Publications by authors named "Ekaterina Blinova"

9 Publications

  • Page 1 of 1

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.
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http://dx.doi.org/10.3390/life10110305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700587PMC
November 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.
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http://dx.doi.org/10.3390/cancers12051316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281187PMC
May 2020

Novel Dimethylacetamide-Containing Formulation Improves Infraorbital Anaesthesia Efficacy in Rats with Periodontitis.

Adv Pharmacol Pharm Sci 2020 14;2020:3058735. Epub 2020 Apr 14.

Department of Operative Surgery and Clinical Anatomy, Department of Pathology, Department of Dentistry, Sechenov University, Moscow 119991, Russia.

Background: To evaluate acute toxicity and local anaesthetic activity of a formulation containing a novel dimethylacetamide derivative, antioxidant, and vasoconstrictor in rats with chronic periodontitis.

Methods: Novel anaesthetic dimethylacetamide-containing formulation LHT-15-32 was studied as 2% water solution. Its acute intravenous and subcutaneous toxicity was determined in mice. Pain sensitivity threshold of the upper second molar was determined in rats with experimental periodontitis. Oxidative stress activity and total antioxidant capacity were determined in rats' gingival mucosa by induced chemiluminescence. Local changes were evaluated in periodontal tissue by morphological examination. Tissue IL-1, IL-10, and TNF-α concentration was quantitatively assessed by an enzyme-linked immunosorbent assay. LHT-15-31 Na-blocking activity was studied on isolated neurons of ' parapharyngeal ganglion. Isolated sciatic nerve of was perfused with different concentrations of LHT-15-32 to assess its conductivity. Statistical analysis was used, and continuous variables were presented as mean ± square deviation. The normality of distribution was determined using ANOVA. Newman-Keuls parametric criterion was used for intergroup comparison. LD indexes were calculated by probit analysis.

Results: LHT-15-32 acute intravenous and subcutaneous toxicity was lower than that of its active substance. The formulation by infraorbital administration induced deep dental anaesthesia which lasted over 70 min and activated the local antioxidant defense system and decreased IL-1 level in gingival tissue. LHT-15-32 triggered tissue reparation around the impacted upper molar in rats assessed five days after administration. At 10 to 10 M concentration, LHT-15-32 inhibited sciatic nerve conductivity and blocked Na channels of isolated neurons in a dose-dependent manner.

Conclusions: The formulation may be considered as an effective and safe approach to anaesthetize upper molars with periodontitis.
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http://dx.doi.org/10.1155/2020/3058735DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7178499PMC
April 2020

Programmed death-ligand 1 signaling pathway involves in bladder cancer growth and progression.

J Carcinog 2019 13;18. Epub 2019 Jun 13.

Department of Clinical Anatomy, Sechenov University, Moscow, Russia.

Context: Exploration of the biological property of programmed death-ligand 1 (PD-L1) signaling that may impact bladder tumor growth in humanized animals and cell culture.

Aims: The aim of this study is to evaluate how PD-L1 signaling involves bladder cancer growth and progression.

Settings And Design: This study design involves experimental and study.

Subjects And Methods: A role of PD-L1 signaling pathway inhibition for bladder cancer growth was assessed in humanized immunodeficient animals carried main molecular subtypes of bladder carcinoma patient-derived xenografts and provided with selective anti-PD-L1 treatment; bladder cancer cells invasiveness was evaluated in mixed RT112/84 cells + CD4 cells culture incubated with PD-L1 blocker durvalumab. We used two-tailed Student's -test to explore differences between main and control subgroups. Significance of intergroup comparison was measured with one-way ANOVA followed by the Tukey's or Newman-Keul's criterion. Survival curves were analyzed with Gehan's criterion with the Yate's correction. Differences were considered statistically significant at < 0.05.

Results: Anti-PD-L1 intervention increased survival of the animals carried both primary and relapsed luminal noninvasive, muscular invasive, and relapsed luminal bladder cancer xenografts. There was significant retardation of tumor volume duplication time in aforementioned subgroups correlated with PD-L1 expression. Durvalumab treatment in concentration-dependent manner inhibited tumor cells invasiveness of mixed RT112 + CD4 culture cells with its maximum at the highest studied concentration (10 μM).

