bluuebunny/crossref_metadata_2025 huggingface dataset:
Performance comparison of timber-based assemblies and other construction solutions for rooftop extensions
Authors: Rissetto R. , Pont U. , Mahdavi A.
Published: November 2018

Population growth in a number of central European cities necessitates the creation of additional living spaces within the existing urban settings. Toward this end, densification via rooftop extension of existing buildings can provide a partial solution. As the requirements regarding energy performance, summer-time thermal comfort, and structural integrity of attic expansions have been increasingly tightened, planners must carefully assess the advantages and disadvantages of different construction possibilities. Focusing specifically on timber construction as a kind of reference, the present contribution includes a comparison of six different (both conventional and novel) construction solutions for roof top extensions in view of different performance criteria, such as ecological footprint, impact on energy indicators, summer overheating mitigation, cost, and construction time. To conduct the comparison in a transparent manner, the selected construction methods were virtually applied to a case-study building and assessed via multiple tools, including a numeric thermal simulation application.
Imagem corporal e comportamento alimentar em estudantes universitárias
Authors: Gaudioso Carlos Eduardo Vilela , Souza José Carlos , Magna Luis Alberto , Botelho Heloísa Nunes
Published: November 2018

Este estudo avaliou a imagem corporal e as atitudes alimentares de uma amostra de estudantes universitárias de uma faculdade do Mato Grosso do Sul, Brasil. Método: quantitativo, exploratório, descritivo e de corte transversal. Participaram da pesquisa 106 alunas. Foram aplicados três instrumentos, sendo um questionário sócio-demográfico; para avaliar a insatisfação com a imagem corporal foi utilizado o Questionário de Imagem Corporal (Body Shape Questionnaire-BSQ) e para a identificação da presença de distúrbios de atitudes alimentares foi utilizado o Teste de Atitudes Alimentares (Eating Attitude Test-EAT-26). Resultados indicaram, pelo EAT26, que 15,2% das alunas tinham escore sugestivo de distúrbio alimentar (acima de 21) e 84,8% escore igual ou inferior a 21, portanto indicativo de ausência de distúrbio alimentar. Tanto a idade quanto o IMC e a frequência semanal de atividade física são semelhantes nos grupos identificados pelo EAT26 como sem distúrbio ou com provável distúrbio alimentar. As médias para a idade em cada grupo foram 24,86 e 25,44 anos; IMC médio de 21,78 e 22,77; e média de 3,83 e 3,33 de vezes/semana de prática de atividade física. Em relação ao BSQ, seu resultado foi conclusivo para 95 alunas, as quais se distribuíram em 74,7% sem transtorno, 11,6% com transtorno leve, 8,4% com transtorno moderado e 5,3% com transtorno grave.
Briefing: A systemic framework for infrastructure need assessment
Authors: Dolan Tom
Published: November 2018

In the absence of a clearly articulated, shared, collaboratively developed and mutually understood strategic vision of the desired outcomes that infrastructure is expected to enable (purpose), it is not possible to fully evaluate system performance gaps or assess infrastructure need. This is significant for any country, region, city, town or community aiming to cost-effectively improve the performance and resilience of its infrastructure systems. A systemic, collaborative, transparent, structured and flexible framework for infrastructure need assessment and decision-making is proposed. The proposed framework is systemic; is built on a set of strategic need assessment principles; explicitly aligns need assessment with the desired outcomes that infrastructure systems are expected to enable; prioritises underlying systemic priorities such as resilience; assesses infrastructure system performance and diagnoses infrastructure need from four perspectives; requires outcomes and needs to be neutrally framed; and prescribes transparent evaluation of options against clearly defined systemic and outcome-aligned selection criteria.
Perfil funcional de pacientes com distonia cervical: uma série de casos
Authors: Santos Carolina Cerqueira , Ribeiro Nildo Manoel da Silva
Published: November 2018

INTRODUÇÃO: A Distonia Cervical (DC) é uma doença dos núcleos da base e tem como consequência movimentos hipercinéticos, sendo a mais comum entre as distonias focais. Além disso, pode ser definida pela presença de contrações involuntárias envolvendo a musculatura cervical. OBJETIVO: descrever o perfil funcional de pacientes com DC, oferecendo maior embasamento focado nas habilidades funcionais desses pacientes. MÉTODOS: Foi realizado um estudo transversal de pacientes atendidos no Ambulatório de Neurociências localizado no Ambulatório Professor Francisco Magalhães Neto, Salvador, Bahia, no período de novembro a dezembro de 2017. RESULTADOS: Foram analisados 6 pacientes: 3 do sexo feminino e 3 do sexo masculino. A maior parte dos pacientes apresentou os sintomas iniciais após algum trauma sofrido, baixo/moderado risco de queda, qualidade de vida (QV) impactada negativamente por limitações físicas, dependência leve e dor moderada. As principais queixas relacionadas à participação social estavam relacionadas a frequentar ambientes públicos, devido à vergonha que sentem por causa dos movimentos involuntários, além da impossibilidade de trabalhar proporcionada pela doença. CONCLUSÕES: O perfil funcional dos pacientes com DC ainda é escasso na literatura. Nesse estudo, a população com DC mostrou sofrer não só impactos na QV por fatores físicos, mas, sobretudo, por fatores emocionais e sociais.
Estresse gravitacional no pós-operatório de cirurgia cardíaca
Authors: Viana Patrícia Alcântara Doval de Carvalho , Lordello Gleide Glícia Gama , Serra Juliana Martini Matos , Rosier Gabriela Lago , Correia Luís Cláudio
Published: November 2018

