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1.


   
    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.


MeSH-main:
МОЛОЧНОЙ ЖЕЛЕЗЫ НОВООБРАЗОВАНИЯ -- BREAST NEOPLASMS (патофизиология, этиология)
КАРЦИНОМА 256 УОКЕРА -- CARCINOMA 256, WALKER (патофизиология, этиология)
ЛАКТОФЕРРИН -- LACTOFERRIN (анализ, метаболизм, терапевтическое применение, физиология)
РОСТА ИНГИБИТОРЫ -- GROWTH INHIBITORS (анализ, диагностическое применение)
МУТАГЕНЫ -- MUTAGENS (анализ)
СТАТИСТИЧЕСКАЯ ОБРАБОТКА ДАННЫХ -- DATA INTERPRETATION, STATISTICAL
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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2.


   
    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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3.


   
    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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4.


   
    Association of circulating miR-21, -205, and -182 with response of luminal breast cancers to neoadjuvant FAC and AC treatment [Text] / V. F. Chekhun [та ін.] // Экспериментальная онкология. - 2020. - Т. 42, № 3. - С. 162-166. - Бібліогр.: в кінці ст.


MeSH-main:
МОЛОЧНОЙ ЖЕЛЕЗЫ НОВООБРАЗОВАНИЯ -- BREAST NEOPLASMS (патофизиология, терапия, этиология)
ЛЕКАРСТВЕННАЯ ТЕРАПИЯ КОМБИНИРОВАННАЯ -- DRUG THERAPY, COMBINATION (использование, тенденции)
ЭКСПРЕССИРУЕМОЙ ПОСЛЕДОВАТЕЛЬНОСТИ МАРКЕРЫ -- EXPRESSED SEQUENCE TAGS
РНК НОВООБРАЗОВАНИЙ -- RNA, NEOPLASM (анализ, диагностическое применение)
НОВООБРАЗОВАНИЙ МАРКЕРЫ БИОЛОГИЧЕСКИЕ -- TUMOR MARKERS, BIOLOGICAL (анализ)
СТАТИСТИЧЕСКАЯ ОБРАБОТКА ДАННЫХ -- DATA INTERPRETATION, STATISTICAL
Annotation: To identify the association of serum miRNAs with neoadjuvant polychemotherapy response in patients with breast cancer of luminal A and B subtypes. Materials and Methods: We analyzed the expression levels of circulating miR-21, -155, -182, -373, -199a, -205, -375 in serum of 182 breast cancer patients using real-time polymerase chain reaction. Each case was characterized by TMN criteria using morphological and immunohistochemical analyses. Results: Serum levels of miR-205 and -375 are associated with the response of luminal A tumors and miR-205 and -21 with the response of luminal B tumors to neoadjuvant polychemotherapy in fluorouracil + doxorubicin + cyclophosphamide and doxorubicin + cyclophosphamide regimens. In addition, we found correlation of miR-155, -182, -199a, -375 with 3-year relapse-free survival of patients. Based on the obtained data, we developed innovative prognostic and predictive panels to assess the drug sensitivity of tumors and lower the risk of breast cancer recurrence, which would significantly improve the treatment outcomes and the quality of life of patients. Conclusions: Serum levels of miR-155, -182, -199a, -205, -375 can be used as predictive and prognostic panel for monitoring BC course in Ukrainian population
Additional Access Points:
Chekhun, V. F.
Borikun, T. V.
Bazas, V. M.
Andriiv, A. V.
Klyusov, O. М.
Yalovenko, T. М.
Lukianova, N. Yu.

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5.


   
    Biomagnetism of tumor in rats with Guerin’s carcinoma after injection of ferromagnetic nanocomposite (Ferroplat): contactless measurement [Text] / I. N. Todor [та ін.] // Экспериментальная онкология. - 2020. - Т. 42, № 3. - С. 204-207. - Бібліогр.: в кінці ст.


MeSH-main:
НОВООБРАЗОВАНИЯ ЭКСПЕРИМЕНТАЛЬНЫЕ -- NEOPLASMS, EXPERIMENTAL (диагностика, этиология)
ДИАГНОСТИКА -- DIAGNOSIS
МАГНИТНЫЕ ПОЛЯ -- MAGNETIC FIELDS
МОДЕЛИ НА ЖИВОТНЫХ -- MODELS, ANIMAL
НАНОКОМПОЗИТЫ -- NANOCOMPOSITES (использование)
СТАТИСТИЧЕСКАЯ ОБРАБОТКА ДАННЫХ -- DATA INTERPRETATION, STATISTICAL
Key words(unnormalized):
карциноми Герена
Annotation: In order to develop fundamentally new technologies for non-invasive and safer diagnosis of cancer, we aimed to detect non-contact magnetic signals from a malignant tumor in animals treated or not-treated with the ferromagnetic nanocomposite Ferroplat. Materials and Methods: Guerin’s carcinoma was used as a model of tumor growth. The biomagnetism of the tumor was evaluated in the dynamics of its growth. Ten days after tumor transplantation, Ferroplat was administered intravenously to half of the animals with the tumor and to half of the control animals. The magnitude of the magnetic signals was determined 1 h and every two days after administration of the nanocomposite using a Superconducting Quantum Interference Device magnetometer of the original design. Results: We have found that the magnetic signals coming from the tumor are significantly higher compared to control tumor-free animals. Intravenous administration of a ferromagnetic nanocomposite (Ferroplat: Fe3O4 + cisplatinum) led to a significant increase of the magnetic signal, especially in the tumor tissue, and inhibition of Guerin’s carcinoma growth. Ferromagnetic nanoparticles (32.7 nm) are retained in malignant cells for a longer time than in normal ones. Conclusion: Tumor cells accumulate iron nanoparticles more intensively than normal ones. Nanocomposite Ferroplat can be used for a targeted delivery of cisplatin to malignant cells
Additional Access Points:
Todor, I. N.
Lukianova, N. Yu.
Primin, M. А.
Nedayvoda, I. V.
Chekhun, V. F.

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6.


    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
Additional Access Points:
Chekhun, V. F.

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7.


    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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8.


    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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9.


    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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10.


    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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