medalphabetМедицинский алфавитMedical alphabet2078-56312949-2807ООО «Альфмед»10.33667/2078-5631-2021-6-19-22medalphabet-2001Research ArticleСтатьиНарушение метаболизма в лизосомах при онкопатологии как маркер нутриционного прогнозаDisorders of metabolism in lysosomes in oncopathology as marker of nutritional prognosishttps://orcid.org/0000-0002-2305-0671ВарванинаГ. Г.VarvaninaG. G.

Варванина Галина Григорьевна , д.м.н., с.н.с. лаборатории научно-диагностических исследований

SPIN-код 8280-4152

Varvanina Galina G., DM Sci, senior researcher at Laboratory of Scientific and Diagnostic Research 

Moscow

https://orcid.org/0000-0003-3084-7563КостюченкоЛ. Н.KostyuchenkoL. N.

Костюченко Людмила Николаевна, д.м.н., проф., акад. РАЕ, рук. лаборатории нутрициологии 

Kostyuchenko Lyudmila N., DM Sci, prof., acad. of RAE, head of Laboratory of Nutritional Science 

Moscow

l.kostyuchenko@mknc.ruГБУЗ «Московский клинический научно-практический центр имени А.С. Логинова Департамента здравоохранения Москвы»РоссияMoscow Clinical Scientific and Practical Centre n.a. A.S. LoginovRussian Federation20210706202116Практическая гастроэнтерология (1)1922Copyright © Варванина Г.Г., Костюченко Л.Н., 20212021Варванина Г.Г., Костюченко Л.Н.Varvanina G.G., Kostyuchenko L.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-alphabet.com/jour/article/view/2001

При онкопатологии роль катепсина L в протеолизе изучена недостаточно, в частности его связь с нутриционным статусом и нутриционным прогнозом.Цель исследования. Определить эффект нарушенного метаболизма в лизосомах и его связь с развитием нутриционной недостаточности.Материал и методы. В исследование включено 56 больных (36 с КРР и 20 с раком ПЖ), контрольную группу составили 14 человек. В сыворотке крови определяли катепсин L, цистатин С, ретинолсвязывающий белок (РСБ-4), преальбумин методом ELISA. Статистический анализ проводили по критерию Манна–Уитни. Результаты представляли в виде медианы (интерквартильный диапазон). Достоверность различий считали существенной при p < 0,05.Результаты. Выявлено, что динамика изменения маркеров эпидермально-мезенхимального перехода свидетельствует о повышении уровня цистатина С (ингибитора катепсинов), снижении уровня РСБ во взаимосязи с катепсином L, что в последующем отражается в снижении уровня преальбумина (маркера соматической протеиновой недостаточности). Катепсин L в комплексе с РСБ определяет один из механизмов развития нутритивной недостаточности и может ее прогнозировать.Вывод. Определение в комплексе РСБ, катепсина L и преальбумина может служить ранним прогностическим маркером нутритивной недостаточности.

With oncopathology, the role of Katepsin L in proteolysis is not sufficiently studied, in particular, its connection with the nutritional status and the nutritional forecast.The purpose of the study. To determine the effect of impaired metabolism in lysosomes and its connection with the development of nutritional failure.Material and methods. The study includes 156 patients (65 with pancreatic cancer, 69 with СP). In the serum, MMP-9, TIMP-1 and GC were determined by the ELISA method. Statistical analysis was carried out by the criterion of Mann–Whitney. The results were presented in the form of medians (intercomdlic range). The reliability of differences was considered essential at p < 0.05.Results. It was revealed that the dynamics of changes in the epidermal-mezenchymal transition markers indicates an increase in the level of cystatin C (inhibitor of cathepsins), a decrease in the level of RSB in relations with the Catencin L, which is subsequently reflected in the reduction of the level of prehalet (marker of somatic protein deficiency). Cathepsin L in the complex with RSB determines one of the mechanisms for the development of nutritional failure and can predict it.Conclusions. The definition in the colprix of the RSB, cathepsin L and prehaletbin can serve as an early prognostic marker of nutritional insufficiency.

