Материалы доступны только для специалистов сферы здравоохранения. Авторизуйтесь или зарегистрируйтесь.
Патогенетические особенности повреждения слизистой оболочки пищевода при гастроэзофагеальной рефлюксной болезни
Патогенетические особенности повреждения слизистой оболочки пищевода при гастроэзофагеальной рефлюксной болезни
Тарасова Г.Н., Смирнова Е.А. Патогенетические особенности повреждения слизистой оболочки пищевода при гастроэзофагеальной рефлюксной болезни. Consilium Medicum. 2017; 19 (8.2. Гастроэнтерология): 7–12. DOI: 10.26442/2075-1753_19.8.2.7-12
________________________________________________
Материалы доступны только для специалистов сферы здравоохранения. Авторизуйтесь или зарегистрируйтесь.
Аннотация
Цель – изучить протеомный паттерн и экспрессию Е-кадгерина в слизистой оболочке пищевода в зависимости от состава патологического гастроэзофагеального рефлюктата у больных с гастроэзофагеальной рефлюксной болезнью (ГЭРБ).
Материалы и методы. В проспективное исследование в параллельных группах включены больные с ГЭРБ – 39 пациентов с кислым и слабокислым характером рефлюктата и 25 – с щелочным и слабощелочным рефлюксом. Диагноз ГЭРБ верифицирован в соответствии со стандартным протоколом обследования. Проводилось протеомное и иммуногистохимическое исследование эзофагобиоптатов из дистальной части пищевода. Масс-спектры получали с помощью тандемного MALDI-TOF/TOF масс-спектрометра Ultraflex II (Bruker Daltonics, Германия). Идентификацию белков и пептидов проводили путем поиска соответствующих кандидатов в базах данных NCBI (National Center for Biotechnology Information) и Swiss-Prot/UniProt. иммуногистохимическое исследование эзофагобиоптатов осуществлялось стрептавидин-биотиновым методом с использованием моноклональных мышиных антител к Е-кадгерину (Dako, США). Для статистического анализа данных использовался пакет модулей программы Statistiсa 10.0 for Windows (StatSoft, США).
Результаты. У больных с ГЭРБ выделены и типированы девять протеинов, ответственных за формирование цитоскелета и пролиферацию эпителиоцитов, а также участвующих в сложных каскадах воспалительных процессов в слизистой оболочке пищевода. В группе пациентов с кислым характером рефлюктата дифференциально экспрессировались винкулин, кальпонин-1, цистатин C; с щелочным – белок-1, стимулируемый гипоксией, прихибитин-2, тиоредоксин. Выявлена тенденция к снижению экспрессии Е-кадгерина у пациентов с щелочным характером рефлюктата.
Заключение. Отличия в белковом профиле и экспрессии E-кадгерина патогенетически обосновывают содержание терапии ГЭРБ с учетом повреждающего характера патологического рефлюктата.
Ключевые слова: гастроэзофагеальная рефлюксная болезнь, протеомный анализ, белки межклеточных контактов, Е-кадгерин.
Materials and methods. This parallel group prospective study included patients with GERD – 39 patients with acidic and slightly acidic nature of reflux and 25 – with alkaline and slightly alkaline reflux. The diagnosis of GERD is verified in accordance with the standard survey protocol. Proteomic and immunohistochemical studies of biopsy from the distal esophagus were conducted. Mass spectra were obtained using a tandem MALDI-TOF/TOF Ultraflex II (Bruker Daltonics, Germany) mass spectrometer. Identification of proteins and peptides was carried out by searching for relevant candidates in the NCBI (National Center for Biotechnology Information) and Swiss-Prot/UniProt databases. Immunohistochemical study of biopsies was carried out by labeled streptavidin-biotin method using monoclonal mouse antibodies to E-cadherin (Dako, the USA). For statistical data analysis, the Statistis 10.0 for Windows (StatSoft, the USA) program package was used.
