Identification of the xenograft and its ascendant sphere-forming cell line as belonging to EBV-induced lymphoma, and characterization of the status of sphere-forming cells

Долгова, Е. В.; Petrova, Daria D.; Proskurina, Anastasia S.; Ritter, Genrikh S.; Kisaretova, Polina E.; Potter, Ekaterina A.; Efremov, Yaroslav R.; Bayborodin, Sergey I.; Karamysheva, T. V.; Romanenko, Margarita V.; Netesov, Sergey V.; Taranov, Oleg S.; Останин, А. А.; Черных, Е. Р.; Bogachev, Sergey S.

doi:10.1186/s12935-019-0842-x

Cited by 7 publications

(11 citation statements)

References 71 publications

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“…Human Epstein-Barr virus–induced B-lymphoma cell line (EBV + B-lymphoma), derived from the aspirate of bone marrow cells of a patient diagnosed with multiple myeloma, was obtained from the Research Institute of Fundamental and Clinical Immunology (Novosibirsk, Russia) ( Dolgova et al, 2019 ). The cells were cultured in Dulbecco’s Modified Eagle’s Medium (DMEM, Gibco, United States) supplemented with 40 μg/ml gentamycin sulfate and 10% fetal bovine serum (FBS) (HyClone, Logan, Utah, United States) at 37°C and 5% CO 2 in a CO 2 incubator (Memmert, United States).…”

Section: Methodsmentioning

confidence: 99%

“…Three rounds of real-time PCR experiments were performed with three samples each. Conversion of real-time PCR data into dsDNA copy numbers was made exactly as described previously ( Dolgova et al, 2019 ).…”

Section: Methodsmentioning

confidence: 99%

“…The assembly of spheres in the culture of Epstein-Barr virus-induced B-lymphoma starts with the formation of a sphere-initiating complex, consisting of a TAMRA + cell and several unstained cells, which occurs within 20 min and looks like the attraction of TAMRA + cells and their TAMRA-counterparts. Thorough examination of this process revealed no signs of active cell migration, such as pseudopodia formation and others, and thus might testify to the Coulomb attraction of differently charged cells (Figures 1A-C) (Dolgova et al, 2016b(Dolgova et al, , 2019. Moreover, in cytological preparations of mouse bone marrow, structures constituted of cell aggregates with TAMRA+/c-Kit/Sca1/CD34+ (HSCs and their multipotent progeny with internalized TAMRA-labeled dsDNA probe) cells in their center were always observed (Dolgova et al, 2013;Ritter et al, 2020) (Figures 1D,E).…”

Section: Introductionmentioning

confidence: 97%

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The new general biological property of stem-like tumor cells Part I. Peculiarities of the process of the double-stranded DNA fragments internalization into stem-like tumor cells

Ritter

Долгова²,

Petrova³

et al. 2022

Front. Genet.

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Stem-like tumor cells of ascites carcinoma Krebs-2 and Epstein-Barr virus–induced B-lymphoma were shown to possess the innate capability of binding and internalizing the TAMRA-labeled double-stranded DNA (dsDNA) probe. The process of binding and internalizing is rather complicated and composed of the following successive stages: 1) initiating electrostatic interaction and contact of a negatively charged dsDNA molecule with a positively charged molecule(s) on the surface of a stem-like tumor cell; 2) binding of the dsDNA probe to a tumor stem cell surface protein(s) via the formation of a strong chemical/molecular bond; and 3) the very internalization of dsDNA into the cell. Binding of DNA to cell surface proteins is determined by the presence of heparin/polyanion-binding sites within the protein structure, which can be competitively blocked by heparin and/or dextran sulfate, wherein heparin blocks only the binding, while dextran sulfate abrogates both binding and internalization. The abrogation of internalization by dextran sulfate implies the role of scavenger receptors in this process. Cells were shown to uptake DNA in amounts constituting ∼0.008% of the haploid genome. Inhibitors of caveolae-dependent internalization abrogate the DNA uptake in Krebs-2 cells, and inhibitors of the clathrin/caveolar mechanism block the internalization in B-lymphoma cells. In the present report, it is shown for the first time that in contrast to the majority of committed tumor cells, stem-like tumor cells of Krebs-2 and B-lymphoma carry a general positive charge on their surface.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

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The new general biological property of stem-like tumor cells Part I. Peculiarities of the process of the double-stranded DNA fragments internalization into stem-like tumor cells

Ritter

Долгова²,

Petrova³

et al. 2022

Front. Genet.

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“…Human B lymphoma cell line, derived from the aspirate of bone marrow cells of a patient diagnosed with multiple myeloma, was obtained from the Research Institute of Fundamental and Clinical Immunology (Novosibirsk, Russia). A detailed description of the cell line is presented in the study [ 58 ]. The cells were cultured in DMEM medium supplemented with 40 μg/mL gentamycin sulfate and 10% fetal bovine serum (FBS) (HyClone, Logan, UT, USA) at 37 °C in a 5% CO 2 incubator (Memmert, USA LLC, Eagle, WI, USA) to 70–80% confluency.…”

Section: Methodsmentioning

confidence: 99%

Analysis of the Biological Properties of Blood Plasma Protein with GcMAF Functional Activity

