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  1. Article ; Online: Modulators of the Nrf2 Signaling Pathway Enhance the Cytotoxic Effect of Standard Chemotherapeutic Drugs on Organoids of Metastatic Colorectal Cancer.

    Razumovskaya, A V / Silkina, M O / Nikulin, S V / Tonevitsky, A G / Alekseev, B Ya

    Bulletin of experimental biology and medicine

    2024  

    Abstract: The activity of known modulators of the Nrf2 signaling pathway (bardoxolone and brusatol) was studied on cultures of tumor organoids of metastatic colorectal cancer previously obtained from three patients. The effect of modulators was studied both as ... ...

    Abstract The activity of known modulators of the Nrf2 signaling pathway (bardoxolone and brusatol) was studied on cultures of tumor organoids of metastatic colorectal cancer previously obtained from three patients. The effect of modulators was studied both as monotherapy and in combination with standard chemotherapy drugs used to treat colorectal cancer. The Nrf2 inhibitor brusatol and the Nrf2 activator bardoxolone have antitumor activity. Moreover, bardoxolone and brusatol also significantly enhance the effect of the chemotherapy drugs 5-fluorouracil, oxaliplatin, and irinotecan metabolite SN-38. Thus, bardoxolone and brusatol can be considered promising candidates for further preclinical and clinical studies in the treatment of colorectal cancer.
    Language English
    Publishing date 2024-05-09
    Publishing country United States
    Document type Journal Article
    ZDB-ID 390407-6
    ISSN 1573-8221 ; 0007-4888 ; 0365-9615
    ISSN (online) 1573-8221
    ISSN 0007-4888 ; 0365-9615
    DOI 10.1007/s10517-024-06093-0
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  2. Article ; Online: Assessing the Efficacy of Anti-Cancer Drugs on Organoid Models Derived from Prostate Cancer.

    Silkina, M O / Razumovskaya, A V / Nikulin, S V / Tonevitsky, A G / Alekseev, B Ya

    Doklady. Biochemistry and biophysics

    2024  Volume 513, Issue Suppl 1, Page(s) S96–S99

    Abstract: It was proven that tumor organoids effectively mirror the phenotypic and genetic traits of the original biomaterial. It was reported that outcomes from drug testing in organoid cultures can accurately represent the clinical response observed in patients. ...

    Abstract It was proven that tumor organoids effectively mirror the phenotypic and genetic traits of the original biomaterial. It was reported that outcomes from drug testing in organoid cultures can accurately represent the clinical response observed in patients. In this study, an organoid culture was derived from biopsy material of prostate cancer (PC). Subsequently, clinical practice drugs, docetaxel and enzalutamide, were tested on this organoid culture. Various techniques for evaluating the efficacy of drugs in vitro were compared. The half-maximal inhibitory concentration of docetaxel was found to be markedly lower compared to that of enzalutamide. However, when tested at clinically relevant concentrations and incubation times, enzalutamide was more effective than docetaxel. Therefore, it is crucial to optimize the testing conditions for drugs on in vitro cultures for their subsequent application in clinical practice.
    MeSH term(s) Male ; Humans ; Docetaxel ; Antineoplastic Agents/pharmacology ; Prostatic Neoplasms/drug therapy ; Prostatic Neoplasms/pathology ; Nitriles ; Organoids/pathology ; Benzamides ; Phenylthiohydantoin
    Chemical Substances Docetaxel (15H5577CQD) ; enzalutamide (93T0T9GKNU) ; Antineoplastic Agents ; Nitriles ; Benzamides ; Phenylthiohydantoin (2010-15-3)
    Language English
    Publishing date 2024-02-09
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2062390-2
    ISSN 1608-3091 ; 1607-6729
    ISSN (online) 1608-3091
    ISSN 1607-6729
    DOI 10.1134/S1607672923700692
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  3. Article: Transcriptome Analysis of Signaling Pathways in Caco-2 Cells Involved in the Formation of Intestinal Villi

    Nikulin, S. V. / Raigorodskaya, M. P. / Sakharov, D. A.

