HOSOYA Yoshinori Jichi Medical School, Medical College, Lecturer, 医学部, 助手 (30275698)
KOBAYASHI Eiji Jichi Medical School, Medical College, Assistant Professor, 医学部, 助教授 (00245044)
TAKIZAWA Toshihiro Jichi Medical School, Medical College, Associate Professor, 医学部, 講師 (90271220)
長島 徹 自治医科大学, 医学部, 助手 (60254926)
土屋 一成 自治医科大学, 医学部, 助手 (90217331)
|Budget Amount *help
¥1,900,000 (Direct Cost : ¥1,900,000)
Fiscal Year 1998 : ¥1,100,000 (Direct Cost : ¥1,100,000)
Fiscal Year 1997 : ¥800,000 (Direct Cost : ¥800,000)
Milky spots are particular structures in the serosal cavity with abundant clasmatacytes to differentiate in situ to exert miscellaneous biological reactions. OK-432, one special strain of a -hemolytic streptococcus, is a potent biological response modifier, and has shown to exert beneficial effects on serosal carcinosis. Having found milky spots demonstrate dramatical reactions after intraserosal instillation of OK-432, the role of milky spots in relation to antineoplastic action of OK-432 was investigated using the OK-432 and BAMC-1 model.
BAMC-1 is a mouse transplantable ascites tumor capable of killing the host within 3 weeks, but, is specifically sensitive to the tumoricidal effect of OK-432. PC-C203U (PC203), another strain of streptococcus processed in the same way as OK-4 32, is less effective in this particular system compared to OK-432, was chosen as the comparative, and saline was used as the control. OK-432 could prolong the lives of BACM-1 inoculated mice, PC203 was less eff
ective in this system, hut gained favorable action compared to the saline control. The mRNA levels of IL-1 beta, TNF-alpha LFN-gamma and MCP-1 were significantly elevated in milky spots, the greater omentum being used as the sauce of milky spots, after the introduction of OK-432. The levels were in parallel with the effectiveness of OK-432, PC203 and saline. So were the number of neutrophiles, concentrations of IL-i beta, IL-6, and MCP-1 in ascites of each test group. The sizes of milky spots were also in parallel with the tumoricidal effectiveness of each test materials. OK-432 was very effective in producing neutrophiles in milky spots, which emerge into the secosal cavity to exert antineoplastic actions. Thus milky spots are the particular sites in the serosal cavity where a series of cytokines production take place after various stimulation, and to produce effector cells in correspondence with the actions of biological response modifiers.
Following projects are on going now with promising results :
1)Effects omentectomy on antineoplastic action of OK-4 32,
2)Analyses of bioactive cellular components in milky spots after the topical application of OK-432 in organ culture,
3)Effect of intestinal microflora of the function and structure of milky spots. Less