Results. Nine proteins responsible for the formation of the cytoskeleton and the proliferation of epithelial cells are identified and typed in patients with GERD. These proteins are involved in complicated cascades of inflammatory processes in the esophageal mucosa. In the group of patients with acidic character of refluxate were differentially expressed vinculin, calponin-1, cystatin C; with alkaline character – protein-1, which is stimulated by hypoxia, prihibitin-2, thioredoxin. The tendency to decrease of E-cadherin expression in patients with alkaline character of refluxate was revealed.
Conclusion. Differences in the protein profile and E-cadherin expression pathogenetically substantiate the content of GERD therapy, especially taking into account the damaging nature of pathological character of refluxate.
Key words: gastroesophageal reflux disease, proteomic analysis, proteins of intercellular contacts, E-cadherin.
Материалы и методы. В проспективное исследование в параллельных группах включены больные с ГЭРБ – 39 пациентов с кислым и слабокислым характером рефлюктата и 25 – с щелочным и слабощелочным рефлюксом. Диагноз ГЭРБ верифицирован в соответствии со стандартным протоколом обследования. Проводилось протеомное и иммуногистохимическое исследование эзофагобиоптатов из дистальной части пищевода. Масс-спектры получали с помощью тандемного MALDI-TOF/TOF масс-спектрометра Ultraflex II (Bruker Daltonics, Германия). Идентификацию белков и пептидов проводили путем поиска соответствующих кандидатов в базах данных NCBI (National Center for Biotechnology Information) и Swiss-Prot/UniProt. иммуногистохимическое исследование эзофагобиоптатов осуществлялось стрептавидин-биотиновым методом с использованием моноклональных мышиных антител к Е-кадгерину (Dako, США). Для статистического анализа данных использовался пакет модулей программы Statistiсa 10.0 for Windows (StatSoft, США).
Результаты. У больных с ГЭРБ выделены и типированы девять протеинов, ответственных за формирование цитоскелета и пролиферацию эпителиоцитов, а также участвующих в сложных каскадах воспалительных процессов в слизистой оболочке пищевода. В группе пациентов с кислым характером рефлюктата дифференциально экспрессировались винкулин, кальпонин-1, цистатин C; с щелочным – белок-1, стимулируемый гипоксией, прихибитин-2, тиоредоксин. Выявлена тенденция к снижению экспрессии Е-кадгерина у пациентов с щелочным характером рефлюктата.
Заключение. Отличия в белковом профиле и экспрессии E-кадгерина патогенетически обосновывают содержание терапии ГЭРБ с учетом повреждающего характера патологического рефлюктата.
Ключевые слова: гастроэзофагеальная рефлюксная болезнь, протеомный анализ, белки межклеточных контактов, Е-кадгерин.
________________________________________________
Materials and methods. This parallel group prospective study included patients with GERD – 39 patients with acidic and slightly acidic nature of reflux and 25 – with alkaline and slightly alkaline reflux. The diagnosis of GERD is verified in accordance with the standard survey protocol. Proteomic and immunohistochemical studies of biopsy from the distal esophagus were conducted. Mass spectra were obtained using a tandem MALDI-TOF/TOF Ultraflex II (Bruker Daltonics, Germany) mass spectrometer. Identification of proteins and peptides was carried out by searching for relevant candidates in the NCBI (National Center for Biotechnology Information) and Swiss-Prot/UniProt databases. Immunohistochemical study of biopsies was carried out by labeled streptavidin-biotin method using monoclonal mouse antibodies to E-cadherin (Dako, the USA). For statistical data analysis, the Statistis 10.0 for Windows (StatSoft, the USA) program package was used.
Results. Nine proteins responsible for the formation of the cytoskeleton and the proliferation of epithelial cells are identified and typed in patients with GERD. These proteins are involved in complicated cascades of inflammatory processes in the esophageal mucosa. In the group of patients with acidic character of refluxate were differentially expressed vinculin, calponin-1, cystatin C; with alkaline character – protein-1, which is stimulated by hypoxia, prihibitin-2, thioredoxin. The tendency to decrease of E-cadherin expression in patients with alkaline character of refluxate was revealed.
