picibanil and Sarcoma-180

It was reported that the symptoms of tumor patients may be alleviated markedly and even the tumor may be regressed completely after acute infection. Bacterin OK-432 has notable inhibitory effect on the growth of various tumors in animals. At present, OK-432 has been used in clinical immunotherapy for tumors with no other adverse events besides fever and leucocytosis. This study was to investigate the effects of combined bacterin on the serum level of interleukin 12(p70)[IL-12(p70)] and the growth of sarcoma 180 (S180) in mice.. After transplantation of S180, the mice were randomized into 5 groups, and received injection of Staphylococcus aureus, Salmonella typhimurium, Mycobacteria phlei, and combined bacterin containing the 3 bacteria strains, respectively, or received no treatment (blank control). The weight of S180 xenografts, the thymus, and the spleen in mice was measured. The serum level of IL-12(p70) was detected by ELISA.. The mean weight of S180 tumors was 1.39 g in Staphylococcus aureus group, 1.50 g in Salmonella typhimurium group, 1.36 g in Mycobacteria phlei group, 0.62 g in combined bacterin group, and 2.40 g in blank control group; the differences among the 5 groups were significant (F=66.73, P<0.001). The mean weight of S180 tumors was significantly lower in the 4 bacterin groups than in control group, and significantly lower in combined bacterin group than in the 3 single bacterin groups (q test, P<0.001). The weights of the thymus and the spleen among the 5 groups had no significant difference (F=2.36, P>0.05; F=1.89, P>0.05). The inhibition rate of tumor growth was significantly higher in combined bacterin group than in Staphylococcus aureus, Salmonella typhimurium, and Mycobacteria phlei groups (74.17% vs. 42.08%, 37.50%, and 43.33%, P<0.01). The mean serum level of IL-12(p70) was 19.44 pg/ml in combined bacterin group, 12.41 pg/ml in Staphylococcus aureus group, 10.35 pg/ml in Salmonella typhimurium group, 11.68 pg/ml in Mycobacteria phlei group, and 4.45 pg/ml in control group; the difference among the 5 groups was significant (F=15.76, P<0.0001), but the difference among the 3 single bacterin groups was not significant (q test, P>0.05), while the differences between other groups were significant (q test, P<0.01).. The chosen bacterins in this study can induce the mice to produce IL-12(p70) and suppress the growth of S180. The effect of the combined bacterin is much better than the single bacterins.

Topics: Animals; Bacterial Vaccines; Body Weight; Cell Proliferation; Female; Interleukin-12; Male; Mice; Mycobacterium phlei; Neoplasm Transplantation; Organ Size; Picibanil; Random Allocation; Salmonella typhimurium; Sarcoma 180; Spleen; Staphylococcus aureus; Thymus Gland

The authors recently measured the Interleukin-1 (IL-1) and Prostaglandin E (PGE) activity of the monocyte-macrophage system (M phi) in vitro. The results indicated that immunodeficiency in cancer patients is closely associated with reduced IL-1 activity and increased PGE activity of M phi. Immunosuppressive factors in the serum of cancer patients seem to play some role in the mechanism of such change. Therefore, when potentiating M phi in nonspecific immunotherapy, it seems important to suppress secretion of PGE (a suppressor factor of M phi origin which is secreted simultaneously) to make this therapy more effective in advanced cancer cases. Based on these results, an animal experiment was carried out in which tumor-bearing mice were treated with OK-432 and Indomethacin (Ind.) (a PG inhibitor). The results of this experiment suggested that this combination therapy reinforces the M phi-mediated immunopotentiation, resulting in a stronger antitumor effect of OK-432. When we used this combination therapy in advanced cancer cases, the changes observed in immunological parameters also indicated an immunopotentiating effect, i.e., an antitumor effect. These results indicate that the optimum application of BRM therapy should be decided on the basis of an understanding of the immunological factors in the patient.

Topics: Adjuvants, Immunologic; Animals; Carcinoma in Situ; Female; Humans; Indomethacin; Interleukin-1; Macrophages; Male; Mice; Mice, Inbred Strains; Monocytes; Picibanil; Prostaglandin Antagonists; Prostaglandins E; Sarcoma 180; Uterine Cervical Neoplasms

Streptococcal acid glycoprotein (SAGP) was purified from the cultured cells of Streptococcus pyogenes Su, and its in vitro and in vivo antitumor activities were investigated in comparison with those of OK-432, a cell preparation of S. pyogenes Su which is used clinically as a potent antitumor agent. SAGP inhibited the growth of several tumor cell lines in vitro at less than 0.1 microgram/ml, while it did not affect the growth of the other tumor and normal cell lines even at 10 micrograms/ml. This selective cytotoxicity is a unique characteristic of SAGP. OK-432 did not show cytotoxicity in vitro. SAGP also showed a considerable life-span-prolonging effect on mice bearing Meth A tumor and inhibited the growth of sarcoma 180 tumor implanted im. The comparison of antitumor activities between SAGP and OK-432 definitely suggested a difference in the mechanisms of their actions, even though they were derived from the same bacterial strain.

