| Author/Editor | Novaković, Srdjan | |
| Title | Vpliv analogov TNF in MDP na maligne tumorje poskusnih živali | |
| Type | monografija | |
| Place | Ljubljana | |
| Publisher | Medicinska fakulteta | |
| Publication year | 1994 | |
| Volume | str. 146 | |
| Language | slo | |
| Abstract | Tumor necrosis factor alpha (TNF-alpha) is a cytokine with numerous biological activities. Among the most important ones belong cytostatic/cytotoxic effect upon tumor cells, stimulation of immune system and its activity as a growth factor. Despite its numerous activities TNF-alpha has only poor clinical value in treatment of cancer patients, chiefly because of serious toxic side effects. We studied the antitumor activities of two analogues to recombinant human TNF-alpha (i.e. TNF Nv3 and LK 801), since we had expected them to retain the antitumor effect while having less pronounced toxic side effects. As the antitumor effect of TNF-alpha is a sum of its direct action upon tumor cells and its indirect action upon the immune system (i.e. stimulation of immune system), we tried to increase (by using nonspecific immunomodulators) its effect upon the immune system, thus improving the therapeutical efficacy of this very cytokine. For this purpose we tested structural analogues to muramyl dipeptide (MDP) LK 409 and LK 410. The experiments were performed with different animal tumor models, that is with subcutaneous sarcomas Sa-1 (on A/J syngenic mice), and with subcutaneous or intraperitoneal B-16 melanomas (on C57B1/6 syngenic mice). On the basis of our results we can summarize that tumor models used in the study are adequate for such kind of research work. LK 801 has a more pronounced antitumor effect in comparison to TNF Nv3, since even 70 per cent of tumor bearing animals treated three times with 2x10 to power 5 units of LK 801 showed (PCR). Also the amount of secreted TNF-alph a in supernatant fluids of a complete response (tumor free 100 days after the treatment), while animals treated with the same dose of TNF Nv3 showed no complete responses. Also the toxic side effects were less severe after treatment with LK 801. Combined therapy with TNF NP3 and structural analogues to MDP exhibited an increased antitumor activity (vs.(trunc.) | |
| Descriptors | MELANOMA, EXPERIMENTAL SARCOMA, EXPERIMENTAL TUMOR NECROSIS FACTOR ACETYLMURAMYL-ALANYL-ISOGLUTAMINE MACROPHAGES PERITONEUM RNA POLYMERASE CHAIN REACTION MICE ANIMALS, LABORATORY |