epiglucan and Fibrosarcoma

Distribution of 3H-labeled (1-->3)-beta-D-glucan([3H]SSG) obtained from the culture filtrate of Sclerotinia sclerotiorum IFO 9395, in various tissues in tumor-bearing mice was examined. [3H]SSG administered intra-peritoneally was mainly detected in liver, spleen, kidney and tumor masses. In contrast to i.p. administration, intra-lesionally administered [3H]SSG was not released from the tumor. Similarly, in a double grafted tumor system, [3H]SSG was located in the administered tumor and not distributed in the distant site tumor, in spite of the fact that significant antitumor effect was shown in both tumor sites in this system. Winn assay confirmed the activation of the systemic antitumor immunity. These results suggested that the distribution of glucans would be one important factor in determining their antitumor effects. However, this would not always be necessary if systemic immunity could be induced.

Topics: Animals; Antineoplastic Agents; beta-Glucans; Fibrosarcoma; Glucans; Immunologic Factors; Injections, Intraperitoneal; Male; Mice; Neoplasm Transplantation; Sarcoma, Experimental; Structure-Activity Relationship; Tissue Distribution

The in vivo antitumour activity of a beta 1----3/1----6 glucan from the fungus Glomerella cingulata was investigated in vivo. The glucan exhibited a strong inhibition of tumour growth of the allogeneic Sarcoma-180 as well as the syngeneic DBA/2-MC.SC-1 fibrosarcoma with inhibition ratios up to 100%. Against the hormone sensitive Noble-Nb-R prostate carcinoma the glucan alone showed a moderate antitumour effect, whereas in combination with diethylstilbestrol an almost complete regression of the tumour could be achieved. It could be demonstrated that a highly ordered structure of the glucan is not essential for the antitumour activity. Since the glucan expressed no direct cytotoxic effects, the immunomodulating activity was investigated in vitro in order to get an indication for a possible mode of action. In the lymphocyte transformation assay the glucan at a dose of 100 micrograms/ml caused a fourfold increase in the proliferation of murine spleen lymphocytes. Moreover, the glucan stimulated the phagocytosis of zymosan by bone marrow macrophages up to 100%. However, the glucan was not able to render macrophages cytotoxic against P-815 mastocytoma cells.

Topics: Animals; Diethylstilbestrol; Drug Screening Assays, Antitumor; Fibrosarcoma; Glucans; Lymphocyte Activation; Macrophage Activation; Male; Mast-Cell Sarcoma; Methylcholanthrene; Mice; Mice, Inbred C3H; Mice, Inbred DBA; Prostatic Neoplasms; Rats; Sarcoma 180; Sizofiran

The distribution of a 3H-labeled chemically modified antitumor beta-glucan, grifolan NMF-5N (I/B), in various tissues after an injection into mice was examined in order to obtain information on distribution of the parent antitumor beta-glucan, grifolan NMF-5N. Grifolan NMF-5N was treated with sodium metaperiodate and sodium borotritide to obtain tritium-labeled grifolan NMF-5N [3H-grifolan (I/B)]. When 3H-grifolan (I/B) was administered into normal mice by intraperitoneal (i.p.) or intravenous (i.v.) injection, radioactivity was detected in various mouse tissues. Next, 3H-grifolan (I/B) was injected into tumor-bearing mice 7 d after the tumor inoculation, which is the most effective administration timing for the antitumor effect of grifolan NMF-5N. The results indicated a strong radioactivity in spleens and tumor masses. These results suggested a close relationship between the antitumor activity and the distribution of grifolan NMF-5N in mice.

Topics: Animals; Antibiotics, Antineoplastic; beta-Glucans; Carcinoma; Fibrosarcoma; Glucans; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, Inbred ICR; Tissue Distribution

Antitumor activity of grifolan NMF-5N, a beta-1,3-glucan obtained from mycelia of Grifola frondosa, was examined. Grifolan NMF-5N showed antitumor activities in allogeneic and syngeneic murine tumor systems. In the allogeneic tumor system, a potent antitumor activity over 95% was observed against the solid form of sarcoma 180 when grifolan NMF-5N was injected intraperitoneally (i.p.) at 25-200 micrograms/mouse daily for 10 successive days. In the syngeneic tumor systems, significant antitumor activities were observed against Meth A fibrosarcoma and MM 46 carcinoma by injection at 100 micrograms/mouse daily for 5 successive days, especially i.p. injection at day 7-11, when the tumor cells were inoculated subcutaneously (s.c.) on day 0. Moreover, when grifolan NMF-5N was injected i.p. every other week, significant antitumor activity was also observed. In addition, a single treatment with grifolan NMF-5N at 500 micrograms/mouse showed antitumor activities. Grifolan NMF-5N exhibited antitumor activities against these two syngeneic tumors by intraveneous (i.v.) injection. However, a marked inhibitory activity was observed by intratumorous (i.t.) injection against Meth A fibrosarcoma but not against MM46 carcinoma. These results suggest that antitumor activities of grifolan NMF-5N in murine syngeneic tumor systems depend on not only dosage but also injection routes and timing.

Topics: Animals; Antibiotics, Antineoplastic; beta-Glucans; Carcinoma; Drug Administration Schedule; Fibrosarcoma; Glucans; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, Inbred ICR; Neoplasm Transplantation; Neoplasms, Experimental