Elena Abakushina - Academia.edu (original) (raw)
Papers by Elena Abakushina
Высокая эффективность радионуклидных методов диагностики не вызывают сомнения. Являясь одним из н... more Высокая эффективность радионуклидных методов диагностики не вызывают сомнения. Являясь одним из наиболее информативных, точных и чув
Vaccines, 2021
In the last decade, an impressive advance was achieved in adoptive cell therapy (ACT), which has ... more In the last decade, an impressive advance was achieved in adoptive cell therapy (ACT), which has improved therapeutic potential and significant value in promising cancer treatment for patients. The ACT is based on the cell transfer of dendritic cells (DCs) and/or immune effector cells. DCs are often used as vaccine carriers or antigen-presenting cells (APCs) to prime naive T cells ex vivo or in vivo. Cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells are used as major tool effector cells for ACT. Despite the fact that NK cell immunotherapy is highly effective and promising against many cancer types, there are still some limitations, including insignificant infiltration, adverse conditions of the microenvironment, the immunosuppressive cellular populations, and the low cytotoxic activity in solid tumors. To overcome these difficulties, novel methods of NK cell isolation, expansion, and stimulation of cytotoxic activity should be designed. In this review, we discuss the basi...
Histochemistry and Cell Biology, 2007
Membrane-associated oligosaccharides are known to take part in interactions between natural kille... more Membrane-associated oligosaccharides are known to take part in interactions between natural killer (NK) cells and their targets and modulate NK cell activity. A model system was therefore developed using synthetic glycoconjugates as tools to modify the carbohydrate pattern on NK target cell surfaces. NK cells were then assessed for function in response to synthetic glycoconjugates, using both cytolysis-associated caspase 6 activation measured by Xow cytometry and IFN-production. Lipophilic neoglycoconjugates were synthesized to provide their easy incorporation into the target cell membranes and to make carbohydrate residues available for cell-cell interactions. While incorporation was successful based on Xuorescence monitoring, glycoconjugate incorporation did not evoke artifactual changes in surface antigen expression, and had no negative eVect on cell viability. Glycoconjugates contained Le x , sulfated Le x , and Le y sharing the common structure motif trisaccharide Le x were revealed to enhance cytotoxicity mediated speciWcally by CD16 + CD56 + NK cells. The glycoconjugate eVects were dependent on saccharide presentation in a polymeric form. Only polymeric, or clustered, but not monomeric glycoconjugates resulted in alteration of cytotoxicity in our system, suggesting that appropriate presentation is critical for carbohydrate recognition and subsequent biological eVects. Keywords NK cell • Neoglycoconjugate • Saccharide • Flow cytometry • Caspase Abbreviations DOPE Dioleoylphosphatidylethanolamine residue FBS Fetal bovine serum Fluo 5-[(5-Aminopenthyl) thioureidyl]Xuorescein residue Glyc Oligosaccharide residue PAA Poly(N-2-hydroxyethylacrylamide) PBMC Peripheral blood mononuclear cells B di Gal 1-3Gal-B tri Gal 1-3(Fuc 1-2)Gal-Le x Gal 1-4(Fuc 1-3)GlcNAc-Le y Fuc 1-2Gal 1-4(Fuc 1-3)GlcNAc-HSO 3 Le x HSO 3-3Gal 1-4(Fuc 1-3)GlcNAc-HSO 3 Le a HSO 3-3Gal 1-3(Fuc 1-4)GlcNAc-SiaLe x Neu5Ac 2-3Gal 1-4(Fuc 1-3)GlcNAc-Sia 2 Neu5Ac 2-8Neu5Ac-3ЈSL Neu5Ac 2-3Gal 1-4Glc-T Gal 1-3GalNAc-T n GalNAc-SiaT n Neu5Ac 2-6GalNAc-asialoGM1 Gal 1-3GalNAc 1-4Gal 1-4Glcglucitol HOCH 2 (CHOH) 4 CH 2
Резюме. Совершенствование методов лечения меланомы кожи, увеличение их эффективности и безопаснос... more Резюме. Совершенствование методов лечения меланомы кожи, увеличение их эффективности и безопасности является основной медицинской проблемой в лечении меланомы. В данном исследовании адоптивная иммунотерапия с использованием активированных in vitro лимфоцитов была проведена 15 пациентам с метастатической меланомой. Оценен фенотип лимфоцитов периферической крови и маркеры активации (HLA-DR, CD25, CD314, CD38, CD69) до и через 3-4 недели после иммунотерапии. Показано, что для пациентов данной группы характерно повышенное содержание в кровяном русле Тreg и CD25 + лимфоцитов, которое не изменилось и после иммунотерапии. Сопроводительная иммунотерапия в комбинации с химиотерапией привела к снижению абсолютного содержания лимфоцитов крови, В-и Т-лимфоцитов, Т-хелперов, NKT-клеток, CD314 + лимфоцитов, а также CD38 + лимфоцитов и незрелых Т-лимфоцитов (CD3 + CD38 + ) (р < 0,05). Однако, наблюдалась положительная динамика в увеличении относительного содержания NK-клеток до 32% и CD69 + NKклеток до 21% и значимое увеличение экспрессии HLA-DR на всех лимфоцитах (р < 0,05). Адоптивная иммунотерапия хорошо переносится больными, характеризуется отсутствием побочных эффектов и может рекомендоваться как сопроводительная к лучевой и химиотерапии.
