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1999 Fiscal Year Final Research Report Summary

Studies of neutrophil depleting therapy against overproduction of cytokines in sepsis or end stage of cancer using monoclonal anti neutrophil antibody (RP3)

Research Project

Project/Area Number 09671220
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionGIFU UNIVERSITY SCHOOL OF MEDICINE

Principal Investigator

UMEMOTO Takao  GIFU UNIVERSITY HOSPITAL LECTURER, 医学部・附属病院, 講師 (40223614)

Co-Investigator(Kenkyū-buntansha) SUGIYAMA Yasuyuki  GIFU UNIVERSITY SCHOOL OF MEDICINE ASSISTANT PROFESSOR, 医学部, 助手 (90211309)
SAJI Shigetoyo  GIFU UNIVERSITY SCHOOL OF MEDICINE PROFESSOR, 医学部, 教授 (80021400)
Project Period (FY) 1997 – 1999
Keywordsneuropenia / RP3 / CLP / interleukin-6 / IL-8 / IL-10 / TNF-α
Research Abstract

(1) The significance of neutrophils in tumor-bearing rats was investigated using monoclonal antibody (RP3) which reduced rat neutrophils selectively. G-CSF, which induced neutrophiis from bone marrow, and/or OK-432, which induced peripheral blood neutrophils and augmented its activity, were used. G-CSF enhanced the tumor growth at an early period after tumor inoculation, while OK-432 reduced it. It is suggested that neutrophils might show biphasic activity against tumor growth according to the tumor-bearing period. Thus, in the early stage of cancer, it may be cytotoxic, while at the end stage of cancer, it may be suppressive.
(2) The peripheral blood neutrophfis of patients with advanced gastric or colorectal cancers increased remarkably, and both their phagocytic activity and superoxide production per neutriohils showed lower values than those of healthy volunteers. The serum interleukin (IL)-6, IL-8 and IL-10 levels of the patients were higher than those of healthy volunteers.
(3) In rat peritonitis model produced by cecal legation and puncture (CLP), the survival rate was decreased with the administration of neutrophil-depleting antibody, RP3, before or 8 hours after CLP, whereas it showed no change with administration 12, 18, 24 or 48 hours after CLP. We also conducted a study to asses cytokine (IL-6, IL-10, TNF-α) production in peripheral blood cells of the CLP model. Heparinized whole blood cells of rats were incubated with LPS for 24 hours. IL-6 or IL-10 production was decreased up to a peak 12-24 hours after CLP. TNF-α could be produced before CLP, decreased after 6 hours and then increased up to 24 hours.

  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] 佐治 重豊: "免疫応答からみたSIRSの病態生理"医学のあゆみ. 181. 32-37 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 佐治 重豊: "進行胃癌患者の免疫能"消化器外科. 20. 1399-1407 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 竹村 茂之: "担癌生体における手術侵襲とステロイド処置前投与の功罪について"Biotherapy. 12. 147-150 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 佐治 重豊: "消化器疾患とサイトカイン"総合臨床. 47. 594-600 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 加藤 元久: "Systemic Inflammatory Response Syndromeと免疫系"臨床免疫. 30. 863-869 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 加藤 禎洋: "担癌末期または敗血症時における好中球の功罪と枯渇化療法の可能性について"Biotherapy. 13. 79-82 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 加藤 禎洋: "ラット腹膜炎モデルにおける好中球と炎症性サイトカインの過剰産生と好中球枯渇化抗体を用いた治療の可能性について"Biotherapy. 13. 569-570 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shigetoyo Saji: "Mechanism of immune response in Pathophysiology of the patients with SIRS : Dose It induce the failure of host defence system?"Journal of clinical and experimental Medicine. 181:1. 32-37 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shigetoyo Saji: "Host immuno-competence of the Patients with advanced gastric cancer"Gastroenterology. 20:9. 1399-1407 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shigeyuki Takemura: "Influence of Preoperative Administration of Corticosteroid on Tumor Bearing Hosts"Biotherapy. 12:1. 147-150 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shigetoyo Saji: "Cytokines in the field of Gastroenterological Disease"Clinic all-round. 47:3. 594-600 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Motohisa Kato, Shigetoyo Saji,: "Systemic inflammatory Response syndrome and immune system"Clinical immunology. 30:6. 863-869 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshihiro Kato: "Studies on Merit or Demerit of Neutrophils For Advanced Tumor-Bearing Hosts and Rat Peritonitis Models, and Significancer of Neutrophil-Depleting Therapy"Biotherapy. 13:1. 89-82 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshihiro Kato: "Overproduction of Neutrophil and Inflammatory Cytokines in a Rat Septic Peritonitis Model, and Influence of a Neutrophil-Depleting Antibody"Biotherapy. 13:5. 569-570 (1998)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2001-10-23  

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