Publications by authors named "Natalia Potoldykova"

9 Publications

  • Page 1 of 1

Pharmacogenetic Testing: A Tool for Personalized Drug Therapy Optimization.

Pharmaceutics 2020 Dec 19;12(12). Epub 2020 Dec 19.

Biobanking Group, Branch of Institute of Biomedical Chemistry "Scientific and Education Center", 109028 Moscow, Russia.

Pharmacogenomics is a study of how the genome background is associated with drug resistance and how therapy strategy can be modified for a certain person to achieve benefit. The pharmacogenomics (PGx) testing becomes of great opportunity for physicians to make the proper decision regarding each non-trivial patient that does not respond to therapy. Although pharmacogenomics has become of growing interest to the healthcare market during the past five to ten years the exact mechanisms linking the genetic polymorphisms and observable responses to drug therapy are not always clear. Therefore, the success of PGx testing depends on the physician's ability to understand the obtained results in a standardized way for each particular patient. The review aims to lead the reader through the general conception of PGx and related issues of PGx testing efficiency, personal data security, and health safety at a current clinical level.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/pharmaceutics12121240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765968PMC
December 2020

Prognostic Role of Expression Status and Tumor-Related MicroRNAs Level in Association with PD-L1 Expression in Primary Luminal Non-Muscular Invasive Bladder Carcinoma.

Life (Basel) 2020 Nov 23;10(11). Epub 2020 Nov 23.

Department of Oncological Urology, Russian National Research Center of Radiology, 125284 Moscow, Russia.

Background: bladder cancer is one of the most common urinary tract malignancies. Establishment of robust predictors of disease progression and outcome is important for personalizing treatment of non-muscular invasive bladder carcinoma (NMIBC). In this study we evaluated association of PD-L1 expression with other prognostic biomarkers, such as expression of miRNA-145 and miRNA-200a, gene expression, and mutation status in tissue specimens of the luminal subtype of newly diagnosed high and low grade NMIBC.

Methods: twenty patients with primary luminal NMIBC were enrolled in the study. Tumor grade and risk level were determined in accordance with European Organization for Research and Treatment of Cancer (EORTC) guidelines and World Health Organization (WHO) classification. Neoplasm molecular subtype and PD-L1 expression level were assessed by immunohistochemistry. We used real-time PCR to evaluate the expression of microRNAs and . We detected hotspot mutations in codons 248 and 249 by Sanger sequencing.

Results: high grade primary luminal NMIBC showed comparatively higher expression of PD-L1 and microRNA-145 than a low grade tumor, whereas the latter had a higher expression and hotspot mutation rate. The tumor grade (HR = 571.72 [11.03-2.96] = 0.002), PD-L1 expression (HR = 2.33 [0.92-1.92] = 0.012), and expression (HR = 0.08 [0.17-0.42] = 0.003) were associated with relapse-free survival.

Conclusions: tumor grade in association with PD-L1 and expression can be considered as a complex predictor for primary luminal NMIBC progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/life10110305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700587PMC
November 2020

Identification of Clinically Significant Prostate Cancer by Combined and mRNA Detection in Urine Samples.

Res Rep Urol 2020 17;12:403-413. Epub 2020 Sep 17.

Department of Molecular Biology and Genetics, Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow, Russia.

Purpose: Preclinical evaluation of and transcript simultaneous detection in urine to diagnose clinical significant prostate cancer (prostate cancer with Gleason score ≥7) in a Russian cohort.

Patients And Methods: We analyzed urine samples of patients with a total serum PSA ≥2 ng/mL: 31 men with prostate cancer scheduled for radical prostatectomy, 128 men scheduled for first diagnostic biopsy (prebiopsy cohort). , , and transcripts were detected by multiplex reverse transcription quantitative polymerase chain reaction, and the results were used for scores for calculation and statistical analysis.

Results: There was no significant difference between clinically significant and nonsignificant prostate cancer PCA3 scores. However, there was a significant difference in the AMACR score (patients scheduled for radical prostatectomy =0.0088, prebiopsy cohort =0.029). We estimated AUCs, optimal cutoffs, sensitivities and specificities for PCa and csPCa detection in the prebiopsy cohort by tPSA, PCA3 score, PCPT Risk Calculator and classification models based on tPSA, PCA3 score and AMACR score. In the clinically significant prostate cancer ROC analysis, the PCA3 score AUC was 0.632 (95%CI: 0.511-0.752), the AMACR score AUC was 0.711 (95%CI: 0.617-0.806) and AUC of classification model based on the score, the AMACR score and total PSA was 0.72 (95%CI: 0.58-0.83). In addition, the correlation of the AMACR score with the ratio of total RNA and RNA of prostate cells in urine was shown (tau=0.347, =6.542e-09). Significant amounts of nonprostate RNA in urine may be a limitation for the AMACR score use.

