58 research outputs found

    The <i>CFTR</i> Gene Germline Heterozygous Pathogenic Variants in Russian Patients with Malignant Neoplasms and Healthy Carriers: 11,800 WGS Results

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    More than 275 million people in the world are carriers of a heterozygous mutation of the CFTR gene, associated with cystic fibrosis, the most common autosomal recessive disease among Caucasians. Some recent studies assessed the association between carriers of CFTR variants and some pathologies, including cancer risk. The aim of this study is to analyze the landscape of germline pathogenic heterozygous CFTR variants in patients with diagnosed malignant neoplasms. For the first time in Russia, we evaluated the frequency of CFTR pathogenic variants by whole-genome sequencing in 1800 patients with cancer and compared this with frequencies of CFTR variants in the control group (1825 people) adjusted for age and 10,000 healthy individuals. In the issue, 47 out of 1800 patients (2.6%) were carriers of CFTR pathogenic genetic variants: 0.028 (42/1525) (2.8%) among breast cancer patients, 0.017 (3/181) (1.7%) among colorectal cancer patients and 0.021 (2/94) (2.1%) among ovarian cancer patients. Pathogenic CFTR variants were found in 52/1825 cases (2.85%) in the control group and 221 (2.21%) in 10,000 healthy individuals. Based on the results of the comparison, there was no significant difference in the frequency and distribution of pathogenic variants of the CFTR gene, which is probably due to the study limitations. Obviously, additional studies are needed to assess the clinical significance of the heterozygous carriage of CFTR pathogenic variants in the development of various pathologies in the future, particularly cancer

    Feasibility of Co-Targeting HER3 and EpCAM Using Seribantumab and DARPin-Toxin Fusion in a Pancreatic Cancer Xenograft Model

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    Pancreatic cancer (PC) is one of the most aggressive malignancies. A combination of targeted therapies could increase the therapeutic efficacy in tumors with heterogeneous target expression. Overexpression of the human epidermal growth factor receptor type 3 (HER3) and the epithelial cell adhesion molecule (EpCAM) in up to 40% and 30% of PCs, respectively, is associated with poor prognosis and highlights the relevance of these targets. Designed ankyrin repeat protein (DARPin) Ec1 fused with the low immunogenic bacterial toxin LoPE provides specific and potent cytotoxicity against EpCAM-expressing cancer cells. Here, we investigated whether the co-targeting of HER3 using the monoclonal antibody seribantumab (MM-121) and of EpCAM using Ec1-LoPE would improve the therapeutic efficacy in comparison to the individual agents. Radiolabeled Tc-99m(CO)(3)-Ec1-LoPE showed specific binding with rapid internalization in EpCAM-expressing PC cells. MM-121 did not interfere with the binding of Ec1-LoPE to EpCAM. Evaluation of cytotoxicity indicated synergism between Ec1-LoPE and MM-121 in vitro. An experimental therapy study using Ec1-LoPE and MM-121 in mice bearing EpCAM- and HER3-expressing BxPC3 xenografts demonstrated the feasibility of the therapy. Further development of the co-targeting approach using HER3 and EpCAM could therefore be justified

    Process Approaches to Utilization of Domestic Low-Grade Fuels for Power Generation

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    Использование местных топливных ресурсов является одним из директивно обозначенных и обсуждаемых путей повышения энергетической безопасности и формирования экономически обоснованных топливно-энергетических балансов регионов Российской Федерации. Для территорий, обладающих локальными проявлениями запасов бурых углей, этот вид ископаемого топлива при наличии благоприятствующих условий имеет преимущественное значение. На примере Таловского месторождения Томской области рассмотрены технически осуществимые варианты вовлечения низкосортных топлив в использование на тепловых электростанциях региона, а также на энергетических объектах промышленного и муниципального назначения. Приоритетным условием реализации всех вариантов, включая сжигание местного угольного топлива «с колёс», в смеси с базовым топливом, поставляемым в регион, в смеси с продуктами термической переработки и др., принято отсутствие или минимизация затрат на реконструкцию действующего основного и вспомогательного оборудования. Для каждой из обсуждаемых технологий обозначены ограничения, которые накладываются свойствами используемого топливаUtilization of domestic fuel resources is one of the ways that are being discussed and defined in the guiding documents to increase the energy security and formation of economically feasible fuel and energy balances in the Russian Federation regions. For the territories possessing occurrences of lignite, this type of fossil fuel is of primary importance under the favorable conditions. Based on the example of Talovskoye deposit in Tomsk region, the technically viable options of low-grade fuels utilization at the regional thermal power plants were considered, as well as at the industrial and municipal power facilities. A high-priority implication for implementing all options, including burning of domestic coal fuel just-in-time, in combination with the basic fuel, supplied to the region together with thermal processing products and other, the absence or minimization of costs for modernization of the operating main and auxiliary equipment is adopted. Limitations, imposed by the utilized fuel properties, are specified for every technology under discussio

