Бібліотека Вінницького національного медичного університету ім. М.І.Пирогова

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Antitumor and genotoxic effects of lactoferrin in Walker-256 tumor-bearing rats [Text] / V. F. Chekhun [та ін.] // Экспериментальная онкология. - 2018. - Т. 40, № 3. - С. 200-204. - Bibliogr. at the end of the art.

Annotation: To investigate the influence of exogenous lactoferrin (LF) on tumor growth, energy and lipid metabolism of Walker-256 carcinosarcoma and to assess genotoxic effects of LF. Materials and Methods: The study was performed on Walker-256 tumor-bearing rats. Total lipids and phospholipids were determined by thin-layer chromatography. Comet assay was used to investigate the genotoxic effects of LF. Results: Daily i.p. administrations of exogenous LF at concentrations of 1 mg/kg and 10 mg/kg starting from the 4th day after tumor transplantation suppressed growth of Walker-256 carcinosarcoma by almost 44%. After treatment with recombinant LF in both doses, the phospholipid composition of Walker-256 carcinosarcoma cells was changed (3-fold increase of phosphatidylethanolamine, 3.4-fold increase of phosphatidylcholine, and 1.8-fold increase of sphingomyelin, while the cardiolipin content decreased by 67%. Exogenous LF was not genotoxic for bone marrow cells (as assessed by the ratio of PCE/NCE, number of micronuclei) and peripheral blood lymphocytes (percentage of DNA in the tail of a comet) in Walker-256 carcinosarcoma-bearing rats. Conclusion: Exogenous LF caused the inhibition of Walker-256 carcinosarcoma growth and a decrease in the microviscosity of plasma cell membranes, and exerted no genotoxicity toward bone marrow cells and peripheral blood of experimental animals. Key Words: lactoferrin, breast cancer, Walker-256 carcinosarcoma, phospholipid content, genotoxicity
Additional Access Points:
Chekhun, V. F.
Storchai, D. M.
Todor, I. N.
Borikun, T. V.
Lukianova, N. Yu.

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Artemisinin modulating effect on human breast cancer cell lines with different sensitivity to cytostatics / V. F. Chekhun [et al.] // Experimental Oncology. - 2017. - Том 39, N 1. - P25-29 : табл. - 21 ref.

MeSH-main:
МОЛОЧНОЙ ЖЕЛЕЗЫ НОВООБРАЗОВАНИЯ -- BREAST NEOPLASMS (лекарственная терапия)
АРТЕМИЗИНИНЫ -- ARTEMISININS
ЛЕКАРСТВЕННАЯ УСТОЙЧИВОСТЬ -- DRUG RESISTANCE
Annotation: To explore effects of Artemisinin on a series of breast cancer cells with different sensitivity to typical cytotoxic drugs (doxorubicin — Dox; cisplatin — DDP) and to investigate possible artemisinin-induced modification of the mechanisms of drug resistance. Materials and Methods: The study was performed on wild-type breast cancer MCF-7 cell line (MCF-7/S) and its two sublines MCF-7/Dox and MCF-7/DDP resistant to Dox and DDP, respectively. The cells were treated with artemisinin and iron-containing magnetic fluid. The latter was added to modulate iron levels in the cells and explore its role in artemisinin-induced effects. The MTT assay was used to monitor cell viability, whereas changes of expression of selected proteins participating in regulation of cellular iron homeostasis were estimated using immunocytochemical methods. Finally, relative expression levels of miRNA-200b, -320a, and -34a were examined by using qRT-PCR. Results: Artemisinin affects mechanisms of the resistance of breast cancer cells towards both Dox and DDP at sub-toxic doses. The former drug induces changes of expression of iron-regulating proteins via different mechanisms, including epigenetic regulation. Particularly, the disturbances in ferritin heavy chain 1, lactoferrin, hepcidin (decrease) and ferroportin (increase) expression (р ≤ 0.05) were established. The most enhanced increase of miRNA expression under artemisinin influence were found for miRNA-200b in MCF-7/DDP cells (7.1 ± 0.98 fold change), miRNA-320a in MCF-7/Dox cells (2.9 ± 0.45 fold change) and miRNA-34a (1.7 ± 0.15 fold change) in MCF-7/S cells. It was observed that the sensitivity to artemisinin can be influenced by changing iron levels in cells. Conclusions: Artemisinin can modify iron metabolism of breast cancer cells by its cytotoxic effect, but also by inducing changes in expression of iron-regulating proteins and microRNAs (miRNAs), involved in their regulation. This modification affects the mechanisms that are implicated in drug-resistance, that makes artemisinin a perspective modulator of cell sensitivity towards chemotherapeutic agents in cancer treatment
Additional Access Points:
Chekhun, V.F.
Lukianova, N.Y.
Borikun, T.V.
Zadvornyi, T.V.
Mokhir, A.

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Association of CD44⁺CD24^-/low with markers of aggressiveness and plasticity of cell lines and tumors of patients with breast cancer [Text] / V. F. Chekhun [та ін.] // Экспериментальная онкология. - 2017. - Т. 39, № 3. - С. 203-211. - Bibliogr. at the end of the art.

