| 1. |
- Bragina, Olga D., et al.
(författare)
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The Evolution of Targeted Radionuclide Diagnosis of HER2-Positive Breast Cancer
- 2022
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Ingår i: ACTA NATURAE. - : RUSSIAN FEDERATION AGENCY SCIENCE & INNOVATION. - 2075-8251 .- 2075-8243. ; 14:2, s. 4-15
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Forskningsöversikt (refereegranskat)abstract
- This review examines the evolution of the radionuclide diagnosis of HER2-positive breast cancer using various compounds as a targeting module in clinical practice: from full-length antibodies to a new group of small synthetic proteins called alternative scaffold proteins. This topic is of especial relevance today in view of the problems attendant to the detection of breast cancer with HER2/neu overexpression, which, in most cases, introduce errors in the treatment of patients. The results of clinical studies of radiopharmaceuticals based on affibody molecules, ADAPTs, and DARPins for SPECT and PET have demonstrated good tolerability of the compounds, their rapid excretion from the body, and the possibility to differentiate tumor sites depending on the HER2/neu status. This indicates that targeted radionuclide diagnosis holds promise and the need to continue research in this direction.
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| 2. |
- Gordeychuk, IV, et al.
(författare)
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Assessment of the Parameters of Adaptive Cell-Mediated Immunity in Naïve Common Marmosets (Callithrix jacchus)
- 2018
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Ingår i: Acta naturae. - : Acta Naturae Ltd. - 2075-8251. ; 10:4, s. 63-69
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Tidskriftsartikel (refereegranskat)abstract
- Common marmosets are small New World primates that have been increasingly used in biomedical research. This report presents efficient protocols for assessment of the parameters of adaptive cell-mediated immunity in common marmosets, including the major subpopulations of lymphocytes and main markers of T- and B-cell maturation and activation using flow cytometry with a multicolor panel of fluorescently labelled antibodies. Blood samples from eight common marmosets were stained with fluorescently labeled monoclonal antibodies against their population markers (CD45, CD3, CD20, CD4, CD8) and lymphocyte maturation and activation markers (CD69, CD62L, CD45RO, CD107a and CD27) and analyzed by flow cytometry. Within the CD45+ population, 22.75.5% cells were CD3- CD20+ and 67.66.3% were CD3+CD20-. The CD3+ subpopulation included 55.75.5% CD3+CD4+CD8- and 34.33.7% CD3+CD4-CD8+ cells. Activation and maturation markers were expressed in the following lymphocyte proportions: CD62L on 54.010.7% of CD3+CD4+ cells and 74.412.1% of CD3+CD8+ cells; CD69 on 2.71.2% of CD3+CD4+ cells and 1.20.5% of CD3+CD8+ cells; CD45RO on 1.60.6% of CD3+CD4+ cells and 1.80.7% of CD3+CD8+ cells; CD107a on 0.70.5% of CD3+CD4+ cells and 0.50.3% of CD3+CD8+ cells; CD27 on 94.62.1% of CD3+ cells and 8.93.9% CD20+ cells. Female and male subjects differed in the percentage of CD3+CD4+CD45RO+ cells (1.90.5 in females vs 1.10.2 in males; p 0.05). The percentage of CD20+CD27+ cells was found to highly correlate with animals age (r = 0.923, p 0.005). The basal parameters of adaptive cell-mediated immunity in nave healthy marmosets without markers of systemic immune activation were obtained. These parameters and the described procedures are crucial in documenting the changes induced in common marmosets by prophylactic and therapeutic immune interventions.
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| 3. |
- Gaponova, A V, et al.
(författare)
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Epithelial-Mesenchymal Transition : Role in Cancer Progression and the Perspectives of Antitumor Treatment.
- 2020
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Ingår i: Acta naturae. - : Acta Naturae Ltd. - 2075-8251. ; 12:3, s. 4-23
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Forskningsöversikt (refereegranskat)abstract
- About 90% of all malignant tumors are of epithelial nature. The epithelial tissue is characterized by a close interconnection between cells through cell-cell interactions, as well as a tight connection with the basement membrane, which is responsible for cell polarity. These interactions strictly determine the location of epithelial cells within the body and are seemingly in conflict with the metastatic potential that many cancers possess (the main criteria for highly malignant tumors). Tumor dissemination into vital organs is one of the primary causes of death in patients with cancer. Tumor dissemination is based on the so-called epithelial-mesenchymal transition (EMT), a process when epithelial cells are transformed into mesenchymal cells possessing high mobility and migration potential. More and more studies elucidating the role of the EMT in metastasis and other aspects of tumor progression are published each year, thus forming a promising field of cancer research. In this review, we examine the most recent data on the intracellular and extracellular molecular mechanisms that activate EMT and the role they play in various aspects of tumor progression, such as metastasis, apoptotic resistance, and immune evasion, aspects that have usually been attributed exclusively to cancer stem cells (CSCs). In conclusion, we provide a detailed review of the approved and promising drugs for cancer therapy that target the components of the EMT signaling pathways.
