Significación pronóstica de la edad, el sexo, la raza y el nivel socioeconómico en pacientes con carcinoma urotelial del tracto urinario superior en estadio III-IV / Prognostic significance of age, sex, race, and socioeconomic status in patients with stage III–IV upper tract urothelial carcinoma

Objetivo Evaluar la tendencia de la incidencia y la supervivencia estratificada por edad, raza, género y nivel socioeconómico (NSE), así como la variación en el tiempo de las diferencias entre los grupos de pacientes con carcinoma urotelial del tracto superior (CUTUS) en estadio III-IV. Métodos Se extrajeron los datos de 7.505 pacientes diagnosticados de CUTUS en estadio III-IV de la base de datos Surveillance, Epidemiology and end results (SEER) entre 2004 y 2015. Las tasas de supervivencia global (SG) y supervivencia cáncer específica (SCE) se evaluaron mediante la curva de Kaplan-Meier y la prueba de rango logarítmico y con análisis de regresión de Cox multivariable. Resultados De los 7.505 pacientes, 3.584 se clasificaron como jóvenes, 2.464 como de mediana edad y 1.461 como ancianos. El año del diagnóstico se clasificó en tres periodos: 2004-2007, 2008-2011 y 2012-2015. La tasa de incidencia de CUTUS fue de 0,69, 0,74 y 0,77 por 100.000 en el primer, segundo y tercer periodo, respectivamente. Las disparidades en la tasa de supervivencia a largo plazo entre hombres y mujeres, y entre pacientes de diferentes razas, se redujeron con el tiempo. No hubo diferencias entre razas en términos de pronóstico (p = 0,078 para la SG y p = 0,167 para la SCE). La diferencia de las tasas de supervivencia entre el grupo de menor NSE y grupo de mayor NSE se redujo a lo largo de los tres periodos de tiempo. Conclusiones Las disparidades en las tasas de supervivencia según sexo, raza y NSE se redujeron con el tiempo, excepto en los pacientes de 74 a 82 años. La edad más avanzada, la raza negra y el NSE bajo, se asocian a peores resultados de supervivencia. En general, la tasa de supervivencia a largo plazo mejoró de forma continuada a lo largo de los tres periodos (AU)

Objective To assess the trend of incidence and survival stratified by age, race, gender and SES and the differences in time between groups in stage III–IV upper tract urothelial carcinoma (UTUC) patients. Methods 7,505 stage III–IV UTUC patients between 2004 and 2015 were extracted from the Surveillance, Epidemiology and End Results (SEER) database. The overall survival (OS) and the cancer-specific survival (CSS) rates were assessed using the Kaplan-Meier curve and log-rank test as well as multivariate Cox regression analysis. Results Among the 7,505 patients, 3,584 were classified as young, 2,464 were classified as middle-aged, and 1,461 were classified as elderly. The years of diagnosis were divided into three periods including 2004-2007, 2008-2011 and 2012-2015. The incidence rates for UTUC were 0.69, 0.74, and 0.77 per 100,000 in the first, second, and third period, respectively. Disparities in the long-term survival rate between male and female patients and among patients of different races narrowed over time. There was no difference in prognosis between races (p = 0.078 for OS and p = 0.167 for CSS). The difference in survival rate between the poor and rich groups narrowed along with the three time periods. Conclusions Survival rate disparities according to sex, race, and socioeconomic status narrowed in time, except in patients aged 74-82 years. Increased age, black race, and poverty are associated with worse survival outcomes. In general, the long-term survival rate improved continuously across the three periods (AU)

CYP2C19*2 gene variant (G681A, rs4244285) as a prognostic marker for the clinical course of multiple myeloma.

