THE EFFECT OF ANTITUMOR DRUGS ON THE COURSE OF TUBERCULOSIS IN THE EXPERIMENT

DOI: https://doi.org/10.29296/24999490-2023-02-04

G.G. Kudriashov(1), T.I. Vinogradova(1), Yu.G. Zmitrichenko(2), M.Z. Dogonadze1, N.V. Zabolotnyh(1), M.E. Dyakova(1),
D.S. Esmedlyaeva(1), P.V. Gavrilov(1), A.A. Azarov(1), G.V. Tochilnikov(2), A.O. Nefedov(1), Yu.S. Krylova(1), P.K. Yablonskii(1, 3)
1-Saint-Petersburg State Research Institute of Phthisiopulmonology of the Ministry of Healthcare of the Russian Federation,
Ligovsky av., 2–4, St. Petersburg, 191036, Russian Federation;
2-N.N. Petrov National Medicine Research Center of oncology,
Leningradskaya str., 68, village Pesochny, St. Petersburg, 197758, Russian Federation;
3-Federal State Budgetary Educational Institution of Higher Education «Saint-Petersburg State University»,
Universitetskaya embankment, 7/9, Saint Petersburg, 199034, Russian Federation

Introduction. Lung cancer and tuberculosis, make a significant affect to the morbidity and mortality of the population in Russia and in the world. Strategy of medication therapy has not been developed for cases when these diseases are combined. The aim of the study was to investigate the effect of antitumor therapy on the course of pulmonary tuberculosis in an experiment. The research was supported by a grant from the Russian Science Foundation No. 22-15-00470 (https://rscf.ru/project/22-15-00470/) Material and methods. The study was performed on 109 mice of the C57BL/6 line at the age of two months. The animals were infected with the reference strain of Mycobacterium tuberculosis (MTB) H37Rv. Antitumor drugs (that used in the treatment regimens of non-small cell lung cancer) were injected intraperitoneally in monotherapy mode. 10 groups were formed: 1 – intact mice 9 (n=10); 2 – mice infected with MTB, without treatment (n=19); 3 – mice infected with MBT + cisplatin injection 10 mg/kg (n=10); 4 – mice infected with MBT + carboplatin injection 100 mg/kg (n=10); 5 – mice infected with MTB + gemcitabine injection 300 mg/kg (n=10); 6 – mice infected with MTB + pemetrexed injection 167 mg/kg (n=10); 7 – mice infected with MTB + etoposide injection 40 mg/kg (n=10); 8 – mice, infected with MTB + paclitaxel injection 30 mg /kg (n=10); 9 – mice infected with MTB + docetaxel injection 30 mg/kg (n=10); 10 – mice infected with MTB + vinorelbin injection 10 mg/kg (n=10). Comparison of clinical, radiological, and laboratory parameters was performed using nonparametric statistics methods. The survival rate was analyzed using the Kaplan-Meyer method. Results. There was a decrease in body weight in all groups of mice infected with MTB compared to intact animals. The lowest body weight gain was observed in group 8, and the greatest increase in group 3. Infiltrative-focal changes in the lungs were detected during computed tomography less frequently in groups 3, 4, 9, 10 in comparison with the control (group 2). The lowest total lung lesion index was recorded in groups 10, 9 and 4 (less than in infection control group). In groups 3, 6, 7, 8 tuberculous lung lesions were more common than in group 2. The most common exudative changes were recorded in groups 3 and 7, and productive changes in groups 6 and 7. The highest level of mycobacterial load was recorded in the lungs of mice in group 7 after etoposide injection. Low survival was observed in groups 3, 5, 10. The highest survival rates were recorded in groups 4, 6, 8. Conclusion. The results of the complex analysis allow us to consider carboplatin and docetaxel as the most promising drugs for the treatment of malignant lung tumors in patients with combined pathology.
Keywords: 
coexistance of lung cancer and tuberculosis, experimental model, antitumor drugs, inflammatory response
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