bluuebunny/crossref_metadata_2025 huggingface dataset:
Remoción de contaminantes y crecimiento del alga Scenedesmus sp. en aguas residuales de curtiembres, comparación entre células libres e inmovilizadas
Authors: Rosales A G , Rodríguez C.D. , Ballen-Segura M.
Published: November 2018

Las aguas residuales de curtiembres conllevan un problema ambiental y de salud, debido a las altas concentraciones de contaminantes como el cromo, sulfuros, entre otros. Una forma de realizar el tratamiento de estas aguas es por medio del uso de microorganismos tales como las microalgas, debido a su capacidad de utilizar los compuestos inorgánicos y acumular metales y otras sustancias contaminantes. Esta capacidad podría verse magnificada con la inmovilización celular en diferentes matrices. En este artículo se presenta una evaluación de la capacidad de crecimiento y de remoción de nitrógeno, fósforo y cromo por parte de la microalga Scenedesmus sp., comparando la eficiencia entre las células libres e inmovilizadas en una matriz de esponja de Luffa. De esta manera, se obtuvo un mayor crecimiento en las células libres en comparación a las inmovilizadas, aunque sin diferencias significativas entre ambos experimentos. En ambos casos se observaron remociones superiores al 90% para NO–3 , NH+4, PO34 y cromo total, así como una reducción importante de la DBO y DQO (> 97 %) que puede deberse a efecto sinérgico con las bacterias presentes en los cultivos de la microalga. Finalmente, los porcentajes de lípidos en ambos casos fueron superiores al 20% indicando que esta biomasa podría presentar un alto potencial como materia prima para la generación de biodiesel.
Effectiveness of gait training in water for patients with Parkinson’s Disease: systematic review
Authors: Silva Costa Priscila , Cartaxo Villas Bôas Elaine Cristina , Pedreira da Fonseca Erika
Published: November 2018

INTRODUCTION: Hydrotherapy is increasingly used in the treatment of patients with neurodegenerative disease, being aimed at improving functionality and reduce falls. Allows safe walking, promotes relaxation and reduces fear of falling. There is a requirement to analyze the methodological quality of existing studies in this context. OBJECTIVE: To systematize the knowledge about the effectiveness of water walking training for people with Parkinson's disease. METHODS: This is a systematic review. We searched the Pubmed and Lilacs database from March 2017 to May 2018 without filters. We included randomized clinical trials that verified the effects of a water gait training protocol for patients with Parkinson's disease. We excluded studies that performed water training, but not specifically gait. A Cochrane Collaboration tool was utilized to evaluate the methodological quality of the studies. RESULTS: Fifteen studies were found in the search, three of these were included. There was different from those between the articles regarding outcomes, in relation to the increase in walking speed. The methodological quality analysis showed randomization and blindness failure in the methodology of the studies. CONCLUSION: It was evidenced that gait training in water has a positive effect on gait velocity and the mobility of these individuals. For a positive clinical outcome in walking, exercises for mobility and balance should be associated. Further randomized clinical trials are necessary for follow the guidelines and have satisfactory methodological quality.
Prevalência de sarcopenia na Doença Pulmonar Obstrutiva Crônica: revisão sistemática
Authors: Caria Kelly Roberta Souza Andrade , Warken Rosa Camelier Fernanda , Cordeiro Natasha , Moreira Airton , Silva dos Santos Bárbara , Assunção Camelier Aquiles
Published: November 2018

INTRODUÇÃO: DPOC está associada a um processo inflamatório sistêmico que pode causar sarcopenia, redução da função e massa muscular, embora sua frequência e intensidade não seja completamente conhecida em portadores dessa enfermidade. OBJETIVO: descrever a prevalência e métodos de identificação da sarcopenia na DPOC através de uma revisão sistemática. MATERIAIS E MÉTODOS: Revisão sistemática utilizando a metodologia PICO e palavras-chave (Chronic Obstructive Pulmonary Disease, Sarcopenia). Foram incluídos estudos publicados que estimaram a prevalência de sarcopenia na DPOC. Excluídos aqueles cujo método não detalhou o diagnóstico da sarcopenia. RESULTADOS: A pesquisa resultou inicialmente em 897 artigos. Desses, 877 foram excluídos, sendo 20 selecionados (15 transversais, cinco longitudinais, um caso/controle). As amostras variaram de 57 a 2.582 participantes, a maioria (70%) conduzida em ambulatório. Um estudo foi de base populacional. A idade média foi de 66 anos. A prevalência de sarcopenia na DPOC variou (4,4% a 86,5%). Os métodos diagnósticos utilizados para determinar massa muscular foram o Dual X-ray Absorptiometry, a bioimpedância e as equações de referência. A força muscular foi estimada utilizando-se a preensão manual em dinamômetros portáteis ou a flexão/extensão do joelho através do dinamômetro isocinético. A capacidade funcional foi avaliada pelo teste de caminhada dos seis minutos ou através do teste de velocidade da marcha. CONCLUSÃO: A prevalência de sarcopenia na DPOC encontrada nos estudos (4,4 a 86,5%) é muito variável. Influenciada não somente pela característica do paciente, mas também pelo local, delineamento e método diagnóstico utilizado. Uma padronização de métodos parece ser necessária para se uniformizar condutas na literatura.
Limiting Dilution & Clonal Expansion v1
Authors: not provided Synthego
Published: November 2018

