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Article: The Multifaceted Role of Connexins in Tumor Microenvironment Initiation and Maintenance.

Kutova, Olga M / Pospelov, Anton D / Balalaeva, Irina V

2023 Volume 12, Issue 2

Abstract: Today's research on the processes of carcinogenesis and the vital activity of tumor tissues implies more attention be paid to constituents of the tumor microenvironment and their interactions. These interactions between cells in the tumor ... ...

Abstract	Today's research on the processes of carcinogenesis and the vital activity of tumor tissues implies more attention be paid to constituents of the tumor microenvironment and their interactions. These interactions between cells in the tumor microenvironment can be mediated via different types of protein junctions. Connexins are one of the major contributors to intercellular communication. They form the gap junctions responsible for the transfer of ions, metabolites, peptides, miRNA, etc., between neighboring tumor cells as well as between tumor and stromal cells. Connexin hemichannels mediate purinergic signaling and bidirectional molecular transport with the extracellular environment. Additionally, connexins have been reported to localize in tumor-derived exosomes and facilitate the release of their cargo. A large body of evidence implies that the role of connexins in cancer is multifaceted. The pro- or anti-tumorigenic properties of connexins are determined by their abundance, localization, and functionality as well as their channel assembly and non-channel functions. In this review, we have summarized the data on the contribution of connexins to the formation of the tumor microenvironment and to cancer initiation and progression.
Language	English
Publishing date	2023-01-28
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2661517-4
ISSN	2079-7737
ISSN	2079-7737
DOI	10.3390/biology12020204
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Article ; Online: The Multifaceted Role of Connexins in Tumor Microenvironment Initiation and Maintenance

Kutova, Olga M. / Pospelov, Anton D. / Balalaeva, Irina V.

Biology (Basel). 2023 Jan. 28, v. 12, no. 2

2023

Abstract: Today’s research on the processes of carcinogenesis and the vital activity of tumor tissues implies more attention be paid to constituents of the tumor microenvironment and their interactions. These interactions between cells in the tumor ... ...

Abstract	Today’s research on the processes of carcinogenesis and the vital activity of tumor tissues implies more attention be paid to constituents of the tumor microenvironment and their interactions. These interactions between cells in the tumor microenvironment can be mediated via different types of protein junctions. Connexins are one of the major contributors to intercellular communication. They form the gap junctions responsible for the transfer of ions, metabolites, peptides, miRNA, etc., between neighboring tumor cells as well as between tumor and stromal cells. Connexin hemichannels mediate purinergic signaling and bidirectional molecular transport with the extracellular environment. Additionally, connexins have been reported to localize in tumor-derived exosomes and facilitate the release of their cargo. A large body of evidence implies that the role of connexins in cancer is multifaceted. The pro- or anti-tumorigenic properties of connexins are determined by their abundance, localization, and functionality as well as their channel assembly and non-channel functions. In this review, we have summarized the data on the contribution of connexins to the formation of the tumor microenvironment and to cancer initiation and progression.
Keywords	carcinogenesis ; cell communication ; connexins ; exosomes ; metabolites ; microRNA ; neoplasms ; peptides
Language	English
Dates of publication	2023-0128
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article ; Online
ZDB-ID	2661517-4
ISSN	2079-7737
ISSN	2079-7737
DOI	10.3390/biology12020204
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Article ; Online: Ferroptosis and Photodynamic Therapy Synergism: Enhancing Anticancer Treatment.

Mishchenko, Tatiana A / Balalaeva, Irina V / Vedunova, Maria V / Krysko, Dmitri V

Trends in cancer

2021 Volume 7, Issue 6, Page(s) 484–487

Abstract: Photodynamic therapy (PDT) is widely used in cancer treatment; however, several challenges compromise its efficiency. We propose a synergistic action between PDT and ferroptotic cell death. PDT acts as a source of reactive oxygen species for the Fenton ... ...

