Forensic medical criteria for the evaluation of the unfavourable outcomes of the roentgeno-endovascular operations on the arteries of the lower extremities
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01.01.2018 |
Goloshchapov-Aksenov R.
Pigolkin Y.
Kicha D.
Morozov K.
Lakunin K.
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Sudebno-Meditsinskaya Ekspertiza |
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0 |
Ссылка
© 2018 Lippincott Williams and Wilkins. All rights reserved. The objective - of the present work was to develop the forensic medical criteria for the evaluation of the unfavourable outcomes of the roentgeno-endovascular operations (REVO) on the arteries of the lower extremities. The study included the analysis of the conclusions based on the results of the commission forensic medical examinations, attorney inquiry reports, query response, medical histories of the hospitalized patients who had undergone the roentgeno-endovascular operations on the arteries of the lower extremities. The criteria for the forensic medical evaluation of the unfavourable outcomes of the roentgeno-vascular operations on the arteries of the lower extremities have been proposed together with the indications for REVO, methods and tools for the performance of these surgical procedures. Particular attention was given to the identification of the signs and prognostics of the unfavourable outcomes of the roentgeno-endovascular operations (both intraoperatively and during the early postoperative period and the subsequent stay in the hospital) and to the risks of the development of the unfavourable outcomes of the surgical interventions following the technically adequate REVO. Special emphasis is placed on the cause-and-effect relationship between the actions or a failure to act on the part of an emergency physician and/or an attending surgeon/cardiovascular surgeon and the possibility of the unfavourable outcomes of the roentgeno-endovascular operations.
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Immediate implant placement into fresh extraction sites using single-drilling bur and two loading procedures: Follow-up results
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01.01.2018 |
Bettach R.
Taschieri S.
Mortellaro C.
Del Fabbro M.
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Journal of Craniofacial Surgery |
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0 |
Ссылка
Copyright © 2018 by Mutaz B. Habal, MD. Modern clinical protocols in implantology aim at shortening the treatment time and reducing duration and discomfort of the surgical phase, while maintaining optimal treatment outcomes. The purpose of this study was to evaluate clinical outcomes of implants immediately placed in extraction sites, using a single drilling step for implant site preparation. One-hundred thirty-three patients (mean age 55.3 ± 12.7 [SD] years, range 20 – 83 years) were treated at 2 clinical centers. Two-hundred sixty-one implants were inserted in fresh postextraction sockets. One-hundred sixty-five implants were immediately loaded (IL) and 96 underwent delayed loading (DL). Implant survival, peri-implant bone level change and patients’ satisfaction were assessed after at least 3 years of function. No patient dropout occurred. The mean follow-up was 63.61 ± 11.52 months (range 39.71 – 85.71 months) from prosthesis delivery. Two IL and 1 DL implant failed in 3 patients. Implant survival was 98.8% and 99% for IL and DL group, respectively. The mean marginal bone loss after 1 year was 0.48 ± 0.40 mm and 0.52 ± 0.34 mm for IL and DL group. No biological nor mechanical complications occurred. All patients demonstrated full satisfaction. The present protocol with single burs for site preparation produced satisfactory clinical outcomes independent of the loading timing. Further long-term comparative studies are needed to confirm the present findings.
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Students' internet addiction: Study and prevention
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01.01.2018 |
Neverkovich S.
Bubnova I.
Kosarenko N.
Sakhieva R.
Sizova Z.
Zakharova V.
Sergeeva M.