CRISPR-Cas9 can be used to generate edited cell pools for a variety of applications. These pools contain a heterogeneous mix of cells, some unedited and some with different genetic alterations at the targeted locus. In order to produce a cell line with a particular edit or knockout, clonal expansion of individual cells is necessary. This protocol describes how to isolate single cells from a CRISPR-edited pool, and expand and genotype the subsequent clonal populations. The isolation of single cells from a knockout cell pool can be accomplished through limiting dilution. While there are more sophisticated means to accomplish single cell plating (e.g., flow cytometry), limiting dilution is a technique that can be carried out with standard pipetting tools. The obvious drawback to this technique is that it relies on statistical probability (based on a Poisson distribution) to deposit a single cell per well. A typical concentration used for limiting dilution is 0.5-1 cells per 100 μl aliquot because it maximizes the probability of obtaining a single cell per well while minimizing the probability of depositing multiple cells per well. At this concentration, one can expect about a third of the wells to contain a single cell and most wells to be empty. It is much less difficult to exclude wells without cells than to sort out heterogeneous populations arising from multiple cells. In this protocol, cells from each edited population are diluted to 0.5-1 cells per 100 μl and plated on at least two 96-well plates (100 μl/well). However, if clonally expanding cells for the first time we recommend plating a higher number of cells (e.g., 4 x 96-well plates per condition). To control for potential health/growth defects caused by the editing, we recommend including mock and/or negative control for single cell dilution, although these do not require multiple 96-well plates. The RELA positive control, however, does not need to be plated out for clonal expansion as it serves mainly as a positive control for transfection and editing efficiency.
Plant leaf tooth feature extraction v1
Authors: Hu Wang , Chu Li , Yan Tian , Haoyu Zhou , Di Tian
Published: November 2018

Previous studies extract features that are not strictly defined in botany; therefore, a uniform standard to compare the accuracies of various feature extraction methods cannot be used. For efficient and automatic retrieval of plant leaves from a leaf database, in this study, we propose an image-based description and measurement of leaf teeth by referring to the leaf structure classification system in botany. First, image preprocessing is carried out to obtain a binary map of plant leaves. Then, corner detection based on the curvature scale-space (CSS) algorithm is used to extract the inflection point from the edges; next, the leaf tooth apex is extracted by screening the convex points; then, according to the definition of the leaf structure, the characteristics of the leaf teeth are described and measured in terms of number of orders of teeth, tooth spacing, number of teeth, sinus shape, and tooth shape.
microC-protocol v1
Authors: Voukantsis Dimitrios , Kahn Kenneth , Hadley Martin , Wilson Rowan , M Buffa Francesca
Published: November 2018

microC is a multiscale virtual microenvironment for perturbation biology. It enables experiments that link genotype to phenotype taking into account the surrounding microenvironment. microC has a modular architecture that enables a wide variety of experiment. Furthermore, it offers easy access to advanced computational modelling and supercomputing resources to the wider scientific community. microC combines agent-based and gene network modelling and uses partial differential equations to simulate interactions among cells. The tool itself does not require any installation on the user’s machine, as it can be accessed using a web browser. Experimental results and data are also available via a web interface. This protocol describes the process of preparing and submiting an experiment with microC, and interpreting the simulation results
Decision Support System for assessing management interventions in a Mental Health ecosystem v1
Authors: Garcia-Alonso Carlos
Published: November 2018

Here it is included the pseudocode for the Decision Support System for assessing management interventions in a Mental Health ecosystem. This pseudocode can be used to reproduce the experiments that we have carried out in Bizkaia (Basque Country, Spain). 1: DSS procedure 2: The solution pool (SP) is cleaned 3: Forj=1 to do → being j the simulation number and the maximum number of simulations 4: For i=1 to do → being i the scenario number and the maximum number of scenarios 5: Fork=1 to do → being k the SHA (DMU) number and the number of SHA 6: Original dataset Sijk → the Monte-Carlo simulation engine selects at random a value for each simulation, variable and SHA k according to their specific statistical distributions. 7: Calculate Dijk and Oijk → the fuzzy inference engine determines the day care and outpatient care fuzzy sets and membership degrees for each SHA 8: Calculate and → the fuzzy inference engine determines the range for variable value interpretation according to the B-MHCCM 9: Interpreted dataset Iijk → the original dataset Sijk are interpreted by the fuzzy inference engine according to the B-MHCCM 10: Calculate RTEijkscores → variable returns to scale Data Envelopment Analysis (DEA) model (both input and output-oriented) 11: Save RTEijk scores in the solution pool 12: end for 13: end for 14: end for 15: end procedure
MECHANISMS OF MELANOMA DRUG RESISTANCE
Authors: Baryshnikova M. A. , Afanasieva D. A. , Ulasov I. V. , Baryshnikov A. Yu.
Published: November 2018

Metastatic melanoma is an aggressive skin cancer, which resistant to antitumor drugs. This review describes the different mechanisms of melanoma resistance and approaches to overcoming it.
LYMPHOCYTE INFILTRATION IN HIGH-CANCER CBA MICE HEPATOCARCINOMAS USING MULTIPHYTOADAPTOGENE EARLY POSTNATAL ONTOGENESIS ADMINISTRATION
Authors: Bocharov E. V. , Karpova R. V. , Vershinskaya A. A. , Kucheryanu V. G. , Bocharova O. A.
Published: November 2018

