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1.

Type of document : Magazine article
Edition cipher :
Author(s) : Chekhun V. F., Storchai D. M., Todor I. N., Borikun T. V., Lukianova N. Yu.
Title : Antitumor and genotoxic effects of lactoferrin in Walker-256 tumor-bearing rats
Place of publication : Экспериментальная онкология. - 2018. - Т. 40, № 3. - С. 200-204 (Cipher ЕУ12/2018/40/3)
Notes : 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
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2.

Type of document : Magazine article
Edition cipher :
Author(s) : Chekhun V.F., Andriiv A.V., Lukianova N.Yu.
Title : 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
Place of publication : Experimental Oncology. - К., 2017. - Том 39, N 1. - С. 65-68: табл. (Cipher ЕУ12/2017/39/1)
Notes : 16 ref.
MeSH-main: МОЛОЧНОЙ ЖЕЛЕЗЫ НОВООБРАЗОВАНИЯ -- BREAST NEOPLASMS
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
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3.

Type of document : Magazine article
Edition cipher :
Author(s) : Chekhun V. F., Todor I. N., Lukianova N. Yu., Horbyk D. M., Lozovskaya Yu. V., Burlaka A. P., Borikun T. V.
Title : Influence of ferromagnetic nanocomposite (ferroplat) on human breast cancer cells of different malignancy degrees: pro/antioxidant balance and energy metabolism
Place of publication : Experimental Oncology. - К., 2018. - Том 40, N 4. - С. 268-274 (Cipher ЕУ12/2018/40/4)
MeSH-main: МОЛОЧНОЙ ЖЕЛЕЗЫ НОВООБРАЗОВАНИЯ -- BREAST NEOPLASMS
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
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4.

Type of document : Magazine article
Edition cipher :
Author(s) : Lukianova N. Yu., Borikun T.V., Chekhun V. F.
Title : Tumor microenvironment-derived miRNAs as prognostic markers of breast cancer
Place of publication : Экспериментальная онкология. - 2019. - Т. 41, № 3. - С. 242-247 (Cipher ЕУ12/2019/41/3)
Notes : 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
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5.

Type of document : Magazine article
Edition cipher :
Author(s) : Zadvornyi T. V., Lukianova N. Yu., Borikun T. V., Vitruk Yu. V., Stakhovsky E. O., Chekhun V. F.
Title : Nanog as prognostic factor of prostate cancer course
Place of publication : Experimental Oncology. - К., 2020. - Том 42, N 2. - С. 94-100 (Cipher ЕУ12/2020/42/2)
MeSH-main: ПРЕДСТАТЕЛЬНОЙ ЖЕЛЕЗЫ НОВООБРАЗОВАНИЯ -- PROSTATIC NEOPLASMS
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
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6.

Type of document : Magazine article
Edition cipher :
Author(s) : Buchynska L. G., Iurchenko N. P., Kashuba E. V., Brieieva O. V., Glushchenko N. M., Mints M., Lukianova N. Yu., Chekhun V. F.
Title : Overexpression of the mitochondrial ribosomal protein S 18-2 in the invasive breast carcinomas
Place of publication : Experimental Oncology. - К., 2018. - Том 40, N 4. - С. 303-308 (Cipher ЕУ12/2018/40/4)
MeSH-main: МОЛОЧНОЙ ЖЕЛЕЗЫ НОВООБРАЗОВАНИЯ -- BREAST NEOPLASMS
ВНУТРИКЛЕТОЧНЫЕ СИГНАЛЬНЫЕ ПЕПТИДЫ И БЕЛКИ -- INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS
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
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7.

