EFFECTIVENESS AND SAFETY OF CARBOPLATIN-CONTAINING ANTITUMOR THERAPY REGIMENS IN A MODEL OF COEXISTANCE OF LUNG CARCINOMA AND TUBERCULOSIS

DOI: https://doi.org/10.29296/24999490-2024-01-05

G.G. Kudriashov(1), Yu.G. Zmitrichenko(2), T.I. Vinogradova(1), M.Z. Dogonadze(1), N.V. Zabolotnyh(1),
M.E. Dyakova(1), D.S. Esmedlyaeva(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. Treatment of the coexistent pathology of lung cancer and tuberculosis remains the prerogative of experimental research, since the optimal treatment strategy for the coexistence of these two diseases has not yet been developed. The purpose was to study the effectiveness and safety of carboplatin-containing antitumor therapy regimens in combination with anti-tuberculosis chemotherapy. Material and methods. The study was conducted on 64 C57BL/6 mice aged two months with a previously modeled coexistant pathology of lung carcinoma and tuberculosis. Depending on the therapy, 4 groups were formed: 1 – control without treatment (n=16), 2 – antitumor (carboplatin + paclitaxel) + antituberculosis therapy (n=16), 3 – antitumor (carboplatin + pemetrexed) + antituberculosis therapy (n=16), 4 – antitumor (carboplatin + gemcitabine) + anti-tuberculosis therapy (n=16). The anti-tuberculosis therapy regimen included the administration of isoniazid, rifampicin, pyrazinamide and ethambutol. The antitumor effect (tumor growth index, tumor growth inhibition), antituberculosis effect (CFU per lung weight), toxicity (clinical blood test parameters, biometric indicators of internal organs), and survival were assessed. Statistical processing was carried out using non-parmetric statistics methods. Results. The lowest average body weight was recorded in group 4 from 7 to 21 days. The greatest differences between groups in the volume of the tumor node were observed from 12 to 16 days of the experiment under the influence of antitumor drugs. At the same time, the greatest inhibition of tumor growth was observed in group 4. On day 9 in group 2 there were signs of the myelo-immunosuppressive effect of antitumor therapy in the form of a decrease in the concentration of leukocytes, lymphocytes and monocytes. In the study groups, there were no statistically significant differences in the survival rate of the experimental and control groups. In all experimental groups, significantly lower spleen MC values were recorded, and in group 4, significantly lower liver MC values were also recorded. The highest level of mycobacterial load was recorded in the control group. The lowest CFU per lung weight was found in the carboplatin and gemcitabine treatment group. Conclusion. Carboplatin-containing chemotherapy regimens for lung carcinoma in tuberculosis-infected mice have both antitumor and antituberculosis effects. The most pronounced antimycobacterial activity was recorded when using a combination of antituberculosis therapy with carboplatin and gemcitabine.
Keywords: 
coexistance of lung cancer and tuberculosis, experimental model, carboplatin-containing antitumor therapy regimens, inflammatory response
Список литературы: 
  1. Крылова Ю.С., Кудряшов Г.Г., Нефедов А.О., Дохов М.А., Захарченко А.О., Яблонский П.К. Сигнальные молекулы опухолевой трансформации при туберкулезе. Молекулярная медицина. 2022; 20 (6): 12–5. https://doi.org/10.29296/24999490-2022-06-02
  2. [Krylova Yu.S., Kudriashov G.G., Nefedov A.O., Dokhov M.A., Zakharchenko A.O., Yablonskii P.K. Signaling molecules of tumor transformation in tuberculosis. Molekulyarnaya meditsina. 2022; 20 (6): 12–5 (in Russian). https://doi.org/10.29296/24999490-2022-06-02]
  3. Кудряшов Г.Г., Нефедов А.О., Точильников Г.В., Змитриченко Ю.Г., Крылова Ю.С., Догонадзе М.З., Заболотных Н.В., Дьякова М.Е., Эсмедляева Д.С., Витовская М.Л., Гаврилов П.В., Азаров А.А., Журавлев В.Ю., Виноградова Т.И., Яблонский П.К. Оригинальная экспериментальная модель туберкулеза и рака легкого. Педиатр. 2022: 13 (5): 33–42. DOI: https://doi.org/10.17816/PED13533-42
  4. [Kudrjashov G.G., Nefedov A.O., Tochil’nikov G.V., Zmitrichenko Ju.G., Krylova Ju.S., Dogonadze M.Z., Zabolotnyh N.V., D’jakova M.E., Jesmedljaeva D.S., Vitovskaja M.L., Gavrilov P.V., Azarov A.A., Zhuravlev V.Ju., Vinogradova T.I., Jablonskij P.K. Original’naja jeksperimental’naja model’ tuberkuleza i raka legkogo. Pediatr. 2022: 13 (5): 33–42 (in Russian). DOI: https://doi.org/10.17816/PED13533-42]
  5. Кудряшов Г.Г., Виноградова Т.И., Змитриченко Ю.Г., Догонадзе М.З., Заболотных Н.В., Дьякова М.Е., Эсмедляева Д.С., Гаврилов П.В., Азаров А.А., Точильников Г.В., Нефедов А.О., Крылова Ю.С., Яблонский П.К. Влияние противоопухолевых препаратов на течение туберкулеза в эксперименте. Молекулярная медицина. 2023; 21 (2): 25–32. https://doi.org/10.29296/24999490-2023-02-04
  6. [Kudrjashov G.G., Vinogradova T.I., Zmitrichenko Ju.G., Dogonadze M.Z., Zabolotnyh N.V., D’jakova M.E., Jesmedljaeva D.S., Gavrilov P.V., Azarov A.A., Tochil’nikov G.V., Nefedov A.O., Krylova Ju.S., Jablonskij P.K. Vlijanie protivoopuholevyh preparatov na techenie tuberkuleza v jekspe-rimente. Molekuljarnaja medicina. 2023; 21 (2): 25–32 (in Russian). https://doi.org/10.29296/24999490-2023-02-04]
  7. Вершинина С. Ф., Стуков А. Н. Экспериментальные опухоли: Практическое руководство. СПб.: Изд-во Галаника, 2018
  8. [Vershinina S. F., Stukov A. N. Jeksperimental’nye opuholi: Prakticheskoe rukovodstvo. SPb.: Izd-vo Galanika, 2018 (in Russian)]
  9. Стуков А. Н., Иванова М. А., Никитин А. К., Сорокин Г. М., Коньков С. А. Индекс роста опухоли как интегральный критерий эффективности противоопухолевой терапии в эксперименте. Вопросы онкологии. 2001; 47 (5): 616–8.
  10. [Stukov A. N., Ivanova M. A., Nikitin A. K., Sorokin G. M., Kon’kov S. A. Indeks rosta opuholi kak integral’nyj kriterij jeffektivnosti protivoopuholevoj terapii v jeksperimente. Voprosy onkologii. 2001; 47 (5): 616–8 (in Russian)]