Purpose of the study. Evaluation of the expression of immunohistochemical tumor markers Ki-67, b-catenin, Bcl-2, P53, connexin 32 and connexin 43 when using 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)-5,6,7-trichloro-1,3-tropolone in mice with xenographs of squamous cell lung cancer.Materials and methods. Subcutaneous PDX models of human squamous cell lung cancer were created in immunodeficient BALB/c Nude mice. A fragment of the patient’s tumor (3 × 3 × 3 mm) was implanted subcutaneously in the right thigh of a previously anesthetized mouse. 200 μl of 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)-5,6,7-trichloro-1,3-tropolone was administered orally using a probe in 12 doses once every 3 days. All animals were divided into groups depending on the tropolone doses: experimental groups 2–5 with doses of 0.0055, 0.055, 0.55 and 2.75 mg/g, respectively. The control group received 1 % starch gel which was tropolone carrier. The animals were euthanized 36 days after the start of the substance administration, and the tumor tissue was isolated and prepared for the IHC study according to the standard protocol. IHC reactions were performed using antibodies for Ki-67, b-catenin, Bcl-2, P53, connexin 32 and connexin 43.Results. Higher tropolone doses were associated with decreased expression of Ki-67, b-catenin, and the Bcl-2 protein, but increased expression of the P53 protein. The dosage of tropolone and expression of connexin 43 were directly proportional.Conclusion. Immunohistochemical analysis of expression of proteins in PDX models of human squamous cell lung cancer when using 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)-5,6,7-trichloro-1,3-tropolone showed the changes indicating its antitumor efficacy and suggesting a possible mechanism of action based on the activation of apoptosis.

Purpose of the study. Was to reveal the antitumor effect of 2‑(6,8‑dimethyl‑5‑nitro‑4‑chloroquinoline‑2‑yl)‑5,6,7‑trichloro‑1,3‑tropolone in subcutaneous PDX models of human lung cancer.Material and methods. The studied tropolone was synthesized using a method of expanding the o‑quinone cycle. Assess to it’s toxic effects was given by the survival and changes in the health status of female Balb/c Nude mice. Antitumor tropolone effects were studied in subcutaneous patient‑derived xenograft (PDX) models of human squamous cell lung cancer in Balb/c Nude mice. The average volumes of tumor nodes and tumor growth inhibition (TGI %) rate were taken into account. Biochemical blood tests and histological analysis of the tumor material were performed in recipient mice.Results. An analysis of acute tropolone toxic effects did not reveal the lethal dose. The maximal TGI was observed on day 36 of the experiment in group 5 which have received 2.75 mg/g tropolone and accounted 73.5 % for females and 74.4 % for males. The average tumor volumes in females of this group were 431.3 ± 1,1 mm3 on day 33 of the experiment, in males – 428.9 ± 1,7 mm3 on day 30, and then the tumor volumes declined. The biochemical analysis of blood and histological examination of the tumor tissue of recipient mice reflect the severity of the antitumor effect on the dose of the studied tropolone.Conclusion. The research demonstrated the antitumor activity of 2‑(6,8‑dimethyl‑5‑nitro‑4‑chloroquinoline‑2‑yl)‑5,6,7‑trichloro‑1,3‑tropolone against subcutaneous PDX models of human NSCLC. The revealed tendencies can be used to search for effective modes of the compound application in clinical practice.

Modern tissue engineering approaches are aimed at developing scaffolds that contribute to the development of the whole variety of intercellular interactions that imitate those in a real object.The purpose of the study was to collect and summarize the data on the creation and use of three-dimensional cellular matrices.Material and Methods. A systematic literature search was conducted in the PubMed, Medline, Cyber Leninka and Elibrary databases. Out of the 315 articles searched, 38 were selected for this review.Results. A review of studies devoted to the development of three-dimensional composite structures (scaffolds) and their application in the field of cellular technologies was carried out. Methods for the manufacture of biocompatible structures using both natural biomaterials and synthetic ones, including various hydrogels and titanium alloys, were considered, and some physical and chemical characteristics were also discussed. The review discussed possible applications of 3D composite structures in oncology as one of the possible tools for expanding the fundamental understanding of the patterns of development of the malignant process, but also for use in the development of effective methods of treatment and the search for new drugs. The prospects for the use of scaffolds in the field of experimental oncology, namely in the creation of various types of tumor models, were outlined.Conclusion. Currently, three-dimensional culture systems are replacing two-dimensional models. Advances in this direction are associated with the creation and development of various variants of cell matrices that contribute to the solution of a number of applied problems in the field of creating three-dimensional tumor models in vitro and in vivo, therapy of malignant tumors and restorative medicine.

