Biopolym. Cell. 1997; 13(6):497-502.
Viruses and Cell
Study of transforming growth factors role in AIDS and Kaposi's sarcoma patients
- Division of Cell Regulatory Systems of O.V. Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine
14/16, Drahomanov Str., Lviv, Ukraine, 79005
- Gromashevsky L.V. Institute of Epidemiology and Infection Diseases, AMS of Ukraine
5, Amosova Str., Kyiv, Ukraine, 03038
- R. E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine
45, Vasilkivska Str., Kyiv, Ukraine, 01022
Earlier we found that the transforming activity of growth factors in blood serum of AIDS and Kaposi's sarcoma patients was considerably higher than that in healthy donors' blood serum. This activity was estimated by studying the ability of serum to induce anchorage-independent growth of NIH-3T3 mouse fibroblasts in the semisolid culture medium supplemented with 0.33 % agar. Here we showed that the treatment of Kaposi's sarcoma patients with laferon (recombinant α2b-interferon) caused a significant decrease in the level of transforming activity in blood serum of all treated patients and this decrease positively correlated with a substantial improvement of their health state. Two cellular models were used for the study of the role of transforming growth factors in the modulation of cytopathogenic effects of HIV-1 infection - MT-4 line of T-lymplwblastoid cells infected with BRU strain of HIV-l (model of acute lytical infection) and the same cells infected with IIIB virus strain (model of chronic infection). Cytopathogenic virus effects were estimated by counting the part of dead cells and the number of giant cells. The amount of p24 virus protein was also determined. It was found that transforming growth factor beta and I or epidermal growth factor (transforming growth factor alpha analogue) increased the negative HIV-l effects in the experimental model of acute infection. The action of these cytokines was not so uniform in the case when the cellular model of chronic infection was use in the study. Thus, HIV-I infection is accompanied by the increased transforming activity of growth factors in blood serum of AIDS and Kaposi's sarcoma patients and these growth factors could be responsible for cytopathogenic effects observed in AIDS patients. This could partially explain why the successful treatment of Kaposi's sarcoma patients with α2b-interferon is accompanied by an decrease of the transforming growth factors activity in blood serum of the treated patients.
 Kusen' SI, Stoika RS. Molecular mechanisms in the action of polypeptide growth factors. Moscow, Nauka, 1985; 236 p.
 Goustin AS, Leof EB, Shipley GD, Moses HL. Growth factors and cancer. Cancer Res. 1986;46(3):1015-29.
 Lazdins JK, Klimkait T, Woods-Cook K, Walker M, Alteri E, Cox D, Cerletti N, Shipman R, Bilbe G, McMaster G. In vitro effect of transforming growth factor-beta on progression of HIV-1 infection in primary mononuclear phagocytes. J Immunol. 1991;147(4):1201-7.
 Kim SJ, Kehrl JH, Burton J, Tendler CL, Jeang KT, Danielpour D, Thevenin C, Kim KY, Sporn MB, Roberts AB. Transactivation of the transforming growth factor beta 1 (TGF-beta 1) gene by human T lymphotropic virus type 1 tax: a potential mechanism for the increased production of TGF-beta 1 in adult T cell leukemia. J Exp Med. 1990;172(1):121-9.
 Sasaki H, Pollard RB, Schmitt D, Suzuki F. Transforming growth factor-beta in the regulation of the immune response. Clin Immunol Immunopathol. 1992;65(1):1-9.
 Roth WK, Brandstetter H, St?rzl M. Cellular and molecular features of HIV-associated Kaposi's sarcoma. AIDS. 1992;6(9):895-913. Review. Erratum in: AIDS 1992 Nov;6(11):following 1410.
 Filchenkov AA, Ivashchenko YuD, Kulik GA. Purification of epidermal growth factor byhydrophobic chromatography. Exp Oncol. 1991; 13(5):71-4.
 Stoika RS, Sushelnitsky SI, Kusen' SI. The influence of transforming growth factor ?, epidermal growth factor and insulin on DNA biosynthesis in mouse fibroblasts of swiss-3T3 line grown in monolayer cultures with low and high cell density. Biopolym Cell. 1992; 8(4):39-43.
 Stoika RS, Yakimovych IA, Antonenko SV. et al. Transforming activity of growth factors in blood serum of AIDS and Kaposi's sarcoma patients. Exp Oncol. 1995; 17: 3-9.
 Korovin SI, Vorontsova AL, Tolstopyatov VA et al. Laferon as an effective tool in the treatment of Kaposi's sarcoma. Laferon in the treatment of cancer and infectious diseases. Rivne, 1996:74-7.
 Filchenkov AA, Stoika RS, Bykorez AI. Transforming growth factors. Kiev: Naukova Dumka, 1994; 292 p.
 Roberts AB, Sporn MB. Transforming growth factors. Cancer Surv. 1985;4(4):683-705. Review.
 Stoika RS, Kusen' SI. Transforming growth factors. Usp Sovrem Biol. 1988. 106(1 (4)):69-84.
 Sushel'nitski? SI, Sto?ka RS, Garas'ko SI, Shafranskaia GI, Kusen' SI. The effect of the beta-type transforming growth factor and its combination with epidermal growth factor and insulin on substrate-dependent proliferation of normal and tumor cells. Tsitologiia. 1989;31(7):767-74.
 Phylchenkov AA. Transforming growth factor a in oncology: current status and future prospects. Exp Oncol. 1993; 15(4): 3-19.