The gene therapy for sepsis by the clarification of STAT3 / SOCS3 which control an inflammatory or an anti-inflammatory reaction

• Project/Area Number: 25462809
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Emergency medicine
• Research Institution: Hokkaido University
• Principal Investigator: Sawamura Atsushi 北海道大学, 医学研究科, 准教授 (00241448)
• Co-Investigator(Renkei-kenkyūsha): GANDO SATOSHI 北海道大学, 大学院医学研究科, 教授 (30125306)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 敗血症病態 / サイトカイン / IL-6 / TNF-αKO / 遺伝子治療 / Western Blotting / 敗血症脳症 / TNF-α / 外傷 / 敗血症 / DIC / 臓器不全

Outline of Final Research Achievements

LPS was administration to each thirty Wild type mice (WT-M) and IL-6 KO mice (IL-M).The case fatality was 96.7% and 46.7%. LPS was administration to each twenty-five Wild type mice (WT-M) and TNF-αKO mice (TNF-M). The case fatality was 100.0% and 32.0%.
The amplification efficiency of SOCS3 (SO-3) was a high price compared with STAT3 (ST-3). Moreover, in the LPS administration group, the amplification efficiency of SO-3 and ST-3 compared with the LPS non-administration group was together restrained. RT-PCR was performed using TNF-M. In TNF-M, the amplification efficiency of ST-3 was clearly restrained compared with SO-3 by the LPS administration group. Moreover, in the LPS non-administration group, the amplification efficiency of ST-3 was a high price in TNF-M compared with WT-M. It thought that the gene of the involvement of IL-6, TNF-α, i.e. 17q21.31 of ST-3 and 17q25.3 of SO-3 related to the developing of the septic clinical condition from above.

Research Products

• [Journal Article] Activated protein C does not increase in the early phase of trauma with disseminated intravascular coagulation: comparison with acute coagulopathy of trauma-shock. (2016)
  • Author(s): S. Jesmin, S. Gando, T. Wada, M. Hayakawa, A. Sawamura
  • Journal Title: Journal Intensive Care Volume: 4(4) Issue: 1 Pages: 1-1
  • DOI: 10.1186/s40560-015-0123-2
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Disseminated intravascular coagulation with the fibrinolytic phenotype predicts the outcome of patients with out-of-hospital cardiac arrest. (2016)
  • Author(s): Wada T, Gando S, Ono Y, Maekawa K, Katabami K, Hayakawa M, Sawamura A.
  • Journal Title: Thrombosis Journal Volume: 14 Issue: 1 Pages: 43-43
  • DOI: 10.1186/s12959-016-0116-y
  • Peer Reviewed / Open Access
• [Journal Article] The response time threshold for predicting favourable neurological outcomes in patients with bystander-witnessed out-of-hospital cardiac arrest. (2016)
  • Author(s): Ono Y, Hayakawa M, Iijima H, Maekawa K, Kodate A, Sadamoto Y, Mizugaki A, Murakami H, Katabami K, Sawamura A, Gando S
  • Journal Title: Resuscitation Volume: 107 Pages: 65-70
  • DOI: 10.1016/j.resuscitation.2016.08.005
  • NAID: 120006347210
  • Peer Reviewed / Open Access
• [Journal Article] Noble-Collip drum Trauma induces disseminated intravascular coagulation but not acute coagulopathy of trauma-shock. (2015)
  • Author(s): Hayakawa M, Gando S, Ono Y, Wada T, Yanagida Y, Sawamura A, Ieko M.
  • Journal Title: Shock Volume: 43 Issue: 3 Pages: 261-267
  • DOI: 10.1097/shk.0000000000000281
  • NAID: 120005712471
  • Peer Reviewed / Open Access
• [Journal Article] Fibrinogen level deteriorates before other routine coagulation parameters and massive transfusion in the early phase of severe trauma: a retrospective observational study. (2015)
  • Author(s): Hayakawa M, Gando S, Ono Y, Wada T, Yanagida Y, Sawamura A.
  • Journal Title: Seminars in Thrombosis and Hemostasis Volume: 41 Issue: 01 Pages: 35-42
  • DOI: 10.1055/s-0034-1398379
  • NAID: 120005693899
  • Peer Reviewed / Open Access
• [Journal Article] Pharmacokinetics and the optimal regimen for levofloxacin in critically ill patients receiving continuous hemodiafiltration. (2015)
  • Author(s): Wada T, Koboyashi M, Ono Y, Mizugaki A, Katabami K, Maekawa K, Miyamoto D, Yanagida Y, Hayakawa M, Sawamura A, Iseki K, Gando S.