The aim . To study the toxicity of 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)-5,6,7-trichloro-1,3-tropolone in vitro and in vivo. Materials and methods. 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)-5,6,7-trichloro-1,3-tropolone was synthesized using a method for expanding the o-quinone cycle during the reaction between 5-nitro-2,6,8-trimethyl4-chloroquinoline and 3,4,5,6-tetrachloro-1,2-benzoquinone while boiled in dioxane. An in vitro experiment was carried out in the human A549 cell line. Cell viability was assessed using the MTT colorimetric assay by reducing the optical density of the experimental samples compared with the control ones. Acute toxicity was studied on 20 BALB/c Nude male mice. The test compound was administered once orally as a suspension in 1% starch gel at three doses: 0.0055 (group 1), 0.055 (group 2) and 0.55 mg / g (group 3). The control group (group 4) received a placebo. Results . We synthesized a new compound, 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)-5,6,7-trichloro-1,3-tropolone. Its structure was established by 1 H nuclear magnetic resonance (NMR), infrared (IR) spectroscopy, and mass spectrometry. The yield was 19.8 g (52%), the melting point was 205–207 ºС, bright yellow crystals (benzene) were observed. The half-maximal inhibitory concentration (IC50) of 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)-5,6,7-trichloro-1,3-tropolone was 0.21 ± 0.01 μM, which was significantly lower (р < 0.05) than the IC50 of cisplatin (3.84 ± 0.23). Following the in vivo experiment, no toxic effect of tropolone was detected when administered once at a dose of 0.0055, 0.055, and 0.55 mg / g. Conclusion . 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)-5,6,7-trichloro-1,3-tropolone demonstrated cytotoxic effects on the A549 cell line at a lower IC50 than cisplatin which is widely used in treatment of cancers, including lung cancer. Insolubility of 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)-5,6,7-trichloro-1,3-tropolone in water and the absence of its toxic effect in the studied modes determine the scope of its application for further study of cumulative and antitumor effects.

Purpose of the study. Was was the creation of a Patient Derived Xenograft (PDX) model of non‑small cell lung cancer in immunodeficient mice adapted to growth in immunodeficient mice.Materials and methods. The study was performed using the tumor material from 14 donors implanted subcutaneously to 132 immunodeficient Balb/c Nude mice. Xenografts were maintained until the third passage. PDXs in the third passage from 3 patients were used to assess the model sensitivity to cisplatin. A histological analysis and genetic tests for the presence of EGFR mutations were performed for donor tumors from 3 patients and the corresponding xenografts in the third passage.Results. We observed a noticeable PDX growth already on the 8th day after the tumor material implantation. Successful xenograft engraftment was noted in 21 of 42 mice (50 %), which were rather successful results. A comparative histological analysis of tumor material from 3 patients showed that the PDX models retained the original histotype. We also demonstrated the identity of the EGFR mutations in the established xenografts from 3 patients and the donor tumors, which proved the value of these PDX models for preclinical studies of substances with potential antitumor activity. The analysis of the xenograft sensitivity to cytostatic cisplatin showed a statistically significant decrease in the growth rate in the xenografts obtained from 2 out of 3 patients, in comparison with the control.Conclusions. The created PDX models can be recommended as test systems for preclinical studies of the effectiveness of new pharmacological substances with potential antitumor activity.

