology

      Volume: 34 Issue: 9 Pages: 1648-1655

    • DOI

      10.1111/jgh.14732

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Endoscopic ultrasound-guided gastrojejunostomy using fully covered metal stent combined with large-loop double-pigtail stent for malignant afferent loop syndrome.2019

    • Author(s)
      Shiomi H, Kobayashi T, Sakai A, Shiomi Y, Masuda A, Bondoc EM, Kodama Y.
    • Journal Title

      Endoscopy.

      Volume: 51(10) Issue: 10 Pages: E303-E304

    • DOI

      10.1055/a-0916-8532

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Type 1 Autoimmune Pancreatitis with Imaging Appearance Similar to That of Malignant Cystic Tumor2019

    • Author(s)
      Ezaki Takeshi、Masuda Atsuhiro、Shiomi Hideyuki、Nakagawa Takashi、Sofue Keitaro、Toyama Hirochika、Zen Yoh、Kodama Yuzo
    • Journal Title

      Case Reports in Gastroenterology

      Volume: 13 Issue: 2 Pages: 265-270

    • DOI

      10.1159/000500477

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] An autopsy case of granulocyte colony-stimulating factor-producing pancreatic adenosquamous carcinoma.2019

    • Author(s)
      Inomata N, Masuda A, Itani T, Hayashi M, Shimada Y, Adachi K, Hashimoto K, Tanaka Y, Tanaka A, Kobayashi T, Sakai A, Shiomi H, Kodama Y.
    • Journal Title

      Clin J Gastroenterol.

      Volume: なし Issue: 3 Pages: 448-454

    • DOI

      10.1007/s12328-019-01067-6

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 膵癌のTLS(Tertiary lymphoid structure)を介した腫瘍免疫機構の解明2022

    • Author(s)
      田中雄志、増田充弘、児玉裕三
    • Organizer
      日本消化器病学会総会 シンポジウム
    • Related Report
      2021 Annual Research Report
  • [Presentation] 背景膵のEUS所見と膵前癌病変の頻度との関連性 早期慢性膵炎所見によるハイリスク膵臓の予測2021

    • Author(s)
      猪股典子、増田充弘、児玉裕三
    • Organizer
      JDDW2021 シンポジウム
    • Related Report
      2021 Annual Research Report
  • [Presentation] 腫瘍存在部位から見た膵癌の術前診断法の妥当性の検証と現状の課題2021

    • Author(s)
      中野遼太、増田充弘、児玉裕三
    • Organizer
      JDDW2021 シンポジウム
    • Related Report
      2021 Annual Research Report
  • [Presentation] 急性膵炎におけるPLCεを介した炎症制御機構の解明2021

    • Author(s)
      辻前正弘、増田充弘、他
    • Organizer
      日本膵臓学会総会 シンポジウム
    • Related Report
      2021 Annual Research Report
  • [Presentation] High risk stigmataを有するIPMN経過観察症例の予後からみた手術適応の検討2021

    • Author(s)
      酒井新、増田充弘、他
    • Organizer
      日本膵臓学会総会 シンポジウム
    • Related Report
      2021 Annual Research Report
  • [Presentation] 膵切除検体を用いたEUSにおける早期慢性膵炎所見の妥当性の検証2021

    • Author(s)
      猪股典子、増田充弘、児玉裕三
    • Organizer
      日本消化器病学会総会 シンポジウム
    • Related Report
      2021 Annual Research Report
  • [Presentation] 膵癌手術例における治療選択マーカーとしてのTLS(Tertiary lymphoid structure)の有用性2021

    • Author(s)
      田中雄志、増田充弘、児玉裕三
    • Organizer
      日本消化器病学会総会 シンポジウム
    • Related Report
      2021 Annual Research Report
  • [Presentation] 膵管内乳頭粘液産生腫瘍に対するERCP下膵液細胞診の役割 腫瘍の病理学的特徴との対比を含めて2019

    • Author(s)
      山川康平、増田充弘、児玉裕三
    • Organizer
      日本消化器内視鏡学会総会 シンポジウム
    • Related Report
      2019 Research-status Report
  • [Presentation] IPMN術後の残膵再発に関与する因子の検討 糖尿病の新規発症及び増悪の関連性2019

    • Author(s)
      中野遼太、増田充弘、藤垣誠治、小林隆、酒井新、塩見英之、児玉裕三
    • Organizer
      日本膵臓学会総会
    • Related Report
      2019 Research-status Report
  • [Book] 【診療ガイドライン改訂後の膵炎診療】EUS所見は何を見ているのか 組織像との対比など2022

    • Author(s)
      猪股典子、山川康平、増田充弘、児玉裕三
    • Total Pages
      7
    • Publisher
      肝胆膵
    • Related Report
      2021 Annual Research Report
  • [Book] 【膵臓症候群(第3版)-その他の膵臓疾患を含めて-】膵炎 1型自己免疫性膵炎(IgG4関連膵炎)2021

    • Author(s)
      酒井新、増田充弘、児玉裕三
    • Total Pages
      5
    • Publisher
      日本臨床
    • Related Report
      2021 Annual Research Report
  • [Book] IPMN由来癌と併存癌 IPMN併存癌の特徴 予後、遺伝子異常など通常型膵癌と比較して2021

    • Author(s)
      辻前正弘、増田充弘、他
    • Total Pages
      5
    • Publisher
      肝胆膵
    • Related Report
      2021 Annual Research Report
  • [Book] IPMNの長期予後 High risk stigmata非切除例の予後2021

    • Author(s)
      酒井新、増田充弘、他
    • Total Pages
      4
    • Publisher
      肝胆膵
    • Related Report
      2021 Annual Research Report
  • [Book] 【肝・胆道系症候群(第3版)-その他の肝・胆道系疾患を含めて-肝外胆道編】肝外胆管(胆管、胆嚢管、総胆管) その他 Oddi括約筋機能不全2021

    • Author(s)
      酒井新、増田充弘、児玉裕三
    • Total Pages
      3
    • Publisher
      日本臨床
    • Related Report
      2021 Annual Research Report

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Published: 2019-04-18   Modified: 2023-01-30  

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