The article presents the results of high-cancer CBA inbred mice liver morphological research while using multiphytoadaptogene early postnatal ontogenesis administration. Moderate and pooly differentiated trabecular and trabecular-acinar hepatocarcinomas were determined. Lymphocytes infiltration and destructive features were microscopically visible in hepatocarcinomas at the age of 22 months. Infiltrated lymphocytes and destructive features in control mouse hepatocarcinomas were not detected.
MONOCLONAL ANTIBODIES ICO-406 AGAINST THE ANTIGEN CD117
Authors: Golubtsova N. V. , Burova O. S. , Baryshnikov K. A. , Oborotova M. V. , Karaseva V. I. , Mamedova L. T. , Zhordania K. I. , Baryshnikova M. A. , Grinevich A. S. , Ivanov P. K. , Baryshnikov A. Yu.
Published: November 2018

MAb against the antigen CD117 - stem marker of human tumor cells. Strain 406 PPI prepared by cell fusion of mouse myeloma NS-1 cells with spleen mice BALB/ C, pre-immunized three times at an interval of two weeks, the cells of the cell line of human melanoma melKor. Merging conducted using a solution of PEG/DMSO. For screening received mAb 406 used human melanoma cell lines which differed in the expression of CD117 antigen FSBSI "N.N. Blokhin RCRC" collection. N.N Blokhin. Antigen expression was studied in immunofluorescence and evaluated on a flow cytometer BD FACS CantoTMII. ICA IC0-406 was compared with commercial ICA against antigen CD 117 (Germany). The results indicated the identity of the frequency of antigen-positive cases and the percentage of antigen cells. ICA IC0-406 block binding to cells melKor ICA anti-CD117. Linking ICA IC0-406 antigen-positive cells causes modulation of antigen CD 117.
DEVELOPMENT AND APPLICATION OF THERAPEUTIC GELS “KOLEGEL” FOR TARGETED DELIVERY OF DRUGS IN TREATMENT OF RECTAL CANCER
Authors: Oltarzhevskaya N. D. , Korovina M. A. , Barsukov U. A. , Malikhov A. G. , Kuzmichev D. V. , Tataev I. Sh.
Published: November 2018

A large part of basic research including medical area studies transportation and delivery of drugs directly to the organs, tissues and cells. This interest has been caused by many reasons, and above all, by huge medical and economic benefits of directed transport, reduced side effects and significant reduction of therapeutic drug doses. LLC «KOLETEX» designs and manufactures therapeutic gels for targeted drug delivery - gels «Kolegel» with various drugs, with the aim to improve effectiveness of radiotherapy and prevent radiation reactions. These gels are widely used in major oncology clinics, they have proven to be highly effective in the treatment of cancer. Their application allows to enhance the effectiveness of radiation exposure due to the introduced modifiers (sensitizers), to protect healthy tissue in the irradiation zone, speed up recovery of mucous membranes, resulting in enhanced treatment efficacy, shorten hospital stay and improve patient’s quality of life.
COMPOSITION OF LHTA-1975, BASED ON TRIS (1-PENTYL-1H-INDOL-3-YL)METHILIUM CHLORIDE - NEW EFFECTIVE ANTITUMOR DRUG
Authors: Treshalin I. D. , Pereverzeva E. R. , Isakova E. B. , Treshalin M. I. , Voznyakovskaya E. V. , Pereverzeva T. B. , Lavrenov S. N.
Published: November 2018

Исследована противоопухолевая активность и проведено доклиническое токсикологическое изучение фармацевтической композиции ЛХТА-1975, содержащей в качестве основного действующего компонента хлорид трис (1-пентил-ІН-индол-3-ил) метилия. Достоверный ростингибирующий эффект показан на мышах с лимфолейкозом Р-388, аденокарциномой молочной железы АК-755 и меланомой В-16. По данным токсикологических исследований препарат имеет значительный интервал между лечебными и токсическими дозами, что потенциально делает его интересным для дальнейшего изучения. При применении в дозах, в 5-10 раз превышающих терапевтические, композиция не вызывала токсических изменений в органах и тканях.
Changes in the morphological, immunological and genetic characteristics of Mel Ibr melanoma cells in response to low concentration of embryo calf serum
Authors: Morozova L. F. , Suraeva N. M. , Burova O. S. , Voronina E. S. , Baryshnikova M. A.
Published: November 2018

Objective: the purpose of the study is research of the changes in phenotypic and genetic characteristics of melanoma cells Mel Ibr cultured in growth medium with low concentration (5 %) of embryo calf serum. Materials and methods. Cell line Меl Ibr was pre-cultured in RPMI-1640 medium with 5 % FBS for 3passages, and then 200-400 cells were replaced on the Petri dish with a diameter of 60 mm and left in the incubator for 14 days to form colonies. Colonies of spindle form cells were cultivated in the same conditions for more than 30 passages. Cells were stained according to the method of Leishman to investigate the morphology. The expression of antigens was determined in the reaction of indirect immunofluorescence. Results. Exposure of Mel Ibr human melanoma cells to low concentration of embryo calf serum resulted in the appearance of a subclone with morphological, immunological and cytogenetical characteristics differed to those of parental cells. The subclone cells distinguished with spindle form, more small size, large nucleus which broadcasted on whole cytoplasm, formation spheroid and sharply reduced percentage of HLA-DR (+) and CD54 (+) cells, a significantly elevated percentage of CD63 (+) cells, and appearance of CD133 (+). The subclone karyotype differed to those of parental cells. Conclusoin. The subclone cells were characterized by the same features as stem tumor cells and could be use as tumor progression model.
EVALUATION OF BIOMODIFIED L-ASPARAGINASE WAS79 SIDE EFFECTS IN CHRONIC EXPERIMENT ON RABBITS
Authors: Pereverzeva E. R. , Treschalin I. D. , Treschalin M. I. , Voznyakovskaya E. V. , Pereverzeva T. B. , Eremkin N. V. , Bulushova N. V. , Sannikova E. P.
Published: November 2018