Conclusions: Obtained data constituted the pivotal role of programmed cell death-1/PD-L1 signaling pathway in bladder cancer development and progression. The results will have major implications for further clinical investigations.
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http://dx.doi.org/10.4103/jcar.JCar_3_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6594057PMC
June 2019

Patient-Derived Non-Muscular Invasive Bladder Cancer Xenografts of Main Molecular Subtypes of the Tumor for Anti-Pd-l1 Treatment Assessment.

Cells 2019 05 31;8(6). Epub 2019 May 31.

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

Background: Establishment of heterotopic patient-derived xenografts of primary and relapsed non-muscular invasive bladder cancer (NMIBC) to explore the biological property of PD-L1 signaling that may impact bladder tumor growth in humanized animals.

Methods: Tumor cells of luminal, basal, and p53 subtypes of primary and relapsed NMIBC were engrafted to irradiated (3.5 Gy) NOG/SCID female mice along with intraperitoneal transplantation of human lymphocytes (5 × 10 cells/mouse); a role of PD-L1 signaling pathway inhibition for bladder cancer growth was assessed in humanized animals that carried PD-L1-expressing main molecular subtypes of bladder carcinoma patient-derived xenografts (PDX) and provided with selective anti-PD-L1 treatment. We used two-tailed Student's test to explore differences between main and control subgroups. Significance of intergroup comparison was measured with one-way ANOVA followed by the Tukey's or Newman-Keul's criterion. Survival curves were analyzed with the Gehan's criterion with the Yate's correction. The Spearman's correlation was used to assess the link between CD8 expression and sPD-L1 serum level. Differences were considered statistically significant at < 0.05.

Results: Heterotopic primary and relapsed luminal, basal, and p53 subtypes of NMIBC PDXs were established. More than 25% of counted tumor cells of all PDX specimens expressed PD-L1, so the tumors were ranged as PD-L1 positive. Anti-PD-L1 intervention increased survival of the animals that carried both primary and relapsed luminal noninvasive, muscular invasive, and relapsed luminal bladder cancer xenografts. There was significant retardation of tumor volume duplication time in aforementioned subgroups correlated with PD-L1 expression. Bad response of p53 mutant subtypes of NMIBC on specific anti-PD-L1 treatment may be associated with low CD8 cells representation into the tumors tissue.

Conclusions: Established PD-L1-positive NMIBC PDXs differently replied on anti-PD-L1 treatment due to both NMIBC molecular subtype and tumor T-suppressors population. The results may have major implications for further clinical investigations.
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http://dx.doi.org/10.3390/cells8060526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6628037PMC
May 2019

Novel aminochromone derivative inhibits tumor growth on xenograft model of lung cancer in mice.

J Adv Pharm Technol Res 2018 Oct-Dec;9(4):130-134

Department of Scientific Research, Federal Research Medical Center of Radiology, Moscow, Russia.

2-Amino-4H-chromene derivatives possess anticancer property proved on different and models of malignancies such breast, nasopharyngeal, bladder, ovary carcinomas, astrocytoma, and osteosarcoma. We assumed it might be effective to apply one of the derivatives as promising approach to lung carcinoma treatment. to evaluate how novel 4-aryl substituted 2-amino-4H-chromene derivative AX-554 impacts tumor growth and progression, as well as possible mechanisms for anticancer effect development on patient-derived heterotopic xenograft model of lung carcinoma in mice. This was an experimental study. 40 nu/nu /c female mice were randomly allocated into four equal groups: Intact, control, reference, and main group. Animals of three latter groups were ingrafted with human-derived lung adenocarcinoma. Antitumor and antimetastatic action of AX-554 novel aminochromone derivative as a substance were studied. Mice survival was registered. Kinase of anaplastic lymphoma (ALK), tubulin Beta-3 (TUBB3), and c-mesenchymal-epithelial transition (MET) concentrations in the prime tumor nodes homogenates were determined by quantitative enzyme-linked immunosorbent assay. Dannet's parametric criterion and the nonparametric exact Fisher test were used. The normality of the distribution was determined using ANOVA. The survival curve was analyzed using Gehan's criterion with the Yates's correction. Aminochromone derivative possesses an inhibitory effect on human lung adenocarcinoma transplanted into nu/nu /c female mice, as well as significant antimetastatic activity. About 50 mg/kg/day AX-554 intragastric course increases animals' life expectancy of more than 3.3 times when compared with the control and induces remission in 60% of cases. The anticancer effect of the derivative is due to anti-ALK-mediated activation of tumor cells apoptosis and suppression TUBB3-dependent cell proliferation.
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http://dx.doi.org/10.4103/japtr.JAPTR_313_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6302682PMC
January 2019

The Study of Viral RNA Diversity in Bird Samples Using De Novo Designed Multiplex Genus-Specific Primer Panels.