    Applied biochemistry and microbiology. 2020 Dec., v. 56, no. 9

    2020  

    Abstract: Caco-2 cells are traditionally used to construct in vitro models of the intestinal barrier. One characteristic of the mature intestine is the presence of villi—connective tissue outgrowths covered with epithelial cells. It was recently shown that Caco-2 ... ...

    Abstract Caco-2 cells are traditionally used to construct in vitro models of the intestinal barrier. One characteristic of the mature intestine is the presence of villi—connective tissue outgrowths covered with epithelial cells. It was recently shown that Caco-2 cells form structures resembling intestinal villi during prolonged cultivation. In this work, we showed via transcriptome analysis that the BMP and PDGF signaling cascades involved in the formation of villi in vivo are significantly altered during the differentiation of Caco-2 cells and, therefore, can participate in the formation of similar structures in vitro. In particular, we found a significant decrease in the expression of the BMP4, BMP7, and BMP8A genes in differentiated cells as compared to undifferentiated cells. We also first discovered periodic fluctuations in transepithelial resistance upon the differentiation of Caco-2 cells. The period of observed fluctuations indicates that they can occur as a result of cell proliferation during villus formation.
    Keywords biochemistry ; cell proliferation ; intestines ; microbiology ; transcriptomics ; villi
    Language English
    Dates of publication 2020-12
    Size p. 898-901.
    Publishing place Pleiades Publishing
    Document type Article
    ZDB-ID 412550-2
    ISSN 1608-3024 ; 0003-6838
    ISSN (online) 1608-3024
    ISSN 0003-6838
    DOI 10.1134/S0003683820090069
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  4. Article: Laminin 521 Modulates the Сytotoxic Effect of 5-Fluorouracil on HT29 Colorectal Cancer Cells

    Raigorodskaya, M. P. / Turchinovich, A. / Tsypina, I. M. / Zgoda, V. G. / Nikulin, S. V. / Maltseva, D. V.

    Applied biochemistry and microbiology. 2020 Dec., v. 56, no. 8

    2020  

    Abstract: The cytotoxic effect of 5-fluorouracil (5FU) and regorafenib (RF), drugs with different mechanisms of action used to treat colorectal cancer, on an HT29 cell line cultured on plastic or laminin 521 (LM-521) has been studied. It is first shown that LM-521 ...

    Abstract The cytotoxic effect of 5-fluorouracil (5FU) and regorafenib (RF), drugs with different mechanisms of action used to treat colorectal cancer, on an HT29 cell line cultured on plastic or laminin 521 (LM-521) has been studied. It is first shown that LM-521 can increase the sensitivity of tumor cells to 5FU. A possible mechanism of the observed effect of LM-521 on the HT29 cell viability is proposed based on transcriptome and proteome analysis. The interaction of β1-containing integrins on the cell surface with LM-521 can activate the FAK/PI3K/Akt signaling pathways and promote phosphorylation of the YAP transcription coactivator and its binding to the complex with the 14-3-3σ protein. The formation of this complex leads to YAP retention in the cytoplasm and prevents its transport to the nucleus and the activation of antiapoptotic gene transcription.
    Keywords cell lines ; cell viability ; colorectal neoplasms ; cytoplasm ; cytotoxicity ; fluorouracil ; integrins ; laminin ; microbiology ; phosphorylation ; proteome ; transcription (genetics) ; transcriptome
    Language English
    Dates of publication 2020-12
    Size p. 870-874.
    Publishing place Pleiades Publishing
    Document type Article
    ZDB-ID 412550-2
    ISSN 1608-3024 ; 0003-6838
    ISSN (online) 1608-3024
    ISSN 0003-6838
    DOI 10.1134/S0003683820080074
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  5. Article: Antitumor Activity of Indole-3-carbinol in Breast Cancer Cells: Phenotype, Genetic Pattern, and DNA Methylation Inversion

    Poloznikov, A. A. / Muyzhnek, E. L. / Nikulin, S. V. / Kaprin, A. D. / Ashrafyan, L. A. / Rozhkova, N. I. / Labazanova, P. G. / Kiselev, V. I.