Objective. The aim of the study was to research the toxicity of L-asparaginase Was79 in rabbits. Materials and methods. Chronic toxicity of L-asparaginase Was79, obtained by modification of native enzyme Wolinella succinogenes in Research Institute of Genetics and Selection, was performed in male and female Russian chinchilla rabbits. L-asparaginase was injected intravenously at the 1 and 5 therapeutic dose (15 x 100 IU/kg or 15 x 500 IU/kg with 24-h interval). The following parameters were tested: body mass, clinical and biochemical blood tests, urinalysis, electrocardiography, pathomorphological evaluation of internal organs. Resutls. The results of the study suggest that the treatment with L-asparaginase Was79 does not influence on the function of heart and kidneys, but damages their structure. Loss in body mass, diarrhea and alteration of stomach and intestine mucosa could be interpreted as evidence of gastrointestinal toxicity. Hematological toxicity was exhibited as a decrease of total leukocyte count, lymphocyte and neutrophils count level in peripheral blood and atrophy of lymphoid tissue of the spleen, thymus and lymph nodes. Elevation of total and direct bilirubin in serum and histopathological findings in liver were found in groups treated with both high and low doses of Was79. Conclusion. Most of these abnormalities were reversible and dose-dependent.
CHANGES IN THE MORPHOLOGICAL AND IMMUNOLOGICAL CHARACTERISTICS OF MEL CHER MELANOMA CELLS IN RESPONSE TO LOW CONCENTRATION OF EMBRYO CALF SERUM
Authors: Morozova L. F. , Suraeva N. M. , Burova O. S. , Barmashov A. E. , Baryshnikova M. A.
Published: November 2018

Background. Human melanoma cell line mel Cher have a different cell forms and is appraised for grade of differentiation as low-diffe-rentiation melanoma. Objective. The purpose of this study was development and characterization of subclone mel Cher 5C. Materials and methods. For received subclone mel Cher 5C was applied method of colony formation in conditions with low concentration of embryo calf serum (5 %). Then was carry out selection spindle-like cells, their long cultivation and estimate morphological and immunological characteristics. Results. Subclone mel Cher 5C cells differed for morphology from primary line mel Cher. This cells had spindle-like form and had capacity to form spherical type colony on the surface of monolayer during their growth. Subclone cells has more intensive growth compare with cells of primary line. Subclone cells had differences by immunological phenotype and didn’t expressed antigene HLA-DR. Conclusions. Subclone cells had a fusiform shape, in the growth process of the formed spheroid colonies monomorphic type, did not Express antigens of histocompatibility complex II.
BONE MARROW IN FOLLICULAR LYMPHOMA PROGNOSIS
Authors: Tupitsyn N. N. , Falaleeva N. A. , Mozhenkova A. V. , Pavlovskaya A. I.
Published: November 2018

Background. Bone marrow is the mostfrequent metastatic site in follicular lymphoma, 40-70 % cases. It’s unfovourable prognostic role is stated in the index FLIPI-2 (Follicular Lymphoma International Prognostic Index-2). Objective. To study both prognostic role of bone marrow involvement and it’s relation to erythropoiesis peculiarities in follicular lymphoma was the purpose of this research. Materials and methods. Histological study was performed in 269 follicular lymphoma patients. Erythropoiesis peculiarities were studied in that patients according to standard myelogram analysis. Results. Bone marrow involvement was noted according to trephine biopsy section staining in 37,9 % of follicular lymphoma case (102 from 269). Bone marrow involvement did not influenced the prognosis (overall survival) in all period of observation (p = 0,18). Longterm survival (more than 48 months) was negatively influenced by bone marrow involvement (p = 0,04). Intertrabecular pattern of follicular lymphoma growth in bone marrow was negative prognostic factor (p = 0,02). We noted negative correlation between bone marrow involvement and the elevation of orthochromic normoblasts in bone marrow of patients with follicular lymphoma. In cause of bone marrow such elevation was noted in 67 %, and in the absense of involvement - in 78 % (p = 0,043). Elevation of orthochromic normoblasts did not influenced the overall survival of follicular lymphoma patients (p = 0,89). Conclusion. Bone marrow involvement in follicular lymphoma plays prognostically unfavourable role in long-time observation periods (later than 48 months). The most unfavourable are the intertrabecular patchy lesions. Involvement of bone marrow is in opposite relations to elevation of orthochromic normoblast, but the latter sign is of no prognostic significance.
IMMUNOLOGICAL PHENOTYPE OF PERIPHERAL BLOOD LYMPHOCYTES OF PATIENTS WITH PRIMARY OPERABLE BREAST CANCER
Authors: Zabotina T. N. , Korotkova O. V. , Hakimova Sh. G. , Borunova A. A. , Tabakov D. V. , Vorotnikov I. K. , Kadagidze Z. G.
Published: November 2018

Objecive. The investigation is devoted to study subpopulation structure of lymphocytes from peripheral blood of patients, suffering from breast cancer. Materials and methods. Peripheral blood of 70 patients with breast cancer and 39 healthy women was analyzed using the flow cytometry method with monoclonal antibodies to CD3, CD4, CD8, CD16, CD56, CD19, CD45 antigens. Results. Statistically significant disturbance of linear structure of lymphocytes (T-cells CD45+/CD3+/CD19-; B-cells CD45+/CD3-/ CD19+; NK-cells CD45+CD3-CD16+56+) detected only in the analysis of individual immunograms, but not in analysis of whole group of breast cancer patients. Conclusion. Based on analysis of frequence of occurrence of disturbances of cancer breast patients with low values of ratio CD4/CD8, it was detected 4 different variants of disturbance.
TECHNOLOGICAL APPROACHES TO IMPROVING THE PROCESS LYOPHILIZATION OF PROTEIN AND PEPTIDE DRUGS
Authors: Blynskaya E. V. , Tishkov S. V. , Alekseev K. V.
Published: November 2018