INTRODUÇÃO: Após a cirurgia cardíaca, a mobilização precoce busca o ganho funcional e um melhor condicionamento para as próximas fases da reabilitação cardiovascular, tendo o estresse gravitacional(EG)um importante papel para o retorno destas atividades, através   da integridade dos mecanismos compensatórios cardiovasculares. OBJETIVO: verificar o comportamento de variáveis circulatórias e respiratórias durante o EG no pós-operatório de cirurgia cardíaca. MÉTODOS E MATERIAIS: Estudo observacional, transversal e analítico, composto por 83 indivíduos adultos clinicamente estáveis, submetidos a cirurgia de revascularização do miocárdio ou abordagem valvar. Excluídos aqueles com dificuldade de compreensão das atividades realizadas, além de comprometimento motor e/ou neurológico que impossibilitassem a realização do EG, de forma adaptada. Foram coletados os dados circulatórios e respiratórios no 1° minuto para cada etapa através do monitor multiparamétrico Gemedical Systems@. RESULTADOS: As frequências cardíaca e respiratória apresentaram um aumento com significância estatística (p ? 0,01), quando analisado seus valores de variação de decúbito dorsal para sedestação e decúbito dorsal para ortostase. CONCLUSÃO: As variáveis hemodinâmicas e respiratórias se comportam de acordo com a resposta fisiológica durante o EG, sugerindo que esse procedimento é seguro no ambiente da terapia intensiva, mesmo se tratando de um pós-operatório de alta complexidade.
Fatores de risco cardiovascular associados à hipertensão arterial sistêmica em escolares
Authors: Soares Raoni , Tosta Larissa Santos , Cavalcante Luciana Ricarte , Zarife André Sant'Anna , Brito Luciara Leite , Fraga-Maia Helena
Published: November 2018

INTRODUÇÃO: A análise conjunta dos hábitos de vida que podem predispor ao aparecimento de doenças cardiovasculares na idade adulta tem papel importante para o conhecimento do perfil de risco cardiovascular de crianças e adolescentes. OBJETIVO: Investigar hábitos alimentares inadequados e fatores de risco cardiovascular associados à Hipertensão Arterial Sistêmica em escolares de 7 a 14 anos de idade, domiciliados no Cabula/Beiru na cidade do Salvador, Bahia, Brasil. MÉTODOS: Estudo transversal com 162 escolares matriculados na rede pública do Ensino Fundamental I, residentes no Distrito Sanitário Cabula Beiru (DSCB), na cidade do Salvador, Bahia. Regressão logística multivariada, não-condicional, hierarquizada, foi usada para avaliar a associação, após ajustes por fatores sociodemográficos e de saúde, entre a HAS, hábitos alimentares inadequados e fatores de risco cardiovascular. RESULTADOS: A prevalência de hipertensão arterial entre os escolares foi estimada em 23,0% e o excesso de peso (OR=4,08; IC95% 1,75 – 9,55), assim como a inatividade física (< 300 min/semana) (OR=5,69; IC95% 1,56 – 20,69), consumo inadequado de doces (OR=2,65; IC95%: 1,01 – 7,00) e de refrigerantes (OR=3,61; IC95%: 1,28 – 10,13) foram os fatores  associados com pressão arterial elevada. CONCLUSÕES: Os dados evidenciam hábitos inadequados de alimentação e fatores de risco cardiovasculares, em especial, sobrepeso ou obesidade e ser insuficientemente ativo. Estes resultados reforçam a necessidade de programas de promoção de saúde e prevenção dos riscos direcionados à parcela mais jovem da população. Recomendamos a adoção de estratégias para o controle do peso e estímulo à prática regular de atividade física nas escolas, bem como ações de educação em saúde no Ensino Fundamental.
SMALL GTPASE ARF6 ACTIVATES mTORCl-DEPENDENT SIGNALING PATHWAY AND STIMULATES GLIOBLASTOMA CELL GROWTH
Authors: Zhuravskaya A. Yu. , Komelkov A. V. , Tchevkina E. M.
Published: November 2018

In this study we first identified role of small GTPase Arf6 in stimulation of proliferation and autonomous growth of human glioblastoma cells. We revealed that Arf6 activates the mTOR complex 1 (mTORCl) and this process is appeared to be an alternative mechanism of mTORC1-signaling activation, independent of PI3K/Akt-signaling pathway. We also showed that Arf6 is a negative regulator of protein kinase ERK1/2 in glioblastoma cells.
ANALYTICAL CHARACTERISTICS OF FLUORESCENT SUSPENSION NANOCRYSTAL-ENCODED MICROARRAY ADAPTED FOR SIMULTANEOUS QUANTITATIVE DETECTION OF FREE AND TOTAL PSA IN SERUM SAMPLES
Authors: Brazhnik K. I. , Sokolova Z. A. , Baryshnikova M. A. , Bilan R. S. , Nabiev I. R. , Sukhanova A. V.
Published: November 2018

Multiplexed suspension systems of anew generation are capable to provide precise quantitative profiling of mul- tipledisease-specific markers in human body fluids. We have developed suspension microarrays based on microbeads encoded with fluorescent nanociystals, that show undeniable advantages overavailable analogues in terms of improved multiplexing capabilities, physical and optical properties, low cost and simplicity of analysisperformance. We have adapted QD-encoded suspension microarrays for the simultaneous detection of two forms of prostate-specific antigen (PSA) in human serum by means of classical flow cytometiy. In the present study, we describe in detail the designed system properties including evaluation the microarray for quantitative analysis of serum markers in comparison to standard clinical approach ELISA, as well asestimation of the most important analytical characteristics, such as analytic sensitivity (limit of detection), reproducibility, reliability and accuracy of the analysis, the linear rangesfor detectable- marker concentrations. Experimental data suggested that the developed diagnostic system quantifies two forms of PSA in blood serum samples of patients with high accuracy, precision and reliability.
STUDY OF ACUTE TOXICITY OF NOVEL ANTITUMOR PREPARATION BASED ON DERIVATIVE OF INDOLOCARBAZOLE - LCS-1208
Authors: Nikolina A. A. , Kul'bachevskaja N. Ju. , Konjaeva O. I. , Chalej V. A. , Ermakova N. P. , Bukhman V. M.
Published: November 2018

