ZALETOK S. Polyamines - markers of tumor growth and targets for anticancer therapy.

Dissertation сovers to study the peculiarities of polyamines metabolism (PA) during tumor growth; to investigate the inhibitors of PA metabolism as an anticancer agents, and to evaluate the interrelationship between PA metabolism in tumors and transcription mediated by NF-кB. It was shown that the activation of synthesis and regular increase of individual fraction of PA is a characteristic features for experimental tumors and human malignant neoplasms with different histological genesis. It was detected that PA-test may be used as acceptable criteria of the therapy efficacy as well as prognostic factor of clinical outcome in patients with ovarian cancer, breast cancer and malignant lymphoma. Experiments in vivo have allowed to shown that promising targets for anticancer therapy are the intermediate of PA metabolism. It was found that the inhibitors of PA metabolism have significantly inhibited the growth of experimental tumors, prolonged the mean survival time of tumor-bearing animals,and may be recommented for the further creation as a means for target therapy of oncological patients. The significant evidences were obtained that PA participation in the regulation of activity of NF-кB transcription factor is one of the molecular functions of PA by tumor growth. It was found that antitumor action of inhibitors of PA metabolism is linked with of NF-кB signaling pathway.