Abstract	Photodynamic therapy (PDT) is widely used in cancer treatment; however, several challenges compromise its efficiency. We propose a synergistic action between PDT and ferroptotic cell death. PDT acts as a source of reactive oxygen species for the Fenton reaction, which may reinforce ferroptosis induction and increase PDT efficacy in anticancer therapy.
MeSH term(s)	Animals ; Carbolines/administration & dosage ; Cell Line, Tumor ; Chlorophyllides/administration & dosage ; Ferroptosis/drug effects ; Humans ; Mice ; Nanoparticle Drug Delivery System ; Neoplasms/drug therapy ; Photochemotherapy/methods ; Photosensitizing Agents/administration & dosage ; Piperazines/administration & dosage ; Reactive Oxygen Species ; Sorafenib ; Treatment Outcome
Chemical Substances	Carbolines ; Chlorophyllides ; Nanoparticle Drug Delivery System ; Photosensitizing Agents ; Piperazines ; RSL3 compound ; Reactive Oxygen Species ; erastin ; phytochlorin (5S2CCF3T1Z) ; Sorafenib (9ZOQ3TZI87)
Language	English
Publishing date	2021-02-25
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2852626-0
ISSN	2405-8025 ; 2405-8033 ; 2405-8033
ISSN (online)	2405-8025 ; 2405-8033
ISSN	2405-8033
DOI	10.1016/j.trecan.2021.01.013
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Article ; Online: Physics of Ice Nucleation and Antinucleation: Action of Ice-Binding Proteins.

Melnik, Bogdan S / Glukhova, Ksenia A / Sokolova Voronova, Evgeniya A / Balalaeva, Irina V / Garbuzynskiy, Sergiy O / Finkelstein, Alexei V

Biomolecules

2023 Volume 14, Issue 1

Abstract: Ice-binding proteins are crucial for the adaptation of various organisms to low temperatures. Some of these, called antifreeze proteins, are usually thought to inhibit growth and/or recrystallization of ice crystals. However, prior to these events, ice ... ...

Abstract	Ice-binding proteins are crucial for the adaptation of various organisms to low temperatures. Some of these, called antifreeze proteins, are usually thought to inhibit growth and/or recrystallization of ice crystals. However, prior to these events, ice must somehow appear in the organism, either coming from outside or forming inside it through the nucleation process. Unlike most other works, our paper is focused on ice nucleation and not on the behavior of the already-nucleated ice, its growth, etc. The nucleation kinetics is studied both theoretically and experimentally. In the theoretical section, special attention is paid to surfaces that bind ice stronger than water and thus can be "ice nucleators", potent or relatively weak; but without them, ice cannot be nucleated in any way in calm water at temperatures above -30 °C. For experimental studies, we used: (i) the ice-binding protein mIBP83, which is a previously constructed mutant of a spruce budworm
MeSH term(s)	Humans ; Carrier Proteins ; Ice ; Physics ; Cold Temperature ; Antifreeze Proteins/genetics
Chemical Substances	Carrier Proteins ; Ice ; Antifreeze Proteins
Language	English
Publishing date	2023-12-30
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2701262-1
ISSN	2218-273X ; 2218-273X
ISSN (online)	2218-273X
ISSN	2218-273X
DOI	10.3390/biom14010054
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Article: Gold standard assessment of immunogenic cell death induced by photodynamic therapy: From in vitro to tumor mouse models and anti-cancer vaccination strategies.

Mishchenko, Tatiana A / Balalaeva, Irina V / Turubanova, Victoria D / Saviuk, Mariia O / Shilyagina, Natalia Yu / Krysko, Olga / Vedunova, Maria V / Krysko, Dmitri V

Methods in cell biology

2023 Volume 183, Page(s) 203–264

Abstract: The discovery of the concept of immunogenic cell death (ICD) is a cornerstone in the development of novel anti-cancer immunotherapeutic approaches. Induction of the ICD pathway by specific anti-cancer therapeutic regimens can eliminate cancer cells by ... ...

