[Accomplishments and perspectives in tumor diagnostics and treatment].

In contemporary medicine cancer has an exceptionally important role, even though it is not a new disease. Tumors are found in all animals and plants, and today are more frequent than before, when they were found predominantly in advanced ages. The frequency occurrence depends of many factors, and it is more frequent in countries with higher degree of civilization, what is the consequence of irradiation of other diseases as well as more pronounced industrialization, leading to in proper nourishment, many sources of intoxication with carcinogenic factors arising from environmental pollution, and even by the use of some diagnostic and therapeutic procedures. Cancer is the result of disturbance in cell growth and differentiation. In the appearance and spreading of tumors many factors are involved. In the Department of Experimental and Clinical Oncology of the Institute for Oncology and Radiology, we in the first place investigated the role of immunity, hormones and central nervous system, predominantly in experimental conditions, based on the investigations on animals, the in vitro investigations is tissue cultures and some disturbances which are found in blood of patients with tumors. As in the processes of carcinogenesis the immune system has in important role, in the immunological investigations we primarily investigated parameters of the status of the immune system in patients with malignant processes. The number and function of particular cell subsets of the immune system was investigated, namely T and B lymphocytes and their subclasses, NK cells and monocytes-macrophages. In the majority of analyzed patients with breast and lung cancer, lymphoproliferative diseases and other malignancies, it was shown that the majority of them had a decreased number of immune cells that correlated with the clinical advances of disease and applied cytostatic therapy. However, it was shown that the function of these cells, primarily NK, but also of T lymphocytes, was markedly decreased even before changes in the cell number, indicating that a functional impairment is present even before the cell number decrease and proportional to the advancement of the disease. As the results of exploring of investigation of the immunological status indicate the concrete defects in the function of the separate components of the immune system, these findings make it possible to direct immunotherapy for the correction of existing defects. The activity and pathways of mechanisms of NK cells and the possibility of their modulation were also investigated. Also, the possibility of the application of mAbs in the precise diagnostics of some malignancies was explored. The role in carcinogenesis was investigated in tumors whose appearance, growth and spreading is hormone-dependent. One of the hormone-dependent tumors is breast cancer. It was shown that they are significantly dependent on estrogen and growth factor presence, steroid-receptor content, and that these characteristics can change during the disease and do not have to be identical in their metastasis. Numerous investigations that we performed were in the in vitro conditions, i.e. in cell cultures. The obtained data show how some tumor cells react to applied agents, cytostatical and biological. However their effect in vivo is very often different, as in the in vivo conditions many other factors are involved, suggesting a need for further investigations of these factors. The role of the central nervous system neurotransmiters in carcinogenesis in experimental animals exposed to chemical cancerogen (5-methylcholantrene) with simultaneous treatment of the monoamine system was investigated. It was shown that monoamines expressed their influence on carcinogenesis by regulating the brain homeostasis, as well as by direct influence on the intracellular processes during cell development and differentiation. The obtained results will direct our further investigations toward obtaining mAbs for receptors for TNFalpha and IFNgamma, transfection of suppressor gene into tumor cell cultures and genes for IL-2 and TNFalpha. At the same time we will work on isolation of malignant melanoma tumor antigen and construction of a vaccine using some epitopes and adjuvantes. We will try to introduce appropriate immunotherapy in the advancedehZAD.