  • Journal Title: Journal of Intensive Care Volume: 3 Issue: 1 Pages: 22-22
  • DOI: 10.1186/s40560-015-0089-0
  • Peer Reviewed / Open Access
• [Journal Article] Effects of prehospital epinephrine administration on neurological outcomes in patients with out-of-hospital cardiac arrest. (2015)
  • Author(s): Ono Y, Hayakawa M, Wada T, Sawamura A, Gando S.
  • Journal Title: Journal of Intensive Care Volume: 3 Issue: 1 Pages: 29-29
  • DOI: 10.1186/s40560-015-0094-3
  • NAID: 120005837943
  • Peer Reviewed / Open Access
• [Journal Article] Rapid evaluation of fibrinogen levels using the CG02N whole blood coagulation analyzer. (2015)
  • Author(s): Hayakawa M, Gando S, Ono Y, Mizugaki A, Katabami K, Maekawa K, Miyamoto D, Wada T, Yanagida Y, Sawamura A.
  • Journal Title: Seminars in Thrombosis and Hemostasis Volume: 41 Issue: 03 Pages: 267-271
  • DOI: 10.1055/s-0035-1547372
  • NAID: 120005740322
  • Peer Reviewed / Open Access
• [Journal Article] Should laryngeal tubes or masks be used for out-of-hospital cardiac arrest patients? American Journal of Emergency Medicine (2015)
  • Author(s): Ono Y, Hayakawa M, Maekawa K, Mizugaki A, Katabami K, Wada T, Sawamura A, Gando S.
  • Journal Title: American Journal of Emergency Medicine Volume: 33 Issue: 10 Pages: 1360-1363
  • DOI: 10.1016/j.ajem.2015.07.043
  • Peer Reviewed / Open Access
• [Journal Article] A multicenter, prospective evaluation of quality of care and mortality in Japan based on the Surviving Sepsis Campaign guidelines (2014)
  • Author(s): Fujishima S, Gando S, et al
  • Journal Title: J Infect Chemother Volume: 20(2) Issue: 2 Pages: 115-120
  • DOI: 10.1016/j.jiac.2013.09.003
  • Peer Reviewed / Open Access
• [Journal Article] Post-marketing surveillance data of thrombomodulin alfa: sub-analysis in patients with sepsis-induced disseminated intravascular coagulation. (2014)
  • Author(s): Eguchi Y, 他11名
  • Journal Title: Journal of Intensive Care Volume: 2 Issue: 1 Pages: 30-30
  • DOI: 10.1186/2052-0492-2-30
  • Peer Reviewed / Open Access
• [Journal Article] Effects of protease activated receptor (PAR) 2 blocking peptide on endothelin-1 levels in kidney tissues in endotoxemic rat model (2014)
  • Author(s): Jesmin S, Shimojo N, Yamaguchi N, et al
  • Journal Title: Life Sci Volume: 102(2) Issue: 2 Pages: 127-33
  • DOI: 10.1016/j.lfs.2014.03.013
  • Peer Reviewed / Open Access
• [Journal Article] Epidemiology of severe sepsis in Japanese intensive care units: a prospective multicenter study (2014)
  • Author(s): Ogura H, Gando S, Saitoh D, Takeyama N, Kushimoto S, Fujishima S, Mayumi T, Araki T, Ikeda H, Kotani J, Miki Y, Shiraishi S, Suzuki K, Suzuki Y, Takuma K, Tsuruta R, Yamaguchi Y, Yamashita N, Aikawa N.
  • Journal Title: J Infect Chemother Volume: 20 Issue: 3 Pages: 157-62
  • DOI: 10.1016/j.jiac.2013.07.006
  • Peer Reviewed / Open Access
• [Journal Article] Hemostasis during the early stages of trauma: comparison with disseminated intravascular coagulation. (2014)
  • Author(s): Oshiro A, 他5名
  • Journal Title: Critical Care Volume: 18(2) Issue: 2 Pages: R61-R61
  • DOI: 10.1186/cc13816
  • Peer Reviewed / Open Access
• [Journal Article] Effects of Rikkunshito (traditional Japanese medicine) on enteral feeding and the plasma ghrelin level in critically ill patients: a pilot study. (2014)
  • Author(s): Hayakawa M, 他6名
  • Journal Title: Journal of Intensive Care Volume: 2 Issue: 1 Pages: 53-53
  • DOI: 10.1186/s40560-014-0053-4
  • NAID: 120005595707
  • Peer Reviewed / Open Access
• [Journal Article] Massive amounts of tissue factor induce fibrinogenolysis without tissu hypoperfusion in rats. (2013)
  • Author(s): Hayakawa M, 他8名
  • Journal Title: Shock Volume: 39 Issue: 6 Pages: 514-519
  • DOI: 10.1097/shk.0b013e318293980d
  • NAID: 120005438221
  • Peer Reviewed / Open Access
• [Journal Article] A multicenter, prospective validation study of the Japanese Association for Acute Medicine disseminated intravascular coagulation scoring system in patients with severe sepsis. (2013)
  • Author(s): Yanagida Y, Gando S, Sawamura A, Hayakawa M, Uegaki S, Kubota N, Homma T, Ono Y, Honma Y, Wada T, Jesmin S.