Conclusion: The AMACR score is a good predictor of clinically significant prostate cancer. Significant amounts of nonprostate RNA in urine may be a limitation for the AMACR score use. Evaluation of the AMACR score and classification models based on it for clinically significant prostate cancer detection with larger samples and a follow-up analysis is promising.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/RRU.S262310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7505712PMC
September 2020

Plasma metabolomic profile in prostatic intraepithelial neoplasia and prostate cancer and associations with the prostate-specific antigen and the Gleason score.

Metabolomics 2020 06 17;16(7):74. Epub 2020 Jun 17.

Laboratory of Pharmacokinetics and Metabolomic Analysis, Institute of Translational Medicine and Biotechnology, I.M. Sechenov First Moscow State Medical University, 2-4 Bolshaya Pirogovskaya St., Moscow, Russia, 119991.

Introduction: The metabolic alterations reflecting the influence of prostate cancer cells can be captured through metabolomic profiling.

Objective: To characterize the plasma metabolomic profile in prostatic intraepithelial neoplasia (PIN) and prostate cancer (PCa).

Methods: Metabolomics analyses were performed in plasma samples from individuals classified as non-cancerous control (n = 36), with PIN (n = 16), or PCa (n = 27). Untargeted [26 moieties identified after pre-processing by gas chromatography/mass spectrometry (GC/MS)] and targeted [46 amino acids, carbohydrates, organic acids and fatty acids by GC/MS, and 16 nucleosides and amino acids by ultra performance liquid chromatography-triple quadrupole/mass spectrometry (UPLC-TQ/MS)] analyses were performed. Prostate specific antigen (PSA) concentrations were measured in all samples. In PCa patients, the Gleason scores were determined.

Results: The metabolites that were best discriminated (p < 0.05, FDR < 0.2) for the Kruskal-Wallis test with Dunn's post-hoc comparing the control versus the PIN and PCa groups included isoleucine, serine, threonine, cysteine, sarcosine, glyceric acid, among several others. PIN was mainly characterized by alterations on steroidogenesis, glycine and serine metabolism, methionine metabolism and arachidonic acid metabolism, among others. In the case of PCa, the most predominant metabolic alterations were ubiquinone biosynthesis, catecholamine biosynthesis, thyroid hormone synthesis, porphyrin and purine metabolism. In addition, we identified metabolites that were correlated to the PSA [i.e. hypoxanthine (r = - 0.60, p < 0.05; r = - 0.54, p < 0.01) and uridine (r = - 0.58, p < 0.05; r = - 0.50, p < 0.01) in PIN and PCa groups, respectively] and metabolites that were significantly different in PCa patients with Gleason score < 7 and ≥ 7 [i.e. arachidonic acid, median (P25-P75) = 883.0 (619.8-956.4) versus 570.8 (505.6-651.8), respectively (p < 0.01)].

Conclusions: This human plasma metabolomic assessment contributes to the understanding of the unique metabolic features exhibited in PIN and PCa and provides a list of metabolites that can have the potential to be used as biomarkers for early detection of disease progression and management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11306-020-01694-yDOI Listing
June 2020

Relapse-Free Survival and PD-L1 Expression in First High- and Low-Grade Relapsed Luminal, Basal and Double-Negative P53-Mutant Non-Muscular Invasive Bladder Cancer Depending on Previous Chemo- and Immunotherapy.

Cancers (Basel) 2020 May 21;12(5). Epub 2020 May 21.

Department of Oncological Urology, Russian National Research Center of Radiology, 3 2nd Botkinsky Proezd, 125284 Moscow, Russia.

The goal of this study was to assess how PD-L1 expression in tissue specimens of patients with main molecular subtypes of NMIBC (luminal, basal and double-negative p53-mutant) associates with relapsed-free survival in dependence on the tumor grade and prior treatment of primary bladder cancer. PD-L1 expressions on the membrane of neoplastic and CD8+ immune cells were assessed in tumor specimens ( = 240) of primary and relapsed luminal, basal and double-negative p53-mutant NMIBC. Association between relapse-free survival and PD-L1 expression was estimated for high- and low-grade relapsed NMIBC according to previous treatment and their molecular profile, using the Kaplan-Meier method, and assessed by using the log-rank test. Potential confounders were adjusted by Cox regression models. In a group of patients who underwent only TUR without intravesical therapy, there were significant differences in relapse time between high- and low-grade tumors in basal and luminal molecular subtypes; for basal relapsed carcinoma, RFS was shorter in cases where tumors were less malignant. Both intravesical mitomycin and Bacillus Calmette-Guerin (BCG) therapy significantly extended the time of recurrence of low-grade luminal and basal bladder malignancies with no intergroup differences in double-negative NMIBC. PD-L1 expression status was associated with RFS for luminal relapsed NMIBCs in the group without previous frontline intervention, and with RFS in the group of patients with luminal relapsed bladder cancer previously utilized BCG. Obtained results may be considered as a promising approach for further clinical implementation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers12051316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281187PMC
May 2020

