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Surgical stress induces immunosuppression and this condition contributes to tumor growth

Research Project

Project/Area Number 23591886
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General surgery
Research InstitutionNational Defense Medical College

Principal Investigator

ONO Satoshi  防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究, 防衛医学研究センター, 准教授 (30531355)

Co-Investigator(Kenkyū-buntansha) TSUJIMOTO Hironori  防衛医科大学校, 病院講師, 研究者 (80554998)
KINOSHITA Manabu  防衛医科大学校, 医学教育部医学科専門課程, 准教授 (70531391)
MIYAZAKI Hiromi  防衛医科大学校, 防衛医学研究センター, 助教 (30531636)
HASE Kazuo  防衛医科大学校, 医学教育部医学科専門課程, 教授 (50511268)
SAITOH Daizoh  防衛医科大学校, 防衛医学研究センター, 教授 (90531632)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords外科侵襲 / 感染 / 腫瘍免疫 / 肝転移 / NK細胞 / 制御性T細胞 / sepsis / IL-10 / TGF-β / エンドトキシン吸着療法 / Interleukin-18 / IL-18受容体 / IFN-γ
Research Abstract

Recently, there has been increasing evidence that postoperative infectious complications after digestive surgery were significantly associated with negative long-term outcome. However, the precise mechanism remains unclear. We studied to determine whether the infection induces enhanced cancer metastases and to investigate the role of natural killer (NK) cells. Mice were treated with colon cancer cells, which have high potential liver metastases. Thereafter, cecal ligation and puncture (CLP) or sham treatment (sham) were done. As a result, the volume of liver metastases and serum cytokine levels were significantly higher in CLP mice than in sham mice. In contrast, hepatic IL-12 levels were significantly decreased in CLP mice. Furthermore, a total number of the liver MNCs and the percentage of NK cells in the liver MNCs were significantly decreased in CLP mice. In conclusion, infectious conditions induced the suppression of cellular immunity, and promoted cancer metastases.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (42 results)

All 2014 2013 2012 2011

All Journal Article (23 results) (of which Peer Reviewed: 22 results) Presentation (17 results) (of which Invited: 6 results) Book (2 results)

  • [Journal Article] Removal of increased circulating CD4+CD25+Foxp3+ regulatory T cells in patients with septic shock using hemoperfusion with polymyxin B-immobilized fibers2013

    • Author(s)
      Ono S, Tsujimoto H, Kinoshita M, Miyazaki H, Hase K, Saitoh D, et al.
    • Journal Title

      Surgery

      Volume: 153 Pages: 262-271

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Immunoenhancing therapy with interleukin-18 against bacterial infection in immunocompromised hosts after severe surgical stress2013

    • Author(s)
      Kinoshita M, Miyazaki H, Ono S, Seki S
    • Journal Title

      J Leukoc Biol

      Volume: 93 Pages: 689-698

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Predictive value of pleural and serum interleukin-6 levels for pneumonia and hypo-oxygenations after esophagectomy2013

    • Author(s)
      Tsujimoto H, Takahata R, Nomura S, Kumano I, Matsumoto Y, Yoshida K, Hiraki S, Aosasa S, Ono S,Yamamoto J, Hase K.
    • Journal Title

      J Surg Res

      Volume: 182

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Glucocorticoid receptor-dependent immunomodulatory effect of ursodeoxycholic acid on liver lymphocytes in mice2013

    • Author(s)
      Takigawa T, Miyazaki H, Kinoshita M, Kawarabayashi N, Nishiyama K, Hatsuse K, Ono S, Saitoh D, Seki S, Yamamoto J
    • Journal Title

      Am J Physiol Gastrointest Liver Physiol

      Volume: 305

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Elevated preoperative C-reactive protein levels are a risk factor for the development of postoperative infectious complications following elective colorectal surgery2013

    • Author(s)
      Kubo T, Ono S, Ueno H, Shinto E, Yamamoto J, Hase K
    • Journal Title

      Langenbeck's Arch Surg

      Volume: 398 Pages: 965-971

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 特集:免疫不全と重症感染症-その病態と対策- 大侵襲手術周術期患者におけるimmunoparalysisと重症感染症2013