Conclusion. Differences in the protein profile and E-cadherin expression pathogenetically substantiate the content of GERD therapy, especially taking into account the damaging nature of pathological character of refluxate.
Key words: gastroesophageal reflux disease, proteomic analysis, proteins of intercellular contacts, E-cadherin.
Полный текст
Список литературы
1. Ивашкин, В.Т., Маев И.В., Трухманов А.С. и др. Клинические рекомендации Российской гастроэнтерологической ассоциации по диагностике и лечению гастроэзофагеальной рефлюксной болезни. Рос. журн. гастроэнтерологии, гепатологии, колопроктологии. 2017; 27 (4): 75–95. / Ivashkin, V.T., Maev I.V., Trukhmanov A.S. i dr. Klinicheskie rekomendatsii Rossiiskoi gastroenterologicheskoi assotsiatsii po diagnostike i lecheniiu gastroezofageal'noi refliuksnoi bolezni. Ros. zhurn. gastroenterologii, gepatologii, koloproktologii. 2017; 27 (4): 75–95. [in Russian]
2. Ивашкин В.Т., Маев И.В., Трухманов А.С. Пищевод Барретта. В 2 т. М.: Шико, 2011. / Ivashkin V.T., Maev I.V., Trukhmanov A.S. Pishchevod Barretta. V 2 t. M.: Shiko, 2011. [in Russian]
3. Трухманов А.С. Гастроэзофагеальная рефлюксная болезнь: клинические варианты, прогноз, лечение: Автореф. дис. … д-ра мед. наук. М., 2008. / Trukhmanov A.S. Gastroezofageal'naia refliuksnaia bolezn': klinicheskie varianty, prognoz, lechenie: Avtoref. dis. … d-ra med. nauk. M., 2008. [in Russian]
4. Jürgens S, Meyer F, Spechler SJ et al. The role of bile acids in the neoplastic progression of Barrett's esophagus – a short representative overview. Z Gastroenterol 2012; 50 (9): 1028–34.
5. Кайбышева В.О., Трухманов А.С., Сторонова О.А. и др. Морфофункциональные изменения в пищеводе при ГЭРБ в зависимости от характера. Клин. перспективы гастроэнтерологии, гепатологии. 2014; 5: 28–36. / Kaibysheva V.O., Trukhmanov A.S., Storonova O.A. i dr. Morfofunktsional'nye izmeneniia v pishchevode pri GERB v zavisimosti ot kharaktera. Klin. perspektivy gastroenterologii, gepatologii. 2014; 5: 28–36. [in Russian]
6. Cross FS, Wangensteen OH. Role of bile and pancreatic juice in production of oesophageal erosions and anaemia. Proc Soc Exp Biol Med 1951; 77: 862–6.
7. Gasiorowska A, Navarro-Rodriguez T. Comparison of the degree of duodenogastroesophageal reflux and acid reflux between patients who failed to respond and those who were successfully treated with a proton pump inhibitor once daily. Am J Gastroenterol 2009; 104 (8): 13.
8. Kunsch S, Linhart T, Fensterer H et al. Prevalence of a pathological DGER (duodeno-gastric-oesophageal reflux) in patients with c linical symptoms of reflux disease. Z Gastroenterol 2008; 46 (5): 409–14.
9. Nguyen DM et al. Medication usage and the risk of neoplasia in patients with Barrett’s esophagus. Clin Gastroenterol Hepatol 2009; 7: 1266–8.
10. Abdel-Latif MM, Inoue H, Kelleher D, Reynolds JV. Factors regulating nuclear factor-kappa B activation in esophageal cancer cells: Role of bile acids and acid. J Cancer Res Ther 2016; 12 (1): 364–73.