Despite significant advances in the drug treatment of various oncological diseases, there is a problem of drug resistance and non-selectivity of their action in relation to targets. Benzimidazoles are structural isosters of nucleic bases due to fused nitrogen nuclei, and they easily interact with biomolecular targets and exhibit, among other things, antitumor activity. The creation of benzimidazole derivatives does not require complex synthetic strategies and the possibility of easy replacement of the benzamidazole core allows the creation of highly selective antitumor agents. The review of modern research presented in the article has shown that there is a wide variety of benzimidazole derivatives for antitumor therapy of various types of cancer with various mechanisms of action. Among the latter, activity against DNA and tubulin protein, directed action on various kinases (cyclin-dependent kinases, AMP-activated protein kinase and checkpoint kinases), against DNA topoisomerases, directed action on apoptotic proteins and oxidative stress enzymes, etc. are shown. Since benzimidazole derivatives demonstrate significant antitumor potential with universal mechanisms for inhibiting the growth and development of tumor cells, the search and development of targeted highly effective antitumor agents continues, including overcoming non-selective toxicity and side effects for the treatment of malignant neoplasms.

Purpose of the study to summarize available data on methods for creating bladder cancer models for their application in preclinical studies. Material and methods. A systematic literature search was conducted in the Elibrary, Pubmed, Googlescholar, CyberLeninka databases. Results. The review shows current data on various bladder cancer models and their application in practice. Bladder cancer pathology, identification of diagnostic markers and the development of new therapies are of the main challenges facing the management of bladder cancer. To solve these problems, it is often necessary to conduct preclinical studies using experimental models. Conclusion. Bladder cancer models that can fully reproduce a human disease in terms of histology and behavior are necessary to study the factors involved in cancer development, progression and metastasis. For this, various experimental models are currently used. Human tumor xenografts in mice are widely used. They can reproduce the main pathophysiological features of cancer biology. However, it is necessary to clearly present all the pros and cons of the selected experimental models. The literature review presents modern data on the etiology of bladder cancer, results of preclinical studies on various experimental models, including orthotopic and heterotopic xenografts.

В обзоре рассматриваются сведения о факторах природного происхождения, перспективных для целей клинической онкологии, и некоторые современные подходы к разработке эффективных методов фитотерапии для лечения онкологических больных. Представлены данные о ряде наиболее известных и распространенных в природе фитохимических веществ, проходящих в настоящее время первые фазы клинических испытаний. Анализируются сведения об отечественных исследованиях по выявлению перспективных противоопухолевых факторов и средств сопровождающего лечения, известных и оригинальных подходах к разработке эффективных режимов фитотерапии. Обсуждаются некоторые результаты исследований, проведенныхс участием авторов в ряде научно-исследовательских учреждений России – Всероссийском научно-исследовательском институте лекарственных и ароматических растений (ФГБНУ ВИЛАР, г. Москва), Национальном медицинском исследовательском центре онкологии им. Н.Н. Блохина (НМИЦ онкологии им. Н.Н. Блохина, г. Москва), Национальном медицинском исследовательском центре онкологии (НМИЦ онкологии, г. Ростов-на-Дону), Южном научном центре РАН (ЮНЦ РАН, г. Ростов-на-Дону), Южном федеральном университете (ЮФУ, г. Ростов-на-Дону). В обзоре представлены сведения литературы, индексируемой в базах данных Scopus, WoS, Pubmed, РИНЦ. Более 60% работ опубликованы за последние 5 лет, 40% работ вышли в печать за последние 3 года.

The humanization of immunodeficient animals allows us to study the growth of xenografts of human malignant tumors and their response to therapeutic effects, taking into account processes in the immune system and tumor zone, which have a significant impact on oncogenesis and the effectiveness of antitumor therapy. Such experimental models are currently considered as the most advanced tool in the development of personalized antitumor treatment. The lines of immunodeficient animals most commonly used for the transplantation of mature and stem human immune cells have been characterized. The main sources of human immune cells when implementing the hu-pbl and hu-cd34+ models, as well as the blt model (as an option to the cd34+ model) are described. The basic procedures necessary for reproducing each model, their modification in adult and newborn animals are outlined as well as the parameters of immunosuppressive radiation exposure, preceding the transplantation of human hematopoietic stem cells. The main results of the humanization of immunodeficient animals and examples of the use of these models for the purposes of fundamental and clinical oncology are described. The main problems of this direction are discussed. The review is based on an analysis of the literature presented in the scopus, web of science, medline, risc and others databases over the past 7 years (over 80 % of literature sources, with more than over 50 % of studies published over the last 3 years).

