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Muramyl dipeptide analogues as potentiators of the antitumor action of endotoxin.
- Source :
-
Cancer immunology, immunotherapy : CII [Cancer Immunol Immunother] 1985; Vol. 19 (3), pp. 205-10. - Publication Year :
- 1985
-
Abstract
- The potentiation of endotoxin-induced necrosis and regression of solid syngeneic Meth A tumors in mice previously observed following administration of N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) was investigated further by use of various muramyl peptide analogues and two unrelated synthetic adjuvants, viz. the pluronic polyol L121 and dimethyldioctadecylammonium bromide (DDA) instead of MDP. All agents were administered in aqueous solution by the IV route. None of the muramyl peptide analogues nor L121 or DDA had any strong antitumor action of their own. Two 6-O-acylated muramyl peptides (L2-MDP and B30-MDP) and muramyl dipeptide stearoyllysine [MDP-Lys (L18)] clearly potentiated endotoxin-induced necrosis and regression. In contrast, MDP with L- instead of D-isoglutamine was completely inactive. Optimal activity of B30-MDP and MDP-Lys (L18) was only achieved by adding of suitable amounts of a nonionic surfactant. L121 and DDA could not replace muramyl peptides as potentiating agent. The combination of endotoxin, MDP, and L121 caused complete tumor regression in all mice, but was highly toxic. On the basis of the data in the literature on the biological response-modifying activities of the agents used it is concluded that the potentiating activity of muramyl peptides cannot yet be related to their immunoadjuvant action or their capacity to activate macrophages or to enhance nonspecific bacterial resistance.
- Subjects :
- Acetylmuramyl-Alanyl-Isoglutamine therapeutic use
Animals
Drug Synergism
Female
Fibrosarcoma drug therapy
Fibrosarcoma pathology
Mice
Mice, Inbred BALB C
Necrosis
Neoplasms, Experimental drug therapy
Neoplasms, Experimental pathology
Poloxalene therapeutic use
Quaternary Ammonium Compounds therapeutic use
Acetylmuramyl-Alanyl-Isoglutamine analogs & derivatives
Antineoplastic Agents
Endotoxins therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 0340-7004
- Volume :
- 19
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Cancer immunology, immunotherapy : CII
- Publication Type :
- Academic Journal
- Accession number :
- 3847290
- Full Text :
- https://doi.org/10.1007/BF00199227