MeSH-main:
МОЛОЧНОЙ ЖЕЛЕЗЫ НОВООБРАЗОВАНИЯ -- BREAST NEOPLASMS (осложнения, патофизиология, этиология)
НОВООБРАЗОВАНИЙ МАРКЕРЫ БИОЛОГИЧЕСКИЕ -- TUMOR MARKERS, BIOLOGICAL (анализ)
ЦИТОСТАТИЧЕСКИЕ СРЕДСТВА -- CYTOSTATIC AGENTS (анализ, терапевтическое применение)
ЛЕКАРСТВЕННАЯ УСТОЙЧИВОСТЬ НОВООБРАЗОВАНИЙ -- DRUG RESISTANCE, NEOPLASM (физиология)
СТАТИСТИЧЕСКАЯ ОБРАБОТКА ДАННЫХ -- DATA INTERPRETATION, STATISTICAL
Annotation: To search for additional molecular-biological markers of cancer stem cell (CSC) involved in the development of intra-tumor heterogeneity for the detection of features of the breast cancer (BC) pathogenesis. Materials and methods: Expression of estrogen receptors (ER), progesterone receptors (PR), Her2/neu, E- and N-cadherin, CD24, CD44, Bcl-2, Bax, Slug, P-gp, glutathione-S-transferase (GST) and metallothionein in cell lines was determined by the immunocytochemical method. Expression of ER, PR, Her2/neu, CD24 and CD44 in the surgical material of BC patients were determined by the immunohistochemical method. The levels of the miRNA were determined using real-time polymerase chain reaction. Results: Cells of high-grade malignancy (HGM), MDA-MB-231 and MDA-MB-468 are characterized by high expression of stem cell markers compared to the cells of low-grade malignancy (LGM), T47D and MCF-7: CD44 levels in T47D and MCF-7 cells were in range of 72-79 points, which is significantly lower than in HGM cells (p 0.05). Also, HGM cells with the properties of CSC were characterized by high expression of antiapoptotic proteins, the transcription factor Slug, and low levels of proapoptotic protein Bax (p 0.05) compared to LGM cells. In cells with CSC characteristics an increased expression of transferrin and its receptor, ferritin, fentorin and hepcidin was revealed indicating activation of the endogenous iron metabolism. The characteristic feature of HGM cells with CSC phenotype were the increased levels of oncogenic miR-221, -155 and -10b by 60%, 92% and 78%, respectively, and decreased levels of oncosuppressive miR-29b, -34a and -200b by 8.4 ± 0.3, 4.6 ± 0.2, and 3.4 ± 0.6 times compared to MCF-7 line cells. It has been established that the development of resistance to cytostatics is accompanied by increased aggressiveness of tumor cells, loss of expression of hormonal receptors and acquiring of stem phenotype. In particular, increased expression of P-gp was observed in BC cells during the development of resistance to doxorubicin, of GST during the development of resistance to cisplatin along with increased CD44 expression (p 0.05). We have revealed the relation between the presence of cells with the CSC phenotype (CD44+CD24-/low) and clinical and pathological characteristics of BC patients, their survival and BC sensitivity to neoadjuvant therapy (p > 0.05). Conclusions: The dependence between the expression of CSC markers and the degree of malignancy of tumor cells, development of resistance to cytostatics in vitro was established as well as the predictive value of the detection of the CSC for the individual prognosis of the BC course and sensitivity of the tumors to the treatment
Additional Access Points:
Chekhun, V. F.
Lukianova, N. Y.
Chekhun, S. V.
Bezdieniezhnykh, N. O.
Zadvomiy, T. V.
Borikun, T. V.
Polishchuk, L. Z.
Klyusov, O. M.

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Boroday, N. V.
Morphological features of doxorubicin-resistant Walker 256 carcinosarcoma and response of mast cells [Text] / N. V. Boroday, V. F. Chekhun // Экспериментальная онкология. - 2018. - Т. 40, № 1. - С. 42-47. - Bibliogr. at the end of the art.

MeSH-main:
КАРЦИНОМА 256 УОКЕРА -- CARCINOMA 256, WALKER (осложнения, патофизиология, терапия, ультраструктура, этиология)
ЛЕКАРСТВЕННАЯ УСТОЙЧИВОСТЬ НОВООБРАЗОВАНИЙ -- DRUG RESISTANCE, NEOPLASM (физиология)
ТУЧНЫЕ КЛЕТКИ -- MAST CELLS (ультраструктура, физиология)
ДОКСОРУБИЦИН -- DOXORUBICIN (анализ)
СТАТИСТИЧЕСКАЯ ОБРАБОТКА ДАННЫХ -- DATA INTERPRETATION, STATISTICAL
ФОТОГРАФИЧЕСКИЕ СНИМКИ -- PHOTOGRAPHS
Annotation: The mechanisms of drug resistance of cancer have not been yet elucidated in details. Recently, the role of mast cells (MCs) in the development of drug resistance has been brought in the limelight. The aim of the study was to examine the morphological features of doxorubicin (DOX)-resistant Walker 256 carcinosarcoma and to assess the response of MCs and histamine content in these cells in relation to the development of resistance to DOX as well as in DOX-resistant tumors. Materials and Methods: The DOX resistance was induced by serial passages of Walker 256 carcinosarcoma in rats in the setting of DOX treatment in vivo. MCs in tumors were detected in the sections by staining with Toluidine Blue O. Histamine content in MCs stained with solution of Water Blue-Orcein was assessed by Astaldi semiquantitative method taking into account different staining intensity. Results: Formation of DOX resistance in the course of serial passages of Walker 256 carcinosarcoma was accompanied by the increase in the number of MCs in tumors and histamine content. Nevertheless, in tumors with phenotype of complete DOX resistance the number of histamine-containing MCs decreased to the same level as in tumors of the original strain that are DOX-sensitive. Conclusion: MCs are involved in formation of DOX resistance in Walker 256 carcinosarcoma
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Chekhun, V. F.

