Publications by authors named "Olga Deryabina"

5 Publications

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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

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

Betulin-3,28-diphosphate as a Component of Combination Cytostatic Drugs for the Treatment of Ehrlich Ascites Carcinoma In Vitro and In Vivo Experiments.

Sci Pharm 2018 Apr 23;86(2). Epub 2018 Apr 23.

Department of Pharmaceutical Chemistry, Federal State Budgetary Educational Institution of Higher Education "Privolzhsky Research Medical University", Ministry of Health of the Russian Federation, Minin sq., 10/1, 603005 Nizhny Novgorod, Russia.

The activity of betulin-3,28-diphosphate (BDP) in combination with the cytostatics such as 5-fluorouracil (5-FU) and hydrazine sulfate (HS) was demonstrated by using the transplanted Ehrlich ascites carcinoma (EAC) in mice. The dose-dependent effect of combination drugs BDP + HS and BDP + 5-FU was revealed by in vitro experiments on rats. The synergetic effect of HS and BDP on oxidative stress and energy metabolism was established. The malonic dialdehyde (MDA) level both in plasma and erythrocytes decreased by 87 ± 2%, and the superoxide dismutase (SOD) activity increased by 105 ± 7% in comparison with the control. The combination of BDP + HS promoted the increase of lactate dehydrogenase (LDH) activity in the reverse reaction by 195 ± 21% compared to the control. The combination drug of 5-FU with BDP caused the synergetic decrease of the lipid peroxidation (LPO) intensity estimated by the MDA level decrease up to 14 ± 4% compared to pure compounds. Betulin-3,28-diphosphate in combination with cytostatics for EAC treatment improved the animal health status, as well as decreased the cytostatics dose that can be used in palliative therapy.
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http://dx.doi.org/10.3390/scipharm86020017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6027669PMC
April 2018