Masaaki Takeshita

Antitumor effect of RBS (rice bran saccharide) on ENNG-induced carcinogenesis

We examined whether orally administered RBS (rice bran saccharide), prepared from rice bran by hot water extraction, increases immunocompetence, inhibits gastrointestinal carcinogenesis with N-ethyl-N′-nitro-N-nitrosoguanidine (ENNG) or shows an antitumor effect. After the administration of RBS, phytohemagglutinin (PHA)- and pokeweed mitogen (PWM)-stimulated blastogenesis of lymphocytes derived from the mesenteric lymph nodes and peripheral blood was enhanced, and the helper/ suppressor T-cell ratio was elevated, and migration activity of peritoneal macrophages was also increased in rats treated continuously with ENNG. ENNG-induced gastrointestinal carcinomas were observed in 43% of those administered RBS (ENNG-RBS) as compared with 88% in the control (ENNG) and 94% in the prednisolone (PRD) group (ENNG-PRD). The 12-month survival rate of rats bearing gastrointestinal cancer was 58% in the ENNG-RBS group as compared with 25% in the ENNG group and 15% in the ENNG-PRD group. RBS prevented the reduction in immunocompetence in the course of carcinogenesis, suppressed carcinogenesis, and prolonged the survival of rats with gastrointestinal cancer. Antitumor activities of RBS are thought to be a kind of host mediated action. The growth inhibition ratio of transplantable ENNG-induced cancer in Wistar rats was 42.1% in the RBS and 51.8% in the 5-FU group. Since little is known about the potent antitumor activity of α-glucan, it would be interesting to consider the relationship between the structure and the biological activities of polysaccharides.

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 Peyers 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 Peyers 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 immunocompetence 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 gastrointestinal malignancies.