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| 4. |
- Buivydiene, A, et al.
(författare)
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Expression Levels of the Uridine-Cytidine Kinase Like-1 Protein As a Novel Prognostic Factor for Hepatitis C Virus-Associated Hepatocellular Carcinomas
- 2017
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Ingår i: Acta naturae. - : Acta Naturae Ltd. - 2075-8251. ; 9:3, s. 108-114
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Tidskriftsartikel (refereegranskat)abstract
- The expression levels of the two novel oncoproteins uridine-cytidine kinase like-1 (UCKL-1) and mitochondrial ribosomal protein S18-2 (MRPS18-2) were assessed in samples of hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCC) using immunohistochemistry. Tissue microarray (TMA) paraffin blocks were prepared from 42 HCC tumor samples with the corresponding peri-tumor tissues and from 11 tissues of a liver with HCV-induced cirrhosis. We found that the UCKL-1 signal in the liver tissues of the peri-tumor zone in the HCC samples was stronger than that in cirrhosis (50 49.44 vs. 24.27 14.53; p = 0.014). The MRPS18-2 expression was weak, and there was no differences between the groups (p = 0.26). Noteworthy, the UCKL-1 protein was expressed at higher levels in peri-tumor tissues in the cases of HCC recurrence; this was confirmed for 27 older patients (63.78 9.22 vs. 53.53 4.07 years, p 0.001), in parallel with enhanced UCKL-1 staining in former HCC nodules (62.69 50.4 vs. 26.0 30.19, p = 0.006) and microvascular invasion (p = 0.02). A multivariate analysis of prognostic factors for HCC recurrence showed that the best predictive factors for these conditions were UCKL-1 expression in tumor, vascular invasion, and HCC treatment modality, other than liver transplantation (odds ratios: 1.029, 18.143 and 11.984, R = 0.633, p = 0.002). In conclusion, the high UCKL-1 expression might be a prognostic factor for HCC relapse, in combination with age and microvascular invasion. MRPS18-2 protein expression has no prognostic significance in the cases of HCV-associated HCC.
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| 5. |
- Pankratov, Dmitry, et al.
(författare)
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Impact of surface modification with gold nanoparticles on the bioelectrocatalytic parameters of immobilized bilirubin oxidase
- 2014
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Ingår i: Acta Naturae. - : Park Media Ltd. - 2075-8251. ; 6:1, s. 102-106
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Tidskriftsartikel (refereegranskat)abstract
- We unveil experimental evidence that put into question the widely held notion concerning the impact of nanoparticles on the bioelectrocatalytic parameters of enzymatic electrodes. Comparative studies of the bioelectrocatalytic properties of fungal bilirubin oxidase from Myrothecium verrucaria adsorbed on gold electrodes, modified with gold nanoparticles of different diameters, clearly indicate that neither the direct electron transfer rate (standard heterogeneous electron transfer rate constants were calculated to be 31±9 s-1) nor the biocatalytic activity of the adsorbed enzyme (bioelectrocatalytic constants were calculated to be 34±11 s-1) depends on the size of the nanoparticles, which had diameters close to or larger than those of the enzyme molecules.
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| 6. |
- Pankratov, Dmitry, et al.
(författare)
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New nanobiocomposite materials for bioelectronic devices
- 2015
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Ingår i: Acta Naturae. - : Park Media. - 2075-8251. ; 7:1, s. 98-101
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Tidskriftsartikel (refereegranskat)abstract
- We have developed and synthesized nanobiocomposite materials based on graphene, poly(3,4-ethylenedioxythiophene), and glucose oxidase immobilized on the surface of various nanomaterials (gold nanoparticles and multi-walled carbon nanotubes) of different sizes (carbon nanotubes of different diameters). Comparative studies of the possible influence of the nanomaterial’s nature on the bioelectrocatalytic characteristics of glucose-oxidizing bioanodes in a neutral phosphate buffer solution demonstrated that the bioelectrocatalytic current densities of nanocomposite-based bioanodes are only weakly dependent on the size of the nanomaterial and are primarily defined by its nature. The developed nanobiocomposites are promising materials for new bioelectronic devices due to the ease in adjusting their capacitive and bioelectrocatalytic characteristics, which allows one to use them for the production of dual-function electrodes: i.e., electrodes which are capable of generating and storing electric power simultaneously.