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Eurasia Journal of Mathematics, Science and Technology Education |
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30 |
Ссылка
© Authors. The information society reveals the social impact of the dissemination of information technologies. The purpose of this article is to study the negative social, psychological, and pedagogical implications of the Internet on young people. The authors analyzed the internet addiction problem among students (14-19 years) from the standpoint of the social health of the individuals and society as a whole. In a pilot study, which involved more than 600 adolescent participants aged 14-19 years (secondary school, college and university students), the authors have defined internet addiction as a complex phenomenon. The prerequisites of its development identify and highlights its formation in stages among students (mild fascination, passion, addiction, attachment). At the ascertaining stage of the experiment, a screening study was carried out to examine the state of internet addiction in young students in social networks. The results showed the necessity to design and implement internet addiction prevention programs for young students, which include three main blocks (motivational and cognitive, practice-oriented, reflexive), and a systematic plan for its implementation in the educational space framework. The stages of the experiment provided evidence of the authors' proposed effectiveness of methodologies for young people aged 14-19 years. This article may be useful to pedagogues, psychologists, and parents of students, social workers, and researchers working in the field of addiction prevention among young people.
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Update of the diagnostic criteria of J-wave syndrome: New concepts and their relevance to cardiology practice (according to materials of J-Wave syndromes expert consensus conference report: Emerging concepts and gaps in knowledge (2016)
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01.01.2018 |
Belenkov Y.
Snezhitskiy V.
Shpak N.
Kuznetsov V.
Martyanova L.
Ardashev A.
Gizatulina Tatyana P.
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Kardiologiya |
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0 |
Ссылка
© 2018 Limited Liability Company KlinMed Consulting. All Rights Reserved. This review includes main positions of the revision of diagnostic criteria of “J-wave syndromes in the J-Wave Syndromes Expert Consensus Conference Report: Emerging Concepts and Gaps in Knowledge” (2016). The article, systematized according to the sections of the above-mentioned document, outlines the questions of terminology, new criteria for diagnosis of the Brugada syndrome (BrS) and early repolarization syndrome (ERS). The section devoted to ERS on the issues of new terminology and standardization of measurements, is supplemented with material from the Consensus Paper - The Early Repolarization Pattern (2015). The article also presents the issues of differential diagnosis in BrS, presents modulating factors, defines acquired Brugada-pattern and Brugada phenocopies. The similarities and differences between BrS and ERS are presented in a comparative aspect.
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Ways to standardise of fetometry in Russia: Intergrowth-21<sup>st</sup> project and its implementation
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01.01.2018 |
Kholin A.
Gus A.
Khodzhaeva Z.
Baev O.
Ryumina I.
Villar J.
Kennedy S.
Papageorghiou A.
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Akusherstvo i Ginekologiya (Russian Federation) |
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0 |
Ссылка
© 2018, Bionika Media Ltd. All rights reserved. The implementation of the INTERGROWTH-21st fetal growth and newborn size for gestation age standards into clinical practice in Russia were discussed and debated. The INTERGROWTH-21st Project was implemented in more than eight countries from 2009 to 2018. All study protocols and primary findings are available online (intergrowth21. org). Briefly, eight diverse urban populations living in demarcated geographical areas were selected where: environments were free from major known pollutants; altitude was less than 1600 m; most women accessed antenatal and delivery care in institutions; mean birth weight was greater than 3100 g; rates of low birth weight (< 2500 g) were less than 10%, and perinatal mortality was less than 20 per 1000 births. The INTERGROWTH-21st study comes as a high-quality response to the common dilemma of lack of standardization in fetal growth assessment. Its use should be encouraged among Russian specialists in maternal-fetal medicine, obstetricians and radiologists.
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The impact of technology acquisition & exploitation on organizational innovation and organizational performance in knowledge-intensive organizations
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01.01.2018 |
Fartash K.
Davoudi S.
Baklashova T.
Svechnikova N.
Nikolaeva Y.
Grimalskaya S.
Beloborodova A.
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Eurasia Journal of Mathematics, Science and Technology Education |
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9 |
Ссылка
© Authors. The present study was conducted in Iran and aimed to analyze the relationships among technology acquisition & exploitation, organizational innovation, and organizational performance. We selected 80 knowledge-intensive organizations as statistical population of the study. Executive managers, senior managers, operational managers, and R & D managers of the companies were considered as appropriate respondents for this study. After the distribution of 320 questionnaires among the respondents, 280 usable questionnaires were gathered. The analysis was done utilizing Structural Equation Modeling (SEM) methodology by LISREL software. The factors analysis and the findings show that technology acquisition & exploitation has a significant positive influence on both organizational innovation and organizational performance. Further, organizational innovation has a significant positive impact on organizational performance.