BACKGROUND: Multiple myeloma (MM) is the most common type of paraproteinemic hemoblastosis, which is characterized by an aggressive course, high mortality and a large number of complications. The G681A variant (*2, rs4244285) of the CYP2C19 gene leads to the formation of an inactive enzyme and, as a consequence, may affect the development and course of MM. The aim of this research was to analyze the effect of the G681A variant of the CYP2C19 gene on the risk of the development of MM and its course. MATERIALS AND METHODS: The study enrolled 158 patients with MM, who underwent standard clinical and laboratory studies: cytological, general clinical, biochemical, as well as molecular cytogenetic and molecular genetic. Cytogenetic analysis of chromosome abnormalities was performed using interphase fluorescence in situ hybridization. Genotyping by the G681A variant of the CYP2C19 gene was performed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: No association was found between the G681A variant of the CYP2C19 gene and the risk of developing MM. The association between the presence of the G allele and GG genotypes with significant changes in clinical and biochemical parameters (plasma cell count, α2-globulin, calcium content) in MM patients has been established. In the presence of the G allele of the CYP2C19 gene, the development of chromosomal rearrangements del(13q14.2) or del(13q34) with significantly increased levels of albumin occurs more frequently. CONCLUSIONS: The G681A variant of the CYP2C19 gene does not affect the risk of developing MM, but it is associated with significant changes in the clinical and biochemical parameters that determine the severity of the disease and its prognosis. Further research is important to develop new target strategies and maintenance therapy for carriers of different variants of the CYP2C19 gene (G681A).

ESR1 gene variants affect FSHR-depended risk of fibrocystic mastopathy in infertile women.

BACKGROUND: The infertile women have an increased risk of developing benign and malignant tumors, in particular, breast cancer. Most studies have examined the role of gene variants in the risk of developing breast cancer, but there is little evidence of genetic risk factors for benign tumors. AIM: To assess the combined genetic risk of developing mastopathy in women with FSHR (rs6165, rs6166) and ESR1 (rs9340799, rs2234693) gene variants. MATERIALS AND METHODS: The study included 87 infertile women (45 with concomitant fibrocystic mastopathy and 42 without mastopathy). RESULTS: For rs9340799 and rs2234693 variants of the ESR1 gene, we did not find any significant differences in the distribution of genotypes in infertile women with or without mastopathy. In patients with mastopathy, there was a reliable increase in the frequency of 307Ala/Ala and 680Ser/Ser genotypes of FSHR gene (χ2 = 6.39, p = 0.012, OR = 4.49 (1.48-13.65)) as compared to patients without mastopathy. In the presence of 307Thr/Thr and 680Asn/Asn genotypes of the FSHR gene, a 4.88-fold reduction of mastopathy risk (χ2 = 8.06, p = 0.005, OR = 0.21(0.07-0.59)) was observed. The frequency of the FSHR and the ESR1 genotypes combinations - 307Thr/Thr+680Asn/Asn+351AG+397TC was significantly decreased in patients with mastopathy. CONCLUSIONS: Our study did not find an association of ESR1 gene variants with the risk of developing of mastopathy in infertile women although heterozygous variants of the ESR1 gene enhanced the "protective" effect of FSHR gene variants and reduced the risk of mastopathy.

A variant of TP53 gene (rs 1625895, 13494g>A) is associated with neoplasm localization in patients with uterine leiomyoma.

BACKGROUND: Uterine leiomyoma (UL) is the most common benign neoplasm of the uterus. It is still unknown surely what exactly initiates transformation of the uterine myometrial cells into UL. AIM: To study the effect of the TP53 gene variants on the risk of development and clinical features of UL. MATERIALS AND METHODS: Case-control study was performed using molecular genetic analyses of variants rs1042522 (119 G>C) and rs1625895 (13494G>A) of TP53 gene in patients with UL and comparison group of healthy women. RESULTS: Investigated TP53 gene variants were not associated with the risk of UL development. The patients with the 13494GG genotype (rs1625895) had significantly more often subserous UL (р < 0.05). In patients with heterozygous variant of TP53 - 13494GA genotype (rs1625895) intramural UL was observed (р < 0.05). CONCLUSIONS: The rs1625895 (13494G>A) variant of TP53 gene was associated with UL localization. The identified dependence of the UL localization on the TP53 gene variant could be useful for personalized approach to treatment.

Prevalence of BRCA1 and BRCA2 genes promoter hypermethylation in breast cancer tissue.

