5 results on '"N. Yu. Safronova"'
Search Results
2. The role of molecular genetic alterations in sensitivity of the adjuvant intravesical therapy for non-muscle invasive bladder cancer
- Author
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D. S. Mikhaylenko, S. A. Sergienko, I. N. Zaborsky, K. N. Saflullin, S. A. Serebryany, N. Yu. Safronova, M. V. Nemtsova, A. D. Kaprin, and B. Ya. Alekseev
- Subjects
Oncology ,bcg therapy ,medicine.medical_specialty ,Urology ,medicine.medical_treatment ,Targeted therapy ,Molecular genetics ,Internal medicine ,medicine ,Adjuvant therapy ,genetic polymorphism ,somatic mutation ,Radiology, Nuclear Medicine and imaging ,mutational load ,Bladder cancer ,business.industry ,Immunotherapy ,medicine.disease ,Primary tumor ,Nephrology ,gene expression ,bladder cancer ,Medicine ,microsatellite instability ,Surgery ,immunotherapy ,business ,Adjuvant ,BCG vaccine - Abstract
Bladder cancer (BC) is represented by non-muscle-invasive forms at the stage Ta, T1, CIS (NMBC) in 75 % of cases. The gold standard of treatment of NMBC patients is transurethral resection, but its implementation does not always allow the patient to be relieved of the recurrence of the disease. In this regard, patients with a low risk of progression after transurethral resection are administered by intravesical chemotherapy, with high risk (T1G2/3) – using instillation with BCG (Bacillus Calmette–Guerin) vaccine. Searching of NMBC markers for laboratory diagnostics, which would help to determine sensitivity or resistance to the planned type of adjuvant therapy remains an actual problem. The data published mainly in the last 5–7 years about genetic predictors of the response to adjuvant chemotherapy and, to a greater extent, immunotherapy with BCG vaccine, are reviewed in this work. Allele combinations in the genes involved in immune response, xenobiotic biotransformation and other loci that are associated with the response to the adjuvant NMBC therapy in meta-analyzes are systematized. Also, expression profiles of mRNA, microRNA and proteins, as well as panels of methylated loci associated with the effectiveness of chemotherapy and immunotherapy of NMBC are considered. It was demonstrated that the somatic mutations sequencing in the primary tumor and the total mutational load using high-throughput sequencing technologies (NGS) identified a number of potential prognostic markers. Perhaps, the mutational load will be more widely used as a highly informative predictor of immunotherapeutic effect in BC: BCG therapy of NMBC and BC targeted therapy using the inhibitors of immune control points, after the standardization of the analysis. This review is intended to oncologists, geneticists, molecular biologists, urologists, pathologists and other specialists working in the field of molecular genetics in oncological urology.
- Published
- 2019
3. Comparative analysis of the PCA3 gene expression in sediments and exosomes isolated from urine
- Author
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D. S. Mikhaylenko, A. A. Novikov, M. V. Grigor’eva, G. D. Efremov, A. V. Sivkov, N. Yu. Safronova, K. S. Sorokin, M. Yu. Zemskova, M. V. Nemtsova, B. Ya. Alekseev, and A. D. Kaprin
- Subjects
PCA3 ,Urology ,pca3 ,Diagnostic accuracy ,Urine ,Biology ,non-invasive diagnostics ,medicine.disease ,Molecular biology ,Exosome ,Prostate cancer ,Oncology ,Nephrology ,Genetic marker ,Gene expression ,medicine ,gene expression ,Urine sediment ,exosome ,Medicine ,Radiology, Nuclear Medicine and imaging ,Surgery - Abstract
Introduction . Prostate cancer (PCa) is one of the common oncological diseases in men. Expression of the PCA3 gene in urine is currently used as a molecular genetic marker of PCa. Objective: to comparative analysis of the PCA3 expression in urine sediments and exosomes for the determination of the biomaterial, which allows detecting the PCA3 expression in more efficient manner. Materials and methods. The 12 patients with different stages of PCa and 8 control samples were examined. Results. The diagnostic accuracy of the PCA3 gene expression analysis in this cohort exceeded 90 %. We had not obtained significant differences in the sensitivity and specificity of the PCA3 hyperexpression in the urine sediments compared with exosomes. This result indicates in favor to using urine sediment for the PCA3 analysis as a biomaterial with less time-consuming sample preparation, although the possible advantage of exosomes for the analysis of the expression marker panels requires further studies.