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Association of rheumatologists of Russia, Russian Society for the study of pain, Russian gastroenterology association, Russian scientific medical society of therapists, association of traumatologists and orthopedists of Russia, Russian Association of pall
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01.01.2018 |
Karateev A.
Nasonov E.
Ivashkin V.
Martynov A.
Yakhno N.
Arutyunov G.
Alekseeva L.
Abuzarova G.
Evseev M.
Kukushkin M.
Kopenkin S.
Lila A.
Lapina T.
Novikova D.
Popkova T.
Rebrov A.
Skorobogatykh K.
Chichasova N.
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Nauchno-Prakticheskaya Revmatologiya |
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8 |
Ссылка
© 2018 Ima-Press Publishing House. All Rights Reserved. In 2015, the experts from various medical associations of Russia elaborated the clinical guidelines "Rational use of nonsteroidal anti-inflammatory drugs (NSAIDs) in clinical practice". These guidelines were drawn up to improve the use of NSAIDs, our country's most popular agents to treat pain in acute and chronic diseases. The main purpose of this paper was to reduce the frequency of potentially dangerous class-specific adverse events (AE) that may arise from the use of NSAIDs. To do this, the authors proposed a NSAID choice algorithm based on the assessment of risk factors for AE, the individual characteristics of various representatives of this drug group, and the possibility of prevention of AE. Since then, new data on the efficacy and safety of NSAIDs have been obtained. This has necessitated the revision and addition of a number of provisions in the 2015 guidelines. It seems that the new version of the guidelines, which has been drawn up based on the analysis of a large number of clinical and epidemiological studies, their meta-analysis, by taking into account the clinical experience and opinion of the world's leading experts, presents more fully the main aspects of the use of NSAIDs in real clinical practice. The guidelines are intended for physicians of all specialties.
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Vaccination against pneumococcal infections in Russian Federation: Social and pharmacoeconomic aspects
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01.01.2018 |
Rudakova A.
Briko N.
Lobzin Y.
Namazova-Baranova L.
Avdeev S.
Ignatova G.
Kostinov M.
Koroleva I.
Polibin R.
Fomin I.
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Jurnal Infektologii |
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0 |
Ссылка
© 2018 Interregional public organization Association of infectious disease specialists of Saint-Petersburg and Leningrad region (IPO AIDSSPbR). All rights reserved. Vaccination against pneumococcal infections by 13-va-lent conjugate vaccine (PCV13) can significantly reduce morbidity and mortality. The study has been aimed to evaluate the social and pharmacoeconomic aspects of PCV13 vaccination of 65-year-old patients with various risks of pneumococcal infection. Material and methods. Markov model with 5 and 15 years time horizon was used for the analysis from the position of the health care system. The analysis was carried out for 65-year-old citizens with low (absence of immunocompromized conditions and chronic diseases), moderate (patients with chronic diseases without immunodeficiency) and high (immunocompromized conditions) risk of pneumococcal infection as well as for the entire population of 65-year-old citizens, regardless of the risk level. In base-case assumption has been made that 1 dose of PCV13 should be administered for the patients from low and moderate risk groups and in the high-risk group 1 dose of PCV13 and in 8 weeks a dose of polysaccharide pneumococcal vaccine (PPV23) should be given. The treatment and physician visit costs have been