The work aimed to investigate the impact of chronic formalin-induced inflammation on the remote malignancy development and longevity in white outbred tumour-bearing rats. Experiments were conducted with 29 white outbred mature male rats divided in three groups: a control, water-injection and main formalin-injection group. Aqueous formaldehyde or same water volume were injected into left ankle joint thrice prior to Guerin’s carcinoma transplantation, 4 weeks past the first injection. The tumour size dynamics, longevity, oedema severity, blood leucocyte count and overall motor activity were estimated with an Open Field test. Statistical analysis was performed with Statistica 6 using the Kruskal—Wallis and Dunn’s test criteria. Formalin administration accelerated the tumour growth in most animals. Nevertheless, longevity increased relative to the control’s maximum in 50% cases. Lethality in such cases was often registered with larger tumours relative to the control group. The pre-tumour traits of inflammatory response and motor dynamics in longer-lived animals have been revealed. A similar trend was registered in water administration trials at a less pronounced inflammatory and algetic response relative to the formalin trials. Putative chronic inflammation-associated mechanisms of anti-tumour resistance have been proposed. A multidirectional effect of formalin-induced inflammation on tumourigenesis is shown for the first time: a prevailing tumour growth acceleration at higher longevity with seldom tumour inhibition cases in white outbred male rats. The mechanisms of inflammation-associated anti-tumour resistance require further research. The results relate to the known effect of musculoskeletal inflammatory conditions on tumourigenesis.

ОЦЕНКА ОСТРОЙ ТОКСИЧНОСТИ СЕЛЕНОРГАНИЧЕСКОГО СОЕДИНЕНИЯ С ПОТЕНЦИАЛЬНЫМ ПРОТИВООПУХОЛЕВЫМ ДЕЙСТВИЕМКит О.И. 1 , Златник Е

The purpose of this study was to create an in vivo model of ovarian cancer allowing control of the dynamics of tumor growth and adequate data on its size. As a model Balb/c Nude mouse lines were used. Removal of the mouse ovary with an implanted tumor fragment under the skin made it easier to visualize and to control the dynamics of xenograft growth.

ФГБУ «Национальный медицинский исследовательский центр онкологии» Минздрава России, Ростов-на-Дону, e-mail: katherine_bio@mail.ru Рак толстой кишки является одной из наиболее распространенных форм онкопатологий. Неблагоприятный прогноз связан с тем, что в большинстве впервые диагностированных случаев наблюдается распространенная форма заболевания. Актуальным направлением экспериментальной онкологии представляются разработка новых терапевтических стратегий и оценка противоопухолевых эффектов перспективных лекарственных препаратов. Неотъемлемым инструментом при проведении доклинических испытаний служат PDX-модели рака человека. Целями настоящего исследования явились создание гетеротопической и ортотопической PDX-моделей рака толстой кишки человека, а также оценка приживления и динамики роста в зависимости от сайта имплантации. Убедительно продемонстрирована 75%-ная приживляемость опухолевого материла. Процедура ксенотрансплантации свежерезецированного опухолевого материала от одного из доноров не привела к формированию опухолевых узлов. Рост PDX-моделей характеризовался наличием непродолжительного латентного периода (30–60 дней), сменяющегося экспоненциальной фазой роста. Результаты процедуры лапаротомии убедительно продемонстрировали наличие экзофитного роста и метастатического поражения. Значимых различий показателей приживляемости ксенографтов, имплантируемых в гетеротопический и ортотопический сайты, не наблюдалось. В результате работы не было установлено взаимосвязи показателей приживления и скорости роста от используемых сайтов имплантации. Полученные результаты могут быть связаны с гетерогенностью опухолевых фрагментов и различным количеством опухолевых стволовых клеток, трансплантируемых в организм модельных животных. Ключевые слова: рак толстого кишечника, PDX-модель, ксенотрансплантат, иммунодефицитные мыши, Balb/c nude.