нутриционный прогнозлизосомыонкопатологиядиагностикаnutrition forecastlysosomesoncopathologydiagnosticsReferencesBray, F., Ferlay, J., Soerjomataram, I., Siegel, R.L., Torre, L.A. and Jemal, A. (2018) Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 68, 394–424. https://doi.org/10.3322/caac.21492.Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R.L., Torre, L.A. and Jemal, A. (2018) Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 68, 394–424. https://doi.org/10.3322/caac.21492.Lankelma J. M., Voorend D. M. Barwari T. et al Cathepsin L, target in cancer treatment? Life Sciences, Volume 86, Issues 7–8, 2010, Pages 225–2333.Lankelma J. M., Voorend D. M. Barwari T. et al Cathepsin L, target in cancer treatment? Life Sciences, Volume 86, Issues 7–8, 2010, Pages 225–2333.Cairns RA, Khokha R, Hill RP. Molecular mechanisms of tumor invasion and metastasis: an integrated view. Current Molecular Medicine 3 (7), 659–671, 2003.Cairns RA, Khokha R, Hill RP. Molecular mechanisms of tumor invasion and metastasis: an integrated view. Current Molecular Medicine 3 (7), 659–671, 2003.Gocheva V, Zeng W, Ke D, Klimstra D, Reinheckel T, Peters C, Hanahan D, Joyce JA. Distinct roles for cysteine cathepsin genes in multistage tumorigenesis. Genes & Development 20 (5), 543–556, 2006.Gocheva V, Zeng W, Ke D, Klimstra D, Reinheckel T, Peters C, Hanahan D, Joyce JA. Distinct roles for cysteine cathepsin genes in multistage tumorigenesis. Genes & Development 20 (5), 543–556, 2006.Vidak E, Javoršek U, Vizovišek M, Turk B. Cysteine Cathepsins and their Extracellular Roles: Shaping the Microenvironment. Cells. 2019; 8 (3): 264. Published 2019 Mar 20. DOI: 10.3390/cells8030264.Vidak E, Javoršek U, Vizovišek M, Turk B. Cysteine Cathepsins and their Extracellular Roles: Shaping the Microenvironment. Cells. 2019; 8 (3): 264. Published 2019 Mar 20. DOI: 10.3390/cells8030264.Костюченко Л. Н. Детоксикационная алиментация паллиативных больных онкологического профиля Медицинский алфавит. Практическая гастроэнтерология, № 17, 2020, с. 15–25. Kostyuchenko L. N. Detoxification alimentation of palliative cancer patients Medical Alphabet. Practical gastroenterology, No. 17, 2020, p. 15–25.Костюченко Л. Н. Детоксикационная алиментация паллиативных больных онкологического профиля Медицинский алфавит. Практическая гастроэнтерология, № 17, 2020, с. 15–25. Kostyuchenko L. N. Detoxification alimentation of palliative cancer patients Medical Alphabet. Practical gastroenterology, No. 17, 2020, p. 15–25.Костюченко Л. Н. Нутрициология в онкологии. Под ред. ЛН Костюченко, М., 2019, 319 с. Kostyuchenko L.N. Nutritionology in Oncology. Ed. L.N. Kostyuchenko, M., 2019, 319 p.Костюченко Л. Н. Нутрициология в онкологии. Под ред. ЛН Костюченко, М., 2019, 319 с. Kostyuchenko L.N. Nutritionology in Oncology. Ed. L.N. Kostyuchenko, M., 2019, 319 p.Kramer L., Turk D., Turk B., The Future of Cysteine Cathepsins in Disease Management, Trends in Pharmacological Sciences, Volume 38, Issue 10, 2017, Pages 873–898.Kramer L., Turk D., Turk B., The Future of Cysteine Cathepsins in Disease Management, Trends in Pharmacological Sciences, Volume 38, Issue 10, 2017, Pages 873–898.Yadati, Tulasi et al. The Ins and Outs of Cathepsins: Physiological Function and Role in Disease Management. Cells, Vol. 9, 7 16–79. 13 Jul. 2020, DOI: 10.3390/cells9071679.Yadati, Tulasi et al. The Ins and Outs of Cathepsins: Physiological Function and Role in Disease Management. Cells, Vol. 9, 7 16–79. 