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Chekhun, V. F.
Can SARS-CJV-2 change individual radiation sensitivity of the patients recovered from COVID-19? (experimental and theoretical backlground) / V. F. Chekhun, E. A. Domina // Experimental Oncology. - 2021. - Том 43, N 3. - P277-280

MeSH-main:
КОРОНАВИРУСНЫЕ ИНФЕКЦИИ -- CORONAVIRUS INFECTIONS (осложнения)
РАДИОТОЛЕРАНТНОСТЬ -- RADIATION TOLERANCE
Annotation: R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology of the National Academy of Science of Ukraine has been studying the mechanisms and specificities of individual radiation sensitivity (IRS) formation in professionals who work in the field of ionizing radiation, cancer patients and representatives of other population groups. Our data based on the use of G2-test in in vitro irradiated blood lymphocytes in late G2-period of cell cycle indicated an increased carcinogenic risk in professionals with high IRS. We suggest that the COVID-19 pandemic could make significant adjustments in the formation of IRS in professionals who have survived the disease and continue to work with ionizing radiation (IR). Increased systemic inflammatory activity, which persists for a long time in COVID-19 patients, in combination with low-dose range irradiation (professionals who continue to work with IR) and with local irradiation in the high-dose range (radiation therapy for cancer patients) may affect IRS. Repeated determination of IRS in professionals who have had COVID-19 infection, using chromosomal G2-radiation sensitivity assay will answer the question: can SARS-CoV-2 coronavirus affect the IRS? The proposed hypothesis of the radiosensitivity evolution needs further experimental validation using a set of radiobiological indices to clarify the mechanism of IRS formation following COVID-19 infection. The detected changes (increase) of human IRS after COVID-19 must be taken into account for personalized planning of radiotherapy of COVID-19 cancer patients
Additional Access Points:
Domina, E. A.

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Chekhun, V. F.
MicroRNAs are a key factor in the globalization of tumor-host relationships [Text] / V. F. Chekhun // Экспериментальная онкология. - 2019. - Т. 41, № 3. - С. 188-194. - Bibliogr. at the end of the art.

Annotation: A new round of molecular oncology development in the post-genomic era significantly changes the conventional understanding of the nature and origin of the malignant process. Increasingly, fundamental phenomena are emerging that change the “canonical” views of the dominant role of gene mutations that contribute to the uncontrolled proliferation and emergence of heterogeneous malignant cells. Recent numerous studies have shown that significant variability in the initiation, proliferation and control of the apoptotic program of tumor cells is due to numerous epigenetic processes, including the level of expression of microRNAs (miRNAs). This paper reviews the literature data and presents the results of own research in which miRNAs have been found to form a molecular phenotype for malignancy. Their role as a “conductor” of the functioning of a genetic-epigenetic orchestra that coordinates various aspects of malignancy has been suggested. MiRNAs have been shown to be an active participant in balancing mechanisms in the development of controversial processes in breast cancer cell lines of varying degrees of malignancy. The analysis of the literature data and the own studies of the expression profile of only a few miRNAs suggests that scientists and clinicians have received a new marker and a target that simultaneously plays the role of an active insider in both the oncogene-oncosuppressor relationship and in the globalization of this process at the tumor-host level. Further investigation of the “alarm” marker in this network will allow to reconsider the molecular genetic classification of neoplastic disease, which will provide the development of a new strategy for cancer therapy
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Chekhun, V. F.
On the 40th anniversary of the international symposium “The role of stem cells in leukemo-and carcinogenesis»: in Kyiv again [Text] / V. F. Chekhun // Экспериментальная онкология. - 2017. - Т. 39, № 3. - С. 162-163

MeSH-main:
ЮБИЛЕИ И ДРУГИЕ ВАЖНЫЕ СОБЫТИЯ -- ANNIVERSARIES AND SPECIAL EVENTS
СЪЕЗДЫ, СИМПОЗИУМЫ -- CONVENTIONS, SYMPOSIUMS
СТВОЛОВЫЕ КЛЕТКИ -- STEM CELLS
НЕОПЛАСТИЧЕСКИЕ ПРОЦЕССЫ -- NEOPLASTIC PROCESSES
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Chekhun, V. F.
Significance of iodine symporter for prognosis of the disease course and efficacy of neoadjuvant chemotherapy in patients with breast cancer of luminal and basal subtypes / V. F. Chekhun, A. V. Andriiv, N. Yu. Lukianova // Experimental Oncology. - 2017. - Том 39, N 1. - P65-68 : табл. - 16 ref.