Most cancer drugs used in a clinical setting are insufficiently effective and insufficiently safe. This prompts the search for novel substances to fight cancer. The aim of this study was to explore the effects of dihydrobromide 2-(3,4-dihydroxyphenyl)-9-diethylaminoethylimidazo[1,2-a] benzimidazole (RU-185) on the growth and metastasis of experimentally induced transplantable Lewis lung carcinoma (LLC). Fifty-five C57/Bl6 male mice (weight 18–20 g) were subcutaneously inoculated with LLC cells. The tested substance (0.5 ml) was administered intragastrically at 50, 220, and 500 mg/kg (groups 1, 2 and 3, respectively) once a day for 10 days starting at 48 h after inoculation. The control group received normal saline. Intragastric administration of the tested substance resulted in significantly longer survival in group 2 only (162.3%) and in the significant reduction of tumor size on day 1 after treatment in all groups. After the end of treatment, tumor sizes in groups 2 and 3 were 3.4 and 1.3 times smaller, respectively, on day 7 and 2.2. and 1.3 times smaller, respectively, on day 14 than in the control group (р < 0,05). The growth delay rate was sustained in group 2 by day 14 after the end of treatment; tumor regression was observed in 20% of the animals. The number of metastases in the lungs was lower in groups 1 and 2 than in the control group (2.6 and 3.1-fold, respectively), and the metastasis inhibition was 68.1% and 80%, respectively. The tested substance RU-185 has an anticancer effect in mice: it results in longer survival, slower growth of the primary tumor and fewer lung metastases of Lewis lung carcinoma.

The review provides information on the mechanisms of the antitumor action of natural and synthetic compounds of the tropolone series, obtained over the past 30 years in studies on cell cultures and, to a lesser extent, in in vivo experiments. Interest in this group of substances is due to the urgent need of clinical oncology for drugs that effectively damage malignant cells and, at the same time, are safe for healthy tissues. The processes that realize the effects of colchicine, hinokithiol (ß-tuyaplicin) and some of their derivatives (derivatives of bistropolone, α-substituted tropolones, etc.) have been studied most fully. Herewith, more numerous mechanisms of realization of the antitumor effect of hinokithiol and its derivatives were revealed in comparison with colchicine. In addition to the disruption in the formation of the cell division spindle, shown for colchicine and colchamine, such phenomena as caspase-dependent apoptosis and some other types of apoptosis, autophagy, limitation of mitochondrial metabolism, DNA damage and demethylation, and accelerated aging of malignant cells etc. have been described. The promising properties of 2‑quinolyl 1,3‑tropolone derivatives have been shown, and the relationship of their antitumor effect with the induction of apoptosis and changes in the activity of the ERK signaling pathway in some types of malignant cells have been revealed. The results indicate a multiplicity of possible ways of the influence of tropolones on the state of malignant cells, the conditions for the implementation of ones need to be clarified, especially with a lack of information about in vivo processes.The review includes information from the literature presented in the Scopus, WoS, Pubmed databases. 35 % of articles have been published in the last 5 years.