calculated using CHI rates for St. Petersburg in 2018. Vaccination cost was calculated using the auction price to purchase PCV13 and PPV23 in 2018. Results. Vaccination of 1 cohort of 65-year-old citizens in Russian Federation within 5 years will result in prevention of 2200 deaths, 3900 cases of invasive pneumococcal diseases (IPD) and 48700 cases of community-acquired pneumonia. In 15 years prevention of about 4,3 thousand deaths, 6,6 thousand IPD and 101,1 thousand cases of CAP will be provided. Within 15-year horizon the cost-effectiveness ratio will be RUR 30,3, 82,4 and 410,0 thousand per QALY in high, moderate and low risk groups, respectively. Even if the time horizon is reduced to 5 years the PCV13 vaccination can be considered as an economically high-efficient intervention in moderate and high risk groups (cost-effectiveness ratio - RUR 279,2 and 221,7 thousand / QALY, respectively). In the 15-year-horizon noting the distribution of 65-year-olds by risk levels the cost-effectiveness ratio of PCV13 in population as a whole will be RUR 216,4 thousand / QALY. If moderate and high risk groups only are vaccinated, the average cost-effectiveness ratio will drop to RUR 67,6 thousand /QALY. At universal PCV13 vaccination of 65 years old in 5 year time horizon return of investment to the health care system budget will be 33.2% and at vaccination of persons with moderate and high risk return of investment will be 44.0%. With the assumption of vaccination during the planned physician visit (without additional visit) the return to the budget will be 46.8% and 60.9% for vaccination of all 65-year-olds and patients from the moderate and high risk groups, respectively. Conclusions. Vaccination of the 65-year-old persons against PCV13 pneumococcal infection in Russian Federation can be considered as a highly socially and economically effective intervention resulting in significant reduction of pneumococcal infection incidence and related mortality. The cost-effectiveness of vaccination is increasing along with the level of the risk. PCV13 vaccination of patients with moderate and high risk only provides a significant reduction in the burden for the health care budget in comparison with the vaccination of the entire population of 65-year-olds.
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ЭРАДИКАЦИЯ H.PYLORI: ОЦЕНКА РИСКА И ВОЗМОЖНОСТИ ПРОФИЛАКТИКИ МЕЖЛЕКАРСТВЕННЫХ ВЗАИМОДЕЙСТВИЙ
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Сереброва Светлана Юрьевна
Романов Дмитрий Владимирович
Несвижский Юрий Владимирович
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АНТИБИОТИКИ И ХИМИОТЕРАПИЯ |
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Современная терапия, направленная на эрадикацию H.pylori, включает комплекс антисекреторных и антибактериальных препаратов, иногда препаратов висмута. Особенностью современных эрадикационных схем является четырнадцатидневное применение антибактериальных средств, назначаемых в высоких суточных дозах и избираемых преимущественно с учётом резистентности микроорганизма к кларитромицину и метронидазолу в соответствующем регионе. Однако каждый компонент эрадикационной схемы может иметь достаточно серьёзные неблагоприятные побочные реакции, а также влиять на биодоступность, биотрансформацию, выведение и потенцирование эффектов лекарственных препаратов, которые больной может принимать одновременно с антихеликобактерной терапией. В статье перечислены наиболее серьёзные и распространённые варианты лекарственных взаимодействий компонентов эрадикационных схем, дано описание механизма их развития, если таковой выяснен. До появления практических рекомендаций относительно профилактики лекарственных взаимодействий препаратов, включаемых в эрадикационные схемы, следует использовать общедоступные базы данных, содержащие сведения о таких взаимодействиях.