Lyophilization of protein and peptide anticancer drugs is a promising method to create a stable and effective parenteral dosage forms. This article reviews the main problems encountered during lyophilization of protein and peptide drugs, and describes the best practices for solving these problems. The ways of optimization and improvement of the freeze-drying are given. Temperatures to improve the properties and prevent the destruction of the cake lyophilizatiе are suggested.
Characteristics of the patients with cutaneous melanoma and multiple primary malignant tumors: clinical observations
Authors: Ponkratova D. A. , Tsyganova I. V. , Vikhrova A. S. , Lushnikova A. A.
Published: November 2018

Background. Multiple primary malignant tumors (MPMT) - 2 or more tumors, arising during patient life - are an important risk factor of cutaneous melanoma (CM). The frequency of MPMT in Russia ranges from 2 to 20 % with the incidence increasing. This tendency is linked mainly with the increasing life expectancy of the patients, with use of a potentially carcinogenic treatment methods, with the influence of adverse environmental factors and genetic predisposition In 15 patients with MPMT, including CM, has revealed a trend towards more frequent family history in male patients. In female patients MPMT included breast, ovarian and renal malignant tumors. CM relapses were observed shortly after surgical removal of the primary tumors. Objective. Clinical and genetic characteristics of patients with MK in MPMT structure. Materials and methods. Disease histories, MPMT structure and CM mutational status (PCR followed by direct sequencing of amplions) were analyzed in 8 male and 7 female patients with MPMT included metastatic CM. Results. A preliminary analysis of 15 patients with metastatic CM in MPMT structure has revealed some gender features. In female patients MPMT more often included breast, ovaries or kidney tumors. Excess body weight or obesity was detected in female patients (5/7) more often than in male patients (4/8). There is a tendency to more frequent family cancer histories in male patients compared to female ones - 3/8 vs. 1/7 in 3/8 male patients somatic mutations in BRAF gene (2) and PDGF gene (1) were identified in CM. The frequency of mutations of BRAF and NRAS genes in CM of female patients was 2 times higher than that of male patients. The combination of CM with bowel cancer was prevalent in male patients. In 2/7 male patients CM was the last tumor in MPMT structure, in 5/7 - the first, with the exception of the patient with primary multiple melanomas, while CM as the first tumor was revealed in 4/7 female patients and last CM - in 1/7 ones. Conclusions. Various combinations of tumors in MPMT structure were characterized in male and female patients. In female patients MPMT included breast, ovarian and renal malignant tumors/were the most frequent, while the combination CM with bowel tumors were prevalent in male ones. In male patients CM was diagnosed as the first tumor more frequently than the last one. The frequency of mutations in BRAF and NRAS genes in MK tumors in female patients with MPMT was 2 times higher than that in male patients. In 15 patients with MPMT, including CM, a trend towards more frequent family cancer history in male patients was revealed. CM relases were observed shortly after surgical removal of the primary tumor.
Clinical assessement of the 8 genes on chromosome 3 with also MGMT gene promoter regions methylaton status in patients with breast cancer luminal hystotype
Authors: Ryabchikov D. A. , Vorotnikov I. K. , Kazubskaya T. P. , Lukina S. S. , Filippova E. A. , Burdennyy A. M. , Loginov V. I.
Published: November 2018

Background. Epigenetic changes of TSG are supposed as the most fine and active genes regulation mechanism in particular breast cancer (BC) genes pathway development. The most valuable results are awaited for methylation role of genes located on the short arm of chromosome 3 with also MGMT gene (10q26) in BC pathogenesis because of their ambiguous data for methylation status in tumors. Objective: to illustrate the specific methylation role of the RASSF1A, SEMA3B, RARß2, RHOA, GPX1, USP4, DAG1, NKIRAS1 and MGMT genes promoter regions in BC pathogenesis. Materials and methods. Sample set of 174 BC patients consists of tumor and surrounding histologically normal tissue that were collected and clinically characterized in the N.N. Blokhin National Medical Research Center of Oncology. Two substantive methods were used to evaluate DNA methylation status. To analyse RASSF1A, SEMA3B, RARß2 and MGMT genes methylation we used polymerase chain reaction specific for the methylated allele. Whereas for analyses RHOA, GPX1, USP4, DAG1, NKIRAS1 promoter regions genes methylation status was used methyl sensitive restriction analyses with 2 methyl sensitive endonuclaeses HpaII and HhaI with subsequent polymerase chain reaction. Results. A statistically significant high frequency of RASSF1A, SEMA3B, RARß2, and MGMT genes methylation in epithelial breast tumors compared with histologically normal tissue from the same patients was shown. Significant correlation of RARß2 and MGMT genes methylation frequency considering the different clinical and morphological characteristics of the malignant process was revealed. The statistically significant relationship between methylation of RASSF1A, RARß2 and MGMT genes and patient survival is shown for the first time. Conclusion. The findings of epigenetic changes in the luminal BC supplement the “molecular picture” of this cancer and contribute to an understanding of its pathogenesis. The revealed features of investigated genes methylation can find clinical application for the development of modern approaches to prognosis, prevention and choice of tactics for treatment of BC in females of the Moscow region.
Experimental evaluation of toxic properties of target antitumor drug aimpila
Authors: Pereverzeva E. R. , Golibrodo V. A. , Treshchalin M. I. , Eremkin N. V. , Tsurkan S. A. , Treshchalin I. D.
Published: November 2018