The research has been devoted to the study of acute toxicity of preparation based on derivative of indolocarba- zole - LCS-1208 in mice of both sexes and in rats of both sexes at intravenous and intraperitoneal administration of the drug. In the experiments the laboratory animals - outbred white rats and hybrid mice (C57Bl/6JxDBA2)Fl (B6D2F1) have been used. On the results of study has been obtained the calculated toxic doses of novel preparation based on derivative of indolocarbazole at intraperitoneal administration of the drug in mice of both sexes.
NONCLINICAL STUDY OF THE TOXICITY OF A NEW ANTICANCER DRUG ОRMUSTIN ON SMALL LABORATORY ANIMALS
Authors: Chaley V. A. , Konyaeva O. I. , Ermakova N. P. , Nikolina A. A. , Bukhman V. M. , Kul’Bachevskaya N. Yu.
Published: November 2018

The paper presents the results of the study of «acute» toxicity and some results of the study of «subchronic» toxicity of Ormustin, a new anticancer drug belonging to nitrosourea class, in small laboratory animals. In the experiments the laboratory animals - hybrid mice (C57Bl/6J×DBA/2)F1 male and female and outbred male and female rats have been used. On the results of study has been obtained the calculated toxic doses of Ormustin at intravenous administration of the drug in mice and rats; has been given the preliminary assessment of the impact of Ormustin on organs and systems of rats at multiple intravenous administration.
INTOXICATION SYMPTOMS IN FOLLICULAR LYMPHMA: PROBABLE PATHOGENESIS AND CLINICAL SIGNIFICANCE
Authors: Falaleeva N. A.
Published: November 2018

Introduction. About 25 % of patients at diagnosis of follicular lymphoma have intoxication symptoms, which are probably induced by endogeneous cytokines. Production of several cytokines may be followed by temperature, lypogenesis disturbances, anorexia, body weight loss and so on. The pathogenesis of intoxication symptoms and its clinical significance are not completely understood in follicular lymphoma. Objective - to investigate the clinical and prognostic significance of presence of intoxication symptoms at the opening stages of follicular lymphomas. Matherials and methods. We’ve characterized a group of 74 follicular lymphoma patients, which had at time of diagnosis B-symptoms. Comparison group included 207 patients without intoxication symptoms. Results. In patients with B-symptoms we noted higher estimation according to ECOG scale, more fequent of haemoglobin diminution less than 120 g/l. It was more frequently noted elevation of LDH levels and diminution of serum total protein concentration. Presense of intoxication symptoms usually indicated the more turmor burden in patients: in 90,5 % advanced disease stages, in 75,7 % involvement of more than 4 nodal zones, in 81,1 % peripheral lymph nodes above diaphragm were involved, in 35,1 % mediastinal lymph nodes, and in 74,3 % of patients retroperitoneal lymph nodes were involved. More frequently in patients with intoxication symptoms more than one extranodal zone was ivolved, especially spleen and hepar. According to FLIPI 64,2 % of follicular lymphoma patients with B-symptoms were of high risk group, and they had worse quality of treatment response: in 25 % of cases progression during or soon after treatment was noted. Intoxication symptoms negatively influensed on overall survival, but not on the duration of treatment response. Conclusion. Intoxication symptoms significantly affects overall survival and survival without progression in follicular lymphoma patients. Key words: follicular lymphoma, intoxication symptom
ESSENTIALS OF THE MOLECuLAR DIAGNOSIS OF ONCOHEMATOLOGICAL DISEASES
Authors: Misyurin A. V.
Published: November 2018

Molecular genetic and molecular biology methods enable one to reveal pathogenetic basis of oncohematological diseases, they are particular useful for diagnostic purpouses, to control and evaluate treatment efficiency. In leukemia patients there are two different types of chromosomal anomalities: some of them give rise for chimeric oncogenes, others activate hyperexpression of regulatory genes. It is necessary to take into account this difference in order to proparely develop molecular genetic tests. Molecular tests are more sensitive to compare with other approaches, due to this fact they are especially useful to monitor residual leukemia cells and for early detection of relapse.
THE USE OF OLIGOSACCHARIDES OF IMMUNOGLOBULIN FOR MODIFICATION OF MONOCLONAL ANTIBODIES
Authors: Grinevich A. S. , Kraeva M. N. , Burova O. S. , Ivanov P. K.
Published: November 2018

Bakground. Monoclonal antibodies are reliable and convenient tool for the diagnosis of human pathologies. Most often they are used as conjugates with fluorescent or other labels. The classical approach of creating such conjugates reduces chemical reactions using monoclonal antibodies protein base. However, for a number of manufacturing monoclonal antibodies conjugate followed by embedding tags in the antigen binding site, which leads to reduction or complete loss of specific activity of the conjugate. The way out of this situation could be the synthesis of fluorescent conjugates, methods of carbohydrate chemistry through spatially distant from the active site of the antibody oligosaccharides. The purpose of the study - to show the fundamental possibility of chemical modification of the oligosaccharides monoclonal antibodies ICO series and get to their base fluorescent conjugates. Materials and methods. We used monoclonal antibodies panel ICO series of high purity. Oligosaccharides monoclonal antibodies oxidized to aldehyde groups, is reacted with a hydrazine derivative of biotin and streptavidin-conjugated flyuoristsiinom. The resulting complex was used for the direct reaction immunofluorescence. Results. All modified monoclonal antibodies retain binding specificity to target cells inherent to native antibodies. Conclusions. This may be an alternative method for conjugating a fluorescent label with monoclonal antibodies to protein synthesis methods which lead to loss of activity of the conjugate.
CREATING LABORATORY TECHNOLOGY OF GENERIC EPIRUBICIN PHARMECEUTICAL DOSAGE FORM
Authors: Orlova O. L. , Polozkova A. P. , Oborotova N. A. , Shprakh Z. S. , Kiseleva M. P. , Borisova L. M. , Dmitrieva M. V. , Rodionova Y. V. , Kohachevskaya S. V. , Eskina T. Y. , Smirnova Z. S.
Published: November 2018