Abstract	The discovery of the concept of immunogenic cell death (ICD) is a cornerstone in the development of novel anti-cancer immunotherapeutic approaches. Induction of the ICD pathway by specific anti-cancer therapeutic regimens can eliminate cancer cells by directly killing them during therapy and by activation of strong and specific anti-cancer immunity, leading to a long-lasting immunological memory that prevents cancer recurrence. ICD encompasses different forms of regulated cell death and can be triggered by many anti-cancer treatment modalities, including photodynamic therapy (PDT). PDT is a multistep procedure involving the accumulation of a light-sensitive dye known as a photosensitizer (PS) in tumor cells, followed by its activation by irradiation with a light of an appropriate wavelength. In the presence of molecular oxygen, the irradiated PS leads to the generation of cytotoxic reactive oxygen species, which can lead to ICD induction in the cancer cells. Here, we first describe in vitro methods to help optimize the PDT procedure for a specific PS. We also provide a collection of protocols and techniques for assessing ICD in vitro, including analysis of the emission of damage associated molecular patterns (DAMPs), efferocytosis, and the maturation and activation state of antigen presenting cells. Next, we describe in detail protocols for diverse tumor mouse models for assessing and characterizing ICD in vivo, such as murine tumor vaccination models. Finally, as an immunotherapeutic vaccine, we suggest using either PDT-induced dead cancer cells, preferably undergoing ICD, or dendritic cells loaded with lysates of PDT-induced cancer cells in a syngeneic orthotopic glioma model. Overall, this methodological article provides a quantitative, comprehensive set of validated tools that can be successfully used, with some adaptations, to identify, optimize and validate novel PSs in vitro and in vivo for the efficient induction of ICD during photodynamic treatment.
MeSH term(s)	Animals ; Mice ; Immunogenic Cell Death ; Neoplasms/drug therapy ; Cell Death ; Photochemotherapy ; Vaccination ; Cell Line, Tumor
Language	English
Publishing date	2023-10-19
Publishing country	United States
Document type	Journal Article
ISSN	0091-679X
ISSN	0091-679X
DOI	10.1016/bs.mcb.2023.05.003
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Article ; Online: A first-in-class β-glucuronidase responsive conjugate for selective dual targeted and photodynamic therapy of bladder cancer.

Otvagin, Vasilii F / Krylova, Lubov V / Peskova, Nina N / Kuzmina, Natalia S / Fedotova, Ekaterina A / Nyuchev, Alexander V / Romanenko, Yuliya V / Koifman, Oscar I / Vatsadze, Sergey Z / Schmalz, Hans-Günther / Balalaeva, Irina V / Fedorov, Alexey Yu

European journal of medicinal chemistry

2024 Volume 269, Page(s) 116283

Abstract: In this report, we present a novel prodrug strategy that can significantly improve the efficiency and selectivity of combined therapy for bladder cancer. Our approach involved the synthesis of a conjugate based on a chlorin- ... ...

Abstract	In this report, we present a novel prodrug strategy that can significantly improve the efficiency and selectivity of combined therapy for bladder cancer. Our approach involved the synthesis of a conjugate based on a chlorin-e
MeSH term(s)	Humans ; Glucuronidase ; Photochemotherapy ; Photosensitizing Agents/pharmacology ; Photosensitizing Agents/therapeutic use ; Urinary Bladder Neoplasms/drug therapy ; Porphyrins/pharmacology ; Cell Line, Tumor ; Nanoparticles/therapeutic use
Chemical Substances	Glucuronidase (EC 3.2.1.31) ; Photosensitizing Agents ; Porphyrins
Language	English
Publishing date	2024-03-05
Publishing country	France
Document type	Journal Article
ZDB-ID	188597-2
ISSN	1768-3254 ; 0009-4374 ; 0223-5234
ISSN (online)	1768-3254
ISSN	0009-4374 ; 0223-5234
DOI	10.1016/j.ejmech.2024.116283
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Article: Effect of chronic β-radiation on long-distance electrical signals in wheat and their role in adaptation to heat stress

Grinberg, Marina A / Gudkov, Sergey V / Balalaeva, Irina V / Gromova, Ekaterina / Sinitsyna, Yuliya / Sukhov, Vladimir / Vodeneev, Vladimir

Environmental and experimental botany. 2021 Apr., v. 184

2021

Abstract: Plants are unavoidably exposed to ionizing radiation (IR) from natural and anthropogenic sources. Along with the chronic irradiation, plants are influenced by other environmental stress factors, to which they must adapt. We suppose that high background ... ...

