Vol 23, No 2 (2018)

Articles

TOPOISOMERASES: FEATURES OF THE ACTION, CLASSIFICATION, CELL FUNCTIONS, INHIBITION, ANTHRAFURANDION

Treshalin M.I., Neborak E.V.

Abstract

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.
Russian Journal of Oncology. 2018;23(2):60-70
pages 60-70 views

STEREOTACTIC RADIOTHERAPY FOR THE TREATMENT OF CLINICAL STAGE I-IIA LUNG CANCER PATIENTS. THE EXPERIENCE OF N.N. BLOKHIN NATIONAL MEDICAL RESEARCH CENTER OF ONCOLOGY

Borisova T.N., Nazarenko A.V., Allakhverdiev A.K., Tkachev S.I., Alieva S.B., Trofimova O.P., Glebovskaya V.V., Laktionov K.K., Breder V.V., Meshcheryakova N.A., Marinov D.T., Fedorova A.A.

Abstract

Introduction: Nowadays the stereotactic radiotherapy (SRT) of clinical stage I-II lung cancer patients is the choice of the treatment modality for functionally inoperable patients. It shows safety and high efficiency in achieving local control. Though there is a range of unsolved issues connected with the prediction of the treatment efficiency and frequency of complications, an integration of new technologies in the planning and treatment process allows widening the search of the predictive factors. Material and methods. Since 2014, 39 patients (17 T1N0M0 patients, 22 T2N0M0 patients) with clinical stage I-IIa lung cancer have undergone SRT. The majority of patients (35) have been recognized as functionally inoperable due to the concurrent broncho-pulmonary pathology, 4 conditionally operable patients have refused an operation. 11 patients had the primary multiple tumors in their anamneses. 36 patients had a peripheral tumor. The options for the fractionation were: 10 Gy × 5 fractions (n = 26) and 7 Gy × 8 fractions (n = 13) - BED = 100 Gy. Results. The median follow-up was 26 months (range: 3-38 months). The 2-year local control was 94%. The isolated local recurrences were not registered. Overall and 2-year recurrence-free survival rate was 84% (95% CI, 70-99) and 83.2% (95% CI: 70.5-99) respectively. During the first year, 4 patients (10%) had the locoregional and distant progression and 3 of them died. 7 patients had experienced pulmonary toxicity of grade 2 or more. One patient with central tumor died from pulmonary hemorrhage (toxicity of grade 5). Grade 3 chest pain was observed in 2 patients, one of them had a rib fracture. One-factor analysis, revealed a reliable influence of the fractionation regimen (р = 0.04) and, close to reliability, the initial SUVmax level (р = 0.07) on the prognosis. A reliable relationship between the radiation toxicity level and dosimetric radiation index (V10, V5, MLD) was not registered. There was a tendency to reliable correlation with the total lung capacity indices (р = 0.058). Conclusions. A search for additional treatment efficiency and toxicity predictors of SRT treatment should include modern approaches to planning and delivery. The total dose delivery regimen and initial tumor SUVmax can be predictive efficiency factors, while the pulmonary tissue volume can be a predictive toxicity factor.
Russian Journal of Oncology. 2018;23(2):71-78
pages 71-78 views

MULTIPLE PRIMARY TUMORS IN CHRONIC LEUKEMIA AND GENERALIZED LYMPHOMAS

Buevich E.I., Kotovshchikova E.F., Lazarev A.F., Ganov D.I.

Abstract

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.
Russian Journal of Oncology. 2018;23(2):79-81
pages 79-81 views

COMPREHENSIVE PHYSICAL ANTIEDEMATOUS THERAPY IN THE TREATMENT OF UPPER LIMB LYMPHOSTASIS

Kurbatov G.K., Lazarev A.F., Bochkarev A.P.