  • Journal Title: Critical Care Volume: 17
  • Peer Reviewed
• [Journal Article] Normal prothrombinase activity, increased systemic thrombin activity, and lower antithrombin levels in patients with disseminated intravascular coagulation at an early phase of trauma: Comparison with acute coagulopathy of trauma-shock (2013)
  • Author(s): Yanagida Y, Gando S, Sawamura A, Hayakawa M, Uegaki S, Kubota N, Homma T, Ono Y, Honma Y, Wada T, Jesmin S
  • Journal Title: Surgery Volume: 154 Issue: 1 Pages: 48-57
  • DOI: 10.1016/j.surg.2013.02.004
  • Peer Reviewed / Open Access
• [Journal Article] Effectiveness of end-expiratory lung volume measurements during the lung recruitment maneuver for patients with atelectasis. (2013)
  • Author(s): Nakahashi S, 他8名
  • Journal Title: Journal of Critical Care Volume: 28 Issue: 4 Pages: 534.e1-534.e5
  • DOI: 10.1016/j.jcrc.2012.11.003
  • Peer Reviewed / Open Access
• [Presentation] DIC and fibrinolysis in patients with trauma and out-of-hospital cardiac arbest. (2016)
  • Author(s): Gando S, Wada T, Ono Y, Maekawa K, Katabami K, Hayakawa M, Sawamura A.
  • Organizer: The 9th Congress of Asian-Pacific Society on Thrombosis and Hemostasis
  • Place of Presentation: Taipei International Convention Center (Taipei, Taiwan)
  • Year and Date: 2016-10-06
  • Int'l Joint Research / Invited
• [Presentation] Disseminated intravascular coagulation during eary phase of out-of-hospital cardiac arrest and resuscitation belongs to the fibrinolytic phonotype. (2016)
  • Author(s): Sadamoto Y, Katabami K, Wada T, Ono Y, Maekawa K, Hayakawa M, Sawamura A, Gando S.
  • Organizer: 29th Annual Congress of European Society of Intensive Care Medicine
  • Place of Presentation: MiCO Milano Congressi (Milano, Italy)
  • Year and Date: 2016-10-01
  • Int'l Joint Research
• [Presentation] Impact of age on the relationship between resuscitation duration and neurologically intact survival after out-of-hospital cardiac arrest. (2016)
  • Author(s): Maekawa K, Hayakawa M, Ono Y, Kodate A, Sadamoto Y, Tominaga N, Mizugaki A, Murakami H, Yshida T, Katabami K, Wada T, Sawamura A, Gando S.
  • Organizer: 29th Annual Congress of European Society of Intensive Care Medicine
  • Place of Presentation: MiCO Milano Congressi (Milano, Italy)
  • Year and Date: 2016-10-01
  • Int'l Joint Research
• [Presentation] The response time threshold for predicting favorable neurological outcomes in patients with bystander-witnessed out-of-hospital cardiac arrest. (2016)
  • Author(s): Ono Y, Hayakawa M, Iijima H, Maekawa K, Kodate A, Sadamoto Y, Mizugaki A, Murakami H, Katabami K, Wada T, Sawamura A, Gando S.
  • Organizer: 29th Annual Congress of European Society of Intensive Care Medicine
  • Place of Presentation: MiCO Milano Congressi (Milano, Italy)
  • Year and Date: 2016-10-01
  • Int'l Joint Research
• [Presentation] Disseminated intravascular coagulation with the fibrinolytic phenotype predicts the outcome of patients with patients with out-of-hospital cardiac arrest. (2016)
  • Author(s): Kodate A, Katabami K, Wada T, Ono Y, Maekawa K, Hayakawa M, Sawamura A, Gando S.
