المؤلفون: Sorokin, Maksim, Buzdin, Anton, Guryanova, Anastasia, Efimov, Victor, Suntsova, Maria, Zolotovskaia, Marianna, Koroleva, Elena, Sekacheva, Marina, Tkachev, Victor, Garazha, Andrew, Kremenchutckaya, Kristina, Drobyshev, Aleksey, Seryakov, Aleksander, Gudkov, Alexander, Alekseenko, Irina, Rakitina, Olga, Kostina, Maria, Vladimirova, Uliana, Moisseev, Aleksey, Bulgin, Dmitry, Radomskaya, Elena, Shestakov, Viktor, Baklaushev, Vladimir, Prassolov, Vladimir, Shegay, Petr, Poddubskaya, Elena, Gaifullin, Nurshat, Li, Xinmin

مصطلحات موضوعية: Autopsy, Cancer research, Differential gene expression analysis, Healthy tissue controls, Molecular pathology, Molecular pathways, RNA sequencing, Tumor matched pathologically normal tissues

الوصف: Normal tissues are essential for studying disease-specific differential gene expression. However, healthy human controls are typically available only in postmortal/autopsy settings. In cancer research, fragments of pathologically normal tissue adjacent to tumor site are frequently used as the controls. However, it is largely underexplored how cancers can systematically influence gene expression of the neighboring tissues. Here we performed a comprehensive pan-cancer comparison of molecular profiles of solid tumor-adjacent and autopsy-derived healthy normal tissues. We found a number of systemic molecular differences related to activation of the immune cells, intracellular transport and autophagy, cellular respiration, telomerase activation, p38 signaling, cytoskeleton remodeling, and reorganization of the extracellular matrix. The tumor-adjacent tissues were deficient in apoptotic signaling and negative regulation of cell growth including G2/M cell cycle transition checkpoint. We also detected an extensive rearrangement of the chemical perception network. Molecular targets of 32 and 37 cancer drugs were over- or underexpressed, respectively, in the tumor-adjacent norms. These processes may be driven by molecular events that are correlated between the paired cancer and adjacent normal tissues, that mostly relate to inflammation and regulation of intracellular molecular pathways such as the p38, MAPK, Notch, and IGF1 signaling. However, using a model of macaque postmortal tissues we showed that for the 30 min - 24-hour time frame at 4ºC, an RNA degradation pattern in lung biosamples resulted in an artifact differential expression profile for 1140 genes, although no differences could be detected in liver. Thus, such concerns should be addressed in practice.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/1rj591mkTest

المؤلفون: Rozenberg, Julian M., Buzdin, Anton A., Mohammad, Tharaa, Rakitina, Olga A., Didych, Dmitry A., Pleshkan, Victor V., Alekseenko, Irina V.

المساهمون: Russian Science Foundation

المصدر: Frontiers in Immunology ; volume 14 ; ISSN 1664-3224

الوصف: Treatment of metastatic disease remains among the most challenging tasks in oncology. One of the early events that predicts a poor prognosis and precedes the development of metastasis is the occurrence of clusters of cancer cells in the blood flow. Moreover, the presence of heterogeneous clusters of cancerous and noncancerous cells in the circulation is even more dangerous. Review of pathological mechanisms and biological molecules directly involved in the formation and pathogenesis of the heterotypic circulating tumor cell (CTC) clusters revealed their common properties, which include increased adhesiveness, combined epithelial-mesenchymal phenotype, CTC-white blood cell interaction, and polyploidy. Several molecules involved in the heterotypic CTC interactions and their metastatic properties, including IL6R, CXCR4 and EPCAM, are targets of approved or experimental anticancer drugs. Accordingly, analysis of patient survival data from the published literature and public datasets revealed that the expression of several molecules affecting the formation of CTC clusters predicts patient survival in multiple cancer types. Thus, targeting of molecules involved in CTC heterotypic interactions might be a valuable strategy for the treatment of metastatic cancers.

الإتاحة: https://doi.org/10.3389/fimmu.2023.1099921Test

المؤلفون: Rakitina, Olga A., Kuzmich, Alexey I., Bezborodova, Olga A., Kondratieva, Sofia A., Pleshkan, Victor V., Zinovyeva, Marina V., Didych, Dmitry A., Sass, Aleksandr V., Snezhkov, Eugene V., Kostina, Maria B., Koksharov, Maksim O., Alekseenko, Irina V.