    Applied biochemistry and microbiology. 2020 Dec., v. 56, no. 9

    2020  

    Abstract: The effect of indole-3-carbinol on the proliferation and migration of MDA-MB-231 breast-cancer cells and healthy MCF-10A breast-tissue cells has been studied. It was shown that indole-3-carbinol reliably reduced the proliferation and migration of MDA-MB- ... ...

    Abstract The effect of indole-3-carbinol on the proliferation and migration of MDA-MB-231 breast-cancer cells and healthy MCF-10A breast-tissue cells has been studied. It was shown that indole-3-carbinol reliably reduced the proliferation and migration of MDA-MB-231 cells and does not significantly affect MCF-10A cells. The incubation of MDA-MB-231 tumor cells with 100 μM indole-3-carbinol for 48 h resulted in a marked decrease in the expression of the Wnt cascade genes CCND1 (by 28%), Sp1 (by 44%), CDK6 (by 47%), as well as the EGFR and FASN genes (by 64 and 22%, respectively). Incubation of the MCF-10A cell line under the same conditions induced a noticeable decrease in the expression of only two genes, EGFR (by 16%) and CDK6 (by 9%). Indole-3-carbinol was also shown to display selective DNA demethylating activity in breast-tumor cells and to reverse the process of abnormal methylation and functional blockage of the antitumor WIF-1 gene. The obtained data indicate that drugs containing indole-3-carbinol as an active component can be potential regulators of epigenetic processes in the complex treatment of breast cancer and other tumors.
    Keywords DNA ; DNA methylation ; antineoplastic activity ; breast neoplasms ; cell lines ; epigenetics ; genes ; microbiology ; phenotype
    Language English
    Dates of publication 2020-12
    Size p. 909-919.
    Publishing place Pleiades Publishing
    Document type Article
    ZDB-ID 412550-2
    ISSN 1608-3024 ; 0003-6838
    ISSN (online) 1608-3024
    ISSN 0003-6838
    DOI 10.1134/S0003683820090070
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  6. Article: [Ribosome Inactivation and the Integrity of the Intestinal Epithelial Barrier].

    Nikulin, S V / Mnafki Krainova, N A / Shilin, S A / Gazizov, I N / Maltseva, D V

    Molekuliarnaia biologiia

    2018  Volume 52, Issue 4, Page(s) 675–682

    Abstract: The mistletoe lectin viscumin (MLI) is a ribosome-inactivating protein from Viscum album widely used in cancer therapy. Its antitumor properties are due to its immunomodulating action, previously demonstrated in experiments involving intravenous, ... ...

    Abstract The mistletoe lectin viscumin (MLI) is a ribosome-inactivating protein from Viscum album widely used in cancer therapy. Its antitumor properties are due to its immunomodulating action, previously demonstrated in experiments involving intravenous, subcutaneous, and oral administration of viscumin. To investigate whether viscumin has a cytotoxic effect on the intestinal epithelium, its safety was assessed using (i) impedance spectroscopy to measure the integrity of the colorectal adenocarcinoma Caco-2 cell monolayer after exposure to viscumin and (ii) a novel technique of determining the portion of viscumin-inactivated ribosomes. It was shown that inactivation of at least 20% of the ribosomes within 6 h did not lead to disruption of the Caco-2 cell monolayer or alter the physicochemical parameters of enterocyte membranes.
    MeSH term(s) Caco-2 Cells ; Cell Membrane/drug effects ; Cell Survival/drug effects ; Colorectal Neoplasms/drug therapy ; Colorectal Neoplasms/pathology ; Electric Impedance ; Enterocytes/drug effects ; Humans ; Intestinal Mucosa/drug effects ; Ribosome Inactivating Proteins, Type 2/pharmacology ; Ribosomes/drug effects ; Ribosomes/genetics ; Toxins, Biological/pharmacology
    Chemical Substances Ribosome Inactivating Proteins, Type 2 ; Toxins, Biological ; mistletoe lectin I
    Language Russian
    Publishing date 2018-08-15
    Publishing country Russia (Federation)
    Document type Journal Article
    ZDB-ID 213542-5
    ISSN 0026-8984
    ISSN 0026-8984
    DOI 10.1134/S0026898418040146
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  7. Article: [Impedance Spectroscopy and Transcriptome Analysis of Choriocarcinoma BeWo b30 as a Model of Human Placenta].

