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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

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
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: ELOVL5

Nikulin, Sergey / Razumovskaya, Alexandra / Poloznikov, Andrey / Zakharova, Galina / Alekseev, Boris / Tonevitsky, Alexander

Frontiers in molecular biosciences

2023 Volume 10, Page(s) 1075704

Abstract: Introduction: ...

Abstract	Introduction:
Language	English
Publishing date	2023-01-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2814330-9
ISSN	2296-889X
ISSN	2296-889X
DOI	10.3389/fmolb.2023.1075704
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Article: Effect of Pristine Multi-Walled Carbon Nanotubes on Formation and Degradation of Bacterial Biofilms

Maksimova, Yu. G. / Bykova, Ya. E. / Zorina, A. S. / Nikulin, S. M. / Maksimov, A. Yu

Microbiology. 2022 Aug., v. 91, no. 4

2022

Abstract: The effect of pristine multi-walled carbon nanotubes (MWCNT) on the biofilms of gram-negative bacteria, typical members of the activated sludge community, and gram-positive rhodococci involved in xenobiotic biodegradation, was investigated. Nanomaterials ...

Abstract	The effect of pristine multi-walled carbon nanotubes (MWCNT) on the biofilms of gram-negative bacteria, typical members of the activated sludge community, and gram-positive rhodococci involved in xenobiotic biodegradation, was investigated. Nanomaterials of this type not only did not inhibit biofilm formation completely, but were shown to have a probiofilm effect on the studied bacteria. In the presence of MWCNT in dynamic equilibrium with suspension cultures, less massive biofilms of Burkholderia dolosa BOS, Rhodococcus erythropolis 4-1, and R. ruber gt1, but reliably more massive biofilms of Acinetobacter guillouiae 11h, Alcaligenes faecalis 2, and R. erythropolis 11-2 were formed. However, after preliminary cell adhesion and in the absence of suspension culture, all studied strains formed reliably more massive biofilms. More pronounced degradation in the presence of MWCNT was observed for the biofilms of motile gram-negative bacteria. The effect of carbon nanomaterials on the metabolic activity and viability of the studied strains was assessed by reduction of a tetrazolium salt and of the redox indicator resazurin, total ATP content, and cell membrane disturbance. The respiratory activity reliably increased in the biofilms of R. erythropolis 11-2 and R. ruber gt1 grown in the presence of MWCNT, as well as in mature biofilms of R. erythropolis IL BIO and R. erythropolis 11-2 grown in LB medium and then treated with MWCNT. MWCNT were shown to have no negative effect on reduction of metabolized stain XTT by the cells. Comprehensive investigation of biofilm formation and metabolic activity of bacterial cells confirmed the absence of cytotoxic effect of pristine MWCNT on the cells of gram-negative activated sludge bacteria and gram-positive rhodococci in biofilms.
Keywords	Acinetobacter ; Alcaligenes faecalis ; Burkholderia ; Rhodococcus erythropolis ; activated sludge ; biochemical pathways ; biodegradation ; biofilm ; carbon nanotubes ; cell adhesion ; cell membranes ; cytotoxicity ; tetrazolium ; viability ; xenobiotics
Language	English
Dates of publication	2022-08
Size	p. 454-462.
Publishing place	Pleiades Publishing
Document type	Article
ZDB-ID	209706-0
ISSN	1608-3237 ; 0026-2617
ISSN (online)	1608-3237
ISSN	0026-2617
DOI	10.1134/S0026261722100861
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Article: ECM-Receptor Regulatory Network and Its Prognostic Role in Colorectal Cancer.

Nersisyan, Stepan / Novosad, Victor / Engibaryan, Narek / Ushkaryov, Yuri / Nikulin, Sergey / Tonevitsky, Alexander

Frontiers in genetics

2021 Volume 12, Page(s) 782699

Abstract: Interactions of the extracellular matrix (ECM) and cellular receptors constitute one of the crucial pathways involved in colorectal cancer progression and metastasis. With the use of bioinformatics analysis, we comprehensively evaluated the prognostic ... ...