Abstract	Plants are unavoidably exposed to ionizing radiation (IR) from natural and anthropogenic sources. Along with the chronic irradiation, plants are influenced by other environmental stress factors, to which they must adapt. We suppose that high background radiation modifies plant response to environmental stressors by influencing the stress signaling which are the crucial players in induction and orchestrating the formation of plant adaptation. Chronic β-radiation (31.3 μGy/h) does not cause pronounced oxidative stress and significant changes in morphometric parameters of wheat seedlings (Triticum aestivum L.). At the same time, chronic IR exposure causes slight activation of transpiration and assimilation, and activates H⁺-ATPase-dependent transmembrane transport. In irradiated plants, there is an increase in the amplitude, velocity and propagation distance of electrical signals induced by a local stimulus. Accordingly, in irradiated plants, photosynthesis and transpiration responses caused by an electrical signal are significantly enhanced. The opposite effect of the electric signal on heat stress resistance was found: after the signal passing, the resistance of control plants increases, but it decreases for irradiated plants. It is assumed that the inversion of the effect is resulted from the enhanced responses of transpiration due to the electrical signals amplification.
Keywords	Triticum aestivum ; anthropogenic activities ; heat stress ; ionizing radiation ; irradiation ; morphometry ; oxidative stress ; photosynthesis ; plant adaptation ; plant response ; seedlings ; stress tolerance ; transpiration ; velocity ; wheat
Language	English
Dates of publication	2021-04
Publishing place	Elsevier B.V.
Document type	Article
Note	NAL-light
ZDB-ID	195968-2
ISSN	0098-8472
ISSN	0098-8472
DOI	10.1016/j.envexpbot.2021.104378
Database	NAL-Catalogue (AGRICOLA)

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Article: Comparative Analysis of Tetra(2-naphthyl)tetracyano-porphyrazine and Its Iron Complex as Photosensitizers for Anticancer Photodynamic Therapy.

Shestakova, Lydia N / Lyubova, Tatyana S / Lermontova, Svetlana A / Belotelov, Artem O / Peskova, Nina N / Klapshina, Larisa G / Balalaeva, Irina V / Shilyagina, Natalia Y

Pharmaceutics

2022 Volume 14, Issue 12

Abstract: Photodynamic therapy (PDT) is a rapidly developing modality of primary and adjuvant anticancer treatment. The main trends today are the search for new effective photodynamic agents and the creation of targeted delivery systems with the function of ... ...

Abstract	Photodynamic therapy (PDT) is a rapidly developing modality of primary and adjuvant anticancer treatment. The main trends today are the search for new effective photodynamic agents and the creation of targeted delivery systems with the function of controlling the release of the agent in the tumor. Recently, the new group of cyanoarylporphyrazine dyes was reported, which combine the properties of photosensitizers and sensors of the local microenvironment. Such unique characteristics allow the release of the photosensitizer from the transport carrier to be assessed in real time in vivo. The aim of the present work was to compare the photophysical and photobiological properties of tetra(2-naphthyl)tetracyanoporphyrazine and its newly synthesized Fe(II) complex. We have shown that the chelation of the Fe(II) cation with the porphyrazine macrocycle leads to a decrease in molar extinction and an increase in the quantum yield of fluorescence and photostability. We demonstrate that the iron cation significantly affects the rate of dye accumulation in cells, the dark toxicity and photodynamic activity, and the direction of the changes depends on the particular cell line. However, in all the cases, the photodynamic index of a metal complex was higher than that of a metal-free base. In general, both of the compounds were found to be very promising for PDT, including for the use with transport delivery systems, and can be recommended for further in vivo studies.
Language	English
Publishing date	2022-11-30
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527217-2
ISSN	1999-4923
ISSN	1999-4923
DOI	10.3390/pharmaceutics14122655
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Article ; Online: Real-Time Fluorescence Visualization and Quantitation of Cell Growth and Death in Response to Treatment in 3D Collagen-Based Tumor Model.