Adv Virol 2018 12;2018:3248285. Epub 2018 Aug 12.

Central Research Institute of Epidemiology, Moscow 111123, Russia.

Advances in the next generation sequencing (NGS) technologies have significantly increased our ability to detect new viral pathogens and systematically determine the spectrum of viruses prevalent in various biological samples. In addition, this approach has also helped in establishing the associations of viromes with many diseases. However, unlike the metagenomic studies using rRNA for the detection of bacteria, it is impossible to create universal oligonucleotides to target all known and novel viruses, owing to their genomic diversity and variability. On the other hand, sequencing the entire genome is still expensive and has relatively low sensitivity for such applications. The existing approaches for the design of oligonucleotides for targeted enrichment are usually involved in the development of primers for the PCR-based detection of particular viral species or genera, but not for families or higher taxonomic orders. In this study, we have developed a computational pipeline for designing the oligonucleotides capable of covering a significant number of known viruses within various taxonomic orders, as well as their novel variants. We have subsequently designed a genus-specific oligonucleotide panel for targeted enrichment of viral nucleic acids in biological material and demonstrated the possibility of its application for virus detection in bird samples. We have tested our panel using a number of collected samples and have observed superior efficiency in the detection and identification of viral pathogens. Since a reliable, bioinformatics-based analytical method for the rapid identification of the sequences was crucial, an NGS-based data analysis module was developed in this study, and its functionality in the detection of novel viruses and analysis of virome diversity was demonstrated.
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http://dx.doi.org/10.1155/2018/3248285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6109506PMC
August 2018

A neonatal death associated with Crimean-Congo hemorrhagic fever (Republic of Kalmykia, Russia, June 2016).

Antiviral Res 2017 10 4;146:146-148. Epub 2017 Sep 4.

Central Research Institute for Epidemiology, Federal Service on Consumer Rights Protection and Human Well-Being Surveillance, Moscow, Russia.

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http://dx.doi.org/10.1016/j.antiviral.2017.08.018DOI Listing
October 2017

Point prevalence survey of antimicrobial utilization in the cardiac and pediatric critical care unit.

Pediatr Crit Care Med 2013 Jul;14(6):e280-8

Department of Pharmacy, The Hospital for Sick Children, Toronto, Ontario, Canada.

Objectives: To determine the rate of documented infections and prevalence of antimicrobial use among pediatric patients admitted to the PICU. To assess the appropriateness of antimicrobial prescribing according to clinical and microbiological findings, Infectious Disease Consult recommendations, and formulary guidelines.

Design: Prospective point prevalence study.

Setting: Cardiac and medical-surgical critical care units (CCCU-PICU) in a tertiary care pediatric teaching hospital in Toronto, Canada.

Patients: All patients admitted to the CCCU-PICU during the week of October 27, 2008 (period A) and February 9, 2009 (period B) were followed until completion of their antimicrobial course(s). Data were collected on infection types and indications, frequency, and types of antimicrobials used. Appropriateness of antimicrobial prescribing was assessed according to predefined criteria by four blinded clinician assessors.

Measurement And Main Results: Forty-two of 60 patients (70%) received antimicrobials in period A and 42 of 53 patients (79%) received antimicrobials in period B. Of the patients on antimicrobials, 45% in period A and 52% in period B had a definitive diagnosis of infection. Pneumonia and sepsis were the most common infections in period A, whereas pneumonia and other respiratory tract infections were the most common in period B. Antimicrobials were commonly prescribed for documented infection (38%) during period A and empiric therapy (47%) during period B. Cefazolin, cefuroxime, vancomycin, and gentamicin were the commonly used antimicrobials during both periods. Inappropriate antimicrobial use ranged from 16.7% to 61.9%, depending on assessors and surveillance period. The most common reasons for inappropriate use were overly broad spectrum, wrong dosage, and unwarranted overlap of spectrum.

Conclusions: There was a high prevalence of antimicrobial use in CCCU-PICU patients. Because a significant proportion of antimicrobial use was deemed inappropriate, interventions are required to optimize antimicrobial use in critically ill children.
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http://dx.doi.org/10.1097/PCC.0b013e31828a846dDOI Listing
July 2013