11. Björkman EV, Edebo A, Oltean M, Casselbrant A. Esophageal barrier function and tight junction expression in healthy subjects and patients with gastroesophageal reflux disease: functionality of esophageal mucosa exposed to bile salt and trypsin in vitro. Scand J Gastroenterol 2013; 48 (10): 1118–26.
12. Dabbs DJ. Diagnostic Immunohistochemistry. 3rd ed. New York: Ch. Livingstone, 2010.
13. Lifschitz-Mercer B, Czernobilsky B, Feldberg E. Expression of the adherens junction protein vinculin in human basal and squamous cell tumors: relationship to invasiveness and metastatic potential. Hum Pathol 1997; 28 (11): 1230–6.
14. Legendre C, Reen FJ, Woods DF. Bile acids repress hypoxia-inducible factor 1 signaling and modulate the airway immune response. Infect Immun 2014; 82 (9): 3531–41.
15. Phelan JP et al. Bile acids destabilise HIF-1a and promote anti-tumour phenotypes in cancer cell models. BMC Cancer 2016: 645–53.
16. Chetty R, Serra S. Nuclear E-cadherin immunoexpression: from biology to potential applications in diagnostic pathology. Advanc Anatom Pathol 2008; 15: 234–40.
17. Jankowski J, Newham P, Kandemir O. Differential expression of e-cadherin in normal, metaplastic and dysplastic esophageal mucosa – a putative biomarker. Int J Oncol 1994; 4 (2): 441–8.
18. Seery JP et al. Abnormal expression of the E-cadherin-catenin complex in dysplastic Barrett's oesophagus. Acta Oncol 1999; 38 (7): 945–8.
19. Swami S, Kumble S, Triadafilopoulos G. E-cadherin expression in gastroesophageal reflux disease, Barrett's esophagus, and esophageal adenocarcinoma: an immunohistochemical and immunoblot study. Am J Gastroenterol 1995; 90 (10): 1808–13.
20. Fein M, Fuchs KH, Freys SM et al. Is duodeno-gastro-esophageal reflux just a bystander of acid reflux? Zentralbl Chir 2002; 127 (12): 1068–72.
21. McQuaid KR, Laine L, Fennerty MB et al. Systematic review: the role of bile acids in the pathogenesis of gastro-oesophageal reflux disease and related neoplasia. Aliment Pharmacol Ther 2011; 34 (2): 146–65.
22. Лищук Н.Б., Симаненков В.И., Тихонов С.В. Дифференцированная терапия «некислых» форм гастроэзофагеальной рефлюксной болезни. Терапевтич. архив. 2017; 89 (4): 57–63. / Lishchuk N.B., Simanenkov V.I., Tikhonov S.V. Differentsirovannaia terapiia «nekislykh» form gastroezofageal'noi refliuksnoi bolezni. Terapevtich. arkhiv. 2017; 89 (4): 57–63. [in Russian]
23. Amaral JD, Viana RJ, Ramalho RM et al. Bile acids: regulation of apoptosis by ursodeoxycholic acid. J Lipid Res 2009; 50 (9): 1721–34.
2. Ivashkin V.T., Maev I.V., Trukhmanov A.S. Pishchevod Barretta. V 2 t. M.: Shiko, 2011. [in Russian]
3. Trukhmanov A.S. Gastroezofageal'naia refliuksnaia bolezn': klinicheskie varianty, prognoz, lechenie: Avtoref. dis. … d-ra med. nauk. M., 2008. [in Russian]
4. Jürgens S, Meyer F, Spechler SJ et al. The role of bile acids in the neoplastic progression of Barrett's esophagus – a short representative overview. Z Gastroenterol 2012; 50 (9): 1028–34.
5. Kaibysheva V.O., Trukhmanov A.S., Storonova O.A. i dr. Morfofunktsional'nye izmeneniia v pishchevode pri GERB v zavisimosti ot kharaktera. Klin. perspektivy gastroenterologii, gepatologii. 2014; 5: 28–36. [in Russian]
6. Cross FS, Wangensteen OH. Role of bile and pancreatic juice in production of oesophageal erosions and anaemia. Proc Soc Exp Biol Med 1951; 77: 862–6.
