Biomedical subjects
Publications and source records attributed to N V Malakhova.
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Spleen cells of tumor-bearing mice suppressed the cytolytic activity of syngeneic LAK cells when added to the mixture of LAK cells and target cells at the beginning of the cytotoxicity test. Spleen cells of MC 14 tumor-bearing mice acquired the suppressor potential as early as 10 days after tumor transplantation; the suppressor activity in the EL 4 and X63-Ag8.653 tumor-bearing animals was first revealed at the 30th day and manifested itself up to the 120th day. The suppressor activity was expressed in a dose-dependent manner, both by unfractionated spleen cells and nylon wool-passed and plastic-adherent sub-populations. Similar results were obtained during the analysis of anti-tumor immunity suppressors in bladder cancer patients. MNC, nylon wool-passed and plastic-adherent cells of patients with stages I-II disease suppressed the cytotoxicity of autologous LAK cells in 2/6 cases; all patients [4] with III-IV stage possessed such suppressor activity. Presumably, the tumor growth induces the activity of suppressor T cells and monocytes/macrophages. The suppressor activity can interfere with the antitumor effect of autologous (syngeneic) LAK cells at the effector stage.
The effect of RIL-2 on the survival of mice with S. aureus--induced peritonitis was studied. Animals received bacterial suspension and RIL-2 as following: bacteria--on days 0, +2, RIL-2--day 0 (group 1); bacteria--days 0, +4, RIL-2--days 0, +2 (group 2); bacteria--days 0, +6, RIL-2--days 0, +2, +4 (group 3). RIL-2 exerted no protective effect in group 1. However, in groups 2 and 3, where the control animals survival was, resp., 56% and 38%, the RIL-2 treatment increased survival up to, resp., 84% and 70%. Antibiotics given instead of RIL-2 in analogous regimen decreased the survival in group 3 to the level of 25%. Thus, RIL-2 proved to be a potent therapeutic agent in the 2nd of 3d studied models of S. aureus--induced peritonitis in mice. The perspectives of RIL-2 use in the treatment of bacterial peritonitis, including porous ones, and of the immunodepression--aggravated conditions are discussed.
The cultivation of peripheral blood lymphocytes (PBL) obtained from patients with colorectal or bladder carcinoma and melanoma and from healthy donors in the presence of interleukin-2 (IL-2) and PHA resulted in the induction of cytotoxic activity against autologous and/or allogeneic tumour cells in 12 out of 13 patients and in 10 out of 10 donors. A higher level of cytolytic activity was achieved when PBL were separated by means of Percoll density gradient (1.077; 1.067 and 1.056 g/ml) centrifugation and the cells of fraction II (1.077-1.067 g/ml) were employed in the experiment, the level of cytotoxicity being elevated in all cases (1.7-fold elevation in donors and 2-fold elevation in patients on the average). The addition of fraction I (1.067-1.056 g/ml) to fraction II prevented (PHA + IL-2)-mediated induction of cytotoxic activity in all the patients, but in 4 out of 10 donors, i.e. cells of fraction I expressed a suppressor activity. The immunofluorescent analysis has shown that fraction II was enriched by T cells (92%) and depleted of monocytes (7%), as compared to unseparated PBL (66% and 27%, respectively). On the contrary, fraction I was characterized by a decreased T cell ratio (36%) and an increased monocyte level (up to 69%).
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Transplacental administration of serotonin metabolite 5-methoxyindole-3-acetic acid possessing blastomogenic activity induced the development of malignant and benign neoplasms (lymphosarcomas, adenomas, hepatomas and other tumours) in 84% of C57BL/6 mouse progeny. The number of neoplasms was significantly higher, than in the control, they appeared earlier and were more malignant.
A considerable blastogenic activity of biogenic methoxyindoles--melatonin, 5-methoxytryptamine (5-MOT) and their common metabolite--5-methoxyindolyl-3-acetic acid (5-MIAA) was established by prolonged s.c. injection in C57BL/6 mice. However, the blastogenic effect of 5-MOT decreased by 26% when its further metabolism to 5-MIAA was blocked for some time and the synthesis of its carcinogenic metabolite was inhibited. These results showed that the blastogenic effect of 5-MOT is not direct; and it is mediated by its transformation to 5-MIAA in the body.
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It was demonstrated in in vivo and in vitro experiments that interleukin-2, obtained by cultivation of donor lymphocytes and purified by gel filtration, induces the production of mouse and human killer lymphocytes possessing high cytolytic activity against tumor cells. Interleukin-2 does not cause irreversible changes of the physiological and morphologic indices of vital activity in mice.
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