The issue of factors that modify the tumor process stays relevant. The effect of unilateral sciatic nerve ligation on the growth of Guerin's transplantable carcinoma and the lifespan of white outbred rats of the same age, which differed in adaptation status and aging rates, was studied.Material and Methods. The motor activity (open field test), the character and tension of the general nonspecific adaptional reactions of the body (AR) according to Garkavi–Kvakina–Ukolova, the dynamics of tumor sizes and the lifespan of rats after Guerin’s carcinoma transplantation were evaluated.Results. The effect of unilateral sciatic nerve ligation differed from the unidirectional negative effects known in tumor-bearing animals after bilateral ligation of the sciatic nerve. In groups with unilateral ligation of the sciatic nerve and a false operation, more than 40 % of animals showed an increase in lifespan compared with the maximum lifespan in the control group. At the same time, in the most cases, the tumor growth rate was similar to the control indicators or exceeded them (more 25 % of cases). A temporary inhibition of tumor growth was observed only in individual animals. There was no direct relationship between tumor growth or lifespan and the degree of decrease in the motor activity of animals 4 weeks after nerve ligation. A correlation between the changes in the ARs and lifespans of animals and, to a lesser extent, the dynamics of tumor growth was observed. The distinct negative effect of increased aging rate, measured by animal weight, on tumor development and lifespan in studied rats was shown, but not in the cases of sciatic nerve ligation. Unilateral sciatic nerve ligation had a multidirectional effect on tumor growth and lifespan in rats with different rates of aging, depending, probably, on the individual pain sensitivity and the individual features of systemic regulation of tumor-bearing animals.Conclusion. The results reflect the complex relationship between processes associated with chronic pain, oncogenesis, aging and features of neuroendocrine and immune regulation of experimental animals. The question of the reasons for the preservation of viability in animals that underwent surgery and ligation of the sciatic nerve, when the tumors reach large sizes, exceeding this indicator in the control group, needs to be clarified.

Aim of the study – the development of a method for obtaining a tumor xenograft model by a subcutaneous transplantation of a porous metal scaffold populated with cultured human lung carcinoma cells. Material and methods. The study included 14 athymic male Balb c/nude mice aged 8-90 weeks, weighing 20-24 g. All animals received injections with cultured human A549 lung carcinoma cells subcutaneously into the right anterolateral area of the back. In animals of the main group (gr.1, n=4), scaffolds with a pore diameter of 0.5 mm made of titanium-aluminum-vanadium alloy using an industrial 3D printer served as carriers of tumor cells. Scaffolds were seeded with 3 million A549 culture cells, and were implanted into the recipient animals after the 7-day incubation. Results were compared with the results of the tumor culture transplantation with Matrigel (100 mcL) in two groups of animals with varying cell suspension dosages: the maximum vaccination dose for in vivo (10×106 cells per mouse, gr.2, n=5) and half the maximum dose (5×106 respectively, gr.3, n=5). Then, the dynamics of tumor growth in the groups of experimental mice was monitored for 55 days: xenograft volumes were calculated using the Shrek’s formula for an ellipsoid. At the end of the experiment, the animals were euthanized by cervical dislocation. Results. Monitoring of the dynamics of xenograft volumes demonstrated the maximal values in mice with implanted scaffolds. The slowest xenograft growth was registered in animals with the maximum vaccination dose of tumor cells with Matrigel. Histological study showed that tumor material obtained from all animals corresponded to A549 lung carcinoma. Conclusions. Porous metal scaffolds, previously incubated with A549 culture cells and implanted subcutaneously in athymic Balb c/nude mice, allows obtaining rapidly growing xenografts with histologically confirmed correspondence to the original tumor.

Znachitel'noe chislo primenyaemyh v klinike protivoopuholevyh sredstv nedostatochno effektivno i bezopasno, chto obuslovlivaet poisk novyh lekarstvennyh substancij. Cel' raboty — izuchit' vliyanie digidrobromida 2-(3,4-digidroksifenil)-9-dietilaminoetilimidazo[1,2-a]benzimidazola (RU185) na rost i metastazirovanie perevivaemoj eksperimental'noj opuholi legkogo L'yuis (LLC). LLC privivali 55 mysham-samkam C57/Bl6 massoj 18–20 g podkozhno. Vnutrizheludochnoe (0,5 ml v sut.) vvedenie preparata nachinali cherez 48 ch posle perevivki opuholi 1 raz v sutki 10 dnej v razovyh dozah 50, 220, 500 mg/kg (gruppy 1, 2 i 3 sootvetstvenno). Mysham kontrol'noj gruppy vvodili fiziologicheskij rastvor. Pri vnutrizheludochnom vvedenii substancii proiskhodilo dostovernoe uvelichenie prodolzhitel'nosti zhizni zhivotnyh tol'ko v gruppe 2 (162,3%), a takzhe znachimoe umen'shenie ob"emov opuholi uzhe na 1-e sutki posle okonchaniya lecheniya. Na 7-e i 14-e sutki ot momenta okonchaniya lecheniya razmery opuholi v gruppah 2 i 3 byli snizheny po sravneniyu s kontrol'noj gruppoj v 3,4 i 1,3 raza (na 7-e sutki) i v 2,2 i 1,3 raza (na 14-e sutki) sootvetstvenno (r < 0,05). Indeks tormozheniya rosta opuholi sohranilsya v gruppe 2 k 14-m sutkam posle okonchaniya lecheniya i u 20% zhivotnyh otmechen regress opuholi. CHislo metastazov v legkih v gruppah 1 i 2 bylo snizheno otnositel'no kontrolya v 2,6 i 3,1 raza sootvetstvenno, a indeks ingibirovaniya metastazirovaniya sostavil 68,1 i 80% sootvetstvenno. Issledovannyj RU-185 okazyvaet protivoopuholevoe dejstvie, chto vyrazheno v uvelichenii prodolzhitel'nosti zhizni zhivotnyh, snizhenii skorosti rosta pervichnoj opuholi, a takzhe chastoty razvitiya i kolichestva legochnyh metastazov eksperimental'noj epidermoidnoj karcinomy legkogo L'yuis myshej.