    • Author(s)
      小野 聡、平木修一、高畑りさ、木村暁史、辻本広紀、齋藤大蔵
    • Journal Title

      ICUとCCU

      Volume: 37 Pages: 593-602

    • Related Report
      2013 Annual Research Report
  • [Journal Article] Neutralization of interleukin-10 or transforming growth factor-βdecreases the percentages of CD4+CD25+Foxp3+ regulatory T cells in septic mice, thereby leading to an improved survival2012

    • Author(s)
      Hiraki S, Ono S, Tsujimoto H, Kinoshita M, Miyazaki H, Saitoh D, Hase K
    • Journal Title

      Surgery

      Volume: 151 Pages: 313-322

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Neutralization of IL-10 restores the down-regulation of IL-18 receptor on NK cells and IFN-γproduction in septic mice, thus leading to an improved survival2012

    • Author(s)
      Hiraki S, Ono S, Kinoshita M, Tsujimoto H, Miyazaki H, Saitoh D, Hase K
    • Journal Title

      Shock

      Volume: 37 Pages: 177-182

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Systemic inflammatory response syndrome as a predictor of anastomotic leakage after esophagectomy2012

    • Author(s)
      Tsujimoto H, Ono S, Hase K, et al.
    • Journal Title

      Surgery Today

      Volume: 42 Pages: 141-146

    • NAID

      10030230723

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] The postoperative serum interleukin-15 concentration correlates with organ dysfunction and the prognosis of septic patients following emergency gastrointestinal surgery2012

    • Author(s)
      Kimura A, Ono S, Tsujimoto H, Miyazaki H, Kinoshita M, Saitoh D, Hase K. et al.
    • Journal Title

      J Surg Res

      Volume: 175

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Video-assisted thoracoscopic surgery for esophageal cancer attenuates postoperative systemic responses and pulmonary complications2012

    • Author(s)
      Tsujimoto H, Ono S, Hase K, et al.
    • Journal Title

      Surgery

      Volume: 151 Pages: 667-73

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Neutralization of IL-10 restores the down-regulation of IL-18 receptor on NK cells and IFN-γ production in septic mice, thus leading to an improved survival2012

    • Author(s)
      Hiraki S, Ono S, Kinoshita M, Tsujimoto H, Takahata R, Miyazaki H, Saitoh D, Seki S, Hase K.
    • Journal Title

      Shock

      Volume: 37 Pages: 177-182

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Neutralization of interleukin-10 or transforming growth factor-β decreases the percentages of CD4+CD25+Foxp3+ regulatory T cells in septic mice, thereby leading to an improved survival2012

    • Author(s)
      Hiraki S, Ono S,Tsujimoto H, Kinoshita M, Takahata R, Miyazaki H, Saitoh D, Hase K
    • Journal Title

      Surgery

      Volume: 151 Pages: 313-322

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] The postoperative serum interleukin-15 concentration correlates with organ dysfunction and the prognosis of septic patients following emergency gastrointestinal surgery2012

    • Author(s)
      Kimura A, Ono S, Hiraki S, Takahata R, Tsujimoto H, Miyazaki H, Kinoshita M, Hatsuse K, Saitoh D, Hase K, Yamamoto J
    • Journal Title

      J Surg Res

      Volume: 175

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Video-assisted thoracoscopic surgery for esophageal cancer attenuates postoperative systemic responses and pulmonary complications2012

    • Author(s)
      Tsujimoto H, Takahata R, Nomura S, Yaguchi Y, Kumano I, Matsumoto Y, Yoshida K, Horiguchi H, Hiraki S, Ono S,Yamamoto J, Hase K.
    • Journal Title

      Surgery

      Volume: 151 Pages: 667-673

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Preoperative toll-like receptor expression in monocytes is associated with host immunological responses following gastrointestinal surgery2011

    • Author(s)
      Ono S, Tsujimoto H, Hiraki S, Kinoshita M, Hase K
    • Journal Title

      World J Surg

      Volume: 35 Pages: 365-371

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Enhancement of neutrophil function by interleukin-18 therapy protects burn-injured mice from methicillin-resistant staphylococcus aureus2011

    • Author(s)
      Kinoshita M, Miyazaki H, Ono S, et al.
    • Journal Title

      Infection and Immunity

      Volume: 79(7) Pages: 2670-2680

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Postoperative serum concentrations of high mobility group box chromosomal protein-1 correlates to the duration of SIRS and pulmonary dysfunction following gastrointestinal surgery2011