Долгова

Кирикович

Левитес

et al. 2022

IJMS

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The main problem related to the studies focusing on group-specific component protein-derived macrophage-activating factor (GcMAF) is the lack of clarity about changes occurring in different types of macrophages and related changes in their properties under the effect of GcMAF in various clinical conditions. We analyzed the antitumor therapeutic properties of GcMAF in a Lewis carcinoma model in two clinical conditions: untreated tumor lesion and tumor resorption after exposure to Karanahan therapy. GcMAF is formed during site-specific deglycosylation of vitamin D3 binding protein (DBP). DBP was obtained from the blood of healthy donors using affinity chromatography on a column with covalently bound actin. GcMAF-related factor (GcMAF-RF) was converted in a mixture with induced lymphocytes through the cellular enzymatic pathway. The obtained GcMAF-RF activates murine peritoneal macrophages (p < 0.05), induces functional properties of dendritic cells (p < 0.05) and promotes in vitro polarization of human M0 macrophages to M1 macrophages (p < 0.01). Treatment of whole blood cells with GcMAF-RF results in active production of both pro- and anti-inflammatory cytokines. It is shown that macrophage activation by GcMAF-RF is inhibited by tumor-secreted factors. In order to identify the specific antitumor effect of GcMAF-RF-activated macrophages, an approach to primary reduction of humoral suppressor activity of the tumor using the Karanahan therapy followed by macrophage activation in the tumor-associated stroma (TAS) was proposed. A prominent additive effect of GcMAF-RF, which enhances the primary immune response activation by the Karanahan therapy, was shown in the model of murine Lewis carcinoma. Inhibition of the suppressive effect of TAS is the main condition required for the manifestation of the antitumor effect of GcMAF-RF. When properly applied in combination with any chemotherapy, significantly reducing the humoral immune response at the advanced tumor site, GcMAF-RF is a promising antitumor therapeutic agent that additively destroys the pro-tumor properties of macrophages of the tumor stroma.

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“…At the core of Karanahan technology and CMLD CP-based chemotherapy is the use of DNAmix and CP. Their combination is rationally motivated and has been shown to be effective in “incurable” cancers, such as Krebs-2, U-87 xenografts, and B cell lymphomas in mice ( 6 , 8 , 78 , 80 , 81 ).…”

Section: Dnamix and Cp Treatments Are Core Elements Of The Karanahan Technology And Cmld Cp-based Chemotherapymentioning

confidence: 99%

Theoretical premises of a “three in one” therapeutic approach to treat immunogenic and nonimmunogenic cancers: a narrative review

Proskurina¹,

Ruzanova²,

Останин³

et al. 2021

Transl Cancer Res TCR

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Objective We describe experimental and theoretical premises of a powerful cancer therapy based on the combination of three approaches. These include (I) in situ vaccination (intratumoral injections of CpG oligonucleotides and anti-OX40 antibody); (II) chronometric or metronomic low-dose cyclophosphamide (CMLD CP)-based chemotherapy; (III) cancer stem cell-eradicating therapy referred to as Karanahan (from the Sanskrit kāraṇa [“source”] + han [“to kill”]). Background In murine models, the first two approaches are particularly potent in targeting immunogenic tumors for destruction. In situ vaccination activates a fully fledged anticancer immune response via an intricate network of ligand–receptor–cytokine interactions. CMLD CP-based chemotherapy primarily targets the suppressive tumor microenvironment and activates tumor-infiltrating effectors. In contrast, Karanahan technology, being aimed at replicative machinery of tumor cells (both stem-like and committed), does not depend on tumor immunogenicity. With this technology, mice engrafted with ascites and/or solid tumors can be successfully cured. There is a significant degree of mechanistic and therapeutic overlap between these three approaches. For instance, the similarities shared between in situ vaccination and Karanahan technology include the therapeutic procedure, the cell target [antigen-presenting cells (APC) and dendritic cells (DC)], and the use of DNA-based preparations (CpG and DNAmix). Features shared between CMLD CP-based chemotherapy and Karanahan technology are the timing and the dose of the cytostatic drug administration, which lead to tumor regression. Methods The following keywords were used to search PubMed for the latest research reporting successful eradication of transplantable cancers in animal models that relied on approaches distinct from those used in the Karanahan technology: eradication of malignancy, cure cancer, complete tumor regression, permanently eradicating advanced mouse tumor, metronomic chemotherapy, in situ vaccination, immunotherapy, and others. Conclusion We hypothesize, therefore, that very potent anticancer activity can be achieved once these three therapeutic modalities are combined into a single approach. This multimodal approach is theoretically curative for any type of cancer that depends on the presence of tumor-inducing cancer stem cells, provided that the active therapeutic components are efficiently delivered into the tumor and the specific biological features of a given patient’s tumor are properly addressed. We expect this multimodal approach to be primarily applicable to late-stage or terminal cancer patients who have...

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Identification of the xenograft and its ascendant sphere-forming cell line as belonging to EBV-induced lymphoma, and characterization of the status of sphere-forming cells

Cited by 7 publications

References 71 publications

The new general biological property of stem-like tumor cells Part I. Peculiarities of the process of the double-stranded DNA fragments internalization into stem-like tumor cells

The new general biological property of stem-like tumor cells Part I. Peculiarities of the process of the double-stranded DNA fragments internalization into stem-like tumor cells

Analysis of the Biological Properties of Blood Plasma Protein with GcMAF Functional Activity

Theoretical premises of a “three in one” therapeutic approach to treat immunogenic and nonimmunogenic cancers: a narrative review

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