НЕКОТОРЫЕ ДОЗОЗАВИСИМЫЕ ЭФФЕКТЫ НОВОГО ПРОИЗВОДНОГО ТРОПОЛОНОВОГО РЯДА, 2-(6,8-ДИМЕТИЛ-5-НИТРО-4-ХЛОРХИНОЛИН-2-ИЛ)-5,6,7-ТРИХЛОР-1,3-ТРОПОЛОНА, У МЫШЕЙ ЛИНИИ BALB/C NUDE ПРИ ЕГО ОДНОКРАТНОМ ПРИЕМЕ Жукова Г.В. 1 , Минкин В.И. 2 , Гончарова А.С. 1 , Шевченко А.Н. 1 , Лукбанова Е.А. 1 , Саяпин Ю.А. 3 , Гусаков Е.А. 2 , Миндарь М.В. 1 , Заикина Е.В. 1 , Курбанова Л.З. 1 , Волкова А.В. 1 , Ходакова Д.В. 1 , Пандова О

Purpose of the study. Was to assess diagnostic informative value of liquid-based cytology optimized with genetic methods for the differential diagnosis of precancerous and malignant diseases of the cervix.Materials and methods. The study included 381 patients. Cervical pathologies were diagnosed with liquid-based cytology only and liquid-based cytology optimized with genetic methods of assessing the expression of miRNA‑20a, miRNA‑375, miRNA‑21 and –23b. Results of liquid-based cytology and genetic methods were verified by histological examination of the material. Statistical analysis was performed using descriptive statistics methods with the calculation of the mean and standard error of the mean. The mean values were compared with the help of the Mann-Whitney test.Results. Diagnostic results of liquid-based cytology were consistent with histological results in 107 (73.8 %) of 145 cervical cancer (CC) patients, in 52 (57.1 %) of 91 patients with high-grade squamous intraepithelial lesions (HSIL), and in 30 (65.2 %) of 46 patients with low-grade squamous intraepithelial lesions (LSIL). Optimization of liquid-based cytology by assessing the expression of miRNA‑21 and miRNA‑23b in the cervical epithelium improved the diagnostic sensitivity of the method from 73.8 % to 80 %, and its specificity from 94.1 % to 97.9 %. The diagnostic sensitivity and specificity of liquid-based cytology for differential diagnosis of CC and HSIL was 87 % and 78.8 %, respectively. Optimization of liquidbased cytology by assessing the expression of miRNA‑20a and miRNA‑375 in the cervical epithelium for the differential diagnosis of CC and HSIL improved the diagnostic sensitivity of the method from 87 % to 95.1 %, and its specificity from 78.8 % to 93.9 %.Conclusions. We revealed the most informative pairs of miRNAs in the cervical epithelium, as an analysis of their expression expanded the possibilities of liquid-based cytology both as a method for diagnosing CC and as a method for the differential diagnosis between CC and HSIL.