7. Gasiorowska A, Navarro-Rodriguez T. Comparison of the degree of duodenogastroesophageal reflux and acid reflux between patients who failed to respond and those who were successfully treated with a proton pump inhibitor once daily. Am J Gastroenterol 2009; 104 (8): 13.
8. Kunsch S, Linhart T, Fensterer H et al. Prevalence of a pathological DGER (duodeno-gastric-oesophageal reflux) in patients with c linical symptoms of reflux disease. Z Gastroenterol 2008; 46 (5): 409–14.
9. Nguyen DM et al. Medication usage and the risk of neoplasia in patients with Barrett’s esophagus. Clin Gastroenterol Hepatol 2009; 7: 1266–8.
10. Abdel-Latif MM, Inoue H, Kelleher D, Reynolds JV. Factors regulating nuclear factor-kappa B activation in esophageal cancer cells: Role of bile acids and acid. J Cancer Res Ther 2016; 12 (1): 364–73.
11. Björkman EV, Edebo A, Oltean M, Casselbrant A. Esophageal barrier function and tight junction expression in healthy subjects and patients with gastroesophageal reflux disease: functionality of esophageal mucosa exposed to bile salt and trypsin in vitro. Scand J Gastroenterol 2013; 48 (10): 1118–26.
12. Dabbs DJ. Diagnostic Immunohistochemistry. 3rd ed. New York: Ch. Livingstone, 2010.
13. Lifschitz-Mercer B, Czernobilsky B, Feldberg E. Expression of the adherens junction protein vinculin in human basal and squamous cell tumors: relationship to invasiveness and metastatic potential. Hum Pathol 1997; 28 (11): 1230–6.
14. Legendre C, Reen FJ, Woods DF. Bile acids repress hypoxia-inducible factor 1 signaling and modulate the airway immune response. Infect Immun 2014; 82 (9): 3531–41.
15. Phelan JP et al. Bile acids destabilise HIF-1a and promote anti-tumour phenotypes in cancer cell models. BMC Cancer 2016: 645–53.
16. Chetty R, Serra S. Nuclear E-cadherin immunoexpression: from biology to potential applications in diagnostic pathology. Advanc Anatom Pathol 2008; 15: 234–40.
17. Jankowski J, Newham P, Kandemir O. Differential expression of e-cadherin in normal, metaplastic and dysplastic esophageal mucosa – a putative biomarker. Int J Oncol 1994; 4 (2): 441–8.
18. Seery JP et al. Abnormal expression of the E-cadherin-catenin complex in dysplastic Barrett's oesophagus. Acta Oncol 1999; 38 (7): 945–8.
19. Swami S, Kumble S, Triadafilopoulos G. E-cadherin expression in gastroesophageal reflux disease, Barrett's esophagus, and esophageal adenocarcinoma: an immunohistochemical and immunoblot study. Am J Gastroenterol 1995; 90 (10): 1808–13.
20. Fein M, Fuchs KH, Freys SM et al. Is duodeno-gastro-esophageal reflux just a bystander of acid reflux? Zentralbl Chir 2002; 127 (12): 1068–72.
21. McQuaid KR, Laine L, Fennerty MB et al. Systematic review: the role of bile acids in the pathogenesis of gastro-oesophageal reflux disease and related neoplasia. Aliment Pharmacol Ther 2011; 34 (2): 146–65.
22. Lishchuk N.B., Simanenkov V.I., Tikhonov S.V. Differentsirovannaia terapiia «nekislykh» form gastroezofageal'noi refliuksnoi bolezni. Terapevtich. arkhiv. 2017; 89 (4): 57–63. [in Russian]
23. Amaral JD, Viana RJ, Ramalho RM et al. Bile acids: regulation of apoptosis by ursodeoxycholic acid. J Lipid Res 2009; 50 (9): 1721–34.