Introduction. Governments around the world seek to reduce rapidly rising health care costs. Using the same high quality and often cheaper than the original brands, generics greatly reduces costs while providing an adequate quality of care. Therefore the development of generic medicines is an important task. The purpose of the study - the reproduction of the pharmaceutical dosage form for creation of national drug-generic epirubicin. Materials and methods. The study used a substance epirubicin (Ph. Eur current edition, Teva Pharmaceutical Industries Ltd., Israel); “Farmorubicin”, production “Pfizer Italia Srl” for “Pfizer Inc.”, Italy / US and excipients conforming to with relevant regulatory documents. Mice transplanted tumor: lymphocytic leukemia P388. Methods: technological, pharmaco-analytical, biological and pharmacological. Results. Pharmaceutical analysis of reproduced generic-drug “Epirubicin-RONC®” showed that itfully meets the requirements of manufacturer’s monograph. The results of “acute” toxicity study in rats and observations of the experimental animals within 30 days after a single administration suggest that both drugs have similar toxicological properties and are almost identical. Generic “Epirubicin RONC®” and “Farmorubicin” in lyophilized dosage form for injection 10.0 mg/vial, administered once, shows equal antitumor effect at two administration routes in mice with transplantable tumor: lymphocytic leukemia P-388. Conclusion. N.N. Blokhin Russian Cancer Research Center Ministry of Health of Russia has been reproduced generic - “Epirubi-cin-RONC®”, which is fully conform to the imported drug.
Proteomic identification of hnRNP family members and other proteins involved in splicing in human cultured cells
Authors: Pashintseva N. V. , Eremina L. S. , Lisitskaya K. V. , Ivanov A. V. , Kovalev L. I. , Kovaleva M. A. , Shishkin S. S.
Published: November 2018

Introduction. Heterogeneous nuclear ribonucleoprotein A1 (hnRNP А1) and other RNA-binding proteins involved in splicing participate in realization of genetic information and can be greatly changed in pathological conditions including tumors. Objective. Proteomic study of hnRNP A1 and other RNA-binding splicing proteins in 10 human malignant and non-malignant cultured cell lines of mesenchymal and epithelial origin. Materials and methods. Two-dimensional gel electrophoresis of adenocarcinomas (LNCaP, DU-145, PC-3, 769-P) and sarcomas (U2-OS, SK-UT-1B, RD) cell lines with following protein identification by matrix-assisted laser desorption ionization mass spectrometry have been carried out. Results. HnRNP А1 has been identified as an abundant protein in all studied malignant cell lines. It has been revealed in lower amount in normal mesenchymal cells compared to malignant cultured cells and achieved undetectable levels in myoblasts after induction of differentiation. Conclusion. High cellular level of hnRNP А1 can suggest high proliferative activity of cells including malignant those. Hence, hnRNP А1 and other RNA-binding splicing proteins hold promise to its further investigation in human transformed cells.
Modern methods of treatment of breast cancer in the elderly
Authors: Ryabchikov D. A. , Chepelova N. K. , Vorotnikov I. K. , Denchik D. A.
Published: November 2018

The prognosis of breast cancer in the elderly is associated with increased risk of various complications. Recommendations for the treatment of breast cancer in this group of patients are controversial and range from radical surgery to conservative therapy. There are no specific clinical recommendations for this age group. It makes this problem relevant.
The influence of drug formulations on the expression of MDM2 and NFkB1 mRNA in the melanoma cell lines
Authors: Ponomarev A. V. , Misyurin V. A. , Rudakova A. A. , Burova O. S. , Misyurin A. V. , Baryshnikova M. A.
Published: November 2018

Introduction. Chemotherapy is an extremely ineffective and unsatisfactory means of treating malignant melanoma due to drug resistance, which is characteristic of this disease. A number of studies have shown that liposomal forms of anticancer drugs are able to overcome the multidrug resistance, but the mechanism by which this occurs is still remained to be elucidated. Aranoza (DNA-alkylating agent, a derivative of nitrosourea) has been approved for the treatment of patients with metastatic melanoma. Objective: to examine the influence of liposomal aranoza as well as the empty liposomes and “liophilisate for the preparation of solution for injections” (aranoza-lio) on the expression of mRNA of p53, MDM2, NFkB1, NFkB2, MyD88. Materials and methods. The study was performed with 10 melanoma cell lines, 4 of which carried the BRAF mutation. The level of p53, MDM2, NFkB1, NFkB2, MyD88 mRNA was investigated by quantitative polymerase chain reaction in real time. Results. Aranoza-lio increased slightly the expression of p53 mRNA in BRAF-mutated cells. We have observed also the increased expression of MDM2 mRNA (p = 0.0013). The expression of NFkB2, MyD88 mRNA did not change significantly as compared to control. Liposomal aranoza increased the expression of NFkB1 mRNA. Conclusion. Based on the data obtained we conclude that the liposomal aranoza triggers the mechanisms that contribute to sensitivity of cells toward anticancer drugs while aranoza-lio favored the enhancing of the expression of MDM2 mRNA and increase the resistance to chemotherapy.
DNA-markers for genetic monitoring of laboratory mouse
Authors: Bukreev Yu. M. , Kosobokova E. N. , Kardashova S. S. , Pinyugina M. V. , Kosorukov V. S.
Published: November 2018

