Background: The possible involvement of p53 signaling, FGFR3 expression, and FGFR3 mutation rates in the prediction of the NMIBC anti-PD-L1 treatment response needs to be clarified. The main aim of our study was to explore predictive value of p53 expression, FGFR3 expression, and its gene mutation status for the therapeutic success of anti-PD-L1 treatment in the patient-derived murine model of recurrent high-PD-L1(+) GATA3(-)/CR5/6(-) high-grade and low-grade NMIBC. Methods: twenty lines of patient-derived xenografts (PDXs) of relapsed high-PD-L1(+) double-negative NMIBC were developed, of which 10 lines represented high-grade tumors and the other ones—low-grade bladder cancer. Acceptors of each grade-related branch received specific anti-PD-L1 antibodies. Animals’ survival, tumor-doubling time, and remote metastasis were followed during the post-interventional period. PD-L1, GATA3, CR5/6, and p53 protein expressions in engrafted tumors were assessed by immunohistochemistry. The FGFR3 expression and FGFR3 mutations in codons 248 and 249 were detected by real-time polymerase chain reaction. Results: The expression of p53 protein is an independent factor affecting the animals’ survival time [HR = 0.036, p = 0.031] of anti-PD-L1-treated mice with low-grade high-PD-L1(+) double-negative NMIBC PDX. The FGFR3 expression and FGFR3 mutation rate have no impact on the anti-PD-L1 treatment response in the interventional groups. Conclusions: p53 expression may be considered as a prognostic factor for the anti-PD-L1 treatment efficacy of low-grade high-PD-L1-positive GATA3(-)/CR5/6(-)-relapsed noninvasive bladder cancer.

The aim of the study was to carry out a comparative morphological and immunohistochemical analysis of peripheral non-small cell lung cancer, which served as a source of a xenograft tumor, and tissues of the third generation of a tumor that developed in animals.Material and methods. We used 19 athymic BALB/c nu/nu mice, which were intraperitoneally injected with 1×106 CD8+ after sublethal irradiation in accordance with the humanization protocol. The transplantation of a tumor obtained from a 64-year-old patient was carried out three times consecutively. Samples of the original and xenograft tumors were automatically stained with hematoxylin and eosin, rabbit anti-CK7, anti-TTF, and anti-Ki67 antibodies. The evaluation of histological samples was carried out in accordance with the WHO recommendations (2015).Results. It has been established that a third-generation tumor developing in the body of athymic humanized mice retains the morphological and immunohistochemical features of the patient's original tumor. The described approach may be used in preclinical and personalized studies in fundamental pharmacology and molecular oncology.

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Introduction: The study aim was to explore a toxicological property and antitumor action of the novel pyridine derivative LHT-17-19 in cell culture and on experimental models of lung cancer in mice. Materials and methods: The study was performed on male and female ICR(CD-1), male BALB/c, male BALB/c nu/nu mice. Pyridine derivative (LHT-17-19) was studied as water-soluble pharmaceutical substance. Acute toxicity was evaluated in groups of 5 animals, and the results were analyzed by Finney. Antitumor and antimetastatic activity was studied in syngeneic and xenograft models of lung cancer in mice. Results and discussion: LHT-17-19 belongs to class 3 of the toxicity classification of chemicals in accordance with GOST 12.1.007–76. The substance demonstrated an antitumor and antimetastatic property in mice with syngeneic tumor Lewis lung carcinoma as well as on the heterotopic tumor model of non-small cell lung cancer in humanized animals. Conclusion: LHT-17-19 belongs to class 3 of the toxicity classification of chemicals in accordance with WHO recommendation. LHT-17-19 exerts antitumor and antimetastatic property on both syngeneic and patient-derived lung cancer xenograft murine models. Graphical abstract