Plasma Sarcosine Measured by Gas Chromatography-Mass Spectrometry Distinguishes Prostatic Intraepithelial Neoplasia and Prostate Cancer from Benign Prostate Hyperplasia.

Lab Med 2020 Nov;51(6):566-573

Laboratory of Pharmacokinetics and Metabolomic Analysis, Institute of Translational Medicine and Biotechnology, I.M. Sechenov First Moscow State Medical University, Moscow, Russia.

Objective: Sarcosine was postulated in 2009 as a biomarker for prostate cancer (PCa). Here, we assess plasma sarcosine as a biomarker that is complementary to prostate-specific antigen (PSA).

Methods: Plasma sarcosine was measured using gas chromatography-mass spectrometry (GC-MS) in adults classified as noncancerous controls (with benign prostate hyperplasia [BPH], n = 36), with prostatic intraepithelial neoplasia (PIN, n = 16), or with PCa (n = 27). Diagnostic accuracy was assessed using receiver operating characteristic curve analysis.

Results: Plasma sarcosine levels were higher in the PCa (2.0 µM [1.3-3.3 µM], P <.01) and the PIN (1.9 µM [1.2-6.5 µM], P <.001) groups than in the BPH (0.9 µM [0.6-1.4 µM]) group. Plasma sarcosine had "good" and "very good" discriminative capability to detect PIN (area under the curve [AUC], 0.734) and PCa (AUC, 0.833) versus BPH, respectively. The use of PSA and sarcosine together improved the overall diagnostic accuracy to detect PIN and PCa versus BPH.

Conclusion: Plasma sarcosine measured by GC-MS had "good" and "very good" classification performance for distinguishing PIN and PCa, respectively, relative to noncancerous patients diagnosed with BPH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/labmed/lmaa008DOI Listing
November 2020

Revelation of Proteomic Indicators for Colorectal Cancer in Initial Stages of Development.

Molecules 2020 Jan 31;25(3). Epub 2020 Jan 31.

V.N. Orekhovich Institute of Biomedical Chemistry, 119121 Moscow, Russia.

Colorectal cancer (CRC) at a current clinical level is still hardly diagnosed, especially with regard to nascent tumors, which are typically asymptotic. Searching for reliable biomarkers of early diagnosis is an extremely essential task. Identification of specific post-translational modifications (PTM) may also significantly improve net benefits and tailor the process of CRC recognition. We examined depleted plasma samples obtained from 41 healthy volunteers and 28 patients with CRC at different stages to conduct comparative proteome-scaled analysis. The main goal of the study was to establish a constellation of protein markers in combination with their PTMs and semi-quantitative ratios that may support and realize the distinction of CRC until the disease has a poor clinical manifestation. Proteomic analysis revealed 119 and 166 proteins for patients in stages I-II and III-IV, correspondingly. Plenty of proteins (44 proteins) reflected conditions of the immune response, lipid metabolism, and response to stress, but only a small portion of them were significant ( < 0.01) for distinguishing stages I-II of CRC. Among them, some cytokines (Clusterin (CLU), C4b-binding protein (C4BP), and CD59 glycoprotein (CD59), etc.) were the most prominent and the lectin pathway was specifically enhanced in patients with CRC. Significant alterations in Inter-alpha-trypsin inhibitor heavy chains (ITIH1, ITIH2, ITIH3, and ITIH4) levels were also observed due to their implication in tumor growth and the malignancy process. Other markers (Alpha-1-acid glycoprotein 2 (ORM2), Alpha-1B-glycoprotein (A1BG), Haptoglobin (HP), and Leucine-rich alpha-2-glycoprotein (LRG1), etc.) were found to create an ambiguous core involved in cancer development but also to exactly promote tumor progression in the early stages. Additionally, we identified post-translational modifications, which according to the literature are associated with the development of colorectal cancer, including kininogen 1 protein (T327-p), alpha-2-HS-glycoprotein (S138-p) and newly identified PTMs, i.e., vitamin D-binding protein (K75-ac and K370-ac) and plasma protease C1 inhibitor (Y294-p), which may also contribute and negatively impact on CRC progression. The contribution of cytokines and proteins of the extracellular matrix is the most significant factor in CRC development in the early stages. This can be concluded since tumor growth is tightly associated with chronic aseptic inflammation and concatenated malignancy related to loss of extracellular matrix stability. Due attention should be paid to Apolipoprotein E (APOE), Apolipoprotein C1 (APOC1), and Apolipoprotein B-100 (APOB) because of their impact on the malfunction of DNA repair and their capability to regulate mTOR and PI3K pathways. The contribution of the observed PTMs is still equivocal, but a significant decrease in the likelihood between modified and native proteins was not detected confidently.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/molecules25030619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7036866PMC
January 2020

