RESUMO
Prostate cancer (PCa) is the most frequently diagnosed among men malignant disease that remains poorly characterized at the molecular level. Advanced PCa is not curable, and the current treatment methods can only increase the life expectancy by several months. Identification of the genetic aberrations in tumor cells provides clues to understanding the mechanisms of PCa pathogenesis and the basis for developing new therapeutic approaches. Here we present data on somatic mutations, namely single nucleotide variations (SNVs), small insertions and deletions, detected in prostate tumor tissue obtained from Russian patients with PCa. Moreover, we provide a raw dataset on the whole exome and targeted DNA sequencing of tumor and non-tumor prostate tissue obtained from Russian patients with PCa and benign prostatic hyperplasia (BPH). This data is available at NCBI Sequence Read Archive under Accession No. PRJNA506922.
RESUMO
Current prostate cancer (PCa) diagnostic tests suffer from insufficient sensitivity and specificity. Novel biomarkers that can be detected by minimally invasive methods are of a particular value. Here we provide two datasets. The first one is on the whole transcriptome profiling by RNA-seq of urine and plasma obtained from patients with PCa and benign prostatic hyperplasia (BPH). The second one represents targeted sequencing of DNA from urine and plasma of patients with PCa and BPH. Both datasets are available at NCBI Sequence Read Archive under Accession No. SRP093707 and No. SRP093842 respectively.
RESUMO
The RNA-seq approach for prostate cancer candidate RNA biomarkers screening in plasma and urine obtained by minimally invasive or noninvasive methods is proved to be feasible. Significant amount of RNA biomarkers associated with prostate cancer according to the literature were found in plasma and urine samples obtained from patients with benign prostatic hyperplasia (BPH). The number of detected markers was shown to vary in accordance with method of library preparation used for transcriptome profiling. The detection of known RNA biomarkers for prostate cancer in urine and plasma samples shows the feasibility of such method for minimally invasive diagnostics. The fact of presence of the same RNA biomarkers in samples from patients with BPH suggests their possible lack of specificity and confirms the need for further research in this area.
Assuntos
Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/urina , Neoplasias da Próstata/sangue , Neoplasias da Próstata/urina , RNA Neoplásico/sangue , RNA Neoplásico/urina , Adulto , Biomarcadores Tumorais/genética , Humanos , Masculino , Neoplasias da Próstata/genética , RNA Neoplásico/genética , Análise de Sequência de RNAAssuntos
Metagenômica/métodos , Proteínas/química , Proteínas/metabolismo , Software , Sequência de Aminoácidos , Celulases/química , Celulases/genética , Celulases/metabolismo , Enzimas/química , Enzimas/metabolismo , Dados de Sequência Molecular , Fases de Leitura Aberta , Conformação Proteica , Estrutura Terciária de Proteína , Proteínas/genética , Homologia de Sequência de AminoácidosRESUMO
Recent studies of cytochrome P-450 gene polymorphism showed that it may influence the outcome of treatment of Helicobacter pylori (Hp) infection. The literature data concerning effects of genetic factors on the results of eradication therapy of peptic ulcer in the Russian population are scarce and the problem needs further investigation. The aim of this work was to examine CYP2C19 polymorphism in a mixed population of the city and region of Moscow and evaluate its effect on the efficiency of eradication therapy of Hp infection. The prospective study of a cohort of 82 patients with Hp-induced gastric and duodenal ulcers examined in conformity with the current health care standards. All the patients received first line eradication therapy during 7 days. Its efficiency was found to be dependent on CYP2C19 polymorphism among other factors.
