Anti-tumor effects of the oral administration of the streptococcal preparation OK-432 (PICIBANIL)--the inhibition of carcinogenesis and growth in rats with ENNG-induced gastrointestinal tumors.
We examined whether the Streptococcal preparation OK-432, an immunopotentiating agent, increases immunocompetence of the gut-associated lymphoid system (GALS), inhibits gastrointestinal carcinogenesis, and has an anti-tumor effect. 14C-labelled OK-432 was orally and intraperitoneally administered to rats, and the distribution of the agent in various organs then serially evaluated. The concentration of OK-432 in Peyer's patches and mesenteric lymph nodes was higher after oral administration than after intraperitoneal administration, and showed a biphasic pattern peaking at 30 minutes and 5 hours following administration, in the Peyer's patches. With regard to immunocompetence, PHA- and PWM-stimulated blastogenesis of lymphocytes derived from the mesenteric lymph nodes and peripheral blood enhanced, and the helper/suppressor T-cell ratio was elevated after the oral administration of OK-432. Moreover, chemotactic activity of peritoneal macrophages was also increased. ENNG-induced gastrointestinal carcinogenesis was observed in 60 per cent of the rats orally administered OK-432 as compared with 88 per cent of the controls. The 13-month survival rate of the rats with gastrointestinal cancer was 50 per cent in those administered OK-432 as compared with 25 per cent in those administered OK-432 as compared with 25 per cent in the controls. When administered orally, the agent prevented reduction in immuno-competence in the course of carcinogenesis, suppressed carcinogenesis, and prolonged the survival of animals with cancer without any of the side effects associated with injection. The oral administration of OK-432 is thus considered to be an effective non-specific immunotherapy against gastro-intestinal malignancies.
Takeshita
M
M
Second Department of Surgery, School of Medicine, Gunma University, Japan.
Makita
F
F
Takeyoshi
I
I
Ishikawa
H
H
Nakamura
S
S
Owada
S
S
Miyamoto
Y
Y
Izuo
M
M
Kurashige
S
S
D000284:Administration, Oral; D000818:Animals; D001688:Biological Products / Q000627:therapeutic use*; D002273:Carcinogens / Q000633:toxicity; D004064:Digestive System / Q000276:immunology; D005770:Gastrointestinal Neoplasms / Q000139:chemically induced / Q000628:therapy*; D007121:Immunocompetence; D008221:Lymphoid Tissue / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008297:Male; D008769:Methylnitronitrosoguanidine / Q000633:toxicity / Q000031:analogs & derivatives; D010844:Picibanil / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D013601:T-Lymphocytes / Q000276:immunology
D001688:Biological Products; D002273:Carcinogens; D008769:Methylnitronitrosoguanidine; D010844:Picibanil; C013525:ENNG