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| 7. |
- Shadrina, OA, et al.
(författare)
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Influence of Drug Resistance Mutations on the Activity of HIV-1 Subtypes A and B Integrases: a Comparative Study
- 2015
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Ingår i: Acta naturae. - : Acta Naturae Ltd. - 2075-8251. ; 7:1, s. 78-86
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Tidskriftsartikel (refereegranskat)abstract
- Integration of human immunodeficiency virus (HIV-1) DNA into the genome of an infected cell is one of the key steps in the viral replication cycle. The viral enzyme integrase (IN), which catalyzes the integration, is an attractive target for the development of new antiviral drugs. However, the HIV-1 therapy often results in the IN gene mutations inducing viral resistance to integration inhibitors. To assess the impact of drug resistance mutations on the activity of IN of HIV-1 subtype A strain FSU-A, which is dominant in Russia, variants of the consensus IN of this subtype containing the primary resistance mutations G118R and Q148K and secondary compensatory substitutions E138K and G140S were prepared and characterized. Comparative study of these enzymes with the corresponding mutants of IN of HIV-1 subtype B strains HXB-2 was performed. The mutation Q148K almost equally reduced the activity of integrases of both subtypes. Its negative effect was partially compensated by the secondary mutations E138K and G140S. Primary substitution G118R had different influence on the activity of proteins of the subtypes A and B, and the compensatory effect of the secondary substitution E138K also depended on the viral subtype. Comparison of the mutants resistance to the known strand transfer inhibitors raltegravir and elvitegravir, and a new inhibitor XZ-259 (a dihydro-1H-isoindol derivative), showed that integrases of both subtypes with the Q148K mutation were insensitive to raltegravir and elvitegravir but were effectively inhibited by XZ-259. The substitution G118R slightly reduced the efficiency of IN inhibition by raltegravir and elvitegravir and caused no resistance to XZ_259.
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| 8. |
- Shevchuk, Z, et al.
(författare)
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Overexpression of MRPS18-2 in Cancer Cell Lines Results in Appearance of Multinucleated Cells
- 2013
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Ingår i: Acta naturae. - : Acta Naturae Ltd. - 2075-8251. ; 5:1, s. 85-89
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Tidskriftsartikel (refereegranskat)abstract
- Human mitochondrial ribosomal protein MRPS18-2 (S18-2) is encoded by a cellular gene that is located on the human chromosome 6p21.3. We discovered that overexpression of the S18-2 protein led to immortalization and de-differentiation of primary rat embryonic fibroblasts. Cells showed anchorage-independent growth pattern. Moreover, pathways characteristic for rapidly proliferating cells were upregulated then. It is possible that the S18-2 overexpression induced disturbance in cell cycle regulation. We found that overexpression of S18-2 protein in human cancer cell lines led to an appearance of multinucleated cells in the selected clones.
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| 9. |
- Starodubova, ES, et al.
(författare)
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Fusion to the Lysosome Targeting Signal of the Invariant Chain Alters the Processing and Enhances the Immunogenicity of HIV-1 Reverse Transcriptase
- 2014
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Ingår i: Acta naturae. - : Acta Naturae Ltd. - 2075-8251. ; 6:1, s. 61-68
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Tidskriftsartikel (refereegranskat)abstract
- Intracellular processing of the antigen encoded by a DNA vaccine is one of the key steps in generating an immune response. Immunization with DNA constructs targeted to the endosomal-lysosomal compartments and to the MHC class II pathway can elicit a strong immune response. Herein, the weakly immunogenic reverse transcriptase of HIV-1 was fused to the minimal lysosomal targeting motif of the human MHC class II invariant chain. The motif fused to the N-terminus shifted the enzyme intracellular localization and accelerated its degradation. Degradation of the chimeric protein occurred predominantly in the lysosomal compartment. BALB/c mice immunized with the plasmid encoding the chimeric protein demonstrated an enhanced immune response, in the form of an increased antigen-specific production of Th1 cytokines, INF- and IL-2, by mouse splenocytes. Moreover, the majority of the splenocytes secreted both cytokines; i.e., were polyfunctional. These findings suggest that retargeting of the antigen to the lysosomes enhances the immune response to DNA vaccine candidates with low intrinsic immunogenicity.
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| 10. |
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