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1991 Fiscal Year Final Research Report Summary

Studies on potentiative effects of antitumor activity by OK-432 activated Neutrophils in combination with CSF

Research Project

Project/Area Number 01480310
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field General surgery
Research InstitutionGifu University School of Medicine

Principal Investigator

SAJI Shigetoyo  Gifu University School of Medicine, Second Dpt. of Surgery Professor, 医学部, 教授 (80021400)

Co-Investigator(Kenkyū-buntansha) SUGIYAMA Yasuyuki  Gifu University School of Medicine, Second Dpt. of Surgery Research Assistant, 医学部, 助手 (90211309)
MIYA Kiichi  Gifu University Hospital School of Medicine, Second Dpt. of Surgery. Assistant P, 医学部附属病院, 講師 (10190729)
AZUMA Shuuji  Gifu University Hospital School of Medicine, Second Dpt. of Surgery. Assistant P, 医学部附属病院, 講師 (90167908)
Project Period (FY) 1989 – 1991
KeywordsG csp / Ok-432 / Neutrophils / Antitumor effects / Cytostatic activity / Chemiluminescence / Immunotherapy / Peritoneal carcinomatosis
Research Abstract

A streptococcal preparation, OK-432(Picibanil) is one of nonspecific immunopotentiator and indused a significant antitumor effects for peritoneal carcinomatosis. The maine mechanism of disappearance of malignant scites and/or cancer cells following OK-432 intraperitoneal (ip) administration is the augmentation of antitumor cytostatic activity of neutrophils induced by OK-432 and may be play in induction phase of macrophage -T cell cascade by IL-1 like cytokines produced by OK-432 activated neutrophils. On the other hand, granulocyte colony stimulating factor (G-CSF) is one of hematopoictic growth factor and is a glycoprotein hormone that specifically stimulates both production and functional activation of neutrophils. In this present investigation, either th6 number of OK-432 activated neutrophilscould be increased by G-CSF or the antitumor activity of G-CSF produced neutrophits could be induced or stimulated by OK-432 were examined, and the following results were obtained.
(1) A numero … More us neutrophils was induced soon after OK-432 ip administration, and showed a high cytostatic activity but no cytolytic activity against YAC-1 cells.
(2) A numerous neutrophils was also induced soon after OK-432 ip administration to rats malignant ascitic model, inhibited tumor growth and showed significant high cytostatic activity against autolougous tumor cells.
(3) From the light and electron microscopic observation, OK-432 activated neutrophils phagdcytosed the streptococci of OK-432 and disintegrated. Then after, protrusion of neutrophils contacted to microvilit of tumor cell membrane and came to destruction.
(4) Peritoneal exudate neutrophils activated with OK-432 showed high phagocytic activity by chemiluminescence assay, while the neutrophils activated with OK-432 in vitro showed only a few stimulation of phagocytosis.
(5) A numerous neutrophils was also induced into peripheral blood and peritoneal cavity soon after G-CSF ip administration, but didn't show any significant increase on both antitumor and phagocytic activities.
(6) The survival days of malignant ascites rats was significant prolonged by G-CSF ip administration after OK-432 ip administration with the interval of 6 hours, while it was unable to prolonged neither G-CSF alone or OK-432 ip administration after G-CSF.
(7) The survival days of tumor incoculated rats Into the back didn't show any proibngatiofi by ip or subcutaneous administration of G-CSF alone or combination with OK-432. Moreover enhamcement like activity on tumor growth was noted in some rarc cases.
(8) When OK-432 was administered intraperitoneally to patients with peritoneal carcinomatosts, almost, the same antitumor effects was also observed with findings the rosette formation of ncutrophils around tumor cells, and it might be suggested the usefulness of combination therapy with OK-432 and G-CSF.
From the above results, It was demonstrated the combination therapy with OK-432 and G-CSF could be augmented the antitumor effect usually, while in cases of end stage of cancer this therapy may be played as adverse effect. Less

  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] 杉山 保幸: "肉眼的腹膜播種性転移陽性胃癌症例に対するMMCとOKー432の術中腹腔内投与について" 癌と化学療法. 17. 1592-1595 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 芥子川 逸和: "OKー432とGーCSFを用いた担癌ラット好中球の抗腫瘍活性増強効果に関する検討" BIOTHERAPY. 5. 1038-1043 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 佐治 重豊: "癌性腹膜炎に対する免疫療法" 消化器外科. 14. 1489-1495 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 佐治 重豊: "癌免疫療法におけるOKー432刺激好中球の役割" Therapeutic Research. 12. 3406-3416 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 芥子川 逸和: "担癌生体における好中球貧食能とOKー432およびGーCSFを用いた好中球の抗腫瘍活性増強法に試みに関する実験的・臨床的研究" 岐阜大学医学部紀要. 39. 238-272 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Saji S, Keshikawa I, Umemoto T: "Antitumor-effects of neutrophils induced by intraperitoneal administration of OK-432." Tumor & Infection. 2. 407-411 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Saji S: "Immunopharmacological effects on OK-432 local therapy" Therapeutic Research. 10. 3830-3842 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Saji S, Kunii Y, Keshikawa I, Umemoto T, Tanemura H, Furuta T: "Electron microscopic findings on tumor cell destruction by OK-432 activated neutrophils using rat malignant ascites model." Oncologia. 23. 108-114 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Keshikawa I, Saji S, Tanemura H, Takahashi H, Kaneda N, Kawai M: "Mechanisms of antitumor effects of neutrophils induced by intraperitoneal administration of OK-432 to rat malignant ascites." Biotherapy. 4. 724-727 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Saji S, Umemoto T, Keshikawa Y, Tanemura H: "Effects of neutrophils on cancer treatment." Tumor & Infection. 3. 361-368 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Saji S: "Experimental study on enhancement of antitumor activity by OK-432 induced neutrophils." Surgery. 52. 595-598 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sugiyama Y, Yoshida A, Takao H, Kunieda K, Miya K, Azuma S, Tanemura H, Furuta T, Saji S: "Intraoperative intraperitoneal administration of Mitomycin C and OK-432 for peritoneal dissemination of gastric cancer." Jpn J Cancer Chemother. 17. 1592-1595 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Keshikawa I, Saji S, Tanemura H, Takahashi H, Kaneda N, Kawai M: "Experimental study on augmentation of antitumor effects of neutrophils activated with OK-43i and/or G-CSF in tumor bearing rats." Biotherapy. 5. 1038-1043 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Saji S, Azuma S, Umemoto T, Kunieda K, Sugiyama Y: "Immunotherapy for malignant ascites." Gastroenterological Surgery. 14. 1489-1495 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Saji S: "Significance of OK-432 activated neutrophils on cancer immunotherapy." Therapeutic Research. 12. 3406-3416 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Keshikawa I: "Experimental and clinical studies on phagocytic activity of neutrophils derived from tumor bearing hosts and augmentation of antitumor activities of neutrophils by use of OK-432 and G-CSF." Acta Sch Med Univ Gifu. 39. 238-272 (1991)

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

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Published: 1993-03-16  

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