Abstract	Interactions of the extracellular matrix (ECM) and cellular receptors constitute one of the crucial pathways involved in colorectal cancer progression and metastasis. With the use of bioinformatics analysis, we comprehensively evaluated the prognostic information concentrated in the genes from this pathway. First, we constructed a ECM-receptor regulatory network by integrating the transcription factor (TF) and 5'-isomiR interaction databases with mRNA/miRNA-seq data from The Cancer Genome Atlas Colon Adenocarcinoma (TCGA-COAD). Notably, one-third of interactions mediated by 5'-isomiRs was represented by noncanonical isomiRs (isomiRs, whose 5'-end sequence did not match with the canonical miRBase version). Then, exhaustive search-based feature selection was used to fit prognostic signatures composed of nodes from the network for overall survival prediction. Two reliable prognostic signatures were identified and validated on the independent The Cancer Genome Atlas Rectum Adenocarcinoma (TCGA-READ) cohort. The first signature was made up by six genes, directly involved in ECM-receptor interaction: AGRN, DAG1, FN1, ITGA5, THBS3, and TNC (concordance index 0.61, logrank test
Language	English
Publishing date	2021-12-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606823-0
ISSN	1664-8021
ISSN	1664-8021
DOI	10.3389/fgene.2021.782699
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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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Article: Impedance Spectroscopy as a Tool for Monitoring Performance in 3D Models of Epithelial Tissues.

Gerasimenko, Tatiana / Nikulin, Sergey / Zakharova, Galina / Poloznikov, Andrey / Petrov, Vladimir / Baranova, Ancha / Tonevitsky, Alexander

Frontiers in bioengineering and biotechnology

2020 Volume 7, Page(s) 474

Abstract: In contrast to traditional 2D cell cultures, both 3D models and organ-on-a-chip devices allow the study of the physiological responses of human cells. These models reconstruct human tissues in conditions closely resembling the body. Translation of these ... ...

Abstract	In contrast to traditional 2D cell cultures, both 3D models and organ-on-a-chip devices allow the study of the physiological responses of human cells. These models reconstruct human tissues in conditions closely resembling the body. Translation of these techniques into practice is hindered by associated labor costs, a need which may be remedied by automation. Impedance spectroscopy (IS) is a promising, automation-compatible label-free technology allowing to carry out a wide range of measurements both in real-time and as endpoints. IS has been applied to both the barrier cultures and the 3D constructs. Here we provide an overview of the impedance-based analysis in different setups and discuss its utility for organ-on-a-chip devices. Most attractive features of impedance-based assays are their compatibility with high-throughput format and supports for the measurements in real time with high temporal resolution, which allow tracing of the kinetics. As of now, IS-based techniques are not free of limitations, including imperfect understanding of the parameters that have their effects on the impedance, especially in 3D cell models, and relatively high cost of the consumables. Moreover, as the theory of IS stems from electromagnetic theory and is quite complex, work on popularization and explanation of the method for experimental biologists is required. It is expected that overcoming these limitations will lead to eventual establishing IS based systems as a standard for automated management of cell-based experiments in both academic and industry environments.
Language	English
Publishing date	2020-01-24
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2719493-0
ISSN	2296-4185
ISSN	2296-4185
DOI	10.3389/fbioe.2019.00474
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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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Article: In vitro and in silico liver models: Current trends, challenges and opportunities.

Poloznikov, Andrey / Gazaryan, Irina / Shkurnikov, Maxim / Nikulin, Sergey / Drapkina, Oxana / Baranova, Ancha / Tonevitsky, Alexander

ALTEX

2018 Volume 35, Issue 3, Page(s) 397–412

Abstract: Most common drug development failures originate from either bioavailability problems, or unexpected toxic effects. The culprit is often the liver, which is responsible for biotransformation of a majority of xenobiotics. Liver may be modeled using "liver ... ...

Abstract	Most common drug development failures originate from either bioavailability problems, or unexpected toxic effects. The culprit is often the liver, which is responsible for biotransformation of a majority of xenobiotics. Liver may be modeled using "liver on a chip" devices, which may include established cell lines, primary human cells, and stem cell-derived hepatocyte-like cells. The choice of biological material along with its processing and maintenance greatly influence both the device performance and the resultant toxicity predictions. Impediments to the development of "liver on a chip" technology include the problems with standardization of cells, limitations imposed by culturing and the necessity to develop more complicated fluidic contours. Fortunately, recent breakthroughs in the development of cell-based reporters, including ones with fluorescent label, permits monitoring of the behavior of the cells embed into the "liver on a chip" devices. Finally, a set of computational approaches has been developed to model both particular toxic response and the homeostasis of human liver as a whole; these approaches pave a way to enhance the in silico stage of assessment for a potential toxicity.
MeSH term(s)	Animals ; Cell Culture Techniques ; Cells, Cultured/drug effects ; Chemical and Drug Induced Liver Injury/prevention & control ; Computer Simulation/trends ; Drug Discovery/trends ; Hepatocytes/drug effects ; Humans ; In Vitro Techniques/trends ; Liver/drug effects
Language	English
Publishing date	2018-05-28
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	165707-0
ISSN	1868-596X ; 1018-4562 ; 0946-7785
ISSN	1868-596X ; 1018-4562 ; 0946-7785
DOI	10.14573/altex.1803221
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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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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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