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Selective immune modulation by injection routes of PSK
WS3-12 A N T I T U M O R E F F E C T OF 0K-432 AND L Y M P H O K I N E S M. Nanjo, Y. Moriya*, S. Hashimoto, E. Kamijo*, M.Kataoka*, M. Saito*, Y. Sugawara*, T. Yoshida, N. I s h i d a * * T o k y o Inst. for I m m u n o p h a r m . , T o k y o , J a p a n . * A p p l i e d Res. Lab., C h u g a i Pharm. Co. Ltd., Tokyo, Japan. * * T o h o k u U n i v e r s i t y , Sendai, Japan. 0K-432, a streptococcal preparation with potent biological response m o d i f y i n g activity, c o u l d cure B A L B / c mice bearing BAMC-I ascites tumor, when the agent was injected i.p. e v e r y o t h e r d a y s for f i v e times. A l t h o u g h a s i n g l e i.p. i n j e c t i o n of e i t h e r OK-432 or a l y m p h o k i n e (IFNor IL-2) s h o w e d o n l y the m i n i m u m antitumor effect the c o m b i n e d administration of b o t h induced stronger therapeutic effects. Futhermore, it w a s s h o w n t h a t the s e q u e n c e of a d m i n i s t r a t i o n of b o t h agents is c r i t i c a l to induce c u r a t i v e effects. Thus, the i n j e c t i o n of O K - 4 3 2 on d a y 2 f o l l o w e d by e i t h e r l y m p h o k i n e s on d a y 4 or d a y 6 w a s e f f e c t i v e w h i l e i n j e c t i o n s of either l y m p h o k i n e s on day 2 f o l l o w e d by OK-432 on day 4 did not show any t h e r a p e u t i c effects. These r e s u l t s may warrant further investigation on p o s s i b l e effective therapeutic p r o t o c o l s with the c o m b i n e d use of OK-432 and lymphokines.
WS3-13 S E L E C T I V E IMMUNE M O D U L A T I O N BY INJECTION ROUTES OF PSK K. Ryoyama and C. Ryoyama D e p a r t m e n t of E x p e r i m e n t a l T h e r a p e u t i c s , Cancer R e s e a r c h Institute, K a n a z a w a University, Kanazawa, Japan G r o w t h i n h i b i t i o n a c t i v i t y levels of adult m o u s e serum are greatly a f f e c t e d by i n j e c t i o n routes of g r o w i n g tumors or of BRM (PSK, OK-432). The p r e s e n t study was d e s i g n e d to study how such i n j e c t i o n routes affect in vivo immune responses. C57BL/6 mice r e c e i v e d a single s.c. or f.p. injection of PSK (125 mg/kg) on Day-7 and an i.p. injection of SRBC (106 or 108 ) on Day 0. After 4 days, one g r o u p of these mice was d e v o t e d to a humoral res p o n s e and the rest mice r e c e i v e d a f.p. i n j e c t i o n of SRBC (108 ) to see 24 hr DTH response. The results o b t a i n e d are as follows: Mitogenic r e s p o n s e s against Con A, PIIA and LPS of splenic and thymic cells of mice w h i c h r e c e i v e d a s.c. or f.p. i n j e c t i o n of PSK 7 days b e f o r e were almost the same as those of normal mice. Splenic h u m o r a l immune responses against SRBC were a u g m e n t e d by a s.c. i n j e c t i o n of PSK. However, a f.p. i n j e c t i o n of PSK s i g n i f i c a n t l y i n h i b i t e d the humoral response. Meanwhile, DTH r e s p o n s e s a g a i n s t SRBC were s l i g h t l y but not s i g n i f i c a n t l y i n f l u e n c e d by the PSK injections. Thus, the p r e s e n t study shows that injection routes of PSK s e l e c t i v e l y m o d i f y s u b s e q u e n t h u m o r a l immune responses.
WS3-14 SER U M I M M U N O S U P P R E S S I V E S U B S T A N C E (IS) AND E F F E C T S OF B I O L O G I C A L R E S P O N S E MODIFIER, PSK ON U R O G E N I T A L TUMORS Y. Nakagami, K. Ikeda, T.T. Lin, H. Ito, Y. K i m o t o and A. Oka D e p a r t m e n t of Urology, F i r s t H o s p i t a l of N i p p o n M e d i c a l School, Tokyo, J a p a n IS is a g l y c o p r o t e i n o b t a i n e d from the a s c i t i c fluids of a d v a n c e d cancer patients, and the serum levels of IS in cancer p a t i e n t s were found to be higher than those of p a t i e n t s w i t h b e n i g n tumors or normal persons. We e x a m i n e d the effects of a fungous p r o t e i n - b o u n d p o l y s a c c h a r i d e , PSK on the serum IS levels in tumor b e a r i n g rats and the p a t i e n t s with u r o g e n t i t a l tumor. B l a d d e r c a r c i n o m a BC-47 was t r a n s p l a n t e d s u b c u t a n e o u s l y in the back of ACI rats, e x a m i n e d the change in the serum level of IS, tumor g r o w t h and sur v i v a l rate. PSK was a d m i n i s t e r e d o r a l l y for 14 time after tumor inoculation, and s e r u m IS was m e a s u r e d by single radial i m m u n o d i f f u s i o n m e t h o d using anti-IS antiserum. Serum IS i n c r e a s e d with tumor growth, but PSK a d m i n i s t r a t i o n i n h i b i t e d the i n c r e a s e in the serum IS levels, r e s u l t i n g in the s u p p r e s s i o n of tumor growth and p r o l o n g a t i o n of survival time. Clinically, serum IS levels i n c r e a s e d with a d v a n c i n g stage of the disease, and the mean IS levels in the group given PSK was lower than that of non PSK group. IS is a u s e f u l p a r a m e t e r for p r e d i c t i n g tumor g r o w t h and the t h e r a p e u t i c e f f e c t of i m m u n o m o d u l a t o r s such as PSK.