2. Ивашкин В.Т., Маев И.В., Трухманов А.С. Пищевод Барретта. В 2 т. М.: Шико, 2011. / Ivashkin V.T., Maev I.V., Trukhmanov A.S. Pishchevod Barretta. V 2 t. M.: Shiko, 2011. [in Russian]
3. Трухманов А.С. Гастроэзофагеальная рефлюксная болезнь: клинические варианты, прогноз, лечение: Автореф. дис. … д-ра мед. наук. М., 2008. / Trukhmanov A.S. Gastroezofageal'naia refliuksnaia bolezn': klinicheskie varianty, prognoz, lechenie: Avtoref. dis. … d-ra med. nauk. M., 2008. [in Russian]
4. Jürgens S, Meyer F, Spechler SJ et al. The role of bile acids in the neoplastic progression of Barrett's esophagus – a short representative overview. Z Gastroenterol 2012; 50 (9): 1028–34.
5. Кайбышева В.О., Трухманов А.С., Сторонова О.А. и др. Морфофункциональные изменения в пищеводе при ГЭРБ в зависимости от характера. Клин. перспективы гастроэнтерологии, гепатологии. 2014; 5: 28–36. / Kaibysheva V.O., Trukhmanov A.S., Storonova O.A. i dr. Morfofunktsional'nye izmeneniia v pishchevode pri GERB v zavisimosti ot kharaktera. Klin. perspektivy gastroenterologii, gepatologii. 2014; 5: 28–36. [in Russian]
6. Cross FS, Wangensteen OH. Role of bile and pancreatic juice in production of oesophageal erosions and anaemia. Proc Soc Exp Biol Med 1951; 77: 862–6.
7. Gasiorowska A, Navarro-Rodriguez T. Comparison of the degree of duodenogastroesophageal reflux and acid reflux between patients who failed to respond and those who were successfully treated with a proton pump inhibitor once daily. Am J Gastroenterol 2009; 104 (8): 13.
8. Kunsch S, Linhart T, Fensterer H et al. Prevalence of a pathological DGER (duodeno-gastric-oesophageal reflux) in patients with c linical symptoms of reflux disease. Z Gastroenterol 2008; 46 (5): 409–14.
9. Nguyen DM et al. Medication usage and the risk of neoplasia in patients with Barrett’s esophagus. Clin Gastroenterol Hepatol 2009; 7: 1266–8.
10. Abdel-Latif MM, Inoue H, Kelleher D, Reynolds JV. Factors regulating nuclear factor-kappa B activation in esophageal cancer cells: Role of bile acids and acid. J Cancer Res Ther 2016; 12 (1): 364–73.
11. Björkman EV, Edebo A, Oltean M, Casselbrant A. Esophageal barrier function and tight junction expression in healthy subjects and patients with gastroesophageal reflux disease: functionality of esophageal mucosa exposed to bile salt and trypsin in vitro. Scand J Gastroenterol 2013; 48 (10): 1118–26.
12. Dabbs DJ. Diagnostic Immunohistochemistry. 3rd ed. New York: Ch. Livingstone, 2010.
13. Lifschitz-Mercer B, Czernobilsky B, Feldberg E. Expression of the adherens junction protein vinculin in human basal and squamous cell tumors: relationship to invasiveness and metastatic potential. Hum Pathol 1997; 28 (11): 1230–6.
14. Legendre C, Reen FJ, Woods DF. Bile acids repress hypoxia-inducible factor 1 signaling and modulate the airway immune response. Infect Immun 2014; 82 (9): 3531–41.
15. Phelan JP et al. Bile acids destabilise HIF-1a and promote anti-tumour phenotypes in cancer cell models. BMC Cancer 2016: 645–53.
16. Chetty R, Serra S. Nuclear E-cadherin immunoexpression: from biology to potential applications in diagnostic pathology. Advanc Anatom Pathol 2008; 15: 234–40.