13 Jul. 2020, DOI: 10.3390/cells9071679.Mori, Jinichi et al. Cystatin C as a p53-inducible apoptotic mediator that regulates cathepsin L activity. Cancer Science, Vol. 107, 3 (2016): 298–306. DOI: 10.1111/cas.12881.Mori, Jinichi et al. Cystatin C as a p53-inducible apoptotic mediator that regulates cathepsin L activity. Cancer Science, Vol. 107, 3 (2016): 298–306. DOI: 10.1111/cas.12881.Zhang M, Caragine T, Wang H et al. Spermine inhibits proinflammatory cytokine synthesis in human mononuclear cells: a counterregulatory mechanism that restrains the immune response. J Exp Med 1997; 185: 1759–68.Zhang M, Caragine T, Wang H et al. Spermine inhibits proinflammatory cytokine synthesis in human mononuclear cells: a counterregulatory mechanism that restrains the immune response. J Exp Med 1997; 185: 1759–68.Ray S, Lukyanov P, Ochieng J. Members of the cystatin superfamily interact with MMP-9 and protect it from autolytic degradation without affecting its gelatinolytic activities. Biochim Biophys Acta 2003; 1652 (2): 91–102.Ray S, Lukyanov P, Ochieng J. Members of the cystatin superfamily interact with MMP-9 and protect it from autolytic degradation without affecting its gelatinolytic activities. Biochim Biophys Acta 2003; 1652 (2): 91–102.Zi M., Xu Y. Involvement of cystatin C in immunity and apoptosis. Immunology letters. 2018. 196, 80–90. https://doi.org/10.1016/j.imlet.2018.01.006Zi M., Xu Y. Involvement of cystatin C in immunity and apoptosis. Immunology letters. 2018. 196, 80–90. https://doi.org/10.1016/j.imlet.2018.01.006Kos J, Krasovec M, Cimerman N, Nielsen HJ, Christensen IJ, Brunner N. Cysteine proteinase inhibitors stefin A, stefin B, and cystatin C in sera from patients with colorectal cancer: relation to prognosis. Clin Cancer Res 2000; 6 (2): 505–11.Kos J, Krasovec M, Cimerman N, Nielsen HJ, Christensen IJ, Brunner N. Cysteine proteinase inhibitors stefin A, stefin B, and cystatin C in sera from patients with colorectal cancer: relation to prognosis. Clin Cancer Res 2000; 6 (2): 505–11.Yadati, Tulasi et al. The Ins and Outs of Cathepsins: Physiological Function and Role in Disease Management. Cells, Vol. 9, 71679. 13 Jul. 2020, DOI: 10.3390/cells9071679.Yadati, Tulasi et al. The Ins and Outs of Cathepsins: Physiological Function and Role in Disease Management. Cells, Vol. 9, 71679. 13 Jul. 2020, DOI: 10.3390/cells9071679.Greer Julia B et al. “Nutrition and Inflammatory Biomarkers in Chronic Pancreatitis Patients. Nutrition in clinical practice: official publication of the American Society for Parenteral and Enteral Nutrition. Vol. 34, 3 (2019): 387–399. DOI: 10.1002/ncp.10186.Greer Julia B et al. “Nutrition and Inflammatory Biomarkers in Chronic Pancreatitis Patients. Nutrition in clinical practice: official publication of the American Society for Parenteral and Enteral Nutrition. Vol. 34, 3 (2019): 387–399. DOI: 10.1002/ncp.10186.Wang Fuchan et al. Retinol-binding protein 4 regulates the biological functions and molecular mechanisms of JEG-3 cells. International Journal of Clinical and Experimental Pathology, Vol. 11, 12. 5877–5884. 1 Dec. 2018.Wang Fuchan et al. Retinol-binding protein 4 regulates the biological functions and molecular mechanisms of JEG-3 cells. International Journal of Clinical and Experimental Pathology, Vol. 11, 12. 5877–5884. 1 Dec. 2018.Винокурова Л. В., Лесько К. А., Бордин Д. С., Дубцова Е. А., Тюляева Е. Ю., Варванина Г. Г. Роль ретинол-связывающего белка в дифференциальной диагностике рака поджелудочной железы. Эффективная фармакотерапия. 2020. Т. 16. № 24. С. 20–26. Vinokurova L. V., Lesko K. A., Bordin D. S., Dubtsova E. A., Tyulyaeva E. Yu., Varvanina G. G. The role of retinol-binding protein in the differential diagnosis of pancreatic cancer. Effective Pharmacotherapy. 2020. Vol. 16. No. 24. P. 20–26.Винокурова Л. В., Лесько К. А., Бордин Д. С., Дубцова Е. А., Тюляева Е. Ю., Варванина Г. Г. Роль ретинол-связывающего белка в дифференциальной диагностике рака поджелудочной железы. Эффективная фармакотерапия. 2020. Т. 16. № 24. С. 20–26. Vinokurova L. V., Lesko K. A., Bordin D. S., Dubtsova E. A., Tyulyaeva E. Yu., Varvanina G. G. The role of retinol-binding protein in the differential diagnosis of pancreatic cancer. Effective Pharmacotherapy. 2020. Vol. 16. No. 24. P. 20–26.

The authors declare that there are no conflicts of interest present.