Bioorganicheskaia khimiia
An experimental model system involving the modification of carbohydrate composition of the target... more An experimental model system involving the modification of carbohydrate composition of the target cell surface with neoglycolipids was developed for studying the role of surface carbohydrates of target cells in the NK-cell-mediated cytotoxicity. The polymeric glycoconjugates of the Glyc-PAA-PEA and Glyc-PAA(Flu)-PEA types (where Glyc was an oligosaccharide residue, PAA poly(acrylamide) polymer, and PEA the phosphatidylethanolamine residue, and Flu fluorescein residue) capable of incorporation into the cell membrane were synthesized. The optimum structures of neoglycoconjugates and conditions for their incorporation into K562 and Raji cell lines, which differ in their sensitivity to the NK-cell-mediated lysis were selected. The mechanism of association of glycoconjugates with the plasma cell membrane and the kinetics of their elimination from the cell surface were investigated using the fluorescent-labeled Glyc-PAA(Flu)-PEA derivatives. The spatial accessibility of the carbohydrate l...
Computational Imaging and Vision, 2005
The spatial relationship "between" is a notion which is intrinsically both fuzzy and contextual, ... more The spatial relationship "between" is a notion which is intrinsically both fuzzy and contextual, and depends in particular on the shape of the objects. The few existing definitions do not take into account these aspects. We propose here definitions which are based on morphological operators and a fuzzy notion of visibility, which correspond to the main intuitive acceptions of the relation. We distinguish between cases where objects have similar spatial extensions and cases where one object is much more extended than the other. These definitions are illustrated on real data from brain images.
Bioorganicheskaia khimiia, 1998
A model system was developed to study the role of cell surface oligosaccharides in cytotoxicity m... more A model system was developed to study the role of cell surface oligosaccharides in cytotoxicity mediated by natural killer (NK) cells. Polymeric glycoconjugates Glyc-PAA-PE and Glyc-PAA(Flu)-PE (where Glyc is the 3-aminopropyl Le(x) residue, PAA is the poly(N-2-hydroxyethylacrylamide) matrix, Flu is the residue of a fluorescein derivative, and PE is the phosphatidylethanolamine residue) were synthesized, and their association with the membranes of living K562 cells was studied.
Meditsinskaia tekhnika
The paper proposes a mathematical model of development of a cell population with a changing proli... more The paper proposes a mathematical model of development of a cell population with a changing proliferative activity. The model is based on the Markov branching process with cells of several types. A procedure for identifying the constructed model by experimental evidence is being developed. An example of model construction and assessment for cultured diploid fibroblasts is given.
According to some modern concepts of aging, the leading role in this process belongs to a prolife... more According to some modern concepts of aging, the leading role in this process belongs to a proliferation activity of the cells constituting the human or animal body (aging/n vivo) or a cell culture (aging/n v/tro, stationary aging) [6]. Because changes in the proliferation activity affect the cell growth kinetics, screening of geroprotectors and geropromotors can be implemented using corresponding model systems of cell populations. However, specific changes of cell growth kinetics induced by aging both in vivo and in vitro remain obscure. Various methods are presently used for studying these processes (auroradiography, cytofluorimetry, high-speed filming, cell counting in a Goryaev chamber, etc.), and there is a discrepancy, between the results obtained by different methods [7, 11]. This, in turn causes a controversial interpretation of the test results.