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Публикация |
Cytokinin activity of N6-benzyladenine derivatives assayed by interaction with the receptors in planta, in vitro, and in silico
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Осолодкин Дмитрий Иванович
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Phytochemistry |
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Biological effects of hormones in both plants and animals are based on high-affinity interaction with cognate receptors resulting in their activation. The signal of cytokinins, classical plant hormones, is perceived in Arabidopsis by three homologous membrane receptors: AHK2, AHK3, and CRE1/AHK4. To study the cytokinin-receptor interaction, we used 25 derivatives of potent cytokinin N6-benzyladenine (BA) with substituents in the purine heterocycle and/or in the side chain. The study was focused primarily on individual cytokinin receptors from Arabidopsis. The main in planta assay system was based on Arabidopsis double mutants retaining only one isoform of cytokinin receptors and harboring cytokinin-sensitive reporter gene. Classical cytokinin biotest with Amaranthus seedlings was used as an additional biotest. In parallel, the binding of ligands to individual cytokinin receptors was assessed in the in vitro test system. Quantitative comparison of results of different assays confirmed the partial similarity of ligand-binding properties of receptor isoforms. Substituents at positions 8 and 9 of adenine moiety, elongated linker up to 4 methylene units, and replacement of N6 by sulfur or oxygen have resulted in the suppression of cytokinin activity of the derivative toward all receptors. Introduction of a halogen into position 2 of adenine moiety, on the contrary, often increased the ligand activity, especially toward AHK3. Features both common and distinctive of cytokinin receptors in Arabidopsis and Amaranthus were revealed, highlighting species specificity of the cytokinin perception apparatus. Correlations between the extent to which a compound binds to a receptor in vitro and its ability to activate the same receptor in planta were evaluated for each AHK protein. Interaction patterns between individual receptors and ligands were rationalized by structure analysis and molecular docking in sensory modules of AHK receptors. The best correlation between docking scores and specific binding was observed for AHK3. In addition, receptor-specific ligands have been discovered with unique properties to predominantly activate or block distinct cytokinin receptors. These ligands are promising for practical application and as molecular tools in the study of the cytokinin perception by plant cells.
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Публикация |
How regularities of mortality statistics explain why we age despite having potentially ageless somatic stem cells
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Крутько Вячеслав Николаевич
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Biogerontology |
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Researchers working in the area of ageing have found numerous manifestations of this process at the molecular biological level, including DNA and protein damage, accumulation of metabolic by-products, lipids peroxidation, macromolecular cross-linking, non-enzymatic glycosylation, anti-oxidant/pro-oxidant misbalance, rising of pro-inflammatory cytokines, etc. This results in an increase in the proportion of cells in growth arrest, reduction of the rate of information processing, metabolic rate decrease, and decrease in rates of other processes characterizing dynamic aspects of the organism’s interaction with its environment. Such staggering multilevel diversity in manifestation of senescence precludes (without methodology of systems biology) development of a correct understanding of its primary causes and does not allow for developing approaches capable of postponing ageing or reducing organisms’ ageing rate to attain health preservation. Moreover, it turns out that damage production and damage elimination processes, the misbalance of which results in the ageing process, can to a large extent be regulated by external signals. The purpose of this report is to provide evidence supporting this view and its compatibility with the regularities of mortality statistics, because the main idea is very simple. Even potentially a non-senescent but certainly not immortal body must start to age under inadequate conditions (like a non-melting piece of ice taken out from the deepfreeze inevitably start to melt at the temperatures above zero Celsius). This conclusion is totally consistent with existing patterns of mortality and with agelessness potential of somatic stem cells. Therefore, there is no need to build up and explore too complicated, computational and sophisticated systems models of intrinsic ageing to understand the origin of this mainly extrinsic root cause of natural ageing, which is controlled by environmental signals. In our case, a simple phenomenological black-box approach with Input–Output analysis is ample. Here Input refers to the environmentally dependent initial force of mortality, whereas Output is a rate of age-related increase of mortality force.
