WS5-15 RESPONSIBLE FACTORS IN THE ANTITUMOUR ACTION OF LENTINAN ON MAMMARY TUMOUR~ A. Yamashita, E. Masuda, Y. Hattori, and A. Kosaka Dept. of Anatomy, Hamamatsu Univ. Sch. of Med., Hamamatsu, Japan. The present study aimed to elucidate what kind of cellular and humoral factors are responsible for the antitumour action of lentinan(LNT) in com- bination with either surgical or medical endocrine therapies on the mammary tumours in both experimental animals and patients. Potential synergism of combination of LNT with either surgical endocrine therapy or medroxyproges- terone acetate(MPA)-injection in inhibiting the growth of chemical carcino- gen induced mammary tumours would be presented. Immunosuppressive side effect of MPA were almost excluded by LNT-treatment. LNT also produced a decrease in blood cortisol and prolactin levels and a reexpression of ERs and PgRs on the tumours. On these basis, nature of antitumour action of LNT would be discussed in connection with a possible mechanism of hormonal homeostasis, particularly with an adreno-ovario-hypophyseal hormonal axis and also a biological response modifying mechanism which renders an immune apparatus of hosts into a normal or hyper-status. The usefullness of LNT- endocrine combination therapy would be shown by a randomized controlled study by long-term follow up over 8 years.

WS5-16 AM3, A BRM OF NATURAL ORIGIN, ANTAGONIZES TNF PRODUCTION Alonso, J.L.; Morej0n, M. and Pivel, J.P. Research Department. Lab. Andromaco S.A. Madrid. SPAIN Bearing in mind that TNF is being linked as a main mediator of endotoxic shock and other pathological states, substances that interfere with TNF production have a great potential for therapeutic use. AM3 a yeast pclysa- ccharide from C. utilis, which lacks deleterious effects, is able when gi- ven orally to inhibit TNF production in several inductive protocols. TNF activity was measured in sere of several adequate strains of mice using a TNF-sensitive target (L929 fibroblasts) cytolytic assay. When the appro- plate dosage of AIM3 was given p.o. six times (once daily), serum-associa- ted TNF activity was much lower when TNF had been induced either by a sin- gle signal or by a double priming-triggering event. In the first case, AM3 partially hampered the TNF-inductive effect of LPS i.v. injected from a representative group of gram-negative species and strains. The TNF levels found in AiM3-treated mice were 5 to almost 20 times less than levels found in untreated mice, with the greatest drop in TNF occurring when S. typhosa LPS was used as a triggering stimulus. In the second case, TNF was induced by priming mice by i.p.-injection of zymosan and triggering again with LPS. AM3-treated mice also showed a significant reduction of TNF levels ( i0 times less) vs untreated controls. The therapeutic potential of this substance is increased by the absence of glucocorticoid type side effects.

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