Type of document : Magazine article
Edition cipher :
Author(s) : Lozovska Yu. V., Naleskina L. A., Zadvorniy T. V., Andrusishina I. M., Zhulkevych I. V., Stakhovskiy E. O., Kunska L. M., Lukianova N. Yu.
Title : Relationship aggressiveness of prostate cancer with tumor-associated serum markers
Place of publication : Фізіологічний журнал. - К., 2019. - Том 65, N 6. - С. 70-80 (Cipher ФУ6/2019/65/6)
MeSH-main: ПРЕДСТАТЕЛЬНОЙ ЖЕЛЕЗЫ НОВООБРАЗОВАНИЯ -- PROSTATIC NEOPLASMS
НОВООБРАЗОВАНИЙ МАРКЕРЫ БИОЛОГИЧЕСКИЕ -- TUMOR MARKERS, BIOLOGICAL
ЛАКТОФЕРРИН -- LACTOFERRIN
C-РЕАКТИВНЫЙ БЕЛОК -- C-REACTIVE PROTEIN
АЛЬБУМИН СЫВОРОТОЧНЫЙ -- SERUM ALBUMIN
Annotation: Досліджено вміст сироваткових пухлиноасоційованих маркерів: лактоферин (ЛФ), С-реактивний протеїн (СРП), альбумін, лактатдегідрогеназа (ЛДГ), співвідношення Ca/Mg та СРП/альбумін, у хворих на рак передміхурової залози залежно від клініко-патологічних характеристик захворювання. Крім того, визначено ступінь злоякісності новоутворень за Глісоном і наявність метастазів у регіонарні лімфатичні вузли. Показано, що у сироватці крові хворих на рак III стадії порівняно із II знижувався у 1,4 раза вміст ЛФ та зменшувалося співвідношення СРП/ альбумін на фоні достовірного збільшення вмісту СРП та співвідношення Ca/Mg (у 2,75 та 1,12 раза відповідно). Водночас у хворих із метастатичним ураженням регіонарних лімфатичних вузлів порівняно із пацієнтами без цих ознак виявлено зменшення у 1,3 раза вмісту ЛФ та альбуміну у 1,16 раза при одночасному зростанні вмісту СРП та співвідношення Ca/Mg (у 2,84 та 1,1 раза відповідно) та зниження СРП/альбумін. Показано, що у сироватці крові хворих із високим ступенем злоякісності новоутворень (8 та 9 балів за шкалою Глісона) та вмістом простатспецифічного антигена (ПСА) більш ніж 4 нг/мл, порівняно зі значеннями у пацієнтів з менш вираженими ознаками пухлинної прогресії, суттєво знижувався вміст сироваткового ЛФ та альбуміну на фоні підвищеного співвідношення Ca/Mg, СРП/альбумін і вмісту ЛДГ. Зазначені відмінності у різних ланках метаболічних шляхів в організмі хворих на рак передміхурової залози з більш агресивним проявом захворювання свідчать про несприятливий перебіг пухлинного процесу. Отримані результати дають підстави вважати, що сироватковий ЛФ може бути використаний як додатковий позапухлинний маркер для прогнозу цього захворювання.
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8.

Type of document : Magazine article
Edition cipher :
Author(s) : Shvets Yu. V., Lukianova N. Yu., Chekhun V. F.
Title : Human microbiota and effectiveness of cancer chemotherapy
Place of publication : Experimental Oncology. - К., 2020. - Том 42, N 2. - С. 82-93 (Cipher ЕУ12/2020/42/2)
MeSH-main: НОВООБРАЗОВАНИЯ -- NEOPLASMS
Annotation: This review presents up-to-date information on the effects of microbiota on the individual chemotherapy sensitivity in cancer treatment. Recent studies have shown that a fine balance between the intestinal microbiota and the immune system is crucial for maintaining an efficacy of cancer chemotherapy. A number of antitumor drugs have complex mechanisms of action involving not only direct effects but also the activity of the intestinal microbiota and the immune system. A unique combination of these factors contributes to the individual chemotherapy sensitivity
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9.

Type of document : Magazine article
Edition cipher :
Author(s) : Lozovska Yu. V., Andrusishina I. M., Lukianova N. Yu., Burlaka A. P., Naleskina L. A., Todor I. N., Chekhun V. F.
Title : The influence of lactoferrin on elemental homeostasis and activity of metal-containing enzymes in rats with Walker-256 carcinosarcoma
Place of publication : Экспериментальная онкология. - 2019. - Т. 41, № 1. - С. 20-25 (Cipher ЕУ12/2019/41/1)
Notes : Bibliogr. at the end of the art.
Annotation: To investigate the content of essential elements (EE): copper, zinc, magnesium, iron and calcium and the evaluation of the activity of metal-containing enzymes — ceruloplasmin (CP), myeloperoxidase (MPO) and the content of transferrin (TF) in blood plasma (BP) and tumor tissue (TT) of animals with Walker-256 carcinosarcoma treated with lactoferrin (LF). Materials and Methods: The study of the EE content and the activity of the abovementioned enzymes was carried out on rats with Walker-256 carcinosarcoma treated with LF at the doses of 1 and 10 mg/kg of body weight. The quantitative content of EE in BP and TT of animals was determined using the inductively coupled plasma atomic emission spectroscopy (ICP-AES). Determination of CP activity, content of TF and hemochromes was performed using the method of electron paramagnetic resonance (EPR), and MPO — by unified biochemical method. Results: The introduction of LF at the doses of 1 and 10 mg/kg resulted in a decrease in the ratio of Cu/Zn in BP and even more expressed decrease of Ca/Mg ratio in TT. Administration of LF, especially at a dose of 10 mg/kg, affected the increase in CP and MPO activity in BP. It has been shown that administration of LF at a dose of 10 mg/kg led to an increase in oxidative products of destruction of the hemoglobin-hemochrom system in the TT, against the background of lowering the TF content. Conclusions: The administration of LF, especially at a dose of 10 mg/kg, led to metabolic alterations associated with inhibition of the tumor process. The detected modulating effect of LF on the content of the EE and the activity of the CP and MPO may be a basis for correction of the elemental balance in carcinogenesis
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10.

Title of magazine :Фізіологічний журнал -2019year т.65,N 6
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