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Публикация |
Oncobox bioinformatical platform for selecting potentially effective combinations of target cancer drugs using high-throughput gene expression data
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Буздин Антон Александрович
Сорокин Максим Игоревич
Поддубская Елена Владимировна
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Cancers |
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Sequential courses of anticancer target therapy lead to selection of drug-resistant cells, which results in continuous decrease of clinical response. Here we present a new approach for predicting effective combinations of target drugs, which act in a synergistic manner. Synergistic combinations of drugs may prevent or postpone acquired resistance, thus increasing treatment efficiency. We cultured human ovarian carcinoma SKOV-3 and neuroblastoma NGP-127 cancer cell lines in the presence of Tyrosine Kinase Inhibitors (Pazopanib, Sorafenib, and Sunitinib) and Rapalogues (Temsirolimus and Everolimus) for four months and obtained cell lines demonstrating increased drug resistance. We investigated gene expression profiles of intact and resistant cells by microarrays and analyzed alterations in 378 cancer-related signaling pathways using the bioinformatical platform Oncobox. This revealed numerous pathways linked with development of drug resistant phenotypes. Our approach is based on targeting proteins involved in as many as possible signaling pathways upregulated in resistant cells. We tested 13 combinations of drugs and/or selective inhibitors predicted by Oncobox and 10 random combinations. Synergy scores for Oncobox predictions were significantly higher than for randomly selected drug combinations. Thus, the proposed approach significantly outperforms random selection of drugs and can be adopted to enhance discovery of new synergistic combinations of anticancer target drugs. View Full-Text
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Публикация |
ЭРАДИКАЦИЯ H.PYLORI: ОЦЕНКА РИСКА И ВОЗМОЖНОСТИ ПРОФИЛАКТИКИ МЕЖЛЕКАРСТВЕННЫХ ВЗАИМОДЕЙСТВИЙ
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Сереброва Светлана Юрьевна (Профессор)
Романов Дмитрий Владимирович (Профессор)
Несвижский Юрий Владимирович (Профессор)
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АНТИБИОТИКИ И ХИМИОТЕРАПИЯ |
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Современная терапия, направленная на эрадикацию H.pylori, включает комплекс антисекреторных и антибактериальных препаратов, иногда препаратов висмута. Особенностью современных эрадикационных схем является четырнадцатидневное применение антибактериальных средств, назначаемых в высоких суточных дозах и избираемых преимущественно с учётом резистентности микроорганизма к кларитромицину и метронидазолу в соответствующем регионе. Однако каждый компонент эрадикационной схемы может иметь достаточно серьёзные неблагоприятные побочные реакции, а также влиять на биодоступность, биотрансформацию, выведение и потенцирование эффектов лекарственных препаратов, которые больной может принимать одновременно с антихеликобактерной терапией. В статье перечислены наиболее серьёзные и распространённые варианты лекарственных взаимодействий компонентов эрадикационных схем, дано описание механизма их развития, если таковой выяснен. До появления практических рекомендаций относительно профилактики лекарственных взаимодействий препаратов, включаемых в эрадикационные схемы, следует использовать общедоступные базы данных, содержащие сведения о таких взаимодействиях.
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Публикация |
Cytokinin activity of N6-benzyladenine derivatives assayed by interaction with the receptors in planta, in vitro, and in silico
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|
Осолодкин Дмитрий Иванович (Доцент)
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Phytochemistry |
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|
Biological effects of hormones in both plants and animals are based on high-affinity interaction with cognate receptors resulting in their activation. The signal of cytokinins, classical plant hormones, is perceived in Arabidopsis by three homologous membrane receptors: AHK2, AHK3, and CRE1/AHK4. To study the cytokinin-receptor interaction, we used 25 derivatives of potent cytokinin N6-benzyladenine (BA) with substituents in the purine heterocycle and/or in the side chain. The study was focused primarily on individual cytokinin receptors from Arabidopsis. The main in planta assay system was based on Arabidopsis double mutants retaining only one isoform of cytokinin receptors and harboring cytokinin-sensitive reporter gene. Classical cytokinin biotest with Amaranthus seedlings was used as an additional biotest. In parallel, the binding of ligands to individual cytokinin receptors was assessed in the in vitro test system. Quantitative comparison of results of different assays confirmed the partial similarity of ligand-binding properties of receptor isoforms. Substituents at positions 8 and 9 of adenine moiety, elongated linker up to 4 methylene units, and replacement of N6 by sulfur or oxygen have resulted in the suppression of cytokinin activity of the derivative toward all receptors. Introduction of a halogen into position 2 of adenine moiety, on the contrary, often increased the ligand activity, especially toward AHK3. Features both common and distinctive of cytokinin receptors in Arabidopsis and Amaranthus were revealed, highlighting species specificity of the cytokinin perception apparatus. Correlations between the extent to which a compound binds to a receptor in vitro and its ability to activate the same receptor in planta were evaluated for each AHK protein. Interaction patterns between individual receptors and ligands were rationalized by structure analysis and molecular docking in sensory modules of AHK receptors. The best correlation between docking scores and specific binding was observed for AHK3. In addition, receptor-specific ligands have been discovered with unique properties to predominantly activate or block distinct cytokinin receptors. These ligands are promising for practical application and as molecular tools in the study of the cytokinin perception by plant cells.