MeSH-main:
МОЛОЧНОЙ ЖЕЛЕЗЫ НОВООБРАЗОВАНИЯ -- BREAST NEOPLASMS (лекарственная терапия)
ХИМИОТЕРАПИЯ АДЪЮВАНТНАЯ -- CHEMOTHERAPY, ADJUVANT
СИМПОРТЕРЫ -- SYMPORTERS
Annotation: The aim of the research was to study the relation between expression of Na⁺/I⁻symporter (NIS) in breast cancer (BC) of different molecular subtypes and sensitivity of BC cells to neoadjuvant chemotherapy (NACT) and to assess whether NIS expression may be used as a predictive marker of treatment efficacy. Materials and Methods: The study included 148 women with BC of stage II–III who were treated at the Precarpathian Clinical Oncology Center during 2012–2017. All patients were treated with NACT that included 2–6 cycles of chemotherapy by FAC, AC scheme with 21 day intervals. NACT efficacy was evaluated every 2 cycles by mammography according to RECIST criteria. Morphological and immunohistochemical study of NIS expression was performed by the standard methods on paraffin sections of surgically resected tumors. Results: The heterogeneity of different molecular BC subtypes regarding response to the NACT has been found. Her2/neu-positive and basal BC subtypes were the least susceptible to the NACT (p 0.05). It was shown that NIS expression is related to the sensitivity of luminal B and basal BC subtypes to the NACT. The highest expression of NIS and impairment of its functional activity was registered in the group of patients with tumors resistant to NACT (stabilization of the disease or its progression) of luminal B (220 ± 8.6 points) and basal subtypes (290 ± 11.3 points) (p 0.05). It was revealed that the disease-free survival of patients with BC of luminal B and basal subtypes was higher in the absence of NIS expression in tumor cells (p 0.05). Conclusions: The results indicate that NIS can be used as an objective criterion for predicting the sensitivity of luminal B and basal BC subtypes to NACT, which will provide improved treatment outcomes in this group of patients
Additional Access Points:
Andriiv, A.V.
Lukianova, N.Yu.

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Complexes of palladium(II) with 1-phenyl-1-hydroxymethylene bisphosphonic acid and their antitumor activity / O. M. Kozachkova [et al.] // The Ukrainian Biochemical Journal. - 2017. - Том 89, N 2. - P106-115

MeSH-main:
ПРОТИВООПУХОЛЕВЫЕ СРЕДСТВА -- ANTINEOPLASTIC AGENTS (терапевтическое применение)
ПАЛЛАДИЙ -- PALLADIUM (терапевтическое применение)
Annotation: Complex formation of K₂[PdCl₄] with 1-phenyl-1-hydroxymethylene bisphosphonic acid (PhHMBP, H₄L) has been studied by pH potentiometry, electron and NMR spectroscopy. It was found that in aqueous solution with physiological concentration of chlorine anions (0.15 mol/l KCl), anionic complexes of the equimolar compositions [PdHLCl₂]^3- (lgβ = 24.51 (0.3)) and [PdLCl₂]^4-(lgβ = 20.74 (0.02)) are formed. In the first coordination sphere palladium was surrounded by two oxygen atoms of two phosphonic groups of the bidentately coordinated ligand with closure of six-membered [O, O] ring, and two chlorine anions. The formation of palladium(II) equimolar complexes with PhHMBP and bidentate coordination of the ligand to the central metal cation was confirmed by³¹P NMR spectroscopy. Cytotoxic activity (IC₅₀ based on metal content) of the synthesized Pd(II) complexes with PhHMBP against human MG-63 osteosarcoma and MCF-7 mammary tumor cells was compared with cisplatin on in vitro models. It was established that cytotoxic activity of the Pd complexes was lower than that of cisplatin. The acute toxicity (LD₅₀ based on metal content) of solutions of Pd(II) complexes with PhHMBP was found to be lower compared to cisplatin. It was shown that the use of solutions of palladium(II) complexes with PhHMBP inhibited tumor growth in mice with sarcoma 180
Additional Access Points:
Kozachkova, O. M.
Tsaryk, N. V.
Trachevskyi, V. V.
Rozhenko, A. B.
Shermolovich, Yu. H.
Guzyr, O. I.
Sharykina, N. I.
Chekhun, V. F.
Pekhnyo, V. I.

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10.

Effects of exogenous lactoferrin on phenotypic profile and invasiveness of human prostate cancer cells (DU145 and LNCaP) in vitro [Text] / T. V. Zadvornyi [та ін.] // Экспериментальная онкология. - 2018. - Т. 40, № 3. - С. 184-189. - Bibliogr. at the end of the art.

Annotation: To investigate the biological effects of exogenous lactoferrin (LF) on phenotypic profile and invasiveness of human prostate cancer (PC) cells in vitro. Materials and Methods: Human PC cell lines (LNCaP, DU-145) were cultured with an exogenous LF at a dose corresponding to IC30. The expression levels of steroid hormone receptors (androgen receptor, estrogen receptor, progesterone receptor), Her2/neu, Ki-67, E- and N-cadherin, were monitored by immunohistochemical analysis. The levels of miRNAs were assessed using q-PCR. The invasive activity of the cells was examined in a standard invasion test. Results: Exogenous LF reduced expression of steroid hormone receptors (ERα and PR) and Ki-67 in both PC cell lines. The expression of E-cadherin increased significantly in LF-treated DU-145 cells. Also, we established the decrease in invasive activity upon LF treatment by 40% and 30% in DU-145 and LNCaP cells, respectively. In DU-145 cells, incubation with exogenous LF resulted in an increase in the expression of oncosuppressive (miR-133a and miR-200b) miRNAs. Conclusions: Exogenous LF causes the changes in phenotypic characteristics of PC cells and levels of oncogenic and oncosuppressive miRNAs involved in the regulation of key cellular processes. Key Words: prostate cancer, exogenous lactoferrin, DU145, LNCaP, miRNA
Additional Access Points:
Zadvornyi, T. V.
Lukianova, N. Y.
Borikun, T. V.
Chekhun, V. F.

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11.

