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Neutrophil extracellular traps in the development of peritoneal metastasis

Research Project

Project/Area Number 17K10606
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Digestive surgery
Research InstitutionJichi Medical University

Principal Investigator

Hosoya Yoshinori  自治医科大学, 医学部, 教授 (30275698)

Co-Investigator(Kenkyū-buntansha) 北山 丈二  自治医科大学, 医学部, 教授 (20251308)
山口 博紀  自治医科大学, 医学部, 教授 (20376445)
大澤 英之  自治医科大学, 医学部, 講師 (60458271)
倉科 憲太郎  自治医科大学, 医学部, 講師 (70382900)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords好中球細胞外トラップ / 腹膜播種 / 胃癌 / 接着 / DNAse 1 / 低比重好中球 / 好中球 / 細胞外トラップ / 腹膜転移 / 癌 / 消化器外科学 / 胃十二指腸外科学
Outline of Final Research Achievements

The number of CD66b (+) low density neutrophils (LDN) with mature phenotype was markedly elevated in postoperative as compared with preoperative lavages in patients who underwent laparotomy due to gastric cancer. Short term culture of the purified LDN produced many threadlike structures positive for SYTOX, suggesting the NETs formation. Human gastric cancer cells, MKN45, OCUM-1 and NUGC-4, were selectively attached on the NETs, which was abolished by DNAse I. Intraperitoneal co-transfer of the LDN with MKN45 in nude mice strongly augments the metastasis formation on peritoneum, which was strongly suppressed by the following IP administration of DNAse I. Many NETs-like structures were detected on the surface of human omental tissue resected by gastrectomy. NETs on peritoneal surface can assist the clustering and growth of free tumor cells disseminated in abdomen. Disruption of the NETs by DNAse might be useful to prevent the peritoneal recurrence after abdominal surgery.

Academic Significance and Societal Importance of the Research Achievements

腹膜播種の成立における腹腔内滲出好中球とNETsの役割を明らかにすると共に、DNAse1投与によるNETsの分解が播種再発の予防につながる可能性があることを見出した。今後の腹膜播種治療における新たな方法論を導く糸口になる成果を得た。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (19 results)

All 2019 2018 2017

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (17 results) (of which Int'l Joint Research: 3 results)

  • [Journal Article] Low density neutrophils (LDN) in postoperative abdominal cavity assist the peritoneal recurrence through the production of neutrophil extracellular traps (NETs)2018

    • Author(s)
      Kanamaru Rihito、Ohzawa Hideyuki、Miyato Hideyo、Matsumoto Shiro、Haruta Hidenori、Kurashina Kentaro、Saito Shin、Hosoya Yoshinori、Yamaguchi Hironori、Yamashita Hiroharu、Seto Yasuyuki、Lefor Alan Kawarai、Sata Naohiro、Kitayama Joji
    • Journal Title

      Sci Rep.

      Volume: 8 Issue: 1 Pages: 632-632

    • DOI

      10.1038/s41598-017-19091-2

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Neutrophil Extracellular Traps Generated by Low Density Neutrophils Obtained from Peritoneal Lavage Fluid Mediate Tumor Cell Growth and Attachment2018

    • Author(s)
      Kanamaru Rihito、Ohzawa Hideyuki、Miyato Hideyo、Yamaguchi Hironori、Hosoya Yoshinori、Lefor Alan Kawarai、Sata Naohiro、Kitayama Joji
    • Journal Title

      Journal of Visualized Experiments

      Volume: 138 Issue: 138 Pages: 00-00

    • DOI

      10.3791/58201

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 開腹術後腹腔内滲出好中球上のPD-L1発現.2019

    • Author(s)
      金丸 理人,大澤 英之,高橋 和也,松本 志郎,春田 英律,倉科 健太郎,山口 博紀, 細谷 好則,佐田 尚宏,北山 丈二.
    • Organizer
      第74回日本消化器外科学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 開腹手術後の腹腔内滲出好中球細胞外トラップの意義.2019

    • Author(s)
      金丸 理人,大澤 英之,高橋 和也,松本 志郎,春田 英律,倉科 憲太郎,山口 博紀,佐久間 康成,堀江 久永,細谷 好則,北山 丈二,佐田 尚宏.
    • Organizer
      第91回日本胃癌学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Neutrophil Extracellular Traps(NETs) on Peritoneal Surface After Abdominal Surgery may enhance peritoeal recurrence.2019

    • Author(s)
      Rihito Kanamaru., Hideyuki Ohzawa., Kazuya Takahashi., Shiro Matsumoto., Takashi Ui., Hidenori Haruta., Kentaro Kurashina., Shin Saito., Hironori Yamaguchi., Yoshinori Hosoya., Naohiro Sata., Joji Kitayama.
    • Organizer
      14th International Symposium on Regional Cancer Therapies
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 消化器癌手術患者の末梢血中低比重好中球と術後転移再発との関連について(Low density neutrophils(LDN) in postoperative peripheral blood may assist the recurrence of gastrointestinal cancer.)2018

    • Author(s)
      熊谷祐子, 金丸理人, 大澤英之, 山口博紀, 佐久間康成, 堀江久永, 細谷好則, 佐田尚宏, 北山丈二
    • Organizer
      第77回日本癌学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] Low density neutrophils(LDN) in surgical patients may assist the recurrence of distant organ in gastrointestinal caner.2018