Detection of Marker miRNAs, Associated with Prostate Cancer, in Plasma Using SOI-NW Biosensor in Direct and Inversion Modes.

Sensors (Basel) 2019 Nov 29;19(23). Epub 2019 Nov 29.

Institute of Biomedical Chemistry (IBMC), Moscow 119121, Russia.

Information about the characteristics of measuring chips according to their storage conditions is of great importance for clinical diagnosis. In our present work, we have studied the capability of chips to detect nanowire biosensors when they are either freshly prepared or have been stored for either one or two years in a clean room. Potential to detect DNA oligonucleotides (oDNAs)-synthetic analogues of microRNAs (miRNAs) 198 and 429 that are associated with the development of prostate cancer (PCa)-in buffer solution was demonstrated using a nanowire biosensor based on silicon-on-insulator structures (SOI-NW biosensor). To provide biospecific detection, nanowire surfaces were sensitized with oligonucleotide probes (oDNA probes) complimentary to the known sequences of miRNA 183 and 484. In this study it is demonstrated that freshly prepared SOI-NW biosensor chips with n-type conductance and immobilized oDNA probes exhibit responses to the addition of complimentary oDNAs in buffer, leading to decreases in chips' conductance at a concentration of 3.3 × 10 M. The influence of storage time on the characteristics of SOI-NW biosensor chips is also studied herein. It is shown that a two-year storage of the chips leads to significant changes in their characteristics, resulting in "inverse" sensitivity toward negatively charged oDNA probes (i.e., through an increase in chips' conductance). It is concluded that the surface layer makes the main contribution to conductance of the biosensor chip. Our results indicate that the detection of target nucleic acid molecules can be carried out with high sensitivity using sensor chips after long-term storage, but that changes in their surface properties, which lead to inversed detection signals, must be taken into account. Examples of the applications of such chips for the detection of cancer-associated microRNAs in plasma samples of patients with diagnosed prostate cancer are given. The results obtained herein are useful for the development of highly sensitive nanowire-based diagnostic systems for the revelation of (prostate) cancer-associated microRNAs in human plasma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/s19235248DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6928824PMC
November 2019

Need for upper urinary tract stenting in cases of ureteral orifice injury during laser enucleation of the prostate.

Int Urol Nephrol 2018 Dec 22;50(12):2173-2177. Epub 2018 Oct 22.

Department of Urology, UT Southwestern Medical Center, Dallas, TX, USA.

Introduction: Benign prostatic hyperplasia (BPH) can be associated with marked intravesical protrusion, placing ureteral orifices at risk for injury during bladder outlet procedures.

Aim: To determine whether ureteral stenting is necessary in cases of ureteral orifice injury during laser enucleation.

Materials And Methods: Retrospective study included 465 patients with bladder outlet obstruction (IPSS > 20, Qmax < 10) secondary to BPH who were managed with thulium fiber laser (ThuFLEP) or holmium laser enucleation of the prostate (HoLEP). In seven patients, the ureteral orifices were injured during surgery (3-HoLEP; 4-ThuFLEP). Three of the seven patients underwent intraoperative stenting of the upper urinary tract (1-HoLEP; 2-ThuFLEP). In four cases, stenting was not performed (2-HoLEP; 2-ThuFLEP). The follow-up period was 6 months.

Results: Postoperatively, none of the patients with a stent in the upper urinary tract exhibited signs of pelvicalyceal system (PCS) dilatation or inhibited urine flow from the kidney (assessed with abdominal ultrasound at 1, 3, 10, and 30 days after surgery). In two patients without stents, follow-up revealed no dilatation of the PCS. The other two patients without stents developed asymptomatic dilatation of the PCS (the pelvis-up to 1.5 cm; the calyx-up to 0.5 cm). At 1 month after surgery, no patients had dilatation of the PCS.

Conclusions: Upper urinary tract stenting in cases of intraoperative ureteral orifice injury during laser enucleation of the prostate for BPH may not be warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11255-018-2007-6DOI Listing
December 2018