Grybach, S. M.
Analysis of the survival of patients with breast cancer depending on age, molecular subtype of tumor and metabolic syndrome [Text] / S. M. Grybach, L. Z. Polishchuk, V. F. Chekhun // Экспериментальная онкология. - 2018. - Т. 40, № 3. - С. 243-248. - Bibliogr. at the end of the art.

Annotation: To analyze the survival of patients with breast cancer (BC) depending on age, molecular subtype of the tumor and the presence of metabolic syndrome. Patients and Methods: We have analyzed the results of examination and treatment of 202 patients with BC of stages I–III. The patients were distributed by age into 2 groups. The group 1 included 86 elderly patients (from 65 to 84 years old), the group 2 — 116 younger patients (from 32 to 64 years). An overall 1-, 3- and 5-year survival rates of the treated patients were assessed. The significance of factors influencing the overall survival (OS) of patients with BC was determined using the methods of statistical analysis. Results: Molecular subtype of BC significantly affects survival rates: in a case of a luminal B subtype the 5-year OS was 71.6 vs 80% (p 0.05) in groups 1 and 2, respectively while in a case of a basal-like subtype it was 60.2% and 71.6% (p 0.05). The presence of metabolic syndrome significantly reduced the 5-year OS (up to 70.7% and 80.6%, p 0.05 in groups 1 and 2, respectively). Conclusion: The OS is lower in elderly patients with BC compared with younger patients, especially in those who suffer from metabolic syndrome. Key Words: breast cancer, elderly age, metabolic syndrome, receptor status, 1-, 3-, 5-year overall survival
Additional Access Points:
Polishchuk, L. Z.
Chekhun, V. F.

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12.

Influence of bacterial lectin on key regulatory links of functional activity of macrophages in mice with Ehrlich carcinoma / A. V. Chumak [et al.] // Experimental Oncology. - 2021. - Том 43, N 3. - P197-203

MeSH-main:
КАРЦИНОМА, ЭРЛИХА ОПУХОЛЬ -- CARCINOMA, EHRLICH TUMOR (лекарственная терапия)
ИММУНОТЕРАПИЯ -- IMMUNOTHERAPY (использование, методы)
МАКРОФАГИ -- MACROPHAGES (действие лекарственных препаратов)
ЭУКАРИОТЫ -- EUKARYOTA
Annotation: Recent studies have shown the potential of using different approaches for immunotherapy in cancer treatment. Macrophages (Mph) are one of the promising targets for immunotherapy. Aim: To investigate changes in the functional activity of Mph in mice with Ehrlich carcinoma by nitric oxide (NO)/arginase (Arg), IRF4/IRF5 and STAT1/STAT6 ratios caused by administration of lectin from B. subtilis IMV-7724. Materials and Methods: From the 2nd day after Ehrlich carcinoma inoculation into female Balb/c mice, lectin from B. subtilis IMV B-7724 (0.02 mg/mouse) was administered for 10 days. The peritoneal Mph were isolated on days 14, 21, and 28 after tumor transplantation and their functional state (NO production, Arg activity and cytotoxic activity) was examined. The levels of mRNA expression of transcription factors STAT-1, STAT-6, IRF5, IRF4 were evaluated. Results: In lectin-treated animals with Ehrlich carcinoma, the functional state of Mph (NO/Arg ratio, index of cytotoxic activity) was maintained at the level of intact mice exceeding the values in untreated animals with Ehrlich carcinoma at late terms of tumor growth (21, 28 days). Analysis of mRNA expression levels of transcription factors in these animals showed a significant increase (p 0.05) in the ratio of STAT1/STAT6 on the day 21 and IRF5/IRF4 on day 28 of tumor growth compared to that in untreated mice. Conclusions: Administration of lectin from B. subtilis IMV B-7724 to mice with Ehrlich carcinoma led to the prevalence of Mph exhibiting the functional properties of M1 type at late-term tumor growth. The transcription factors of the STAT and IRF signaling pathways are involved in the process of Mph polarization induced by lectin from B. subtilis IMV B-7724
Additional Access Points:
Chumak, A. V.
Fedosova, N. I.
Shcherbina, V. M.
Cheremshenko, N. L.
Karaman, O. M.
Chekhun, V. F.

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13.

Influence of ferromagnetic nanocomposite (ferroplat) on human breast cancer cells of different malignancy degrees: pro/antioxidant balance and energy metabolism / V. F. Chekhun [et al.] // Experimental Oncology. - 2018. - Том 40, N 4. - P268-274