Reproduction in Domestic Animals, 2011
Culture techniques of antral follicle-like structure (AFLS) derived from cumulus-oocyte complexes... more Culture techniques of antral follicle-like structure (AFLS) derived from cumulus-oocyte complexes (COCs) might provide important insights into follicular development and oocyte maturation. This study was undertaken to investigate the effects of embedding bovine COCs individually (one COC) or in groups (4-5 COCs) in collagen gels on the formation of AFLS and the meiotic status of oocytes. The observations of AFLS formation were performed every second day for 14 days. The AFLS was formed at Day 2 or 4 after the start of culture (Day=0), irrespective of the culture methods. The mean diameters of AFLS during Days 4-14 using the individual culture method were significantly higher (p<0.05) than those using the group culture method. However, the AFLS formation rate in the individual culture method was significantly lower compared to that in the group culture method (26.1% vs 62.7%, p<0.01). Almost all oocytes had undergone the germinal vesicle breakdown stage, irrespective of the culture method or AFLS formation. In conclusion, comparison with the individual culture method revealed that the mean diameters of AFLS in the group culture method were smaller, but more COCs formed AFLS. The group culture method might be useful for evaluating the various hypotheses of follicular formation and interfollicular communication. However, improvement of the group culture system is necessary to prevent the meiotic resumption of oocytes, because the AFLS formation is dependent on the cumulus/granulosa cells surrounding oocytes.
Histochemistry and Cell Biology, 2007
Membrane-associated oligosaccharides are known to take part in interactions between natural kille... more Membrane-associated oligosaccharides are known to take part in interactions between natural killer (NK) cells and their targets and modulate NK cell activity. A model system was therefore developed using synthetic glycoconjugates as tools to modify the carbohydrate pattern on NK target cell surfaces. NK cells were then assessed for function in response to synthetic glycoconjugates, using both cytolysis-associated caspase 6 activation measured by Xow cytometry and IFN-production. Lipophilic neoglycoconjugates were synthesized to provide their easy incorporation into the target cell membranes and to make carbohydrate residues available for cell-cell interactions. While incorporation was successful based on Xuorescence monitoring, glycoconjugate incorporation did not evoke artifactual changes in surface antigen expression, and had no negative eVect on cell viability. Glycoconjugates contained Le x , sulfated Le x , and Le y sharing the common structure motif trisaccharide Le x were revealed to enhance cytotoxicity mediated speciWcally by CD16 + CD56 + NK cells. The glycoconjugate eVects were dependent on saccharide presentation in a polymeric form. Only polymeric, or clustered, but not monomeric glycoconjugates resulted in alteration of cytotoxicity in our system, suggesting that appropriate presentation is critical for carbohydrate recognition and subsequent biological eVects.
Высокая эффективность радионуклидных методов диагностики не вызывают сомнения. Являясь одним из н... more Высокая эффективность радионуклидных методов диагностики не вызывают сомнения. Являясь одним из наиболее информативных, точных и чув
Vaccines, 2021
In the last decade, an impressive advance was achieved in adoptive cell therapy (ACT), which has ... more In the last decade, an impressive advance was achieved in adoptive cell therapy (ACT), which has improved therapeutic potential and significant value in promising cancer treatment for patients. The ACT is based on the cell transfer of dendritic cells (DCs) and/or immune effector cells. DCs are often used as vaccine carriers or antigen-presenting cells (APCs) to prime naive T cells ex vivo or in vivo. Cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells are used as major tool effector cells for ACT. Despite the fact that NK cell immunotherapy is highly effective and promising against many cancer types, there are still some limitations, including insignificant infiltration, adverse conditions of the microenvironment, the immunosuppressive cellular populations, and the low cytotoxic activity in solid tumors. To overcome these difficulties, novel methods of NK cell isolation, expansion, and stimulation of cytotoxic activity should be designed. In this review, we discuss the basi...