المصدر: Frontiers in Immunology; 2024, p1-14, 14p

مصطلحات موضوعية: GENETIC transformation, CYTOTOXIC T cells, DRUG side effects, COLON cancer, MYELOID cells

مستخلص: Background: Immune checkpoint blockade (ICB) is rapidly becoming a standard of care in the treatment of many cancer types. However, the subset of patients who respond to this type of therapy is limited. Anotherway to promote antitumoral immunity is the use of immunostimulatory molecules, such as cytokines or T cell co-stimulators. The systemic administration of immunotherapeutics leads to significant immune-related adverse events (irAEs), therefore, the localized antitumoral action is needed. One way to achieve this is intratumoral non-viral gene-immune therapy, which allows for prolonged and localized gene expression, and multiple drug administration. In this study, we combined the previously described non-viral gene delivery system, PEG-PEI-TAT copolymer, PPT, with murine OX40L-encoding plasmid DNA. Methods: The resulting OX40L/PPT nanoparticles were characterized via gel mobility assay, dynamic light scattering analysis and in vitro transfection efficiency evaluation. The antitumoral efficacy of intratumorally (i.t.) administered nanoparticles was estimated using subcutaneously (s.c.) implanted CT26 (colon cancer), B16F0 (melanoma) and 4T1 (breast cancer) tumor models. The dynamics of stromal immune cell populations was analyzed using flow cytometry. Weight loss and cachexia were used as irAE indicators. The effect of combination of i.t. OX40L/PPT with intraperitoneal PD-1 ICB was estimated in s.c. CT26 tumor model. Results: The obtained OX40L/PPT nanoparticles had properties applicable for cell transfection and provided OX40L protein expression in vitro in all three investigated cancer models. We observed that OX40L/PPT treatment successfully inhibited tumor growth in B16F0 and CT26 tumor models and showed a tendency to inhibit 4T1 tumor growth. In B16F0 tumor model, OX40L/PPT treatment led to the increase in antitumoral effector NK and T killer cells and to the decrease in pro-tumoral myeloid cells populations within tumor stroma. No irAE signs were observed in all 3 tumor models, which indicates good treatment tolerability in mice. Combining OX40L/PPT with PD-1 ICB significantly improved treatment efficacy in the CT26 subcutaneous colon cancer model, providing protective immunity against CT26 colon cancer cells. Conclusion: Overall, the anti-tumor efficacy observed with OX40L non-viral gene therapy, whether administered alone or in combination with ICB, highlights its potential to revolutionize cancer gene therapy, thus paving the way for unprecedented advancements in the cancer therapy field. [ABSTRACT FROM AUTHOR]

: Copyright of Frontiers in Immunology is the property of Frontiers Media S.A. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Rakitina, Olga, A. Kondratieva, Sofia, Bezborodova, Olga, Kuzmich, Alexey, Zhukova, Lyudmila, Alekseenko, Irina V., Didych, Dmitry

مصطلحات موضوعية: Bioinformatics and computational biology not elsewhere classified, Cancer cell biology, Animal cell and molecular biology, Solid tumours, Tumour immunology

الوصف: This file represents Supplementary Data for BMC Research Notes article entitled "The T-cell dependent transcriptomic changes in subcutaneous murine colon cancer model CT26". The file includes Supplementary Figures 1 and 2, Supplementary Tables 1 and 2, and Supplementary Methods. ...

الإتاحة: https://doi.org/10.6084/m9.figshare.25908406Test
https://figshare.com/articles/figure/The_T-cell_dependent_transcriptomic_changes_in_subcutaneous_murine_colon_cancer_model_CT26_-_Supplementary_Data/25908406Test

المؤلفون: Rakitina Olga Nikolaevna

المصدر: Vestnik Volgogradskogo Gosudarstvennogo Universiteta. Seriâ 2. Âzykoznanie, Vol 23, Iss 4, Pp 93-99 (2014)

مصطلحات موضوعية: landscape term, semantics, semantic word structure, connotation, denotation, folk text., Language and Literature

الوصف: German folk landscape lexis, its functioning and text components' influence are studied in the aspect of interaction of some factors, such as a key role of denotative components while conceptualizing landscape's objects and their material characteristics; folk genre's purpose while actualizing its connotative features of social space; the influence of text units (actualizators) and their semantics on 'expansion' of meanings in landscape term structures. Due to the analysis of functional features of these words, two main features of the space have been determined – representation of landscape's objects and their material characteristics (size, length, quantity, material, stuff) and realization of their social features ('safe/unsafe', 'unavailable/available', 'useless/useful', etc.). The dominance of the material component in the semantic structure of landscape terms is noted in the designations of mountainous terrain. The social characteristics are presented with subjective interpretation of individual properties and elements of the relief. The conditions of interaction between the members and the landscape contexts are disclosed in the analysis of phrases in which the social characteristics of the complexes express meanings ('size', 'unavailable', 'safe', etc.). The study shows that folk texts of different genres (fairy tales, proverbs and sayings) is a valuable source of lexical material, as they reflect the stable interactions between connotative components and the semantics of fairy tales texts, proverbs and sayings. Thus, they should be taken into consideration while translating German folk texts to Russian language.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1998-9911Test; https://doaj.org/toc/2409-1979Test