MeSH-main:
МОЛОЧНОЙ ЖЕЛЕЗЫ НОВООБРАЗОВАНИЯ -- BREAST NEOPLASMS (метаболизм, патофизиология)
Annotation: To study the effect of Ferroplat (FrP) on the indexes of pro/antioxidant balance and energy metabolism in breast cancer cells of different malignancy degree and different sensitivity to drug therapy. Materials and Methods: The study was carried out on breast cancer cells of low (T47D, MCF-7) and high malignancy degree (MCF-7/DDP (cisplatin-resistant), MDA-MB-231, MDA-MB-468) using cell culture techniques, immunocytochemical, biochemical, biophysical methods, flow cytometry and polarography. Results: We established that the addition of FrP to the culture medium reduces the activity of glucose-6-phosphate dehydrogenase (G6PDH), superoxide dismutase (SOD) and the level of non-protein thiols by 32–41% (p 0.05). At the same time, there was an increase of the total level of ROS and the rate of NO generation by inducible NO synthase by 1.7–2.5 times (p 0.05). This testifies that FrP disturbs the antioxidant balance in cells, resulting in their death. Also, the use of FrP led to a decrease in the rate of oxygen absorption in MCF-7 and T47D cells by 26% and 25%, respectively (p 0.05). In cells of high malignancy degree this index decreased by 38–40% under the influence of FrP. Incubation of MCF-7 and T47D cells with the indicated agent also reduced the content of phospholipid cardiolipin by 15–16% (p 0.05), and in MDA-MB-231, MCF-7/DDP, MDA-MB-468 cells — by 29%, 30% and 32%, respectively. In addition, the effect of FrP caused a decrease in the levels of Mg2+ and lactate in MCF-7 and T47D cells by 21–29% and 14–24%, respectively, whereas in MDA-MB-231, MDA-MB-468, MCF-7/DDP cells — by 34–38% and 32–35%, respectively. In this case, the agent raised the level of glucose in the cells of low malignancy degree by 20–23% (p 0.05), and in the cells of high malignancy degree and with the phenotype of drug resistance — by 31–36%. However, the nanocomposite did not affect the activity of lactate dehydrogenase in all studied breast cancer cells. Conclusion: The study has shown that FrP has an effect on the pro/antioxidant balance and energy metabolism of cancer cells. In addition, the denoted effect of FrP was more pronounced in the breast cancer cells with a high malignancy degree and the phenotype of drug resistance
Additional Access Points:
Chekhun, V. F.
Todor, I. N.
Lukianova, N. Yu.
Horbyk, D. M.
Lozovskaya, Yu. V.
Burlaka, A. P.
Borikun, T. V.

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14.

Karaman, O. M.
Macrophages - a perspective target for antineoplastic immunotherapy / O. M. Karaman, A. V. Ivanchenko, V. F. Chekhun // Experimental Oncology. - 2019. - Том 41, N 4. - P282-290

Annotation: The review discusses the data on the functional/phenotypic M1/M2 types of macrophages and their chimeric forms, the molecular mechanisms of polarization of these cells, and their role in the development of malignant tumors. Information on the prognostic value of the presence (density and location) of M1/M2 cells in tumor tissue is analyzed. Our own results evidence on the necessity of determination of the functional/phenotypic state of M1/M2 macrophages from different biological niches in the dynamics of tumor growth, in particular in terms of NO level and arginase activity
Additional Access Points:
Ivanchenko, A. V.
Chekhun, V. F.

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15.

Lukianova, N. Yu.
Tumor microenvironment-derived miRNAs as prognostic markers of breast cancer [Text] / N. Yu. Lukianova, T. V. Borikun, V. F. Chekhun // Экспериментальная онкология. - 2019. - Т. 41, № 3. - С. 242-247. - Bibliogr. at the end of the art.

Annotation: To study expression of miRNA derived from tumor microenvironment in patients with breast cancer (BC) as the aspect of tumor-host interaction. Materials and Methods: The expression levels of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 (HER2/neu) were analyzed in tissue of BC using immunohistochemical method. Relative expression levels of the miR-155, -320a, and -205 were examined in tissue and sera from BC patients using quantitative reverse transcription polymerase chain reaction. Results: Serum and tissue miR-155, -320a, and -205 levels in patients with BC are of low diagnostic value as such for differentiation of malignant and non-malignant breast neoplasms. Nevertheless, we established the relation of circulating and tissue miR-155, -320a, and -205 to lymph node metastases and basal breast cancer subtype. Conclusions: Changes of miR-155, -320a, and -205 expression in tumor tissue and sera of BC patients provide information about major clinical-pathological characteristics of BC
Additional Access Points:
Borikun, T.V.
Chekhun, V. F.

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16.

Macrophage polarization in dynamics of Lewis lung carcinoma growth and metastasis [Text] = Зміни поляризації макрофагів у динаміці росту метастазуючої карциноми Льюїс / A. V. Chumak [та ін.] // Экспериментальная онкология. - 2021. - Т. 43, № 1. - P15-20. - Bibliogr. at the end of the art.