    Isolation of a human lactoferrin biosimilar from frozen milk of goat producers

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    This study offers an additional source of information on isolation and purification of the human lactoferrin biosimilar from frozen milk of goat producers. Thanks to the application of an improved technique of raw material degreasing, a milk filtrate with complete absence of the fat part was obtained, which as a result had a favorable effect on the yield and properties of the finished product, whose quality was confirmed by methods of MALDI-TOF mass spectrometry and microbiological analysis. As a result 135 g of human lactoferrin biosimilar was obtained from 75 liters of frozen milk

    Feasibility of Co-Targeting HER3 and EpCAM Using Seribantumab and DARPin&ndash;Toxin Fusion in a Pancreatic Cancer Xenograft Model

    No full text
    Pancreatic cancer (PC) is one of the most aggressive malignancies. A combination of targeted therapies could increase the therapeutic efficacy in tumors with heterogeneous target expression. Overexpression of the human epidermal growth factor receptor type 3 (HER3) and the epithelial cell adhesion molecule (EpCAM) in up to 40% and 30% of PCs, respectively, is associated with poor prognosis and highlights the relevance of these targets. Designed ankyrin repeat protein (DARPin) Ec1 fused with the low immunogenic bacterial toxin LoPE provides specific and potent cytotoxicity against EpCAM-expressing cancer cells. Here, we investigated whether the co-targeting of HER3 using the monoclonal antibody seribantumab (MM-121) and of EpCAM using Ec1&ndash;LoPE would improve the therapeutic efficacy in comparison to the individual agents. Radiolabeled 99mTc(CO)3-Ec1&ndash;LoPE showed specific binding with rapid internalization in EpCAM-expressing PC cells. MM-121 did not interfere with the binding of Ec1&ndash;LoPE to EpCAM. Evaluation of cytotoxicity indicated synergism between Ec1&ndash;LoPE and MM-121 in vitro. An experimental therapy study using Ec1&ndash;LoPE and MM-121 in mice bearing EpCAM- and HER3-expressing BxPC3 xenografts demonstrated the feasibility of the therapy. Further development of the co-targeting approach using HER3 and EpCAM could therefore be justified

    A Unique Observation of a Patient with Vulto-van Silfhout-de Vries Syndrome

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    Introduction: Vulto-van Silfhout-de Vries Syndrome (VSVS; OMIM#615828) is a rare hereditary disease associated with impaired intellectual development and speech, delayed psychomotor development, and behavioral anomalies, including autistic behavioral traits and poor eye contact. To date, 27 patients with VSVS have been reported in the literature. Materials and Methods: We describe a 23-year-old male patient with autism spectrum disorder (ASD) who was admitted to the gastroenterological hospital with signs of pseudomembranous colitis. ASD was first noted in the patient at the age of 2.5 years. Later, he developed epileptic seizures and important growth retardation. Prior to the hospitalization, chromosomal aberrations, Fragile X syndrome, and aminoacidopathies/aminoacidurias associated with ASD were excluded. Whole-genome sequencing (WGS) was prescribed to the patient at 23 years old. Results: The patient had a heterozygous carrier of &ldquo;de novo&rdquo; variant c.662C &gt; T (p.S221L) in exon 4 of the DEAF1 gene. c.662C &gt; T had not been previously described in genomic databases. According to the ACMG criteria, this missense variant was considered to be pathogenic. VSVS was diagnosed in the patient. Conclusions: The phenotype of the patient is very similar to the data presented in the world literature. However, growth retardation and cachexia, which have not been described previously in the articles, are of interest

    Fuel resources of Tomsk region for alternative energy usage

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    Актуальность исследования обусловлена важностью рационального формирования регионального топливно-энергетического баланса, направленного на преодоление зависимости от доминирования внешних (привозных) топливных ресурсов. Это способствует энергетической безопасности территории и соответствует задачам обеспечения природоохранной стратегии и энергоэффективности. Цель: сравнить местные топливные ресурсы по пригодности для эффективного использования в топливно-энергетическом балансе Томской области. Объекты: топливно-энергетический комплекс Томской области и его текущий баланс, топливно-энергетические ресурсы региона, нефтегазовые углеводороды, бурый уголь, торф, растительная биомасса в виде естественного и техногенного органического сырья. Методы: систематизация информации из открытых источников, аналитический обзор и оценочные исследования. Результаты. Краткая характеристика энергобаланса Томской области показывает его энергодефицитность. Обобщены публикации по топливно-энергетическому комплексу региона в разрезе как централизованных, так и децентрализованных источников тепло- и электроснабжения. Подтверждена тенденция к возрастанию неудовлетворения спроса на энергопотребление и низкая конкурентоспособность по сравнению с другими участниками Объединённой энергосистемы Сибири. Рассмотрено все многообразие топливных запасов территории области, подходящих под определение топливноэнергетические ресурсы, приведена информация о их исследованности, разведанных и оцененных запасах, доступности и положении относительно потенциальных потребителей. Приведена информация о теплотехническом качестве местных топливно-энергических ресурсов и возможности их использования с учетом характеристик имеющегося на энергопредприятиях области топливоиспользующего оборудования. Выводы. Условиям выбора альтернативного твердого топлива для энергетического использования в наибольшей мере по сравнению с другими ресурсами соответствует бурый уголь Таловского месторождения.Relevance of the research is determined by the importance of rationalized regional fuel and energy balance plan organization which is directed towards overcoming dependence on outsourced (imported) fuel resources. This conduces to energy security of the territories and correlates to the goals of environmental protection strategy and energy efficiency. Goal: comparing local fuel resources by the suitability for effective usage in the fuel and energy balance plan of Tomsk region. Objects: fuel and energy complex of Tomsk region and its current balance; region fuel and energy resources, oil and gas hydrocarbons, brown coal, peat, green biomasses in forms of natural and anthropogenic organic fuel. Methods: systematizing information from open sources, analytical review and appraisal procedure. Results. Brief characteristic of Tomsk region energy balance shows its energy deficiency. The publications regarding fuel energy complex of region are summed up. Tendency of increasing unsatisfaction of demand on energy consumption was confirmed as well as low level of competitiveness comparing to other members of United energy system of Siberia. All variety of region's fuel storages which can be defined as fuel energy resources were examined, the level of their research, the proved and evaluated reserves as well the accessibility of their location to potential consumers were examined too. The information about heat engineering qualities of local fuel and energy resources are provided as well as information regarding possibilities of their usage with account of characteristics of presented equipment of energy companies. Conclusion. The brown coal of Talovsk deposit meets the main selection criterion for alternative fossil fuel for energy usage unlike other candidates

