Publications by authors named "Tatiana Demura"

3 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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November 2020

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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May 2019

Structural, immunohistochemical and molecular features of placentas and placental sites after in vitro fertilization with donor eggs (surrogate motherhood).

Eur J Obstet Gynecol Reprod Biol 2019 Jul 13;238:68-72. Epub 2019 May 13.

Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya str. 8, bld.2, 119991, Moscow, Russian Federation.

Objective: to identify structural, immunohistochemical and molecular features of placentas and placental sites afterin vitro fertilization (IVF) with donor eggs (surrogate motherhood).

Study Design: morphological and immunohistochemical studies were performed on placental material obtained after delivery by caesarean section. The study included 26 women patients whose pregnancy resulted from IVF with a donor egg (IVF-SM group). The comparison group included 13 women patients whose pregnancy occurred after IVF with their own eggs (IVF-OE). Immunohistochemistry of biopsy material was performed using mouse antibodies to total cytokeratin (clone AE1/AE3) and murine antibodies to HLA-DR (clone TAL.1B5). Molecular studies were performed on DNA samples isolated from venous blood. HLA-DNA-TEH reagent kits and polymerase chain reaction were used for genotyping the main human histocompatibility complex class II (DQA1, DQB1 and DRB1).

Results: Histological examination of placenta in IVF-SM group showed a high incidence of central ischemic infarctions (69% of cases), dissociated cotyledon development (61%), pathological villus immaturity (46%) and massive perivillous fibrin deposition (73%). This group also had a pronounced lymphoplasmacytic deciduitis, which was 2 times higher than in the control group, and an expressed inflammatory process in the placental sites. Remodeling of the spiral arteries was incomplete in more than 40% of cases, and 30% of spiral arteries had no gestational changes. In comparison group, a complete gestational adjustment was found in more than 90% of spiral arteries. A focal lymphohistiocytic infiltration in perivascular regions, and a decrease in the number of multinucleated cells as compared with the control were also observed. For seven female surrogate mothers and their children, allelic polymorphisms of genes of HLA II class were studied.

Conclusion: Placental material of women from IVF-SM group is characterized by complex immune response in sites of tight contact between maternal and fetal tissues. The immune pathogenesis is associated with an increase in the number of HLA-DR positive cells, defects in remodeling of the spiral arteries, development of areas of chronic inflammation in perivascular regions, and a decrease in the number of multinucleated cells. Genetic incompatibility between alleles of HLA II genes can be a molecular predictor of impaired immune tolerance.
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July 2019