    • Author(s)
      Yuko Kumagai, Rihito Kanamaru, Hidenori Tsukui, Satomi Shiba, Hiromi Hatakeyama, Junko Shinohara, Hideyuki Ohzawa, Hisanaga Horie, Yoshinori Hosoya, Naohiro Sata and Joji Kitayama.
    • Organizer
      第17回自治医科大学シンポジウム
    • Related Report
      2018 Research-status Report
  • [Presentation] Neutrophil extracellular traps(NETs) on peritoneal surface after open abdominal surgery.2018

    • Author(s)
      Kanamaru Rihito, Hideyuki Ohzawa, Kazuya Takahashi, Shiro Matsumoto, Hiedenori Haruta, Kentaro Kurashina, Hironori Yamaguchi, Yasunaru Sakuma, Hisanaga Horie, Yoshinori Hosoya, Joji Kitayama and Naohiro Sata
    • Organizer
      第17回自治医科大学シンポジウム
    • Related Report
      2018 Research-status Report
  • [Presentation] 好中球細胞外トラップ(NET’s)による開腹術後腹膜再発促進機構(Neutrophil extracellular traps(NETs) on postoperative peritoneal surface may support the tumor recurrence on peritoneum.)2018

    • Author(s)
      金丸理人, 大澤英之, 高橋和也, 松本志郎, 春田英律, 倉科憲太郎, 山口博紀, 佐久間康成, 堀江久永, 細谷好則, 佐田尚宏, 北山丈二
    • Organizer
      第77回日本癌学会総会記事
    • Related Report
      2018 Research-status Report
  • [Presentation] 開腹手術後の腹腔内滲出好中球由来細胞外トラップ(NETs)の臨床的意義2018

    • Author(s)
      金丸理人, 大澤英之, 松本志郎, 春田英律, 倉科憲太郎, 宮戸秀世, 山口博紀, 細谷好則, 佐田尚宏, 北山丈二
    • Organizer
      第73回日本消化器外科学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 開腹手術後の腹腔内滲出好中球由来細胞外トラップ(NETs)の臨床的意義2018

    • Author(s)
      金丸理人, 大澤英之, 松本志郎, 宇井崇, 春田英律, 宮戸秀世, 倉科憲太郎, 斉藤心, 山口博紀, 佐久間康成, 堀江久永, 細谷好則, 佐田 尚宏, 北山 丈二
    • Organizer
      第39回癌免疫外科研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] 治癒切除を受けた消化器癌術後患者へのメトホルミン内服による生存率改善について2018

    • Author(s)
      熊谷祐子, 大澤英之, 津久井秀則, 金丸理人, 芝聡美, 堀江久永, 細谷好則, 佐久間康成, 佐田尚宏, 北山丈二
    • Organizer
      第73回日本消化器外科学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 消化器癌手術患者における末梢血中低比重好中球(Low Density Granulocyte)の術中推移2018

    • Author(s)
      熊谷祐子, 金丸理人, 津久井秀則, 大澤英之, 倉科憲太郎, 鯉沼広治, 佐久間康成, 堀江久永, 細谷好則, 佐田尚宏, 北山丈二
    • Organizer
      第118回日本外科学会定期学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 当院における漿膜浸潤胃癌R0切除症例における術中出血量と生命予後の関係2018

    • Author(s)
      金丸理人, 大澤英之, 高橋和也, 松本志郎, 宇井崇, 春田英律, 倉科憲太郎, 宮戸秀世, 齋藤心, 山口博紀, 佐久間康成, 堀江久永, 細谷好則, 佐田尚宏, 北山丈二
    • Organizer
      第90回日本胃癌学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] Neutrophil extracellular traps (NETs) in abdominal cavity have supportive roles on postoperative development of peritoneal metastasis.2017

    • Author(s)
      Rihito Kanamaru, Hidenori Tsukui, Shin Saito, Kentaro Kurashina, Takashi Ui, Shiro Matsumoto, Hironori Yamaguchi, Yasunaru Sakuma, Hisanaga Horie, Yoshinori Hosoya, Naohiro Sata, Joji Kitayama.
    • Organizer
      AACR 2017 Annual Meeting
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Low-density neutrophills(LDN)in circulating blood of postoperative patients may participate in the development of distant recurrence through the production of neutrophil extracellular traps(NETs).2017

    • Author(s)
      Kumagai Yuko,Kanamaru Rihito, Ohzawa Hideyuki, Horie Hisanaga, Hosoya Yoshinori, Sata Naohiro, Kitayama Joji.
    • Organizer
      AACR Tumor Immunology and immunotherapy
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 胃癌腹膜再発における開腹術後の腹腔内滲出液中low density granulocytes(LDG)の意義2017

    • Author(s)
      金丸 理人,津久井 秀則,斉藤 心,倉科 憲太郎,宇井 崇,春田 英律,松本 志郎,安部 望,高橋 和也,山口 博紀,佐久間 康成,堀江 久永,細谷 好則,佐田 尚宏,北山 丈二
    • Organizer
      第117回日本外科学会定期学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] Exudative low density granulocytes assist peritoneal recurrence vai the production of neutrophil extracellular traps.2017

    • Author(s)
      北山丈二,金丸理人,津久井秀則,大澤英之,山口博紀,松本志郎,倉科健太郎,宮戸秀世,細谷好則,佐田尚宏
    • Organizer
      第76回日本癌学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] Neutrophil Extracellular Traps(NETs)on postoperative peritoneum may assist peritoneal recurrence after curative gastrectomy(消化器癌腹膜再発における開腹術後の腹腔内微小環境の検討)2017

    • Author(s)
      北山丈二,金丸理人,大澤英之,宮戸秀世,山口博紀,松本志郎,春田英律,倉科憲太郎,細谷好則,佐田尚宏
    • Organizer
      第28回日本消化器癌発生学会総会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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