- Published
- 2017
4. [PCA3 AND TMPRSS2:ERG GENES EXPRESSION IN BIOPSIES OF BENIGN PROSTATE HYPERPLASIA, INTRAEPITHELIAL NEOPLASIA, AND PROSTATE CANCER]
- Author
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D S, Mikhaylenko, D V, Perepechin, M V, Grigoryeva, T A, Zhinzhilo, N Yu, Safronova, G D, Efremov, and A V, Sivkov
- Subjects
Gene Expression Regulation, Neoplastic ,Male ,Oncogene Proteins, Fusion ,Antigens, Neoplasm ,Reverse Transcriptase Polymerase Chain Reaction ,Biopsy ,Prostatic Hyperplasia ,Humans ,Prostatic Neoplasms - Abstract
Morphological analysis of the biopsies for prostate cancer (PCa) often is a difficult task due to heterogeneity and multifocality of tumors. At the same time, a lot of data exist about the potential molecular genetic markers of PCa. The aim of our study is to determine of PCA3 and TMPRSS2:ERG genes expression in benign hyperplasia (BPH), low and high grade intraepithelial neoplasia (PIN), PCa for revealing of diagnostic value of those genes expression in benign and precancerous changes in prostate. Total RNA was isolated from 53 biopsies, reverse transcription was performed, gene expression was determined by real time PCR (RT-PCR) then deltaCt index was determined as Ct(PCA3)--Ct(KLK3). Average deltaCt and its SD in BPH were 8.28 ± 3.13, low PIN--8.56 ± 2.64, high PIN--8.98 ±1.69, PCa--1.08 ± 2.36. We have demonstarted that deltaCt did not differ in patients with BPH, low and high grade PIN, whereas significantly increased in PCa relative to any of the three groups listed above (p0.0001). Expression of TMPRSS2:ERG was absent in BPH, PIN, but it was detected in 40% (4/10) of PCa cases. ROC-analysis showed that the AUC (area under ROC-curve with 95% CI, p0.0001) was 0.98 ± 0.02 in the analysis of a combination of overexpression of PCA3 and TMPRSS2:ERG. Thus, the expression analysis of the PCA3 and chimeric oncogene TMPRSS2:ERG in biopsy cannot be used for differential diagnosis of BPH, low and high grade PIN. However, overexpression of PCA3 and expression of TMPRSS2:ERG are characteristic in PCa. Expression analysis of these genes by the proposed RT-PCR modification at the threshold level deltaCt 3,22 has diagnostic accuracy 90% to detect PCa in biopsy specimens.
- Published
- 2016
5. Detection of Rare Mutations by Routine Analysis of KRAS, NRAS, and BRAF Oncogenes
- Author
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G. D. Efremov, D. S. Mikhailenko, Vladimir V Strelnikov, B. Ya. Alekseev, and N. Yu. Safronova
- Subjects
0301 basic medicine ,Neuroblastoma RAS viral oncogene homolog ,Proto-Oncogene Proteins B-raf ,Skin Neoplasms ,Tissue Fixation ,Colorectal cancer ,DNA Mutational Analysis ,Biology ,medicine.disease_cause ,Real-Time Polymerase Chain Reaction ,General Biochemistry, Genetics and Molecular Biology ,GTP Phosphohydrolases ,Proto-Oncogene Proteins p21(ras) ,03 medical and health sciences ,symbols.namesake ,0302 clinical medicine ,Germline mutation ,medicine ,Humans ,neoplasms ,Melanoma ,Sanger sequencing ,Mutation ,Paraffin Embedding ,Base Sequence ,Membrane Proteins ,General Medicine ,Exons ,medicine.disease ,digestive system diseases ,Introns ,Neoplasm Proteins ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer research ,symbols ,KRAS ,Colorectal Neoplasms ,V600E ,Algorithms - Abstract
Molecular genetic analysis of KRAS, NRAS, and BRAF genes was carried out in order to develop an optimal algorithm for detection of minor mutations. We analyzed 35 melanoma and 33 colorectal cancer specimens. Frequent G12D/V/A/C/S mutations were detected in KRAS. The most frequent BRAF mutation in melanoma was V600E, the percentage of rare mutations is significant for DNA diagnosis (24%). Identification of rare BRAF mutations 1790C→G (L597R), 1798_1799delinsAA (V600K), 1798_1799delinsAG (V600R), and 1799_1800delinsAA (V600E) and NRAS mutation 38G→T (G13V) was possible only by Sanger sequencing. The combination of real-time PCR and sequencing can improve analysis sensitivity and ensure concordance of the tested loci with the international recommendations.
- Published
- 2016
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