    Nikulin, S V / Knyazev, E N / Gerasimenko, T N / Shilin, S A / Gazizov, I N / Zakharova, G S / Poloznikov, A A / Sakharov, D A

    Molekuliarnaia biologiia

    2019  Volume 53, Issue 3, Page(s) 467–475

    Abstract: Placenta is a highly specialized organ that is necessary for successful gestation. Several models of the placental barrier are used to study how it functions, including the transplacental transport of xenobiotics. One of these models, human ... ...

    Abstract Placenta is a highly specialized organ that is necessary for successful gestation. Several models of the placental barrier are used to study how it functions, including the transplacental transport of xenobiotics. One of these models, human choriocarcinoma cell line BeWo is widely used in vitro. Notably, cancerous BeWo cells form multilayer structures that normally are not found in the human placenta. Here, we aim to develop techniques suitable for monitoring BeWo b30 cells in culture. To assess the state of BeWo b30 cells growing on a membrane, we use impedance spectroscopy, which allows us to estimate the number of cell layers by the change in the electrical parameters of the biological system. In mature BeWo b30 cell cultures, we also note a significant increase in the expression of genes encoding metallothioneins (particularly, MT1B, MT1F, and MT2A) and syncytins (ERVW-1 and ERVFRD-1), which can be used as biomarkers reflecting the development of mature phenotypic characteristics, namely, trophoblastic invasion and formation of the syncytium.
    MeSH term(s) Cell Culture Techniques ; Cell Line, Tumor ; Choriocarcinoma/genetics ; Choriocarcinoma/pathology ; Dielectric Spectroscopy ; Female ; Gene Expression Profiling ; Humans ; Models, Biological ; Placenta/cytology ; Placenta/metabolism ; Pregnancy
    Language Russian
    Publishing date 2019-07-08
    Publishing country Russia (Federation)
    Document type Journal Article
    ZDB-ID 213542-5
    ISSN 0026-8984
    ISSN 0026-8984
    DOI 10.1134/S0026898419030133
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  8. Article ; Online: Application of Impedance Spectroscopy for the Control of the Integrity of In Vitro Models of Barrier Tissues.

    Nikulin, S V / Gerasimenko, T N / Shilin, S A / Zakharova, G S / Gazizov, I N / Poloznikov, A A / Sakharov, D A

    Bulletin of experimental biology and medicine

    2019  Volume 166, Issue 4, Page(s) 512–516

    Abstract: We compared available methods for monitoring the integrity of in vitro models of barrier tissues and studied the possibility of using impedance spectroscopy to solve this problem. It was demonstrated (theoretically and experimentally) that TEER ... ...

    Abstract We compared available methods for monitoring the integrity of in vitro models of barrier tissues and studied the possibility of using impedance spectroscopy to solve this problem. It was demonstrated (theoretically and experimentally) that TEER measurements are not sufficiently sensitive to detect small defects in the cell barrier that significantly affect its permeability. For obtaining reliable results, it is necessary to set a sufficiently high threshold TEER, which leads to the loss of many intact samples. At the same time, impedance spectroscopy has all advantages of the classical method of measuring TEER (it is rapid and non-invasive method), while its application in combination with the methods of machine learning allows reliable detection of defects in the cell barrier.
    MeSH term(s) Caco-2 Cells ; Dielectric Spectroscopy/methods ; Electric Impedance ; Humans ; Intestinal Mucosa/metabolism
    Language English
    Publishing date 2019-02-19
    Publishing country United States
    Document type Journal Article
    ZDB-ID 390407-6
    ISSN 1573-8221 ; 0007-4888 ; 0365-9615
    ISSN (online) 1573-8221
    ISSN 0007-4888 ; 0365-9615
    DOI 10.1007/s10517-019-04384-5
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  9. Article ; Online: Transcriptome Guided Drug Combination Suppresses Proliferation of Breast Cancer Cells.