Histochemistry and Cell Biology, 2007
Membrane-associated oligosaccharides are known to take part in interactions between natural kille... more Membrane-associated oligosaccharides are known to take part in interactions between natural killer (NK) cells and their targets and modulate NK cell activity. A model system was therefore developed using synthetic glycoconjugates as tools to modify the carbohydrate pattern on NK target cell surfaces. NK cells were then assessed for function in response to synthetic glycoconjugates, using both cytolysis-associated caspase 6 activation measured by Xow cytometry and IFN-production. Lipophilic neoglycoconjugates were synthesized to provide their easy incorporation into the target cell membranes and to make carbohydrate residues available for cell-cell interactions. While incorporation was successful based on Xuorescence monitoring, glycoconjugate incorporation did not evoke artifactual changes in surface antigen expression, and had no negative eVect on cell viability. Glycoconjugates contained Le x , sulfated Le x , and Le y sharing the common structure motif trisaccharide Le x were revealed to enhance cytotoxicity mediated speciWcally by CD16 + CD56 + NK cells. The glycoconjugate eVects were dependent on saccharide presentation in a polymeric form. Only polymeric, or clustered, but not monomeric glycoconjugates resulted in alteration of cytotoxicity in our system, suggesting that appropriate presentation is critical for carbohydrate recognition and subsequent biological eVects. Keywords NK cell • Neoglycoconjugate • Saccharide • Flow cytometry • Caspase Abbreviations DOPE Dioleoylphosphatidylethanolamine residue FBS Fetal bovine serum Fluo 5-[(5-Aminopenthyl) thioureidyl]Xuorescein residue Glyc Oligosaccharide residue PAA Poly(N-2-hydroxyethylacrylamide) PBMC Peripheral blood mononuclear cells B di Gal 1-3Gal-B tri Gal 1-3(Fuc 1-2)Gal-Le x Gal 1-4(Fuc 1-3)GlcNAc-Le y Fuc 1-2Gal 1-4(Fuc 1-3)GlcNAc-HSO 3 Le x HSO 3-3Gal 1-4(Fuc 1-3)GlcNAc-HSO 3 Le a HSO 3-3Gal 1-3(Fuc 1-4)GlcNAc-SiaLe x Neu5Ac 2-3Gal 1-4(Fuc 1-3)GlcNAc-Sia 2 Neu5Ac 2-8Neu5Ac-3ЈSL Neu5Ac 2-3Gal 1-4Glc-T Gal 1-3GalNAc-T n GalNAc-SiaT n Neu5Ac 2-6GalNAc-asialoGM1 Gal 1-3GalNAc 1-4Gal 1-4Glcglucitol HOCH 2 (CHOH) 4 CH 2
Резюме. Совершенствование методов лечения меланомы кожи, увеличение их эффективности и безопаснос... more Резюме. Совершенствование методов лечения меланомы кожи, увеличение их эффективности и безопасности является основной медицинской проблемой в лечении меланомы. В данном исследовании адоптивная иммунотерапия с использованием активированных in vitro лимфоцитов была проведена 15 пациентам с метастатической меланомой. Оценен фенотип лимфоцитов периферической крови и маркеры активации (HLA-DR, CD25, CD314, CD38, CD69) до и через 3-4 недели после иммунотерапии. Показано, что для пациентов данной группы характерно повышенное содержание в кровяном русле Тreg и CD25 + лимфоцитов, которое не изменилось и после иммунотерапии. Сопроводительная иммунотерапия в комбинации с химиотерапией привела к снижению абсолютного содержания лимфоцитов крови, В-и Т-лимфоцитов, Т-хелперов, NKT-клеток, CD314 + лимфоцитов, а также CD38 + лимфоцитов и незрелых Т-лимфоцитов (CD3 + CD38 + ) (р < 0,05). Однако, наблюдалась положительная динамика в увеличении относительного содержания NK-клеток до 32% и CD69 + NKклеток до 21% и значимое увеличение экспрессии HLA-DR на всех лимфоцитах (р < 0,05). Адоптивная иммунотерапия хорошо переносится больными, характеризуется отсутствием побочных эффектов и может рекомендоваться как сопроводительная к лучевой и химиотерапии.
Bioorganicheskaia khimiia
An experimental model system involving the modification of carbohydrate composition of the target... more An experimental model system involving the modification of carbohydrate composition of the target cell surface with neoglycolipids was developed for studying the role of surface carbohydrates of target cells in the NK-cell-mediated cytotoxicity. The polymeric glycoconjugates of the Glyc-PAA-PEA and Glyc-PAA(Flu)-PEA types (where Glyc was an oligosaccharide residue, PAA poly(acrylamide) polymer, and PEA the phosphatidylethanolamine residue, and Flu fluorescein residue) capable of incorporation into the cell membrane were synthesized. The optimum structures of neoglycoconjugates and conditions for their incorporation into K562 and Raji cell lines, which differ in their sensitivity to the NK-cell-mediated lysis were selected. The mechanism of association of glycoconjugates with the plasma cell membrane and the kinetics of their elimination from the cell surface were investigated using the fluorescent-labeled Glyc-PAA(Flu)-PEA derivatives. The spatial accessibility of the carbohydrate l...
Computational Imaging and Vision, 2005
The spatial relationship "between" is a notion which is intrinsically both fuzzy and contextual, ... more The spatial relationship "between" is a notion which is intrinsically both fuzzy and contextual, and depends in particular on the shape of the objects. The few existing definitions do not take into account these aspects. We propose here definitions which are based on morphological operators and a fuzzy notion of visibility, which correspond to the main intuitive acceptions of the relation. We distinguish between cases where objects have similar spatial extensions and cases where one object is much more extended than the other. These definitions are illustrated on real data from brain images.