MeSH-main:
КАРЦИНОМА ЛЬЮИС ЛЕГКОГО -- CARCINOMA, LEWIS LUNG
НОВООБРАЗОВАНИЙ МЕТАСТАЗЫ -- NEOPLASM METASTASIS (патология)
МОДЕЛИ НА ЖИВОТНЫХ -- MODELS, ANIMAL
Annotation: To assess the functional state of macrophages based on various manifestations of their activity at the different stages of metastatic tumor growth in C57Bl mice. Materials and Methods: On days 7, 14, 21 and 28 after Lewis lung carcinoma transplantation to C57Bl mice, macrophages from various anatomic sites were isolated and tested on their cytotoxicity, metabolic activity, NO production and arginase activity. Results: In the populations of peritoneal and splenic macrophages, on days 7 and 21 of tumor growth antitumor (M1) cells prevailed while on days 14 and 28 tumor-promoting (M2) macrophages predominated. In the population of lung macrophages, cells with M1 phenotype were in the majority in the early stages of tumor growth. On days 21 and 28, M1 cells were gradually substituted by cells exhibiting M2 phenotype. This shift correlated with metastasis to lungs. Conclusion: Lewis lung carcinoma growth is accompanied by the gradual change in macrophage polarization from antitumor (M1) towards tumor-promoting (M2) type. These changes were more evident in population of lung macrophages and correlated with the parameters of metastasis
Оцінити стан макрофагів мишей лінії С57Вl за різними проявами їх функціональної активності на різних стадіях росту метастазуючої пухлини. Матеріали та методи: У дослідженні використовували мишей лінії C57Bl з епідермоїдною метастазуючою карциномою легені Льюїс. На 7-, 14-, 21- та 28-й день після перещеплення пухлини макрофаги з різних ніш були виділені та піддані функціональному аналізу. Результати: Макрофаги, отримані з різних біологічних ніш у інтактних тварин, за дослідженими показниками функціональної активності мали фенотип М1. У популяціях макрофагів, отриманих з селезінки та перитонеальної порожнини мишей лінії С57Вl на 7-і 21-шу доби росту карциноми легені Льюїс переважали клітини з протипухлинними властивостями (М1), на 14- та 28-му добу — клітини з пропухлинними властивостями (М2). У популяції легеневих макрофагів на ранніх стадіях пухлинного процесу переважали клітини з фенотипом М1, до 28-ї доби спостерігали поступову їх поляризацію до фенотипу М2. Такі зміни корелювали з показниками метастазування в легені в ці терміни. Висновок: Aналіз показників функціональної активності макрофагів свідчить про їх поступову поляризацію від клітин з проти- (М1) до клітин з пропухлинними (М2) властивостями в динаміці росту карциноми легені Льюїс. Виявлені зміни були найбільш вираженими в популяції легеневих макрофагів та мали кореляційний зв’язок з показниками метастазування
Additional Access Points:
Chumak, A. V.
Fedosova, N.I.
Cheremshenko, N. L.
Symchych, T. V.
Voyeykova, I. M.
Chekhun, V. F.

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17.

Molecular-genetic models for prognosis of development of tumors of reproductive system in women with family history of cancer [Text] / O. V. Paliychuk [та ін.] // Экспериментальная онкология. - 2018. - Т. 40, № 1. - С. 59-67. - Bibliogr. at the end of the art.

MeSH-main:
НОВООБРАЗОВАНИЯ -- NEOPLASMS (врожденный)
РЕПРОДУКТИВНОЕ ЗДОРОВЬЕ -- REPRODUCTIVE HEALTH (тенденции)
ЖЕНЩИН ЗДОРОВЬЕ -- WOMEN'S HEALTH (тенденции)
ЛИНЧА СИНДРОМ II -- LYNCH SYNDROME II (диагностика, патофизиология, этиология)
ГЕНЫ СУПРЕССОРЫ ОПУХОЛЕВОГО РОСТА -- GENES, TUMOR SUPPRESSOR
ГЕНЫ BRCA1 -- GENES, BRCA1 (физиология)
ГЕНЫ BRCA2 -- GENES, BRCA2 (физиология)
МУТАЦИЯ -- MUTATION (физиология)
РИСКА СТЕПЕНИ ОЦЕНКА -- RISK ADJUSTMENT (использование, статистика, тенденции)
СТАТИСТИЧЕСКАЯ ОБРАБОТКА ДАННЫХ -- DATA INTERPRETATION, STATISTICAL
Annotation: To develop a prognostic molecular genetic model for assessing the risk of development of benign and malignant tumors of female reproductive organs (FRO) in patients from cancer-affected families. Patients and Methods: The work presents the data on a comprehensive clinical examination of 210 women (90 patients with FRO cancer with aggregation of tumor pathology in families, 65 patients with benign pathology of FRO from cancer-affected families, 55 women — control group of healthy women without family history of cancer). Clinical genealogical analysis, morphological examination of tumors and molecular genetic studies of genomic DNA from peripheral blood and tumors were carried out. Results: It was established that in the families of patients with benign and malignant pathology of FRO, malignant tumors associated with Lynch II syndrome are observed. Based on the analysis of detected ESR-1, CYP 2D6*4 and mutations in BRCA1/2 genes in cancer patients and in patients with benign pathology, molecular genetic models have been developed to assess the individual risk of development of benign and malignant tumors of FRO. It has been established that these molecular genetic models and combinations of gene mutations and gene polymorphisms (SNP) by the intergene interaction that was analyzed, were found to be reliable in assessing the risk of benign and malignant pathology of the mammary gland and ovary. Conclusions: The model, which included the polymorphic variants of the T397C(ESR1)/CYP 2D6*4 genes was of the best predictive accuracy for the evaluation of the risk of benign tumors of the FRO (71.68%) and the highest reliability (p 0.001). At the same time, all identified models of intergene interaction in the development of malignant pathology of FRO were reliable, prognostically significant with high reproduction and almost identical accuracy (65.00–68.23%). The obtained results indicate a high informativeness of such molecular genetic indices as the polymorphism of ESR1 and CYP 2D6*4 genes and mutations in BRCA1/2 genes to assess the risk of benign or malignant tumors of FRO in families of patients with family history of cancer
Additional Access Points:
Paliychuk, O. V.
Polishchuk, L. Z.
Rossokha, Z. I.
Chekhun, V. F.

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18.