  • Organizer: 29th Annual Congress of European Society of Intensive Care Medicine
  • Place of Presentation: MiCO Milano Congressi (Milano, Italy)
  • Year and Date: 2016-10-01
  • Int'l Joint Research
• [Presentation] A Case of severe methemoglobinemia due to sodium nitrite poisoning. (2015)
  • Author(s): Katabami K
  • Organizer: 12th Congress of the World Federation of Socienties of Intensive and Critical Care Medicine in collaboration with WFCCN and WFPICCS
  • Place of Presentation: Convention and Exhibition Center (Seoul, Korea)
  • Year and Date: 2015-08-31
  • Int'l Joint Research
• [Presentation] Role of activated protein C and soluble fibrin in the early phase of trauma with disseminated intravascular coagulation: Comparison with acute coagulopathy of trauma-shock. (2015)
  • Author(s): Gando S
  • Organizer: XXV Congress of the International Society on Thrombosis and Haemostasis and 61st Annual SSC Meeting, June 21, 2015 Toronto
  • Place of Presentation: Toronto Convention Center (Tronto, Canada)
  • Year and Date: 2015-06-22
  • Int'l Joint Research
• [Presentation] Anticoagulation mechanisms are impaired in the early phase of trauma with DIC. (2015)
  • Author(s): Gando S
  • Organizer: 18th International Meeting of the Danubian League Against Thrombosis and Haemorrhagic Disorders
  • Place of Presentation: the Hotel Radon Plaza (Sarajevo, Bosnia and Herzegovina)
  • Year and Date: 2015-05-14
  • Int'l Joint Research
• [Presentation] Impaired coagulation mechanisms in trauma patients with disseminated intravascular coagulation and acute coagulopathy trauma-shock. (2015)
  • Author(s): Gando S
  • Organizer: 16th Annual NATA Symposium on Patient Blood Management, Haemostasis and Thrombosis
  • Place of Presentation: Prague Congress Centre (Prague, Czechoslovakia)
  • Year and Date: 2015-04-16
  • Int'l Joint Research
• [Presentation] The overproduction of nitric oxide induced by angiogenic and coagulation factors leads to multiple organ dysfunction syndrome associated with post-cardiac arrest syndrome. (2014)
  • Author(s): Wada T
  • Organizer: The European Society of Intensive Care Medicine 27th Annual Congress.
  • Place of Presentation: CCIB バルセロナ、スペイン
  • Year and Date: 2014-09-27 – 2014-10-01
• [Presentation] JAAM DIC score can predict patient death and massive transfusion in trauma. (2014)
  • Author(s): Gando S
  • Organizer: 49th International Congress of the European Society for Surgical Research
  • Place of Presentation: Budapest Marriott Hotel ブダペスト、ハンガリー
  • Year and Date: 2014-05-21 – 2014-05-24
• [Presentation] Increased thrombin activation and lower antithrombin levels in patients with DIC and acute coagulopathy of trauma-shock(ACOTS) (2013)
  • Author(s): Gando S, Yanagida Y, Sawamura A, Hayakawa M, Kubota N, Ono Y, Wada T, Yamamoto H
  • Organizer: 17th International Meeting of the Danubian League against Thrombosis and Haemorrhagic disorders (DLTH)
  • Place of Presentation: Venue Congress Center ALDIS(Hradec Kralove,CZECH REPUBLIC)
• [Presentation] Normal prothrombinase activity, increased systemic thrombin activity, and lower antithrombin levels in patients with disseminated intravascular coagulation at an early phase of trauma: comparison with acute coagulopathy of trauma-shock (2013)
  • Author(s): Gando S, Yanagida Y, Sawamura A, Hayakawa M, Kubota N, Wada T, Ono Y, Yamamoto H
  • Organizer: XXIV Congress of the International Society on Thrombosis and Haemostasis
  • Place of Presentation: Amsterdam RAI (Amsterdam,Netherlands)
• [Presentation] Effects of Rikkunshito (traditional Japanese Kampo) on enteral feeding and plasma ghrelin concentration in critically ill patients: A double-blind, randomized, controlled trial. (2013)
  • Author(s): Hayakawa M, Yamamoto H, Ono Y, Wada T, Yanagida Y, Sugano M, Sawamura A, Takeda H, Gando S
  • Organizer: The European Society of Intensive Care Medicine 26th Annual Congress
  • Place of Presentation: Palais des congres (Paris,FRANCE)
• [Presentation] Cerebral fat embolism syndrome in severe trauma patients (2013)
  • Author(s): Sawamura A, Yanagida Y, Wada T, Yamamoto H, Miyamoto D, Ono Y, Sugano M, Hayakawa H, Gando S
  • Organizer: The European Society of Intensive Care Medicine 26th Annual Congress
  • Place of Presentation: Palais des congres (Paris,FRANCE)