BACKGROUND: Recent advances in the treatment of breast cancer (BC) have been related to the personalization of therapy. The methylation status of the promoter regions of tumor suppressor genes such as BRCA1 and BRCA2 is supposed to be useful as a prognostic factor in BC patients. AIM: To investigate the frequency of hypermethylation in the promoter regions of BRCA1 and BRCA2 genes in tumor tissue of BC patients, and the relation of hypermethylation to the clinical course of the disease. MATERIALS AND METHODS: Molecular genetic studies were performed on 50 BC tissue samples in order to determine the methylation status of the promoter regions of the BRCA1 and BRCA2 genes. RESULTS: Hypermethylation of the BRCA1 promoter region was detected in 34% of BC cases, hypermethylation of the BRCA2 promoter region - in 50% of cases, and hypermethylation of the promoter region of both genes - in 20% of cases. A significant increase in the incidence of hypermethylation of the BRCA2 promoter region was found in the group of patients older than 56 years, mainly in patients with triple-negative breast cancer and without family history of BC. CONCLUSIONS: The high frequency of hypermethylation in the promoter regions of BRCA1 and BRCA2 genes, as well as their co-methylation in tumor tissue of BC patients has been detected.

[REORGANIZATION OF THE ULTRASTRUCTURE OF NEOCORTICAL NEURONS IN RATS TREATED WITH CELL-FREE DNA].

Neuron ultrastructure was studied in layers III-V of rat brain neocortex 24 hours after intraperitoneal (n=3) or intravenous (n=3) injection of cell-free DNA (7.7x10(-5) g/kg body weight). A plastic restructuring of nuclear chromatin, nucleolar hypertrophy, deep invaginations of nuclear envelope, hyperplasia of mito- chondria and their close contact with other organelles and the nucleus, formation of cytoplasmic tubulovesicular bodies which may promote enhanced synaptic vesicle transport to presynaptic axonal terminals, activation of astrocyte glia were found. The data obtained suggest that injection of cell-free DNA lead to pronounced ultrastructural reorganization in neocortical neurons directed to protein synthesis activation, enhancement of synaptic transmission efficiency, as well as intensification of energy metabolism, that may contribute to reparative and compensatory restorative processes in cerebral ischemic pathology.

[The role of medical faculty of the Emperor Moscow University in development of zemstvo medicine].

The article demonstrates the important role that medical faculty of the Emperor Moscow University played in development of zemstvo medicine. Many of its graduates were zemstvo physicians and provided qualified medical care.

[The activities of the Russian Society of Red Cross during the First World War].

During the First World War, the Russian Society of Red Cross used experience of previous wars expanded its activities. The medical service functioned in the conditions of cruel war. For the first time in history, the weapon of mass destruction was applied The merit of the Russian society of Red Cross was development of specialized medical care.

[The significance of activities in the Imperial Orthodox Palestine Society for progression of medicine in the Middle East (to the 130th anniversary of foundation)].

The article deals with the history of foundation of the Imperial Orthodox Palestine Society in Jerusalem and its input into progression of medicine in the Middle east. The medical activity of Russian physicians in medical institutions of the Society is reflected too.

Heat shock proteins HSP70 and HSP90 in pea seedlings under clinorotation of different duration.

We have previously shown an increase in the Hsp70 and Hsp90 level in pea seedlings (cv. Damir) in response to clinorotation. In this work, Western-blot analysis of the Hsp70 and Hsp90 under clinorotation of different duration--from hours to days--was carried out with pea seedlings (cv. Intensive) with more intensive seed germination and seedling growth. Under clinorotation, the higher Hsp70 and Hsp90 amounts in the germinating seeds seem to be caused by some deceleration of their hydrolysis that correlated with common slowing down of seedling growth. Time-dependent changes in response to clinorotation were determined: some temporary increase in the Hsps level with the maximum for the Hsp70 at 2 h of clinorotation and for the Hsp90--at 6 h and their subsequent returning to the control level.

Xylenol orange adsorbed on silica surface as a solid phase reagent for lead determination using diffuse reflectance spectroscopy.

The solid-phase reagents on the base of xylenol orange and its complex with Fe(III) immobilized on silica surface were obtained. The interaction of Pb(II) with developed reagents was studied. The conditions of quantitative recovery of Pb(II) from diluted solutions, such as acidity of aqueous phase, the amount of the sorbent, the volume of solutions and the time of equilibrium reaching, were examined. The tolerance limits of metal ions in the sorption of Pb(II) at pH 4.5-5.5 are reported. The capabilities of immobilized xylenol orange for Pb(II) pre-concentration prior to its diffusion reflectance spectroscopic detection was evaluated. The detection limit was 2 mug l(-1). The developed method was applied to Pb(II) determination in natural water and foodstuffs.