Publications by authors named "Irina Suslova"

3 Publications

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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