    • Author(s)
      Takahata R, Ono S, Tsujimoto H, Kinoshita M, Miyazaki H, Saitoh D, Hase K
    • Journal Title

      J Surg Res

      Volume: 170

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Postoperative serum concentrations of high mobility group box chromosomal protein-1 correlates to the duration of SIRS and pulmonary dysfunction following gastrointestinal surgery2011

    • Author(s)
      Takahata R, Ono S, Tsujimoto H, Hiraki S, Kimura A, Kinoshita M, Miyazaki H, Saitoh D, Hase K.
    • Journal Title

      J Surg Res

      Volume: 170

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] One-step nucleic acid amplication (OSNA) for the application of sentinel node concept in gastric cancer2011

    • Author(s)
      Yaguchi Y,Sugasawa H, Tsujimoto H, Takata H, Nakabayashi K, Ichikura T, Ono S, Hiraki S, Sakamoto N, Horio T, Kumano I, Otomo Y, Mochizuki H, Yamamoto J, Hase K.
    • Journal Title

      Ann Surg Oncol

      Volume: 18 Pages: 2289-2296

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Preoperative toll-like receptor expression in monocytes is associated with host immunological responses following gastrointestinal surgery.2011

    • Author(s)
      Ono S, Tsujimoto H, Hiraki S, Kinoshita M, Hase K.
    • Journal Title

      World J Surg

      Volume: 35 Pages: 365-371

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Enhancement of neutrophil function by interleukin-18 therapy protects burn-injured mice from methicillin-resistant staphylococcus aureus2011

    • Author(s)
      Kinoshita M, Miyazaki H, Ono S, Inatsu A, Nakashima H, Tsujimoto H, Shinomiya N, Saitoh D, Seki S.
    • Journal Title

      Infection and Immunity

      Volume: 79 Pages: 2670-2680

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Augmented bacterial elimination by Kupffer cells after IL-18 pretreatment via IFN-g produced from NK cells in burn-injured mice.2011

    • Author(s)
      Miyazaki, H., Kinoshita M., Ono S., Nakashima M., Hara E., Ohno H., Seki S., and Saitoh D
    • Journal Title

      Burns

      Volume: 37 Pages: 1208-1215

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] 外科侵襲後の生体反応の特性と対策2014

    • Author(s)
      小野 聡
    • Organizer
      産業医科大学学内講演会
    • Place of Presentation
      北九州市
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 外科侵襲後の免疫応答の病態解析とその対策に関する研究2013

    • Author(s)
      小野聡、辻本広紀、木下学、長谷和生、齋藤大蔵, 他
    • Organizer
      第113回日本外科学会定期学術集会
    • Place of Presentation
      福岡(シンポジウム)
    • Related Report
      2013 Final Research Report
  • [Presentation] The Predictive Value of Endotoxin Activity Assay for The Incidence of Postoperative Infectious Complications Following Elective Gastrointestinal Surgery2013

    • Author(s)
      Ono S, Miyazaki H, Tsujimoto H, Kinoshita M, Hase K, Saitoh D, et al.
    • Organizer
      Thirty-sixth Annual Conference on Shock
    • Place of Presentation
      San Diego, California, USA
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] (シンポジウム)外科侵襲後の免疫応答の病態解析とその対策に関する研究2013

    • Author(s)
      小野 聡、辻本広紀、平木修一、高畑りさ、木村暁史、久保 徹、松本佑介、吉田一路、堀口寛之、野村信介、青笹季文、木下 学、山本順司、長谷和生、齋藤大蔵
    • Organizer
      第113回日本外科学会定期学術集会
    • Place of Presentation
      福岡
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] (ランチョン)血液凝固線溶系の変動と免疫応答からみた外傷後の生体反応の特性2013

    • Author(s)
      小野 聡
    • Organizer
      第27回日本外傷学会総会・学術集会
    • Place of Presentation
      久留米
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 手術侵襲の軽減は癌の長期予後を改善するか?2013

    • Author(s)
      小野 聡
    • Organizer
      兵庫県消化器外科研究会2013
    • Place of Presentation
      神戸
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 消化器外科周術期の病態解析におけるEndotoxin Activity Assay測定の意義に関する検討2013