Bioorganicheskaia khimiia, 1998
A model system was developed to study the role of cell surface oligosaccharides in cytotoxicity m... more A model system was developed to study the role of cell surface oligosaccharides in cytotoxicity mediated by natural killer (NK) cells. Polymeric glycoconjugates Glyc-PAA-PE and Glyc-PAA(Flu)-PE (where Glyc is the 3-aminopropyl Le(x) residue, PAA is the poly(N-2-hydroxyethylacrylamide) matrix, Flu is the residue of a fluorescein derivative, and PE is the phosphatidylethanolamine residue) were synthesized, and their association with the membranes of living K562 cells was studied.
Meditsinskaia tekhnika
The paper proposes a mathematical model of development of a cell population with a changing proli... more The paper proposes a mathematical model of development of a cell population with a changing proliferative activity. The model is based on the Markov branching process with cells of several types. A procedure for identifying the constructed model by experimental evidence is being developed. An example of model construction and assessment for cultured diploid fibroblasts is given.
According to some modern concepts of aging, the leading role in this process belongs to a prolife... more According to some modern concepts of aging, the leading role in this process belongs to a proliferation activity of the cells constituting the human or animal body (aging/n vivo) or a cell culture (aging/n v/tro, stationary aging) [6]. Because changes in the proliferation activity affect the cell growth kinetics, screening of geroprotectors and geropromotors can be implemented using corresponding model systems of cell populations. However, specific changes of cell growth kinetics induced by aging both in vivo and in vitro remain obscure. Various methods are presently used for studying these processes (auroradiography, cytofluorimetry, high-speed filming, cell counting in a Goryaev chamber, etc.), and there is a discrepancy, between the results obtained by different methods [7, 11]. This, in turn causes a controversial interpretation of the test results.
Reproduction in Domestic Animals, 2011
Culture techniques of antral follicle-like structure (AFLS) derived from cumulus-oocyte complexes... more Culture techniques of antral follicle-like structure (AFLS) derived from cumulus-oocyte complexes (COCs) might provide important insights into follicular development and oocyte maturation. This study was undertaken to investigate the effects of embedding bovine COCs individually (one COC) or in groups (4-5 COCs) in collagen gels on the formation of AFLS and the meiotic status of oocytes. The observations of AFLS formation were performed every second day for 14 days. The AFLS was formed at Day 2 or 4 after the start of culture (Day=0), irrespective of the culture methods. The mean diameters of AFLS during Days 4-14 using the individual culture method were significantly higher (p<0.05) than those using the group culture method. However, the AFLS formation rate in the individual culture method was significantly lower compared to that in the group culture method (26.1% vs 62.7%, p<0.01). Almost all oocytes had undergone the germinal vesicle breakdown stage, irrespective of the culture method or AFLS formation. In conclusion, comparison with the individual culture method revealed that the mean diameters of AFLS in the group culture method were smaller, but more COCs formed AFLS. The group culture method might be useful for evaluating the various hypotheses of follicular formation and interfollicular communication. However, improvement of the group culture system is necessary to prevent the meiotic resumption of oocytes, because the AFLS formation is dependent on the cumulus/granulosa cells surrounding oocytes.
Histochemistry and Cell Biology, 2007
Membrane-associated oligosaccharides are known to take part in interactions between natural kille... more Membrane-associated oligosaccharides are known to take part in interactions between natural killer (NK) cells and their targets and modulate NK cell activity. A model system was therefore developed using synthetic glycoconjugates as tools to modify the carbohydrate pattern on NK target cell surfaces. NK cells were then assessed for function in response to synthetic glycoconjugates, using both cytolysis-associated caspase 6 activation measured by Xow cytometry and IFN-production. Lipophilic neoglycoconjugates were synthesized to provide their easy incorporation into the target cell membranes and to make carbohydrate residues available for cell-cell interactions. While incorporation was successful based on Xuorescence monitoring, glycoconjugate incorporation did not evoke artifactual changes in surface antigen expression, and had no negative eVect on cell viability. Glycoconjugates contained Le x , sulfated Le x , and Le y sharing the common structure motif trisaccharide Le x were revealed to enhance cytotoxicity mediated speciWcally by CD16 + CD56 + NK cells. The glycoconjugate eVects were dependent on saccharide presentation in a polymeric form. Only polymeric, or clustered, but not monomeric glycoconjugates resulted in alteration of cytotoxicity in our system, suggesting that appropriate presentation is critical for carbohydrate recognition and subsequent biological eVects.