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тезис
Публикация |
How regularities of mortality statistics explain why we age despite having potentially ageless somatic stem cells
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|
Крутько Вячеслав Николаевич (Профессор )
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Biogerontology |
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Researchers working in the area of ageing have found numerous manifestations of this process at the molecular biological level, including DNA and protein damage, accumulation of metabolic by-products, lipids peroxidation, macromolecular cross-linking, non-enzymatic glycosylation, anti-oxidant/pro-oxidant misbalance, rising of pro-inflammatory cytokines, etc. This results in an increase in the proportion of cells in growth arrest, reduction of the rate of information processing, metabolic rate decrease, and decrease in rates of other processes characterizing dynamic aspects of the organism’s interaction with its environment. Such staggering multilevel diversity in manifestation of senescence precludes (without methodology of systems biology) development of a correct understanding of its primary causes and does not allow for developing approaches capable of postponing ageing or reducing organisms’ ageing rate to attain health preservation. Moreover, it turns out that damage production and damage elimination processes, the misbalance of which results in the ageing process, can to a large extent be regulated by external signals. The purpose of this report is to provide evidence supporting this view and its compatibility with the regularities of mortality statistics, because the main idea is very simple. Even potentially a non-senescent but certainly not immortal body must start to age under inadequate conditions (like a non-melting piece of ice taken out from the deepfreeze inevitably start to melt at the temperatures above zero Celsius). This conclusion is totally consistent with existing patterns of mortality and with agelessness potential of somatic stem cells. Therefore, there is no need to build up and explore too complicated, computational and sophisticated systems models of intrinsic ageing to understand the origin of this mainly extrinsic root cause of natural ageing, which is controlled by environmental signals. In our case, a simple phenomenological black-box approach with Input–Output analysis is ample. Here Input refers to the environmentally dependent initial force of mortality, whereas Output is a rate of age-related increase of mortality force.
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тезис
Публикация |
Oncobox bioinformatical platform for selecting potentially effective combinations of target cancer drugs using high-throughput gene expression data
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Буздин Антон Александрович (Заведующий лабораторией)
Сорокин Максим Игоревич (Научный сотрудник)
Поддубская Елена Владимировна (Старший научный сотрудник)
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Cancers |
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Sequential courses of anticancer target therapy lead to selection of drug-resistant cells, which results in continuous decrease of clinical response. Here we present a new approach for predicting effective combinations of target drugs, which act in a synergistic manner. Synergistic combinations of drugs may prevent or postpone acquired resistance, thus increasing treatment efficiency. We cultured human ovarian carcinoma SKOV-3 and neuroblastoma NGP-127 cancer cell lines in the presence of Tyrosine Kinase Inhibitors (Pazopanib, Sorafenib, and Sunitinib) and Rapalogues (Temsirolimus and Everolimus) for four months and obtained cell lines demonstrating increased drug resistance. We investigated gene expression profiles of intact and resistant cells by microarrays and analyzed alterations in 378 cancer-related signaling pathways using the bioinformatical platform Oncobox. This revealed numerous pathways linked with development of drug resistant phenotypes. Our approach is based on targeting proteins involved in as many as possible signaling pathways upregulated in resistant cells. We tested 13 combinations of drugs and/or selective inhibitors predicted by Oncobox and 10 random combinations. Synergy scores for Oncobox predictions were significantly higher than for randomly selected drug combinations. Thus, the proposed approach significantly outperforms random selection of drugs and can be adopted to enhance discovery of new synergistic combinations of anticancer target drugs. View Full-Text
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Публикация |