Abstract
Aim of the study. The possibility of using antitumor drugs against the background of active tuberculosis is an unresolved problem of modern medicine. The aim of the experimental study was to study the course of tuberculosis infection against the background of antitumor therapy for lung cancer and combined antitumor and anti-tuberculosis chemotherapy.
Material and methods. The study was conducted on two-month-old C57BL/6 mice infected by intravenous injection of the reference strain Mycobacterium tuberculosis H37Rv. On the third day after infection, antitumor drugs (isoniazid, rifampicin, pyrazinamide and ethambutol) and/or a combination of anti-tuberculosis and antitumor drugs were given out. There were 2 control groups (infection control and control of anti-tuberculosis therapy) and 14 experimental groups (in dependence of antitumor drugs of cisplatin, carboplatin, gemcitabine, pemetrexed, etoposide, paclitaxel and docetaxel). Clinical, laboratory, bacteriological, morphological and morphometric parameters, and mortality were evaluated. Nonparametric methods of medical statistics were used.
Results. The isolated use of cisplatin, etoposide and docetaxel led to an increase in the mortality of experimental animals compared with infection control. However, there were no differences in survival between the experimental and control groups in the groups of combined use of antitumor (ATT) and anti-tuberculosis (ATBT) drugs. The combination of ATBT and gemcitabine was accompanied by a significantly lower level of inflammatory response (decreased activity of ceruloplasmin). The maximum inflammatory response was recorded with a combination of ATBT and pemetrexed, which was expressed in an increase in the activity of elastase, transaminases and ADA-1. There was a decrease in the intensity of MTB reproduction in all groups of combined therapy when comparing ATT with a combination of ATT +ATBT. It should be noted that the complete elimination of MTB was achieved only with the combination of ATBT with gemcitabine and etoposide.
Conclusion. The combination of anti-tuberculosis therapy with antitumor drugs does not reliably lead to a fatal progression of the infectious process in the lungs and in some cases makes it possible to achieve complete suppression of the reproduction of Mycobacterium tuberculosis. The most promising schemes of antitumor therapy in conditions of active tuberculosis infection are schemes using carboplatin and gemcitabine, taking into account low mortality, lower toxicity and better effect of anti-tuberculosis therapy against the background of combined use
Keywords
Authors and affiliations
G.G. Kudryashov(1), T.I. Vinogradova(1), Yu.G. Zmitrichenko(2), Yu.S. Krylova(1), M.Z. Dogonadze(1), N.V. Zabolotnyh(1),
M.E. Dyakova(1), D.S. Esmedlyaeva(1), G.V. Tochilnikov2, A.O. Nefedov(1), G.M. Agafonov(1, 3), P.K. Yablonskiy(1, 3)
1-Saint-Petersburg State Research Institute of Phthisiopulmonology of the Ministry of Healthcare of the Russian Federation,
Ligovskiy ave., 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 emb., 7/9, Saint Petersburg, 199034, Russian Federation
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