Introduction. The use of standardized model is required at preclinical researches of drug safety and efficiency. Apart of veterinary control the leading laboratories of the world use genetic monitoring of animals. Objective: to develop the method for detecting genetic contamination of laboratory mouse based on microsatellite DNA markers analysis. Materials and methods. We tested two lines of mice C57BL/6J and BALB/cJLac. We used 5 primers: (GAG)6C, (CTC)6C, (CTC)6A, AG9-1, AG9-2. We weighted the results of рolymerase chain reaction using 1.5 % agarous gel. Results. Three of tested primers allowed to distinguish 2 lines of mice statistically reliably. Two mice lines were bred to control the results. Our data shows track of every line gives a boots in assortment of alleles in locuses. We composed a table of alleles assortment in locuses for every line based of results. Conclusion. Our results prove that this method provides fast, reliable and cost-effective way of genetic monitoring.
Expression profiles of potential target genes in disseminated gastric cancer
Authors: Kipkeeva F. M. , Muzaffarova T. A. , Narimanov M. N. , Malekhova O. A. , Bogush T. A. , Karpukhin A. V.
Published: November 2018

Objective is the investigation of messenger RNA quantitative expression profiles of potential target genes among disseminated gastric cancer cases. Materials and methods. Quantitative real-time polymerase chain reaction on paired tumor-normal samples. Results. The most frequently (25-41 % of cases) an increased level of messenger RNA in the tumor with respect to normal tissue was observed for the genes of TGF-ß (transforming growth factor ß), NRP-1 (neuropiline 1) and VEGF (vascular endothelial growth factor) family genes. For the first time a correlation between the expression levels of the three genes: NRP-1, TGF-ß and VEGFR-2, and the inverse correlation of the levels of VEGF and bFGF gene expression were found. Conclusion. The revealed correlation between the expression of TGF-ß, NRP-1 and VEGFR-2 genes is apparently due to the interaction of NRP-1 with the products of two other genes and may be associated with a high metastatic potential of the progressing tumor in disseminated gastric cancer. The observed inverse correlation of the VEGF-A and bFGF gene expression may indicate the stimulation of angiogenesis in the tumor with reduced activity of the VEGF pathway by activating the bFGF signaling pathway. The results obtained should be taken into account under targeted therapy.
Quantitative assesment of coexpression of cytokeratins and mesenchimal cells marker vimentin in serous ovarian cancer
Authors: Bogush T. A. , Arefieva A. A. , Kaliuzhny S. A. , Bogush E. A. , Tjulandin S. A. , Polotsky B. E. , Davydov M. M.
Published: November 2018

Background. Epithelial-mesenchymal transition (EMT) is a factor related to metastatic potential of tumor cells. The most distinguishing feature of this transformation is expression of protein vimentin, which is not common for epithelial cells. Data of EMT level and clinical significance of the marker is ambiguous in prognosis of tumor different localization including ovarian cancer. Objective is characterization of EMT in ovarian cancer tissue based on quantitative analysis of co-expression level of epithelial cytokeratins and mesenchymal cells marker vimentin. Materials and methods. A quantitative assessment of co-expression level of cytokeratins and vimentin was performed by double immunofluorescence staining method (58 surgery specimens of ovarian cancer stage III), associated with flow cytometry. Results. Double immunofluorescence staining method, developed and used in the current study, was used for quantitative assessment of EMT level based on value of cytokeratin and vimentin co-expression in epithelial cells. Epithelial cells co-expressed these markers, were detected in 100 % tumor investigated with individual value differences from 10 to 86 %. Average co-expression level of cytokeratins and vimentin in subgroups with high and low level value related to median 42 % significantly varied and were 28,5 ± 7,5 and 56,3 ± 11,8 % (p = 0,02) respectively. Conclusions Serous ovarian cancer is molecular heterogeneous group with principal differences in level of EMT tumor phenotype between various patients. In half of the cases the disease is characterized by high metastatic potential of tumor cells. Co-expression of cyto-keratins and vimentin in all the tumors investigated is evidenced clinical significance of this molecular characteristic in ovarian cancer pathogenesis.
Study of level and selectivity of liposomal form of photosensitiser hydroxyaluminium tetra-3-phenylthiophthalocyanine accumulation on transplantable mice tumor models at different ways of transplantation
Authors: Meerovich G. A. , Borisova L. M. , Bud’Ko A. P. , Kiseleva M. P. , Nikolaeva L. L. , Meerovich I. G. , Lantsova A. V. , Chernova S. V. , Oborotova N. A.
Published: November 2018