Assuntos
Hidrocarboneto de Aril Hidroxilases/genética , DNA Bacteriano/genética , Úlcera Duodenal/genética , Infecções por Helicobacter/genética , Helicobacter pylori/genética , Polimorfismo Genético , Úlcera Gástrica/genética , Adulto , Biópsia , Citocromo P-450 CYP2C19 , Sistema Enzimático do Citocromo P-450/genética , Úlcera Duodenal/tratamento farmacológico , Úlcera Duodenal/microbiologia , Endoscopia Gastrointestinal , Feminino , Seguimentos , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/isolamento & purificação , Humanos , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Masculino , Estudos Prospectivos , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/microbiologiaRESUMO
The frequence of mutations in the rifampicin resistant (RIF(r)) clones of microorganisms after adaption to ofloxacin and metronidazole was investigated to estimate the biological cost of H. pylori rifampicin (RIF) resistance. Mutations in rpoB gene responsible for RIF resistance of H. pylori were shown to have biological cost and be compensated by additional mutations in the microorganism genome. Comparison of the mutation frequency in the presence of metroniazole demonstrated that the acquired resistance to RIF resulted in changing of the adaptative capacity of the RIF(r) clones of H. pylori to metronidazole. Thus, a significant increase of the mutation frequency (> 700 times) in one of the RIF(r) clones and a broad spectrum of the mutations responsible for resistance to metronidazole vs. the H. pylori initial strain 26695 were observed. The findings could be evident of the fact that the adaptation to RIF changed the properties of the cell on one hand in such a way that its mutation capacity increased and that the target selection on the other hand revealed hypermutable cells, likely usual for the bacterial population.
Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Helicobacter pylori/efeitos dos fármacos , Adaptação Biológica , Proteínas de Bactérias/genética , RNA Polimerases Dirigidas por DNA/genética , Genes Bacterianos , Helicobacter pylori/genética , Metronidazol/farmacologia , Mutação , Ofloxacino/farmacologiaRESUMO
Data on cytological diagnosis of hepatic tumors (1996-2006) are evaluated. The potential of cytological examination for identification of the biological mechanism and histological pattern of such malignancies were demonstrated. Cytological examination of puncture bioptates established such diagnostic features as sensitivity (90%), specificity (88%), and effectiveness (89%) as well as prognostic significance of positive (99%) and negative (41%) results.
Assuntos
Biópsia por Agulha , Neoplasias Hepáticas/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/patologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Linfoma não Hodgkin/patologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
To detect point mutations A2115C, A2143G/C, and A2143G in the 23S rRNA gene of Helicobacter pylori associated with resistance of the microorganism to clarithromycin, a new powerful way of analysis was used. This method involved the reaction of minisequencing followed by MALDI-TOF mass spectrometry of reaction products. In ten analyzed clarithromycin-resistant clinical isolates of H. pylori obtained in Russia, the resistance was found to be mediated only by mutation A2144G in the 23S rRNA gene.
Assuntos
Antibacterianos , Claritromicina , Farmacorresistência Bacteriana/genética , Helicobacter pylori/genética , Mutação Puntual , RNA Bacteriano/genética , RNA Ribossômico 23S/genética , Antibacterianos/farmacologia , Claritromicina/farmacologia , Genes Bacterianos/genética , Genes de RNAr/genética , HumanosRESUMO
Using multilocus sequence typing (MLST), 22 Helicobacter pylori isolates from Russia have been characterized. All of the Russian strains were assigned to a single population, hpEurope.
Assuntos
Genes Bacterianos/genética , Helicobacter pylori/genética , Filogenia , Genética Populacional , Humanos , Federação Russa , Análise de Sequência de DNARESUMO
The transcription profiles of four Helicobacter pylori clinical isolates (two cag-negative and two cag-positive) were compared in stationary growth phase using a cDNA-macroarray. The correlation coefficient value between total transcription profiles of clinical isolates H. pylori varied from 0.70 to 0.83. For 44 groups of genes (total number 66) belonging to various functional classes of H. pylori, the correlation coefficient value between these isolates exceeded 0.7, and for 14 groups the value exceeded 0.9. These groups included genes encoding components involved in cell division, adaptations to atypical conditions, electron transport, salvage of nucleosides and nucleotides, glycolysis/gluconeogenesis, folding and stabilization of proteins, translation factors, anaerobic metabolism, and amino acids and amine metabolism. Expression of 52 genes significantly differed between H. pylori clinical isolates. Some of these genes determine microorganism virulence. They include: cytotoxin-associated gene (cagA), genes encoding neutrophil-activating protein (napA), major flagellar protein (flaA), and vacuolizing cytotoxin (vacA), some genes encoding outer membrane proteins (omp), urease alpha and beta subunits (ureA and ureB), and some regulatory proteins, and genes encoding stress-related proteins, such as the chaperone and heat shock protein genes (groEL and dnaK).