    DR5-Selective TRAIL Variant DR5-B Functionalized with Tumor-Penetrating iRGD Peptide for Enhanced Antitumor Activity against Glioblastoma

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    TRAIL (TNF-related apoptosis-inducing ligand) and its derivatives are potentials for anticancer therapy due to the selective induction of apoptosis in tumor cells upon binding to death receptors DR4 or DR5. Previously, we generated a DR5-selective TRAIL mutant variant DR5-B overcoming receptor-dependent resistance of tumor cells to TRAIL. In the current study, we improved the antitumor activity of DR5-B by fusion with a tumor-homing iRGD peptide, which is known to enhance the drug penetration into tumor tissues. The obtained bispecific fusion protein DR5-B-iRGD exhibited dual affinity for DR5 and integrin αvβ3 receptors. DR5-B-iRGD penetrated into U-87 tumor spheroids faster than DR5-B and demonstrated an enhanced antitumor effect in human glioblastoma cell lines T98G and U-87, as well as in primary patient-derived glioblastoma neurospheres in vitro. Additionally, DR5-B-iRGD was highly effective in a xenograft mouse model of the U-87 human glioblastoma cell line in vivo. We suggest that DR5-B-iRGD may become a promising candidate for targeted therapy for glioblastoma

    The Reasoning of a Responsible Investment Position in the Structure of the Stock Exchange Market

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    Purpose: To substantiate the place and role of the responsible investment in the structure of the stock exchange market. Methods: Structure-functional in order to form an idea of the structure of the stock exchange market, determining the place and role of responsible investment elements in the stock market organization; systematic analysis to identify current trends and patterns in the functioning of the socially responsible investment segment by geographical regions of the world; statistical and graphical methods for quantitative and visual presentation of the results of the stock market sectors analysis, represented by responsible investment elements. Findings: The definition of «responsible investment» and «stock market» has been clarified; a number of subjects, objects and forms of responsible investment, which are elements of the stock market, are singled out and substantiated; the generalization of activities of stock exchanges in the field of responsible investing is carried out; the dynamics of stock market sector indicators, which are represented by elements of responsible investment, are analyzed; key reporting standards used by stock exchanges in disclosing ESG issues are analyzed. Theoretical Implications: A comprehensive assessment of the functioning of socially responsible investment segment as part of the stock market is carried out, the place and role of responsible investing in the stock market structure are substantiated, which creates a basis for the development of effective measures to increase the stock market efficiency of Ukraine and its transformation into an effective and stable source of investment resources. Future Research: The results can be used in the context of further study of the stock market transformation in Ukraine on the basis of a socially responsible trajectory and fractal analysis. Paper Type: Theoretical. The study was performed within the state budget research "Fractal model of the stock market transformation in Ukraine: socially responsible investment to achieve the Sustainable Development Goals" № 0121U100473

    Application of translinguism in teaching foreign languages to students (specialty “Ecology”)

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    This article explores the concept of translinguism and its application in the educational environment. The authors have developed a learning model that includes flipped classroom, face-to-face classes, team work and project-based learning. The study involved 3rd year students (N=26) of Peter the Great St. Petersburg Polytechnic University (SPbPU), studying in the field of “Ecology”. During one semester (February 2020 - June 2020), students studied the discipline “Spanish” in English according to proposed methodology. The study examined the impact of the proposed model on the study of the Spanish language and the development of translational competence. For the analysis descriptive statistics and pairsamples Students’s t-test were conducted. Interviews were also conducted with students to analyze their perception of the new learning model. Generally, the overall quality of students’ Spanish knowledge improved. According to the descriptive results, students developed their translingual competence significantly. Thus, it can be assumed that the proposed learning model positively influenced students’ level of such competence. The results of the interview showed that students positively evaluate the proposed teaching model, and also consider it to be effective for learning Spanish and developing translingualism
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