peptidoglycan-pentapeptide-mdap3 and Lung-Neoplasms

The effects of preoperative treatment with dimethyltriazene p-(3,3-dimethyl-1-triazeno) benzoic acid potassium salt (DM-COOK) followed by surgery and non-specific immunotherapy with the peptidoglycan monomer PGM have been evaluated using the Lewis lung carcinoma implanted i.m. in BD2F1 female mice. The survival time of mice treated with this combination is prolonged and the percentage of animals cured is markedly increased as compared with untreated controls or with mice treated with DM-COOK or PGM alone. The synergism between DM-COOK and PGM could be attributed to the capacity of the triazene to render the treated tumor cells more antigenic, combined with the favourable effects of PGM to restore host defense mechanisms. In this combined treatment, the use of cyclophosphamide at dosages having the same activity displayed by PGM alone does not ameliorate the results obtained with DM-COOK alone.

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Adjuvants, Immunologic; Animals; Combined Modality Therapy; Cyclophosphamide; Female; Lung Neoplasms; Mice; Mice, Inbred C57BL; Peptidoglycan; Triazenes

The water-soluble peptidoglycan monomer (PGM) isolated from the culture fluid of Brevibacterium divaricatum, which has immunostimulating activity, has been examined for its antitumor effects in C57BL mice bearing Lewis lung carcinoma. The formation of spontaneous lung metastases from SC tumor implants is significantly inhibited. The growth of SC primary tumors, including advanced ones, is also significantly inhibited, though to a less pronounced extent than the growth of metastases. The effects on metastases are evident with all treatment schedules used, whereas those on SC primary tumors are treatment schedule-dependent. The treatment with PGM was found to be therapeutically useful when combined with surgical removal of IM implants; in conditions where a single post-operative treatment was ineffective, combined post-operative and immediately pre-operative administration of PGM significantly increased (by 40%) the survival time of treated animals over that of controls undergoing surgery only.

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Animals; Female; Immunotherapy; Lung Neoplasms; Mice; Mice, Inbred C57BL; Neoplasms, Experimental; Peptidoglycan; Solubility

B-16 melanoma-bearing mice received intravenously or intratumorally one or multiple injections of peptidoglycan monomer (PGM) derived from Brevibacterium divaricatum cell wall. Multiple injections of this non-toxic, water-soluble, low-molecular-weight peptidoglycan reduced the growth rate of tumor nodule on the leg, but did not significantly prolong the survival of tumor-bearing mice. One milligram of PGM administered 3 or 7 days after tumor inoculation inhibited formation of pulmonary metastases, induced either by intravenous injection of malignant cells or seeded spontaneously from tumor nodules in the legs before amputation. The inhibition reached about 50% of control values in saline-treated mice. Addition of PGM to in vitro cultures of B-16 melanoma cells did not change their growth rate. The phagocytic activity in the lungs, but not in the spleen and liver, was significantly augmented 3 and 7 days after treatment with PGM. These data indicate that the antimetastatic potency of PGM is probably due to activation of local (pulmonary) macrophages and not due to direct cytotoxic effects on B-16 melanoma cells or to activation of systemic antineoplastic defence.

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Animals; Cell Survival; Lung; Lung Neoplasms; Melanoma; Mice; Mice, Inbred C57BL; Neoplasms, Experimental; Peptidoglycan; Phagocytosis