Background. Currently, the drugs, acting directly on tumor molecular or cellular targets, are actively designed. Target antitumor drug aimpila is atractyloside alpha-fetoprotein noncovalent complex. The development of this formulation is based on the ability of alpha-fe-toprotein, as a transport protein, to deliver cytotoxic agents into the cells that have alpha-fetoprotein receptors. Objective: to investigate the toxicity of aimpila in chronic experiment on rabbits. Materials and methods. The study was performed in male and female “Soviet chinchilla” rabbits. Final drug formulation (aimpila in gelatin capsules) was administrated per os at 1 and 10 therapeutic doses (0.05 and 0.5 mg/kg respectively) for 30 days with interval of 24 h. During the study dynamics of body weight, hematological parameters, blood biochemical parameters, electrocardiography and urinalysis were performed for all animals. Five animals in each group were sacrificed in days 1 and 30 post treatment, then their internal organs were subjected to histological evaluation. Results. The study demonstrates that the treatment with aimpila for 30 days in single therapeutic dose of 0.05 mg/kg had no effect on the clinical and laboratory parameters or the morphological structure of the internal organs of rabbits. Signs of hepato-, nephro-, cardio-and gastrointestinal toxicity were found in group of rabbits, treated with high dose of drug. The structural damages in liver were clinically supported with a significant increase of aspartate aminotransferase level in serum. Pathological changes in the kidneys were accompanied by a significant increase of urobilinogen and ketone bodies levels in the urine. Signs of cardio- and gastrointestinal toxicity were documented only by microscopic pathology observation. These abnormalities were reversible within 30 days. Conclusions. Aimpila formulation displayed dose-dependent and reversible toxicity and can be recommended to further investigation.
Standardization of lyophilized dosage form of dimeric macrocyclic tannin
Authors: Shprakh Z. S. , Ignat’Eva E. V. , Yartseva I. V. , Sasov S. A. , Orlova O. V. , Polozkova A. P. , Hochenkov D. A. , Korolev A. M. , Malyutina N. M.
Published: November 2018

Background. Over the last years the studies have increased interest in screening antitumor and anti-angiogenic substances that block several mechanisms of angiogenesis activation in tumors. A great attention is paid to development of effective and low toxic drugs as inhibitors of angiogenesis which are derived from herbal raw material. The article is devoted to the results of standardization of the dosage form of dimeric macrocyclic tannin (DMT) obtained from Chamerion angustifolium (L.) Holub in N.N. Blokhin National Medical Research Center of Oncology, which has a great potential as an antiangiogenic agent. Objective: to determine quality criteria for standardization of the drug “DMT, lyophilisate for preparation of solution for injections 100 mg”. Materials and methods. The study used “DMT, lyophilisate for preparation of solution for injections 100 mg” and DMT substance. Methods: spectrophotometry, infrared spectroscopy, high performance liquid chromatography, potentiometry, polarimetry. Results. Quality criteria for lyophilized DMT dosage form were determined with the account of Russian State Pharmacopoeia (XIII edn.) requirements to the drugs for injections and methods for their evaluation were defined. Conclusions. Laboratory studies demonstrated that the determined quality criteria and the defined methods for their evaluation are feasible for adequate quality control of dosage form “DMT, lyophilisate for preparation of solution for injections 100 mg”.
Molecular-genetic mechanisms of initiation, promotion and progression of tumors
Authors: Lyzhko N. A.
Published: November 2018

Carcinogenesis - the process of turning a normal cell into a tumor cell under the influence of the mutations that accumulate in the cell. The cause of tumor cells is the accumulation of her mutation. The accumulation of cell mutations occurs as a result of the occurrence of genetic instability. The process of tumor development is divided into 3 main stages: initiation, promotion and progression. At the stage of initiation of cell receives the first mutational hit, which leads to disruption of its genetic stability. Most often, mutations are subjected to proto-oncogenes, genes-tumor suppressors, and genes governing DNA repair processes. At this stage there is an accumulation in the cell genetic damage that lead to an increase of the degree of malignancy. The next step in the transformation of cells in a tumor is promoted. This period has transformed as a result of mutations cells acquire a number of properties that help it to survive in the environment. They no longer respond to signals from the environment, acquire, auto- and paracrine stimulation signals of proliferation, the inhibition of apoptosis, genetic instability, changes in the morphology of the cells, the lack of replicative aging. Cells of tumour clone is constantly mutating under the pressure of selection by the immune system of the body. This leads to qualitative changes of the phenotype of tumor cells, the emergence is one of many tumor clones. This stage is called “tumor progression”. As a result of increasing tumor mass requires greater amount of nutrients. The stimulation of angiogenesis. By reducing the degree of affinity of the cells to the substrate and increase its mobility, there are secondary foci, metastases. The development of tumor process captures new areas in the body in Spite of the constant improvement of methods of therapy of tumors, the number of patients who achieve long-term remission is not great. So researchers are looking for ways for more complete and in-depth study of the pathogenesis of tumors, since this will facilitate the development of more effective approaches to therapy of tumors. This article briefly describes the main stages of tumor development.
Molecular-biological characteristics of triple negative breast cancer
Authors: Atakhanova N. E. , Almuradova D. M. , Dudina I A.
Published: November 2018