Background. Current work is devoted to the study in vivo of concentration and selectivity of accumulation of infrared photosensitizer (PS) hydroxyaluminium tetra-3-phenylthiophthalocyanine in liposomal form in intramuscularly and subcutaneously transplanted mice tumor models in comparison to normal tissues. Objective: to study the level and selectivity of accumulation of hydroxyaluminium tetra-3-phenylthiophthalocyanine liposomal form on mice tumor models in order to optimize the transplantation approach and the starting of photodynamic treatment. Materials and methods. A range of transplantable mice tumors was used in the study: solid carcinoma Ehrlich (ELD) and solid sarcoma S-37, epidermoid Lewis lung carcinoma (LLC) and colon adenocarcinoma (AKATOL). For the assessment of concentration of PS in tissues was evaluated by fluorescence spectroscopy in vivo. Results. The optimum transplantation approaches were shown to be as follows. Solid carcinoma Ehrlich (ELD) provided the highest accumulation of PS when transplanted intramuscularly. Five hours after administration concentration of PS in tumor achieves more than 7 mg/kg, with selectivity in comparison to normal tissue 3 : 1. The maximum concentration of PS in sarcoma S-37 was observed with subcutaneous transplantation, achieving at 5 h after administration the value of 5.4 mg/kg with selectivity of accumulation 4.3: 1. Both LLC and AKATOL showed optimum results with intramuscular transplantation. Maximum concentration of PS in LLC was observed 5 h after administration, achieving 7.5 mg/kg with selectivity exceeding 4. Concentration of photosensitizer in AKATOL 7h post administration achieved 6.8 mg/kg with selectivity about 2. Conclusions. Liposomal form of PS with intravenous administration selectively accumulates in tumors. The obtained experimental data allows to recommend the method of listed tumors models transplantation for the studies of PS.
Possibilities of application of genetic and serum oncomarkers in early diagnostics of breast cancer
Authors: Ryabchikov D. A. , Dudina I. A. , Vorotnikov I. K. , Denchik D. A. , Shusharin A. S. , Abdullaeva E. I.
Published: November 2018

Currently, mammography is the main screening method for diagnosing breast cancer (BC); but the process of carcinogenesis begins long before the appearance of a visualized tumor. For successful early diagnosis of breast cancer, a systematic approach is required, that includes all stages of tumor development. On the example of BC we consider the possibilities of integrating the recent scientific achievements of oncogenetics and proteomics with standard methods. In this article we investigate the possibilities of using genetic research, serum cancer markers and radiation methods for early diagnosis of BC. This article also presents potential options for managing high-risk development of this disease.
Relationship between deletion and point mutations of p53 and drug resistance to aranoza in human melanoma cell lines
Authors: Ponomarev A. V. , Solodovnik A. A. , Mkrtchyan A. S. , Finashutina Yu. P. , Turba A. A. , Misyurin V. A. , Misyurin A. V. , Baryshnikova M. A.
Published: November 2018

Aranosa, nitrozourea derivative is a DNA-methylating agent that has been approved for treatment of patients with disseminated melanoma. Aranoza effect is based on DNA damage and then as a result apoptosis mechanisms start launching. The important role in this process must be played by p53 protein, and its different dysfunctions can result in drug resistance. Objective. The purpose is to study p53 mutational status in cell lines of human skin metastatic melanoma and to estimate its connection with сell lines resistance to aranoza. Materials and methods. The research was conducted on 14 cell lines of human skin metastatic melanoma. Aranoza IC50 for cell lines was determined by MTT-test. The 17р chromosome’s condition was estimated by fluorescence in situ hybridization. The presence of point mutations in DNA-binding domain of human p53 was researched by Sanger sequencing. Results. Skin metastatic melanoma cell lines had different sensitivity to aranoza. Almost all cell lines were heterogeneous in the condition of 17 th chromosome. P53 point mutations were found in 2 cell lines. But one part of resistant cell lines almost didn’t have any mutational disorders of p53, another part of resistant lines on the contrary had plenty of p53 mutational disorders. Conclusion. The correlation of resistance and p53 mutations can be established for one part of human skin metastatic melanoma cell lines. But for another part of human skin metastatic melanoma cell lines resistance most likely are driven by other mechanisms.
Тhe technology of creation and quality testing of immunofluorescent probes with dye alexa-488 for analysis of celular populations by flow cytometry
Authors: Kopyrulina M. E. , Zakharova E. N. , Zabotina T. N. , Blokhin D. Yu. , Ivanov P. K.
Published: November 2018

Fluorescent probes based on monoclonal antibodies (MAb) are widely used in scientific and clinical research in the field of oncology, hematology, immunology, epidemiology. Objective: to create of fluorescent probes based on the MAb and the fluorescent dye Alexa-488 for the analysis of cellular populations by flow cytometry. Materials and methods. MAb to B lymphocyte antigen (clone ICO-180), fluorescent dye Alexa-488 were used in the work. MAb was isolated from ascitic fluid by combined purification of the immunoglobulin fraction with caprylic acid and salting out with ammonium sulfate. Gel filtration on a PD-10 column was used to purify the conjugates (immunofluorescent probes, IFP), the concentration and labeling density of the IFP were determined spectrophotometrically. The determination of the working titer of the IFP was performed using the antibody titration method proposed by C.C. Stewart. Results. The optimal time of incubation of MAb with a fluorophore was experimentally determined. The optimal conditions for labeling MAb of the IСO series with the dye are: a carbonate buffer with pH 8,3, the concentration of antibodies in the reaction mixture is 1 mg/ml, molar ratio of active dye – 10–100 mmol per 1 mmol of protein, the incubation time is 90 minutes, the temperature is 18–25 °C. We obtained a panel of conjugates of MAb with Alexa-488, differing in their different labeling densities. Evaluation of the biological activity of the resulting conjugates was carried out on peripheral blood cells of donors in the concentration range of MAb 0,5–100 μg/ml. Conclusion. The optimal conditions for labeling MAb of the IСO series with the dye are: a carbonate buffer with pH 8,3, the concentration of antibodies in the reaction mixture is 1 mg/ml, the incubation time is 90 minutes, the temperature is 18–25 °C. The optimum density of labeling is in the range 5–13,5 M:M, the optimal concentration of antibodies is in the range of 5–25 μg/ml.
Тhe comparative pathomorphologic research of the inner organs of rats on the precliniсal study of vincristinе-ROnC and vincristinе-teva
Authors: Abramova T. V. , Merkulova I. B. , Kulbachevskaya N. Yu. , Konyaevа O. I. , Ermakova N. P. , Chaley V. A. , Bukhman V. M.
Published: November 2018