17. Jankowski J, Newham P, Kandemir O. Differential expression of e-cadherin in normal, metaplastic and dysplastic esophageal mucosa – a putative biomarker. Int J Oncol 1994; 4 (2): 441–8.
18. Seery JP et al. Abnormal expression of the E-cadherin-catenin complex in dysplastic Barrett's oesophagus. Acta Oncol 1999; 38 (7): 945–8.
19. Swami S, Kumble S, Triadafilopoulos G. E-cadherin expression in gastroesophageal reflux disease, Barrett's esophagus, and esophageal adenocarcinoma: an immunohistochemical and immunoblot study. Am J Gastroenterol 1995; 90 (10): 1808–13.
20. Fein M, Fuchs KH, Freys SM et al. Is duodeno-gastro-esophageal reflux just a bystander of acid reflux? Zentralbl Chir 2002; 127 (12): 1068–72.
21. McQuaid KR, Laine L, Fennerty MB et al. Systematic review: the role of bile acids in the pathogenesis of gastro-oesophageal reflux disease and related neoplasia. Aliment Pharmacol Ther 2011; 34 (2): 146–65.
22. Лищук Н.Б., Симаненков В.И., Тихонов С.В. Дифференцированная терапия «некислых» форм гастроэзофагеальной рефлюксной болезни. Терапевтич. архив. 2017; 89 (4): 57–63. / Lishchuk N.B., Simanenkov V.I., Tikhonov S.V. Differentsirovannaia terapiia «nekislykh» form gastroezofageal'noi refliuksnoi bolezni. Terapevtich. arkhiv. 2017; 89 (4): 57–63. [in Russian]
23. Amaral JD, Viana RJ, Ramalho RM et al. Bile acids: regulation of apoptosis by ursodeoxycholic acid. J Lipid Res 2009; 50 (9): 1721–34.
________________________________________________
2. Ivashkin V.T., Maev I.V., Trukhmanov A.S. Pishchevod Barretta. V 2 t. M.: Shiko, 2011. [in Russian]
3. Trukhmanov A.S. Gastroezofageal'naia refliuksnaia bolezn': klinicheskie varianty, prognoz, lechenie: Avtoref. dis. … d-ra med. nauk. M., 2008. [in Russian]
4. Jürgens S, Meyer F, Spechler SJ et al. The role of bile acids in the neoplastic progression of Barrett's esophagus – a short representative overview. Z Gastroenterol 2012; 50 (9): 1028–34.
5. Kaibysheva V.O., Trukhmanov A.S., Storonova O.A. i dr. Morfofunktsional'nye izmeneniia v pishchevode pri GERB v zavisimosti ot kharaktera. Klin. perspektivy gastroenterologii, gepatologii. 2014; 5: 28–36. [in Russian]
6. Cross FS, Wangensteen OH. Role of bile and pancreatic juice in production of oesophageal erosions and anaemia. Proc Soc Exp Biol Med 1951; 77: 862–6.
7. Gasiorowska A, Navarro-Rodriguez T. Comparison of the degree of duodenogastroesophageal reflux and acid reflux between patients who failed to respond and those who were successfully treated with a proton pump inhibitor once daily. Am J Gastroenterol 2009; 104 (8): 13.
8. Kunsch S, Linhart T, Fensterer H et al. Prevalence of a pathological DGER (duodeno-gastric-oesophageal reflux) in patients with c linical symptoms of reflux disease. Z Gastroenterol 2008; 46 (5): 409–14.
9. Nguyen DM et al. Medication usage and the risk of neoplasia in patients with Barrett’s esophagus. Clin Gastroenterol Hepatol 2009; 7: 1266–8.
10. Abdel-Latif MM, Inoue H, Kelleher D, Reynolds JV. Factors regulating nuclear factor-kappa B activation in esophageal cancer cells: Role of bile acids and acid. J Cancer Res Ther 2016; 12 (1): 364–73.