Topics: Animals; Bacterial Proteins; Cell Line; Cells, Cultured; Glycoproteins; Mice; Mice, Inbred ICR; Neoplasms, Experimental; Picibanil; Sarcoma 180; Streptococcus pyogenes

Antineoplastic effects of carnosine (CAR) and beta-alanine (ALA), were examined in vivo using ddY mice implanted with the solid tumor Sarcoma-180. The sarcoma was treated with trypsin, 10(5) cells were implanted subcutaneously in the back of the animals, and CAR and ALA were administered subcutaneously 2 cm from the implantation site starting on the next day. The animals treated with ALA alone showed prolongation of survival to a T/C value of 132%; the growth of the tumor was inhibited and mortality reduced in those treated with CAR alone. Regression of the tumor was observed in the animals treated with either drug. The effects of these agents were enhanced when administered in combination with the non-specific active immuno-enhancing agent OK-432. More than half the animals treated with CAR and OK-432 survived the observation period (T/C greater than 218%), and survival was prolonged in those treated with ALA and OK-432 to a T/C value of 132%. The agents also showed potent antineoplastic effects on Sarcoma-180 when the tumor had been attenuated in vivo with mitomycin C (MMC).

Topics: Alanine; Animals; Antineoplastic Agents; beta-Alanine; Carnosine; Dipeptides; Male; Mice; Mitomycin; Mitomycins; Picibanil; Sarcoma 180

Correlation between antitumor activity and effects on some biological properties, such as phagocytic activity of the reticuloendothelial system, the third component of complement (C3) activation, hepatic drug-metabolizing activities and pentobarbital-induced narcosis, of antitumor agents from various natural sources such as B B (Broncasma Berna), GU-P (Grifora umbellata polysaccharide), OK-432, PS-K (Polysaccharide Kureha), and RA-P (Rumex acetosa polysaccharide) were studied with female ICR mice implanted with Sarcoma 180 solid tumor. All of these agents depressed aniline hydroxylase and aminopyrine demethylase activities, prolonged the duration of pentobarbital-induced narcosis, and significantly enhanced the phagocytic activity and C3 activity. Especially, RA-P which has the strongest antitumor activity was the most effective in changing these activities. The biological activities of GU-P at a dose of 10 mg/kg reached the same level as that found with PS-K at a dose of 100 mg/kg. a possible mechanism of inhibition of Sarcoma 180 solid tumor growth by the treatment with the antitumor agents could be interpreted as due to the C3 activation, the stimulation of phagocytic activity and depression of the hepatic microsomal drug-metabolizing system in tumor-bearing mice.

Topics: Animals; Antineoplastic Agents; Complement Activation; Complement C3; Female; Liver; Mice; Mice, Inbred ICR; Pentobarbital; Phagocytosis; Pharmaceutical Preparations; Picibanil; Polysaccharides; Proteoglycans; Sarcoma 180

Topics: Adjuvants, Immunologic; Animals; Biological Products; Immunotherapy; Lacticaseibacillus casei; Mice; Picibanil; Pseudomonas aeruginosa; Pseudomonas Infections; Sarcoma 180

Intralesional injection of bradykinin at the dose of 500 micrograms or 1000 micrograms in oil or gelatin was effective in inhibiting the growth of Sa 180 cells in ddY mice. Ulcer formation in tumor was observed at a high rate in these bradykinin-treated groups. Combined use of bradykinin with a streptococcal preparation (OK-432) was more effective in inhibition of tumor growth compared with that in oil. Similar bradykinin-induced inhibition was observed in a spontaneous mammary tumor of C3H (MM 46) mice. These results suggest that increase in cellular influx and activation of infiltrated cells within a tumor are important factors to induce tumor inhibition effectively.

Topics: Animals; Biological Products; Bradykinin; Emulsions; Female; Gelatin; Male; Mice; Oils; Picibanil; Sarcoma 180; Time Factors

Immune modulators injected 24 h before encephalomyocarditis virus significantly increase antiviral resistance in mice when interferon is administered 1 h after the virus. These immune modulators can be crude bacterial extracts or synthetic drugs. In some cases, the responses are additive; in others, they are clearly cooperative. To protect the mice against the development of 180 TG Crocker sarcomas, the association of bacterial extracts and interferon is highly effective under the condition that the drug concentrations and chronological order and number of injections are well defined. In contrast, the conjunction of interferon and synthetic immune modulators, in particular cimetidine, result in delayed tumor development with no significant change in the final survival rate in the experimental model described here.

Topics: Adjuvants, Immunologic; Animals; Carcinoma, Ehrlich Tumor; Cimetidine; Ditiocarb; Encephalomyocarditis virus; Enterovirus Infections; Interferon Type I; Mice; Peptides, Cyclic; Picibanil; Sarcoma 180

Topics: Animals; Antibody Formation; Biological Products; Blood Proteins; Cell Division; Female; Glycoproteins; Mice; Molecular Weight; Picibanil; Sarcoma 180; Species Specificity