In accordance with Russian Federal program of import substitution of foreign medicines quality of Russian drugs in the N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia, played vincristine-RONC (VC-RONC), which as a drug – the generic’s passed preclinical pharmacological and toxicological testing in comparison with foreign firms vincristine Teva of Israel (VC-Teva). The aim. The aim of present study was the comparative pathomorphological evaluation of the effect of VC-RONC and VC-Teva on the internal organs of rats. Materials and methods. Used 50 weinbrenner male rats, at 10 rats per group. VC-RONC and VC-Teva rats were administered intravenously 3 times daily at aquatoxicity total dose corresponding to the MTD and 1/2 MTD. Control rats in the same regime intravenously administered of 0,9 % sodium chloride solution. Rats were deduced from the experience of 3 and 30 days after the end of administration of the drugs. Conducted macroscopic and histological examination of internal organs by conventional methods, including fixation of the material in 10 % formalin and coloring sections with hematoxylin and eosin. The micropreparations of the internal organs was analyzed under light microscope at magnifications of 100, 400, 1000. Results. VC-RONC, as VC-Teva in cumulative doses of 0,5 and 0,25 mg/kg in 3 days after the end of introductions in the internal organs of rats cause similar slightly pronounced morphological changes: hypoplasia in the bone marrow and spleen, destructive changes in the testes, focal degenerative changes in the kidney and liver of individual rats. On the 30th day after the application of both drugs, some rats regardless of the dose occurred similar symptoms residual morphological changes in the bone marrow, testes, kidneys and liver. Conclusion. Based on the results of macroscopic and histological examination the conclusion about the similarity of the influence of VC-RONC and VC-Teva on the internal organs of rats was made.
Development and validation of aranosa assay in the dosage form
Authors: Shprakh Z. S. , Ignаteva E. V. , Yartseva I. V.
Published: November 2018

Background. Aranosa, a drug of nitrosoalkylureas class, was developed and studied at N.N. Blokhin NMRCO, Russia, and at present it is produced by N.N. Blokhin NMRСO branch “Naukoprofi”. One of the stages of the drug standardization is the development of an assay technique for quantitative determination of active substance in the final drug dosage form.

Objective. Development and validation of an assay for quantitative determination of Aranosa in the dosage form.

Materials and methods. The study used “Aranosa, lyophilisate for solution for injection 0.5 g”; Аranosa, substance-powder (N.N. Blokhin NMRCO branch “Naukoprofi”); polyvinylpyrrolidone low-molecular medical; sorbic acid. Method: spectrophotometry.

 Results. An assay was developed for quantitative spectrophotometric determination of Aranosa in the dosage form “Aranosa, lyophilisate for solution for injection 0.5 g”. Validation was performed to prove reliability and accuracy of the obtained results. The assay was evaluated by validation characteristics, such as specificity, linearity, trueness, precision.

Conclusions. The developed assay is provided with trueness, repeatability, precision, and linearity and can be used in the range of 80– 120 % of nominal Aranosa content in the dosage form.
Neoantigens in tumor immunotherapy
Authors: Baryshnikova M. A. , Kosobokova E. N. , Kosorukov V. S.
Published: November 2018

Malignant tumors are known to have complex mutational profiles and harbor concurrent alterations in many somatic genes. The inher ent genetic heterogeneity is a critical determinant of cancer cells. The term of neoantigens was introduce to emphasize that these antigens are specific for cancer cells and are absent in normal tissue. Neoantigenes are highly immunogenic and at present are considered to be the target molecules in cancer therapy. Although the neoantigens have been known for a long time, their study and use became possible with the increase in the availability of mass cluster sequencing to detect all mutations in tumors and bioinformatic algorithms predicting what mutated peptides will be highly affine to human leukocyte antigen autologous molecules with subsequent activation of the immune response.
Lymphocytes blast-transformation reaction: modification for allergological practice
Authors: Manina I. V. , Sergeev V. Yu. , Golubtsova N. V. , Sergeev A. Yu.
Published: November 2018

Introduction. Lymphocytes blast-transformation reaction (RBLT) is necessary for patient’s inspection with immunologic infringements. It is applied in the different fields of medicine to identification of a sensitization to antigens (allergens).

Research objective – to modify and automate RBTL for application in routine laboratory practice.

Materials and methods. RBTL, antigens (allergens). Software: Windows 7; Intel Pentium G4500 CPU. Digital CMOS video camera, Mikmed-6 microscope.

Results. We analyzed difficulties when using RBTL in laboratory allergological practice. We created program files for automation of RBTL.

Conclusion. We adapted and automated RBTL for laboratory diagnostics using.
Synthesis and biological evaluation of paclitaxel conjugates with prostate-specific membrane antigen inhibitor for the treatment of prostate cancer . .
Authors: Ber A. P. , Machulkin A. E. , Kovalchuk M. V. , Vorobyova N. S. , Beloglazkina E. K. , Kovalev S. V. , Kotelyanskiy V. E. , Mazhuga A. G.
Published: November 2018

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Metformin: new perspectives in chemoprevention and therapy of cancer
Authors: Shestakov A. V. , Saprina T. V. , Anufrak I. A. , Gonchikova O. E. , Chernysheva A. L.
Published: November 2018

According to modern data, metformin is a unique drug, which can act not only as sugar-reducing medicine, but also as an antiproliferative element. More and more new researches about metformin effects in oncologic patients appear during last decades. A lot of researchers suppose that metformin is a new promising medicine for chemopreventive and neoadjuvant cancer therapy. This literature review covers current researches of metformin in context of it»s possible antiproliferative effects.
Expression of epithelial marker CK19 in mice with mammary adenocarcinoma afterexposure to fito-anti-estrogen secoisolariciresinol
Authors: Shubina I. Zh. , Treshalina E. M. , Kuznetsov S. A. , Smirnova G. B. , Borisova Yu. A. , Sitdikova S. M. , Sitdikova M. V. , Shprakh Z. S.
Published: November 2018