Abstract

The aim of the study was to decrease or to eliminate upper limb lymphostasis with the use of comprehensive physical antiedematous therapy (CPhAT) in patients after the radical treatment of breast cancer. Material and methods. The work was based on data about 30 patients. There are presented the CPhAT technique, the results of the treatment and ways to evaluate the effectiveness of the treatment. To evaluate the results of the treatment, we used the technique developed by ourselves, consisting in immersing first the healthy upper limb, then the affected upper limb in a vessel with a disinfectant. The degree of edema (lymphostasis) and the evaluation of the effectiveness of treatment were determined according to the difference of the displaced fluid (patent for invention No. 2169358). The method is ultra-precise in comparison with a centimeter tape. Results. The developed comprehensive treatment of the upper limb lymphostasis allows achieving the complete regression of stage I-II edema, and volume decrease of III-IV stage edema in 83% patients. Using the developed complex treatment of edema of the upper limb prevents its recurrence in the next three years in 90% patients.
Russian Journal of Oncology. 2018;23(2):82-83
pages 82-83 views

IDENTIFICATION OF CELLS OBTAINED FROM BLOOD OF ONCOLOGICAL PATIENTS WITH HEMOCYTOFILTRATION

Grigoruk O.G., Lazarev A.F., Chimitov A.A., Khankhashanova T.D., Bazulina L.M., Shoykhet Y.N.

Abstract

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.
Russian Journal of Oncology. 2018;23(2):84-89
pages 84-89 views

KI-67 INDEX AND TYPE OF HSP70 EXPRESSION IN THE FORMATION OF PROGNOSTIC GROUPS OF PATIENTS WITH PAPILLARY THYROID CANCER

Ivanov A.A., Avdalyan A.M., Lushnikova E.L., Molodykh O.P., Zorkina Y.N., Kruglova N.M., Lazarev A.F.

Abstract

The aim of our work was to determine the possibility of stratification of papillary thyroid cancer (PTC) patients into prognosis groups depending on the Ki-67 index and the type of HSP70 expression. The study included 89 patients with a known prognosis for the period of 2005-2017, treated for PTC over the period of 2005-2013. The immunohistochemical study was carried out with Ki-67 and HSP70 antibodies on the Ventana XT Steiner device using standard protocols. The method of tissue matrices was used to standardize the study. Different variants of PTC, depending on the level of Ki-67 expression in combination with the HSP70 response allowed identifying 3 groups of PTC prognosis. The favorable prognosis group included patients with samples with cytoplasmic type of HSP70 expression and Ki-67 response < 6.3%, with mixed type of HSP70 expression and Ki-67 response < 6.3%, with cytoplasmic HSP70 expression and Ki-67 response > 6.3%. The intermediate prognosis group consisted of patients with tumors with mixed type of HSP70 expression and Ki-67 response > 6.3%, with nuclear HSP70 expression and Ki-67 response < 6.3%. The group of poor prognosis included patients with nuclear HSP70 expression and Ki-67 response > 6.3%. In the group of favorable prognosis, the 10-year survival rate was 89.6 ± 3.5%. In the intermediate prognosis group, the 10-year survival rate was 45 ± 14.5% and in the unfavorable prognosis group, no patient survives 6 years.
Russian Journal of Oncology. 2018;23(2):90-95
pages 90-95 views

THE ROLE OF LYMPHODISSECTION IN THE TREATMENT OF PATIENTS WITH DISSEMINATED OVARIAN CANCER

Nikogosyan S.O., Mamajonov H.I., Levchenko N.E.

Abstract

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.
Russian Journal of Oncology. 2018;23(2):96-101
pages 96-101 views

STAGES OF THE DEVELOPMENT OF OVARIAN CANCER SURGERY: LITERATURE REVIEW

Kozhevnikova O.V., Nikogosyan S.O., Kuznetsov V.V., Ananyev V.S.

Abstract

The review article considers the course of the development, improvement, and introduction of combined operations in ovarian cancer into the surgical practice of oncogynecologists, analyzes the results of the activity of major oncological centers, as well as the positive and negative aspects of the “aggressive” surgery in ovarian cancer.
Russian Journal of Oncology. 2018;23(2):102-106
pages 102-106 views

OPIOID-INDUCED HYPERALGESIA IN PATIENTS WITH CHRONIC PAIN SYNDROME OF ONCOLOGICAL GENESIS

Bobrova O.P., Shnayder N.A., Dykhno Y.A., Petrova M.M.

Abstract

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.
Russian Journal of Oncology. 2018;23(2):107-112
pages 107-112 views

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