    • Author(s)
      小野 聡、久保 徹、高畑りさ、木村暁史、松本佑介、吉田一路、平木修一、辻本広紀、青笹季文、長谷和生
    • Organizer
      第68回日本消化器外科学会総会
    • Place of Presentation
      宮崎
    • Related Report
      2013 Annual Research Report
  • [Presentation] 免疫機能からみた周術期管理のトピックスー腸管は本当に重要か-2013

    • Author(s)
      小野 聡
    • Organizer
      第11回秋田県NST研究会
    • Place of Presentation
      秋田市
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 外科侵襲後の生体反応における免疫不全の病態解析とその対策に関する検討2012

    • Author(s)
      小野聡、辻本広紀、宮崎裕美、木下学、長谷和生、齋藤大蔵, 他
    • Organizer
      第112回日本外科学会定期学術集会
    • Place of Presentation
      千葉(パネルディスカッション)
    • Related Report
      2013 Final Research Report
  • [Presentation] 外科系学会における侵襲学研究の位置づけと今後の展望2012

    • Author(s)
      小野聡
    • Organizer
      第27回日本Shock学会
    • Place of Presentation
      東京(シンポジウム)
    • Related Report
      2013 Final Research Report
  • [Presentation] 消化器外科周術期の病態形成における制御性T細胞の役割とその対策に関する検討2012

    • Author(s)
      小野聡、辻本広紀、長谷和生, 他
    • Organizer
      第67回日本消化器外科学会総会
    • Place of Presentation
      富山
    • Related Report
      2013 Final Research Report
  • [Presentation] (パネルディスカッション)外科侵襲後の生体反応における免疫不全の病態解析とその対策に関する検討2012

    • Author(s)
      小野 聡、辻本広紀、平木修一、高畑りさ、木村暁史、矢口義久、熊野 勲、松本佑介、吉田一路、堀口寛之、宮崎裕美、木下 学、山本順司、長谷和生、齋藤大蔵
    • Organizer
      第112回日本外科学会定期学術集会(千葉)
    • Place of Presentation
      幕張メッセ
    • Related Report
      2012 Research-status Report
  • [Presentation] 消化器外科周術期の病態形成における制御性T細胞の役割とその対策に関する検討2012

    • Author(s)
      小野 聡、平木修一、辻本広紀、高畑りさ、松本佑介、木村暁史、久保 徹、熊野 勲、吉田一路、長谷和生
    • Organizer
      第67回日本消化器外科学会総会
    • Place of Presentation
      富山国際会議場
    • Related Report
      2012 Research-status Report
  • [Presentation] 免疫機能からみた周術期管理のトピックス2012

    • Author(s)
      小野 聡
    • Organizer
      横浜周術期管理フォーラム2012
    • Place of Presentation
      横浜市
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] 敗血症の新たな治療戦略2011

    • Author(s)
      小野 聡
    • Organizer
      外科領域における敗血症治療を考える会(招待講演)
    • Place of Presentation
      川越市
    • Related Report
      2011 Research-status Report
  • [Presentation] 重症敗血症の病態解析における多項目サイトカイン同時測定の意義2011

    • Author(s)
      小野 聡、辻本広紀、平木修一、高畑りさ、木村暁史、矢口義久、松本佑介、吉田一路、野村信介、木下 学、宮庄拓、山本順司、長谷和生、齋藤大蔵
    • Organizer
      第111回日本外科学会定期学術集会
    • Place of Presentation
      東京
    • Related Report
      2011 Research-status Report
  • [Presentation] 敗血症患者の病態と免疫機能2011

    • Author(s)
      小野 聡
    • Organizer
      第11回甲信急性血液浄化療法研究会(招待講演)
    • Place of Presentation
      甲府
    • Related Report
      2011 Research-status Report
  • [Book] 敗血症(セプシス) 救命治療の最前線 セプシス治療薬の日本での活用2014

    • Author(s)
      小野 聡
    • Total Pages
      399
    • Publisher
      医薬ジャーナル社
    • Related Report
      2013 Annual Research Report
  • [Book] 周術期感染管理テキスト 重症敗血症、敗血症性ショック2012

    • Author(s)
      小野 聡
    • Total Pages
      230
    • Publisher
      編集:日本外科感染症学会、(株)診断と治療社、東京
    • Related Report
      2012 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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