Introduction.Phyto-anti-estrogen secoisolariciresinol (SECO) has similar effectiveness to that of Tamoxifen (TAM), a member of selection estrogen receptor modulators, in estrogen-positive models of murine mammary adenocarcinoma and human breast cancer in vivo. Due to its antagonistic and agonistic functions Tamoxifen may enhance risk of development of uterine adenocarcinoma while providing effective prophylactics of breast cancer metastases. SECO effect on proliferative activity of circulating or disseminating tumor cells (occult metastases) is still unclear. We used epithelial cell marker – intracellular cytokeratin 19 (CK19) to study SECO function in terms of possible metastatic process, since prognostic significance of CK19 is well established for identifying occult metastases and breast cancer dissemination.

Objective.To evaluate risk of tumor cell dissemination in mice with transplanted mammary adenocarcinoma after exposure to SECO and TAM.

Materials and methods.Mice BDF 1 [C57Bl6j × DBA2] bearing Са755 of the 3rd passage were used for the experiments. CK19 expression was evaluated 24 hours after 10-day course of SECO in the effective single doses of 250 mg/kg or ТАM 50 mg/kg. Flow cytometry, immunofluorescence with light and luminescence microscopy were performed to evaluate CK19 expression.

Results.Parameter GMFI ± SD (geometric mean fluorescence intensity ± SD) for CK19 expression in SECO and TAM groups in blood accounted for 28.87 ± 13.70 and 28.02 ± 9.50 and in control tumor growth (CTG) group GMFI ± SD was 31.94 ± 5.02; while in bone marrow it was 30.14 ± 2.33, 39.07 ± 2.30 and 32.48 ± 3.75, respectively.

Conclusion.The results of the study showed similar expression of epithelial intracellular marker CK19 in blood in the studied groups of mice bearing mammary adenocarcinoma Ca755 sensitive to SECO and TAM exposure. GMFI for CK19 expression in bone marrow was lower in SECO group than in TAM (р = 0.0003). The data obtained in the murine model demonstrated no enhanced risk of tumor cell dissemination while performing treatment by phyto-anti-estrogen SECO in therapeutic regimen.
MicroRNA expression in melanocytes and melanoma cells
Authors: Petkevich A. A. , Shubina I. Sh. , Abramov A. A. , Mamedova L. T. , Samoilenko I. V. , Kiselevsky M. V.
Published: November 2018

Diagnostic biomarkers cancer diagnostics at preclinical stage seem to be a very promising strategy to increase effectiveness of anti-cancer treatment. Currently there are no such biomarkers available for daily routine practice. However, there are some candidate molecules in research that possibly can be used as biomarkers for early diagnosis, one of them is microRNA. MicroRNA is a small, 20–25 bp, non-coding RNA that is highly involved into epigenetic regulation of gene expression. These molecules participate in malignant transformation of normal cells into cancer cells including melanoma. And moreover, definite expression level of some microRNAs are essential for normal differentiation and function of human cells. Changes in microRNA profile are one of the reasons for malignant tumor development. Identification of these changes may help to develop diagnostic systems to start anti-cancer treatment at early stages.
The influence of the drug LHS-1208 on cardiovascular system
Authors: Ermakova N. P. , Merkulova I. V. , Konyaeva O. I. , Kulbachevskaya N. Yu. , Abramova T. V. , Chaley V. A. , Nikolina A. A. , Bukhman V. M.
Published: November 2018

Introduction.This article presents a fragment of a preclinical toxicological study of a new Russian anticancer drug derived from n-glycoside indolokarbazole LCS-1208 – study of cardiotoxicity, which is one of the specific complications of anticancer chemotherapy.

Objective.Preclinical toxicological study of the effect of the drug LCS-1208 on the cardiovascular system of animals to assess its cardiotoxic effects.

Materials and methods.Studies were conducted on 40 healthy non-harmless mongrel male rats and 4 dogs Beagle, male and female. The drug was administered daily 15 times to rats-intraperitoneal in total doses of 50, 100 and 200 mg/kg; to dogs – intravenously in total doses of 20 and 30 mg/kg. The period of observation of rats was 30 days, for dogs was 60 days. Changes in electrocardiogram indices, macroscopic and histological picture of heart changes and changes in biochemical parameters of enzymes activity – lactate dehydrogenase and aspartate aminotransferase were evaluated.

Results.In rats LCS-1208 throughout the period of observation caused functional changes in electrocardiogram: increase in PQ and QT intervals and cardiac rhythm disturbance (loss of R wave), which indicates a violation of electrical conductivity. Morphological changes in the heart muscle were detected on the 3rd day of observation in total doses of 100 and 200 mg/kg, which remained until 30 days of observation only in animals receiving the drug in the total dose of 200 mg/kg. In some dogs for different periods of observation the drug caused functional changes in the electrical activity of the heart: an increase in the QRS interval, the inversion of the T wave, the appearance of a deep Q wave and an increase in the activity of lactate dehydrogenase and aspartate aminotransferase compared to back ground indicators. Morphological changes in the heart muscle were detected on the 3rd day of observation only in the total dose of 30 mg/kg, which persisted up to 60 days of observation.

Conclusion.It was found that the new Russian anticancer drug LHC-1208, a derivative of indocarbazole N-glycoside, has a cardiotoxic effect, causing functional changes in the cardiovascular system of rats in all doses studied, and in dogs only in the maximum dose. Morphologically, cardiotoxicity is not confirmed in animals receiving a minimal dose of the drug, but only in animals receiving the maximum dose of the drug.