Grant-in-Aid for General Scientific Research (B)
|Allocation Type||Single-year Grants|
|Research Institution||Gifu University School of Medicine|
SAJI Shigetoyo Gifu University School of Medicine, Second Dpt. of Surgery Professor, 医学部, 教授 (80021400)
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)
種村 広巳 岐阜大学, 医学部附属病院, 講師 (60092946)
吉田 明彦 岐阜大学, 医学部附属病院, 助手 (90210674)
|Project Period (FY)
1989 – 1991
Completed(Fiscal Year 1991)
|Budget Amount *help
¥4,200,000 (Direct Cost : ¥4,200,000)
Fiscal Year 1991 : ¥1,400,000 (Direct Cost : ¥1,400,000)
Fiscal Year 1990 : ¥1,000,000 (Direct Cost : ¥1,000,000)
Fiscal Year 1989 : ¥1,800,000 (Direct Cost : ¥1,800,000)
|Keywords||G csp / Ok-432 / Neutrophils / Antitumor effects / Cytostatic activity / Chemiluminescence / Immunotherapy / Peritoneal carcinomatosis / 好中球数増殖法 / 腹腔内遊出細胞(PEC) / 好中球の抗腫瘍活性 / 好中球貧食能 / OKー432とGーCSF併用投与 / OK-432刺激好中球 / 腹腔内遊出好中球(PEN) / 好中球貧食能(CL活性) / 抗腫瘍作用 / 細胞障害活性(cytostatic活性) / G-CSF / KW2228|
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
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