11. Björkman EV, Edebo A, Oltean M, Casselbrant A. Esophageal barrier function and tight junction expression in healthy subjects and patients with gastroesophageal reflux disease: functionality of esophageal mucosa exposed to bile salt and trypsin in vitro. Scand J Gastroenterol 2013; 48 (10): 1118–26.
12. Dabbs DJ. Diagnostic Immunohistochemistry. 3rd ed. New York: Ch. Livingstone, 2010.
13. Lifschitz-Mercer B, Czernobilsky B, Feldberg E. Expression of the adherens junction protein vinculin in human basal and squamous cell tumors: relationship to invasiveness and metastatic potential. Hum Pathol 1997; 28 (11): 1230–6.
14. Legendre C, Reen FJ, Woods DF. Bile acids repress hypoxia-inducible factor 1 signaling and modulate the airway immune response. Infect Immun 2014; 82 (9): 3531–41.
15. Phelan JP et al. Bile acids destabilise HIF-1a and promote anti-tumour phenotypes in cancer cell models. BMC Cancer 2016: 645–53.
16. Chetty R, Serra S. Nuclear E-cadherin immunoexpression: from biology to potential applications in diagnostic pathology. Advanc Anatom Pathol 2008; 15: 234–40.
17. Jankowski J, Newham P, Kandemir O. Differential expression of e-cadherin in normal, metaplastic and dysplastic esophageal mucosa – a putative biomarker. Int J Oncol 1994; 4 (2): 441–8.
18. Seery JP et al. Abnormal expression of the E-cadherin-catenin complex in dysplastic Barrett's oesophagus. Acta Oncol 1999; 38 (7): 945–8.
19. Swami S, Kumble S, Triadafilopoulos G. E-cadherin expression in gastroesophageal reflux disease, Barrett's esophagus, and esophageal adenocarcinoma: an immunohistochemical and immunoblot study. Am J Gastroenterol 1995; 90 (10): 1808–13.
20. Fein M, Fuchs KH, Freys SM et al. Is duodeno-gastro-esophageal reflux just a bystander of acid reflux? Zentralbl Chir 2002; 127 (12): 1068–72.
21. McQuaid KR, Laine L, Fennerty MB et al. Systematic review: the role of bile acids in the pathogenesis of gastro-oesophageal reflux disease and related neoplasia. Aliment Pharmacol Ther 2011; 34 (2): 146–65.
22. Lishchuk N.B., Simanenkov V.I., Tikhonov S.V. Differentsirovannaia terapiia «nekislykh» form gastroezofageal'noi refliuksnoi bolezni. Terapevtich. arkhiv. 2017; 89 (4): 57–63. [in Russian]
23. Amaral JD, Viana RJ, Ramalho RM et al. Bile acids: regulation of apoptosis by ursodeoxycholic acid. J Lipid Res 2009; 50 (9): 1721–34.
Авторы
Г.Н.Тарасова*, Е.А.Смирнова
ФГБОУ ВО «Ростовский государственный медицинский университет» Минздрава России. 344022, Россия, Ростов-на-Дону, Нахичеванский пер., д. 29
*doctor-gastro@yandex.ru
Rostov State Medical University of the Ministry of Health of the Russian Federation. 344022, Russian Federation, Rostov-on-Don, per. Nakhichevanskii, d. 29
*doctor-gastro@yandex.ru
ФГБОУ ВО «Ростовский государственный медицинский университет» Минздрава России. 344022, Россия, Ростов-на-Дону, Нахичеванский пер., д. 29
*doctor-gastro@yandex.ru
________________________________________________
Rostov State Medical University of the Ministry of Health of the Russian Federation. 344022, Russian Federation, Rostov-on-Don, per. Nakhichevanskii, d. 29
*doctor-gastro@yandex.ru
Цель портала OmniDoctor – предоставление профессиональной информации врачам, провизорам и фармацевтам.