Breast cancer is the most common disease in women all over the world. In the structure of cancer morbidity, breast cancer ranks first and its frequency is steadily increasing. In the world, about 1.67 million new cases are diagnosed and every year more than 500,000 women die from breast cancer. Triple negative breast cancer (TNBC) is about 15–20 % of all breast tumors; is more common in women of fertile age. TNBC is characterized by a lack of expression of estrogen, progesterone receptors and HER-2/neu, which significantly complicates the treatment of this disease, which is characterized by aggressive course, the maximum risk of recurrence during the first 3 yearsafter surgical treatment, and rapid metastasis and decreased life expectancy. This article presents a review of the literature on the molecular-biological characteristics of TNBC. The article also describes the main approaches to targeted therapies for each subtype.
Modern methods of assessing the effectiveness of radiation therapy in cervical cancer
Authors: Kryazheva V. S. , Chekalova M. A. , Kuznetsov V. V.
Published: November 2018

Cervical cancer (CC) in recent years has increased significantly. The main cause of death in patients with СС IIB–IV stages are the recurrence and metastasis of tumors, often with involvement of pelvic and lumbar lymph nodes. Ultrasound diagnosis is one of the leading places in modern oncology, because of such advantages as non-invasive, harmless method, the possibility of multiple studies, the availability and relatively low price of the study. Currently, ultrasound appears more new, additional methods aimed at improving the qualityand information content of the image. One of such methods is elastography, to assess the elasticity of tissue by assessing the hardness of the formation in real time non-invasive manner. Despite the fact that separate research points to advances in modern technology, there is no information under what situations their use is most informative, or impractical, due to existing limits of the method. In other words, there is a need for the formation of algorithm of using ultrasonic techniques to achieve optimum results when assessing the effectiveness of treatment of СС.
Expression of the apoptosis-releated genes in patients with newly diagnosed chronic lymphocytic leukemia in clinical data context
Authors: Zakharov S. G. , Golenkov A. K. , Misyurin A. V. , Kataeva E. V. , Rudakova A. A. , Baryshnikova M. A. , Mitina T. A. , Trifonova E. V. , Vysotskaya L. L. , Chernykh Yu. B. , Klinushkina E. F. , Belousov K. A. , Finashutina Yu. P. , Misyurin V. A.
Published: November 2018

Introduction.The given data of fundamental studies of apoptosis processes in B-cell lymphocytic leukemia (B-CLL) testifies about the complexity and variety of mechanisms affecting the kinetics of normal cells and tumor lymphocytes in this disease. It is important to study the severity of clinical manifestations of the disease depending on the expression of the genes that modulate apoptosis.

The purposeof the study is to compare the activity of genes encoding apoptosis modulators, the cell cycle and cancer-testicular PRAME protein with clinical manifestations of the disease in primary patients with B-CLL.

Materials and methods.The level of expression of the proapoptotic genes FAS, TRAIL, TNFR2, DR4/5 and DR3, as well as the HSP27, XIAP genes, blocking apoptosis was determined in 23 patients with newly diagnosed chronic B-CLL. In addition, expression of genes TP53 and P21 and cancer-testis gene PRAME are tested.

Results.According to the multivariate regression analysis, the FAS gene expression in the onset of the disease had the greatest impact on the clinical characteristics of the disease. In this connection, the patients were divided into groups with normal (group) and low gene level (group II). A low level of FAS expression (Me 387 %) was associated with stage II disease (p = 0.03), a large number of lympho cytes (p = 0.001), fewer erythrocytes (p = 0.08), and a lower level of TNFR2 gene expression (p = 0.08), high level of expression of XIAP, HSP27, P21. Overall, the anti-apoptotic potential in Group II patients was higher, which was accompanied by more pronounced clinical manifestations of the disease.

Conclusions.The increased anti-apoptotic potential of tumor lymphocytes in newly diagnosed B-CLL is accompanied by a larger tumor mass and greater clinical and hematological manifestation of the disease.
Comparative in vivo studying of potential antineoplastic properties among of amino-acid derivative glycosides of the indolocarbazole (detailed report)
Authors: Golubeva I. S. , Goryunova O. V. , Yavorskaya N. P.
Published: November 2018

Introduction.The existence of the active metabolite (amino acid) residue in the of an indolocarbazole molecule changes physical-chemical and pro-medicinal properties of aminoacid derivatives glycosides of indolocarbazole. The computer method has earlier foretold low probability of their cytotoxic activity in vitro that was confirmed in the MTT-test on 5 lines of tumor cells. The same computer method predicted significant probability of antineoplastic activity of aminoacid derivatives glycosides of indolocarbazole in vivo that demands the experimental check.

 Purpose of the study– assessment of aminoacid derivatives glycosides of indolocarbazole as potential antitumor medications.

Materials and methods.The research of antineoplastic activity of aminoacid derivatives glycosides of indolocarbazole was performed on mice tumoral models – cervical cancer СС5. Abdominal injections were made to CBA/Lac mice 5 times a day with 24 h interval. Observation of animals was continued till their death. The antineoplastic effect of medicines was estimated according to tumor growth inhibition, increase in life expectancy of experiental mice in comparison with control animals.

Results.The optimum dose for this number of compounds, equal to 100 mg/kg is titrated. The antineoplastic activity of aminoacid derivatives glycosides of indolocarbazole on the model СС5 is estimated.

Conclusions.On the basis of the obtained data the expanded research of antineoplastic properties of the selected 5 aminoacid derivatives glycosides of indolocarbazole is supposed to perform in vivo.
Expression rate of ALK tyrosine kinase and TAG-72 oncoprotein in primary skin melanoma
Authors: Titov K. S. , Rotin D. L. , Kazakov A. M. , Micheeva O. U. , Telezhnikova I. M. , Ryabchikov D. A.
Published: November 2018

Objective.Determine the frequency of occurrence of tyrosine kinase expression of the mutated ALK and TAG-72 gene among patients with primary melanoma of the skin, to identify their association with a number of histological parameters, and to assess the diagnostic value of the determination of ALK and TAG-72.