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WS3-13 S E L E C T I V E IMMUNE M O D U L A T I O N BY INJECTION ROUTES OF PSK K. Ryoyama and C. Ryoyama D e p a r t m e n t of E x p e r i m e n t a l T h e r a p e u t i c s , Cancer R e s e a r c h Institute, K a n a z a w a University, Kanazawa, Japan G r o w t h i n h i b i t i o n a c t i v i t y levels of adult m o u s e serum are greatly a f f e c t e d by i n j e c t i o n routes of g r o w i n g tumors or of BRM (PSK, OK-432). The p r e s e n t study was d e s i g n e d to study how such i n j e c t i o n routes affect in vivo immune responses. C57BL/6 mice r e c e i v e d a single s.c. or f.p. injection of PSK (125 mg/kg) on Day-7 and an i.p. injection of SRBC (106 or 108 ) on Day 0. After 4 days, one g r o u p of these mice was d e v o t e d to a humoral res p o n s e and the rest mice r e c e i v e d a f.p. i n j e c t i o n of SRBC (108 ) to see 24 hr DTH response. The results o b t a i n e d are as follows: Mitogenic r e s p o n s e s against Con A, PIIA and LPS of splenic and thymic cells of mice w h i c h r e c e i v e d a s.c. or f.p. i n j e c t i o n of PSK 7 days b e f o r e were almost the same as those of normal mice. Splenic h u m o r a l immune responses against SRBC were a u g m e n t e d by a s.c. i n j e c t i o n of PSK. However, a f.p. i n j e c t i o n of PSK s i g n i f i c a n t l y i n h i b i t e d the humoral response. Meanwhile, DTH r e s p o n s e s a g a i n s t SRBC were s l i g h t l y but not s i g n i f i c a n t l y i n f l u e n c e d by the PSK injections. Thus, the p r e s e n t study shows that injection routes of PSK s e l e c t i v e l y m o d i f y s u b s e q u e n t h u m o r a l immune responses.
WS3-14 SER U M I M M U N O S U P P R E S S I V E S U B S T A N C E (IS) AND E F F E C T S OF B I O L O G I C A L R E S P O N S E MODIFIER, PSK ON U R O G E N I T A L TUMORS Y. Nakagami, K. Ikeda, T.T. Lin, H. Ito, Y. K i m o t o and A. Oka D e p a r t m e n t of Urology, F i r s t H o s p i t a l of N i p p o n M e d i c a l School, Tokyo, J a p a n IS is a g l y c o p r o t e i n o b t a i n e d from the a s c i t i c fluids of a d v a n c e d cancer patients, and the serum levels of IS in cancer p a t i e n t s were found to be higher than those of p a t i e n t s w i t h b e n i g n tumors or normal persons. We e x a m i n e d the effects of a fungous p r o t e i n - b o u n d p o l y s a c c h a r i d e , PSK on the serum IS levels in tumor b e a r i n g rats and the p a t i e n t s with u r o g e n t i t a l tumor. B l a d d e r c a r c i n o m a BC-47 was t r a n s p l a n t e d s u b c u t a n e o u s l y in the back of ACI rats, e x a m i n e d the change in the serum level of IS, tumor g r o w t h and sur v i v a l rate. PSK was a d m i n i s t e r e d o r a l l y for 14 time after tumor inoculation, and s e r u m IS was m e a s u r e d by single radial i m m u n o d i f f u s i o n m e t h o d using anti-IS antiserum. Serum IS i n c r e a s e d with tumor growth, but PSK a d m i n i s t r a t i o n i n h i b i t e d the i n c r e a s e in the serum IS levels, r e s u l t i n g in the s u p p r e s s i o n of tumor growth and p r o l o n g a t i o n of survival time. Clinically, serum IS levels i n c r e a s e d with a d v a n c i n g stage of the disease, and the mean IS levels in the group given PSK was lower than that of non PSK group. IS is a u s e f u l p a r a m e t e r for p r e d i c t i n g tumor g r o w t h and the t h e r a p e u t i c e f f e c t of i m m u n o m o d u l a t o r s such as PSK.
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