الوصول الحر: https://doaj.org/article/ef321f9fc6ff4e1eb10b1b546e3fb1c3Test

المؤلفون: Druzhkova, Irina, Shirmanova, Marina, Ignatova, Nadezhda, Dudenkova, Varvara, Lukina, Maria, Zagaynova, Elena, Safina, Dina, Kostrov, Sergey, Didych, Dmitry, Kuzmich, Alexey, Sharonov, George, Rakitina, Olga, Alekseenko, Irina, Sverdlov, Eugene

المصدر: International Journal of Molecular Sciences; Nov2020, Vol. 21 Issue 21, p8119, 1p

مصطلحات موضوعية: CANCER cells, COLORECTAL cancer, COLLAGEN, SECOND harmonic generation, EXTRACELLULAR matrix, CANCER cell culture

مستخلص: Collagen, the main non-cellular component of the extracellular matrix (ECM), is profoundly reorganized during tumorigenesis and has a strong impact on tumor behavior. The main source of collagen in tumors is cancer-associated fibroblasts. Cancer cells can also participate in the synthesis of ECM; however, the contribution of both types of cells to collagen rearrangements during the tumor progression is far from being clear. Here, we investigated the processes of collagen biosynthesis and remodeling in parallel with the transcriptome changes during cancer cells and fibroblasts interactions. Combining immunofluorescence, RNA sequencing, and second harmonic generation microscopy, we have explored the relationships between the ratio of epithelial (E) and mesenchymal (M) components of hybrid E/M cancer cells, their ability to activate fibroblasts, and the contributions of both cell types to collagen remodeling. To this end, we studied (i) co-cultures of colorectal cancer cells and normal fibroblasts in a collagen matrix, (ii) patient-derived cancer-associated fibroblasts, and (iii) mouse xenograft models. We found that the activation of normal fibroblasts that form dense collagen networks consisting of large, highly oriented fibers depends on the difference in E/M ratio in the cancer cells. The more-epithelial cells activate the fibroblasts more strongly, which correlates with a dense and highly ordered collagen structure in tumors in vivo. The more-mesenchymal cells activate the fibroblasts to a lesser degree; on the other hand, this cell line has a higher innate collagen remodeling capacity. Normal fibroblasts activated by cancer cells contribute to the organization of the extracellular matrix in a way that is favorable for migratory potency. At the same time, in co-culture with epithelial cancer cells, the contribution of fibroblasts to the reorganization of ECM is more pronounced. Therefore, one can expect that targeting the ability of epithelial cancer cells to activate normal fibroblasts may provide a new anticancer therapeutic strategy. [ABSTRACT FROM AUTHOR]

: Copyright of International Journal of Molecular Sciences is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Kuzmich, Alexey^1,2 (AUTHOR) akuzmich@ibch.ru, Rakitina, Olga² (AUTHOR) dmitrydid@gmail.com, Didych, Dmitry² (AUTHOR) vk@ibch.ru, Potapov, Victor² (AUTHOR) mzinov@mail.ru, Zinovyeva, Marina² (AUTHOR), Alekseenko, Irina^1,2,3 (AUTHOR) edsverd@gmail.com, Sverdlov, Eugene^1,4 (AUTHOR)

المصدر: Polymers (20734360). Aug2020, Vol. 12 Issue 8, p1695. 1p.

مصطلحات موضوعية: *PLATELET-derived growth factor receptors, *GREEN fluorescent protein, *FIBROBLASTS, *DNA, *NUCLEAR proteins, *GENE transfection

مستخلص: Nuclear proteins, like histone H2A, are promising non-viral carriers for gene delivery since they are biocompatible, biodegradable, bear intrinsic nuclear localization signal, and are easy to modify. The addition of surface-protein-binding ligand to histone H2A may increase its DNA delivery efficiency. Tumor microenvironment (TME) is a promising target for gene therapy since its surface protein repertoire is more stable than that of cancer cells. Cancer-associated fibroblasts (CAFs) are important components of TME, and one of their surface markers is beta-type platelet-derived growth factor receptor (PDGFRβ). In this study, we fused histone H2A with PDGFRβ-binding peptide, YG2, to create a novel non-viral fibroblast-targeting DNA carrier, H2A-YG2. The transfection efficiency of histone complexes with pDNA encoding a bicistronic reporter (enhanced green fluorescent protein, EGFP, and firefly luciferase) in PDGFRβ-positive and PDGFRβ-negative cells was estimated by luciferase assay and flow cytometry. The luciferase activity, percentage of transfected cells, and overall EGFP fluorescence were increased due to histone modification with YG2 only in PDGFRβ-positive cells. We also estimated the internalization efficiency of DNA-carrier complexes using tetramethyl-rhodamine-labeled pDNA. The ligand fusion increased DNA internalization only in the PDGFRβ-positive cells. In conclusion, we demonstrated that the H2A-YG2 carrier targeted gene delivery to PDGFRβ-positive tumor stromal cells. [ABSTRACT FROM AUTHOR]