Vol 23, No 2 (2018)

Introduction. Topoisomerases influence on DNA topology and are capable of running down their super spiraling molecules by importation of one- or two-chained ruptures with the subsequent restitution and also the negative super rounds or catenae’s. Topoisomerases are known to be targets for antineoplastic therapy. Inhibitors of these enzymes of various nature and chemical structure are widely used for the suppression of tumor Topoisomerase I and/or II activity with the blocking cells in the phase G2 and a delay of their introduction in mitosis. Such difficult curable tumors as colorectal cancer, carcinoma of the stomach, non-small cell lung cancer and so forth are the most sensitive to these drugs. The search of perspective antineoplastic inhibitors is implemented generally in ranks of the non-camptothecin agents among which heterocyclic condensed nitrogenous compounds, in particular, anthrafurandiones show the most significant results. The review of thematic literature from 2011 to 2018 is devoted to the description of properties of topoisomerase as targets and their inhibitors from perspective classes. Objectives: 1. The analysis of signal characteristics of topoisomerases as targets for anticancer non-camptothecin inhibitors. 2. Identification of structure-activity relationship in the ranks of potential inhibitors of topoisomerases. 3. The choice of the most perspective non-camptothecin topoisomerase inhibitors among heterocyclic condensed nitrogenous compounds on the basis of the comparative analysis of structure and properties. Material and methods. Materials of 79 scientific articles published in the leading biological, biochemical and chemical journals of the different countries within the 8 last years are subjected to the analysis. The structure of the review meets the purpose and tasks of the scientific analysis. Results. The analysis of the thematic literature showed topoisomerases to be relevant targets for antineoplastic therapy of severe oncological pathology. In this regard, intensive search of various pharmaceuticals among topoisomerase inhibitors is performed in recent years. Researchers modify the known basic structures as well as synthesize new compounds. The discovery of a top-directional effect of the known medicines expands the data on their mechanism of the action. To identify the topoisomerase inhibitory activity of the drug the methods with the use of plasmid DNA is applied. The cytotoxic activity, apoptosis induction, including the caspases activation, modification of mitochondrial potential, influence on p53 and others are examined in parallel studies. The research directed on the identification of new effective non-camptothecin oral topoisomerase inhibitors among the anthracyclines derivatives are of undoubted relevance. Such agents, in contrast to Doxorubicin (anthracycline antibiotic widely used for tumor therapy), have moderate toxicity and allow to control the growth of solid tumors and leukemia in mono-therapy mode. Conclusion. In terms of searching of original antineoplastic agents, a class of heterocyclic condensed nitrogenous compounds, first of all, the anthraquinones showing properties of topoisomerase inhibitors is one of the most promising. The results of chemical and biological research of the compounds of this series were laid in a basis of the design of medicinal substances and their drug formulations. Prognostically significant data obtained in preclinical testing allow us to hope that obtained antitumor agents will be highly effective on a clinical stage of trials.

There are presented results of the analysis of case histories of 418 patients with generalized lymphomas and chronic leukemia, among whom 49 patients had information about multiple primary cancers. Among these patients, 37 were diagnosed as generalized lymphoma, 8 - multiple myeloma and 4 - chronic myelomonocytic leukemia. Most often hemoblastosis combined with skin cancer (17 patients), bowel cancer (11 patients) and lung cancer (9 patients). 3 patients had hemoblastosis combination with prostate, as well as kidney, stomach, and thyroid malignant diseases. Among all cases, 44 patients had two multiple primary tumors, 4 patients had three tumors. In this work, the analysis of patients is given according to the age-gender structure, time of the onset of the development of tumors. As an example, the short information about 4 patients with hematological malignancies in combination with other tumors is given.

This article presents the outcomes of our own research of the detection of circulating cells in the peripheral blood of 48 patients with oncological diseases, using hemocytofiltration. The observed circulating cells (21 cases, 43.8%) have been represented by three variants: more often in the form of “bare” atypical nuclei (76.2% cases), also single conserved tumor cells (14.3%) and large shapeless single cells, probably of non-epithelial nature (9.5%). The difficulties of identifying the obtained cells in light microscopy and technical aspects of the usage of immunocytochemical techniques have been discussed.

For many years ovarian cancer (OC) has remained the leading cause of mortality from gynecological cancer diseases. The problem of late diagnosis of ovarian cancer remains still unresolved in more than 70% of patients when the diagnosis is established at advanced stages. The standard approach to the treatment of patients is to perform surgical removal of the tumor at the first stage, which often pursues both therapeutic and diagnostic purposes, as it allows performing the disease restaging and assessing its prevalence. To date, the question of the relevance of implementation and the extent of lymph node dissection still remains open. In this regard, in this article, we want to present the available evidence base regarding the use of the performing retroperitoneal lymph node dissection in advanced OC patients.

The role of mechanisms of the onset of opioid-induced hyperalgesia in patients with chronic pain syndrome of oncological genesis is highlighted according to the review of results of the search for Russian and English articles in the scientific bases of PubMed, Scopus, Web of Science, eLibrary. The importance of genetic factors predetermining the development of opioid-induced hyperalgesia is shown. The key role of pharmacological preparations for relief of chronic pain in the conditions of opioid-induced hyperalgesia is presented.