Summary
The antitumor and antimetastatic activities of the water-soluble peptidoglycan monomer GlnNAc-Mur-NAc-L-Ala-D-iso-Gln-meso-diamminopimelic acid (θ-NH2)-D-Ala-D-Ala (PGM), which has immunostimulant effects, have been evaluated in CBA mice bearing MCa mammary carcinoma. The antineoplastic effects of PGM depend strictly on the dosage and treatment schedule used. Though a significant inhibition of the primary tumor growth is observed over a wide range of dosage, only the IV administration of daily doses of 50 mg/kg/day on days 1, 5, 10, 15 inhibits spontaneous lung metastasis formation and in parallel prolongs the survival time of the treated mice. The magnitude of the antimetastatic effects of PGM depends on the degree of dissemination of the tumor, and is greater when the number of metastatic foci is low. Examination of the therapeutic potential of PGM in combination with surgery has further indicated that the timing of administration plays an important role in the overall effectiveness of this substance. A 5-day interval is necessary between two consecutive injections for the induction of significant increases of the survival times.
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References
Baldwin RW (1982) Manipulation of host resistance in cancer therapy. Semin Immunopathol 5:113–125
Fidler IJ, Sone S, Fogler WE, Barnes ZL (1981) Eradication of spontaneous metastases and activation of alveolar macrophages by intravenous injection of liposomes containing muramyl dipeptide. Proc Natl Acad Sci USA 78:1680–1684
Giraldi T, Sava G, Cuman R, Nisi C, Lassiani L (1981) Selectivity of the antimetastatic and cytotoxic effects of p-(3,3-dimethyl-1-triazeno)benzoic acid potassium salt, (±)1,2-di-(3,5-dioxopiperazin-1-yl)propane and cyclophosphamide in mice bearing Lewis lung carcinoma. Cancer Res 41:2524–2528
Hršak I, Tomašić J, Pavelić K, Valinger Z (1978) Stimulation of humoral immunity by peptidoglycan monomer from Brevibacterium divaricatum. Z Immunitaetsforsch Immunobiol 155:312–318
Hršak I, Novak D, Tomašić J (1980) Immunostimulating activity of peptidoglycan monomer (PGM) on in vivo primary response to sheep erythrocytes, Salmonella typhymurium and Newcastle disease virus. Period Biol 82:147–151
Hršak I, Tomašić J, Osmak M (1983) Immunotherapy of B-16 melanoma with peptidoglycan monomer. Eur J Cancer Clin Oncol 19:681–686
Ikekawa T, Ikeda Y, Tukuoka F (1975) Antitumor activity of polysaccharides from Serratia marcescens. Gann 66:317–318
Keglević D, Ladešić B, Hadzija O, Tomašić J, Valinger, Z, Pokorny M, Naumski R (1974) Isolation and study of the composition of a peptidoglycan complex excreted by the biotin-requiring mutant of Brevibacterium divaricatum NRRL-2311 in the presence of penicillin. Eur J Biochem 42:389–400
Keglević D, Ladešic B, Tomašić J, Valinger Z, Naumski R (1979) Isolation procedure and properties of monomer unit from lysozyme digest of peptidoglycan complex excreted into the medium by penicillin-treated Brevibacterium divaricatum mutant. Biochim Biophys Acta 585:273–281
Leibovici J, Michiwitz M, Shezen E, Wolman M, Sandbank U (1981) Combined treatment of Lewis lung carcinoma by tumor excision and levan. Oncology 38:31–34
Nakahara W, Fukuota F, Maeda Y, Aoki K (1964) The host-mediated antitumor effect of some plant polysaccharides. Gann 55:283–288
North RJ, Dye ES, Mills CD, Chandler JP (1982) Modulation of antitumor immunity — immunobiological approaches. Semin Immunopathol 5:193–220
Poliak-Blazi M, Boranić M, Marzan B, Radačić M (1981) A transplantable aplastic mammary carcinoma of CBA mice. Veterinarski Arhiv 51:99–107
Sadler TE, Castro JE (1976) The effects of Corynebaterium parvum and surgery on Lewis lung carcinoma and its metastases. Br J Surgery 63:292–296
Sava G, Giraldi T, Lassiani L, Nisi C (1979) Mechanism of the antimetastatic action of dimethyltriazenes. Cancer Treat Rep 63:93–98
Sava G, Giraldi T, Nisi C, Bertoli G (1982) Prophylactic antimetastatic treatment with aryldimethyltriazenes as adjuvants to surgical tumor removal in mice bearing Lewis lung carcinoma. Cancer Treat Rep 66:115–120
Sava G, Giraldi T, Tomašić J, Hršak I (1983) Immunotherapy of Lewis lung carcinoma with hydrosoluble peptidoglycan monomer (PGM). Cancer Immunol Immunother 15:84–86
Sokal RR, Rohlf FJ (1969) Single classification analysis of variance. In: Biometry. Freeman, San Francisco, pp 204–252
Trešceć A, Iskrić S, Hršak I, Tomašić J (1983) Effect of immunoadjuvant peptidoglycan monomer on liver cytochrome P-450. Biochem Pharmacol 32:2354–2357
Usui S, Urano M, Koike S, Kobayashi Y (1976) Effects of PS-K, a protein polysaccharide, on pulmonary metastases of C3H mouse squamous cell carcinoma. J Natl Cancer Inst 56:185–187
Yamamoto T, Yamashita T, Tsubura E (1981) Inhibition of pulmonary metastasis of Lewis lung carcinoma by glucan, schizophyllan. Invasion Metastasis 1:71–84
Yarkoni E, Lederer E, Rapp HJ (1981) Immunotherapy of experimental cancer with a mixture of synthetic muramyl dipeptide and trehalose dimicolate. Infect Immun 32:273–276
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Sava, G., Tomašic, J. & Hršak, I. Antitumor and antimetastatic activity of the immunoadjuvant peptidoglycan monomer PGM in mice bearing MCa mammary carcinoma. Cancer Immunol Immunother 18, 49–53 (1984). https://doi.org/10.1007/BF00205399
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DOI: https://doi.org/10.1007/BF00205399