Materials and methods.Paraffin blocks with surgical material from 40 patients with primary skin melanoma. For routine histological examination, the material was fixed with 10 % neutral formalin for 24 h, poured into paraffin, sections were prepared with a thickness of 4–5 μm, stained with hematoxylin and eosin. IHC study with monoclonal antibodies D57.3 to ALK was performed on an immunostender – Ventana, with antibodies B72.3 to TAG-72 – on Thermo Fischer. As a detection system used: Envision – for TAG-72 and Ventana – for ALK.

Results.ALK mutation was detected in 7 (12 %), TAG-72 – 4 (10 %) cases. Evaluation of the correlation force between the presence of ALK and TAG-72 showed a direct average coupling strength (correlation coefficient was 0.31). A direct correlation of the mean force between the presence of TAG-72 oncoprotein, ALK mutation and ulceration in the patient was found – the correlation coefficient was 0.53 and 0.68, respectively. There was a statistically significant association between the presence of ALK and lymphoid infiltration, which in most cases (57 %) was pronounced (p <0.05).

Conclusion.Comparing the positive sign of the expression of ALK – 17.5 % and TAG-72 – 10 %, and the positive of their simultaneous detection – 7.5 %, it can be concluded that further studies to determine their diagnostic value are promising. The presence of severe lymphoid infiltration in ALK-positive patients claims a diagnostic value in primary skin melanoma.
Estudiantes Universitarios: prosumidores de recursos digitales y mediáticos en la era de Internet
Authors: Bonilla-del-Río Mónica , Diego-Mantecón Jose Manuel , Lena-Acebo Francisco Javier
Published: November 2018

A pesar de la relevancia que los recursos digitales y mediáticos han adquirido en nuestra sociedad, la adquisición de competencias para su uso adecuado y responsable en el contexto educativo no está garantizada. Este trabajo busca analizar los hábitos de producción y utilización de los recursos digitales y mediáticos de una muestra de 252 universitarios españoles, con el objetivo de conocer su competencia digital y su aprovechamiento para un uso educativo. Los resultados revelan una competencia media/alta de los universitarios en cuanto al manejo de los recursos mediáticos y digitales, así como una percepción positiva de la red como fuente valiosa de la que adquirir conocimiento y ampliar información. Admiten utilizar los recursos digitales y mediáticos para trabajar de forma colaborativa y ayudarse en tareas académicas, aunque no producen contenido académico o información en plataformas educativas; es decir, se consideran consumidores mediáticos, pero no productores. Se observó además que los universitarios mayores de 25 años son prosumidores más activos, en lo que se refiera a contenidos e información relacionada con temas académicos, que los estudiantes menores de 26 años, quienes utilizan más las redes para producir y compartir datos personales.
Motivación y realidad aumentada: Alumnos como consumidores y productores de objetos de aprendizaje. Motivation and augmented reality: Students as consumers and producers of learning objects
Authors: Marín-Díaz Verónica , Cabero-Almenara Julio , Gallego-Pérez Oscar Manuel
Published: November 2018

La incorporación de herramientas digitales a la enseñanza supone en un gran número de casos una modificación de la actitud del estudiante hacia los contenidos. Así encontramos como la Realidad Aumentada, poco a poco se ha ido incorporando a las aulas, provocando una revolución en la forma de entender las materias a estudiar, generando una mayor motivación por parte del alumnado por desarrollar su proceso de aprendizaje. En el este artículo se presentan los resultados de la aplicación de la RA como recurso potenciador de la motivación por el aprendizaje en un grupo de alumnos de la Universidad de Sevilla del grado de Pedagogía y que cursaban la materia Tecnología Educativa. A través del modelo de Keller (1983) se ha comprobar si la utilización de esta tecnología propiciaba una mayor motivación hacia el estudio. Tras el desarrollo en el aula de una acción de innovación docente, donde los alumnos se convirtieron en consumidores y creadores de materiales  y la posterior aplicación del modelo propuesto, se pudo concluir a través de los resultados alcanzados que los estudiantes participantes mostraron una mayor motivación hacia el aprendizaje de los contenidos de la materia en la que de desarrollo la investigación
La iglesia de las Santas Justa y Rufina en Orihuela. Evidencias constructivas para la posible intervención de este Bien de Interés Cultural
Authors: Spairani Berrio Silvia , Berrio Yolanda Spairani , Cereceda Miguel Louis , Gisbert Luis Jaime Morales
Published: November 2018

En este artículo se ha efectuado un análisis histórico, arquitectónico y constructivo de la Iglesia de las Santas Justa y Rufina en Orihuela, así como una exposición del estado actual del monumento para aportar directrices que garanticen una intervención coherente y respetuosa con un Bien de Interés Cultural, donde un crisol de arquitecturas góticas, renacentistas y barrocas conviven. Además, se plantean evidencias para la reflexión sobre las hipótesis respecto a la bóveda central de adscripción cronológica incierta. Tras analizar la historia de la construcción del Templo y sus sistemas constructivos se detecta que la Iglesia ha sufrido numerosas modificaciones en el tiempo y el espacio, e incluso se llegó a declarar en ruina a principios del siglo XX; las grietas vivas actuales denotan movimientos generados, entre otras causas, por la subsidencia del terreno que afecta a la ciudad.