Nanog as prognostic factor of prostate cancer course / T. V. Zadvornyi [et al.] // Experimental Oncology. - 2020. - Том 42, N 2. - P94-100

MeSH-main:
ПРЕДСТАТЕЛЬНОЙ ЖЕЛЕЗЫ НОВООБРАЗОВАНИЯ -- PROSTATIC NEOPLASMS (терапия)
Annotation: The variability of the clinical course of prostate cancer (PC) indicates the need to find factors that could predict the aggressive potential of neoplasms accounting the biological characteristics of tumor cells. In this context, the role of NANOG, a transcription factor involved in maintaining pluripotency and one of the markers of cancer stem cells (CSCs), is being actively studied today. Aim: To investigate the level of NANOG mRNA in tumor tissue of patients with PC and to analyze the possibility of its use as a marker of the disease course. Materials and Methods: The study involved 85 patients with PC of stages II–IV. Morphological and immunohistochemical studies were performed on serial paraffin sections of resected PC using monoclonal antibodies to Ki-67 and androgen receptor. NANOG and miR-214 mRNA expression in tumor cells was analyzed by real-time reverse transcription polymerase chain reaction. The identification of CSCs was performed by double-labeled immunohistochemical method using primary antibodies to CD24 and CD44. Results: We have revealed notable variability of NANOG mRNA levels in tumor tissue of patients with PC (mean 4.18 ± 0.65 a.u. with individual deviations from 0.11 ± 0.03 a.u. to 15.24 ± 0.36 a.u.). According to NANOG mRNA levels, two groups of the PC patients were delineated: group 1 and group 2, with the average NANOG mRNA levels of 2.12 ± 0.16 a.u., and 8.68 ± 1.24 a.u., respectively. The NANOG mRNA levels in tumor tissue of PC patients of groups 1 and 2 correlated with preoperative serum prostate-specific antigen level (r = 0.58; p 0.05 and r
Additional Access Points:
Zadvornyi, T. V.
Lukianova, N. Yu.
Borikun, T. V.
Vitruk, Yu. V.
Stakhovsky, E. O.
Chekhun, V. F.

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19.

Oncology in the mainstream of the National academy of sciences of Ukraine: to the 100th anniversary of the academy / ed. V. F. Chekhun // Experimental Oncology. - 2018. - Том 40, N 4. - P258-260

MeSH-main:
ОНКОЛОГИЯ МЕДИЦИНСКАЯ -- MEDICAL ONCOLOGY (организация и управление, тенденции)
АКАДЕМИИ И ИНСТИТУТЫ -- ACADEMIES AND INSTITUTES (история, организация и управление, тенденции)
УКРАИНА -- UKRAINE
Annotation: Fluctuation of time is determined by the order and sequence of historical events of global and/or local scale, the harmonization of which reflects the dynamics of the development of society. The top of universal values of this process was and remains the academic science, which is based on the principles of an inextricable triad: education, science and culture. The intellectual and creative “explosion” of the 20th and the beginning of the 21st century has fundamentally changed human consciousness and priority values. Along with the knowledge of physical, natural phenomena and the search for energy sources, man has become not only a subject, but also an object of research. The pace of development of the life sciences reached the apogee. The struggle for higher expectancy and quality of life is a priority of modern science. The key problem of biomedical research has been and remains malignant neoplasms, which dynamics becomes a threat of civilizational scale
Additional Access Points:
Chekhun, V. F. \ed.\

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20.

Overexpression of the mitochondrial ribosomal protein S 18-2 in the invasive breast carcinomas / L. G. Buchynska [et al.] // Experimental Oncology. - 2018. - Том 40, N 4. - P303-308

MeSH-main:
МОЛОЧНОЙ ЖЕЛЕЗЫ НОВООБРАЗОВАНИЯ -- BREAST NEOPLASMS (диагностика, метаболизм, патофизиология)
ВНУТРИКЛЕТОЧНЫЕ СИГНАЛЬНЫЕ ПЕПТИДЫ И БЕЛКИ -- INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS (метаболизм)
Annotation: Recent studies allow to consider the mitochondrial ribosomal protein S18-2 (MRPS18-2, S18-2) as a potential oncoprotein, which suggests the need for further characterization of its expression in tumors of different genesis including breast cancer (BC). The aim of the study was to analyze the expression of the S18-2 protein in BC of luminal A and basal subtypes. Materials and Methods: Operational material of BC patients stage І–ІІ (luminal A subtype, n = 30, and basal subtype, n = 10) was studied with the use of morphological, immunohistochemical, statistical and bioinformatic methods. Results: Using the immunohistochemical analysis, we found that the S18-2 protein showed the nuclear signal in 66.7% of luminal A subtype BC samples and 80.0% of basal subtype BC samples. The variability of the S18-2 expression in both the luminal A and basal subtypes of BC was revealed. Noteworthy, the number of cells expressing S18-2 in high-proliferating tumors of luminal A and basal subtype is significantly higher than in tumors with a low proliferative potential (p 0.05). In 10 samples of luminal A subtype, the nuclear S18-2 signal was higher than median value. Moreover, the S18-2 protein was overexpressed in 4 out of such 10 samples. Metastases in the lymph nodes were found in 3 out of 4 patients with the stage II BC, low differentiation grade of the tumor and high proliferative activity. The bioinformatic analysis confirms our preliminary findings that the trend for increasing expression of the S18-2 protein in tumors correlates with the aggressiveness of malignant BC. Conclusion: The S18-2 protein may be a marker of cancer aggressiveness in BC patients
Additional Access Points:
Buchynska, L. G.
Iurchenko, N. P.
Kashuba, E. V.
Brieieva, O. V.
Glushchenko, N. M.
Mints, M.
Lukianova, N. Yu.
Chekhun, V. F.

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