Sencha, Ludmila M / Dobrynina, Olga E / Pospelov, Anton D / Guryev, Evgenii L / Peskova, Nina N / Brilkina, Anna A / Cherkasova, Elena I / Balalaeva, Irina V

International journal of molecular sciences

2022 Volume 23, Issue 16

Abstract: The use of 3D in vitro tumor models has become a common trend in cancer biology studies as well as drug screening and preclinical testing of drug candidates. The transition from 2D to 3D matrix-based cell cultures requires modification of methods for ... ...

Abstract	The use of 3D in vitro tumor models has become a common trend in cancer biology studies as well as drug screening and preclinical testing of drug candidates. The transition from 2D to 3D matrix-based cell cultures requires modification of methods for assessing tumor growth. We propose the method for assessing the growth of tumor cells in a collagen hydrogel using macro-scale registration and quantification of the gel epi-fluorescence. The technique does not require gel destruction, can be used for real-time observation of fast (in seconds) cellular responses and demonstrates high agreement with cell counting approaches or measuring total DNA content. The potency of the method was proven in experiments aimed at testing cytotoxic activity of chemotherapeutic drug (cisplatin) and recombinant targeted toxin (DARPin-LoPE) against two different tumor cell lines genetically labelled with fluorescent proteins. Moreover, using fluorescent proteins with sensor properties allows registration of dynamic changes in cells' metabolism, which was shown for the case of sensor of caspase 3 activity.
MeSH term(s)	Cell Line, Tumor ; Cell Proliferation ; Cisplatin ; Collagen ; Fluorescence
Chemical Substances	Collagen (9007-34-5) ; Cisplatin (Q20Q21Q62J)
Language	English
Publishing date	2022-08-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23168837
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Article: Far-Red Fluorescent Murine Glioma Model for Accurate Assessment of Brain Tumor Progression.

Mishchenko, Tatiana A / Balalaeva, Irina V / Klimenko, Maria O / Brilkina, Anna A / Peskova, Nina N / Guryev, Evgenii L / Krysko, Dmitri V / Vedunova, Maria V

Cancers

2022 Volume 14, Issue 15

Abstract: Glioma is the most common brain tumor, for which no significant improvement in life expectancy and quality of life is yet possible. The creation of stable fluorescent glioma cell lines is a promising tool for in-depth studies of the molecular mechanisms ... ...

Abstract	Glioma is the most common brain tumor, for which no significant improvement in life expectancy and quality of life is yet possible. The creation of stable fluorescent glioma cell lines is a promising tool for in-depth studies of the molecular mechanisms of glioma initialization and pathogenesis, as well as for the development of new anti-cancer strategies. Herein, a new fluorescent glioma GL261-kat cell line stably expressing a far-red fluorescent protein (TurboFP635; Katushka) was generated and characterized, and then validated in a mouse orthotopic glioma model. By using epi-fluorescence imaging, we detect the fluorescent glioma GL261-kat cells in mice starting from day 14 after the inoculation of glioma cells, and the fluorescence signal intensity increases as the glioma progresses. Tumor growth is confirmed by magnetic resonance imaging and histology. A gradual development of neurological deficit and behavioral alterations in mice is observed during glioma progression. In conclusion, our results demonstrate the significance and feasibility of using the novel glioma GL261-kat cell line as a model of glioma biology, which can be used to study the initialization of glioma and monitor its growth by lifetime non-invasive tracking of glioma cells, with the prospect of monitoring the response to anti-cancer therapy.
Language	English
Publishing date	2022-08-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14153822
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