    Shkurnikov, M Yu / Poloznikov, A A / Nikulin, S V / Schumacher, U / Wicklein, D / Stürken, C / Galatenko, V V / Alekseev, B Ya

    Bulletin of experimental biology and medicine

    2019  Volume 166, Issue 5, Page(s) 656–660

    Abstract: One of actively developing trends in modern pharmacology is the use of the transcriptome analysis for drug repositioning. We have previously detected two molecular markers of relapses in patients with malignant breast tumors: ELOVL5 and IGFBP6. Poor ... ...

    Abstract One of actively developing trends in modern pharmacology is the use of the transcriptome analysis for drug repositioning. We have previously detected two molecular markers of relapses in patients with malignant breast tumors: ELOVL5 and IGFBP6. Poor prognosis is associated with low expression of these markers. Here we analyze the effects of simvastatin and a new potential proteasome inhibitor K7174 inducing expression of IGFBP6 and EVOVL5 on the proliferation of breast cancer cells MDA-MB-231 and DU4475. Compound K7174 potentiates the inhibitory effect of simvastatin on the proliferation of DU4475 cells characterized by low expression of ELOVL5-IGFBP6 pair, but not on the proliferation of MDA-MB-231 cells with high expression of these markers.
    MeSH term(s) Acetyltransferases/genetics ; Breast Neoplasms/microbiology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cell Proliferation/genetics ; Drug Combinations ; Epithelial-Mesenchymal Transition/drug effects ; Epithelial-Mesenchymal Transition/genetics ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Insulin-Like Growth Factor Binding Proteins/genetics ; Neoplasm Recurrence, Local ; Simvastatin/pharmacology ; Transcriptome/drug effects ; Transcriptome/genetics
    Chemical Substances Drug Combinations ; Insulin-Like Growth Factor Binding Proteins ; Simvastatin (AGG2FN16EV) ; Acetyltransferases (EC 2.3.1.-) ; fatty acid elongases (EC 2.3.1.-)
    Language English
    Publishing date 2019-03-22
    Publishing country United States
    Document type Journal Article
    ZDB-ID 390407-6
    ISSN 1573-8221 ; 0007-4888 ; 0365-9615
    ISSN (online) 1573-8221
    ISSN 0007-4888 ; 0365-9615
    DOI 10.1007/s10517-019-04412-4
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  10. Article ; Online: Elimination of a Viscumin-Ferromagnetic Nanoparticles Conjugate from the Tumor Nodule in Mice.

    Maltseva, D V / Nikulin, S V / Sergeeva, N S / Tonevitskaya, S A / Sakharov, D A

    Bulletin of experimental biology and medicine

    2017  Volume 163, Issue 6, Page(s) 745–748

    Abstract: External magnetic field is characterized by low toxicity and existence of magnetic properties, which contributes to an interest in the development of products from ferromagnetic nanoparticles (FNP) for antitumor therapy. Previously we synthesized a ... ...

    Abstract External magnetic field is characterized by low toxicity and existence of magnetic properties, which contributes to an interest in the development of products from ferromagnetic nanoparticles (FNP) for antitumor therapy. Previously we synthesized a conjugate of ferromagnetic magnetite nanoparticles and viscumin (mistletoe lectin I, MLI), which exhibits the antitumor activity. Studying the pharmacological properties of this conjugate (FNP-MLI) was directed to the evaluation of FNP-MLI elimination after intratumor injection in mice. The elimination rate of FNP-MLI was much lower than that of native plant MLI. The presence of FNP-MLI was not accompanied by undesired changes in the tumor tissue. The use of a FNP-MLI conjugate allowed us to prolong the time of MLI presence in tissues without increasing the dose of exogenous lectin. These features contribute to the prolongation of an immunomodulatory effect of MLI.
    Language English
    Publishing date 2017-10
    Publishing country United States
    Document type Journal Article
    ZDB-ID 390407-6
    ISSN 1573-8221 ; 0007-4888 ; 0365-9615
    ISSN (online) 1573-8221
    ISSN 0007-4888 ; 0365-9615
    DOI 10.1007/s10517-017-3894-8
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