Механизмы действия ребамипида: систематизация литературных данных

1. Naito Y, Yoshikawa T. Rebamipide: a gastrointestinal protective drug with pleiotropic activities. Expert Rev Gastroenterol Hepatol 2010; 4 (3): 261–70.
2. Звяглова М.Ю., Князев О.В., Парфенов А.И. Фармакологический и клинический профиль ребамипида: новые терапевтические мишени. Терапевтический архив. 2020; 92 (2): 104–11. DOI: 10.26442/00403660.2020.02.000569
[Zvyaglova M.Yu., Knyazev O.V., Parfenov A.I. Pharmacological and clinical feature of rebamipide: new therapeutic targets. Therapeutic Archive. 2020; 92 (2): 104–11. DOI: 10.26442/00403660.2020.02.000569 (in Russian).]
3. Arakawa T, Higuchi K, Fujiwara Y et al. 15th anniversary of rebamipide: looking ahead to the new mechanisms and new applications. Dig Dis Sci 2005; 50 (Suppl. 1): S3–S11. DOI: 10.1007/s10620-005-2800-9
4. Genta RM. Review article: the role of rebamipide in the management of inflammatory disease of the gastrointestinal tract. Aliment Pharmacol Ther 2003; 18 (Suppl. 1): 8–13. DOI: 10.1046/j.1365-2036.18.s1.5.x
5. Arakawa T, Kobayashi K, Yoshikawa T, Tarnawski A. Rebamipide: overview of its mechanisms of action and efficacy in mucosal protection and ulcer healing. Dig Dis Sci 1998; 43 (9 Suppl.): 5S–13S.
6. Miller SB. Prostaglandins in health and disease: an overview. Semin Arthritis Rheum 2006; 36 (1): 37–49. DOI: 10.1016/j.semarthrit.2006.03.005
7. Cryer B. Mucosal defense and repair. Role of prostaglandins in the stomach and duodenum. Gastroenterol Clin North Am 2001; 30 (4): 877–vi. DOI: 10.1016/s0889-8553(05)70218-1
8. Wallace JL. Prostaglandins, NSAIDs, and gastric mucosal protection: why doesn't the stomach digest itself? Physiol Rev 2008; 88 (4): 1547–65. DOI: 10.1152/physrev.00004.2008
9. Маев И.В., Самсонов А.А., Андреев Д.Н. Гастропатии, индуцированные нестероидными противовоспалительными средствами: патогенетически обоснованные подходы к профилактике и терапии. Фарматека. 2016; 2: 49–54.
[Maev I.V., Samsonov A.A., Andreev D.N. Gastropatii, indutsirovannye nesteroidnymi protivovospalitel'nymi sredstvami: patogeneticheski obosnovannye podkhody k profilaktike i terapii. Farmateka. 2016; 2: 49–54 (in Russian).]
10. Tarnawski AS, Chai J, Pai R, Chiou SK. Rebamipide activates genes encoding angiogenic growth factors and Cox2 and stimulates angiogenesis: a key to its ulcer healing action? Dig Dis Sci 2004; 49 (2): 202–9. DOI: 10.1023/b:ddas.0000017439.60943.5c
11. Sun WH, Tsuji S, Tsujii M et al. Induction of cyclooxygenase-2 in rat gastric mucosa by rebamipide, a mucoprotective agent. J Pharmacol Exp Ther 2000; 295 (2): 447–52.
12. Murata H, Yabe Y, Tsuji S et al. Gastro-protective agent rebamipide induces cyclooxygenease-2 (COX-2)
in gastric epithelial cells. Dig Dis Sci 2005; 50 (Suppl. 1): S70–5. DOI: 10.1007/s10620-005-2809-0
13. Suetsugu H, Ishihara S, Moriyama N et al. Effect of rebamipide on prostaglandin EP4 receptor gene expression in rat gastric mucosa. J Lab Clin Med 2000; 136 (1): 50–7. DOI: 10.1067/mlc.2000.107303
14. Tanigawa T, Watanabe T, Ohkawa F et al. Rebamipide, a mucoprotective drug, inhibits NSAIDs-induced gastric mucosal injury: possible involvement of the downregulation of 15-hydroxyprostaglandin dehydrogenase. J Clin Biochem Nutr 2011; 48 (2): 149–53. DOI: 10.3164/jcbn.10-75
15. Iijima K, Ichikawa T, Okada S et al. Rebamipide, a cytoprotective drug, increases gastric mucus secretion in human: evaluations with endoscopic gastrin test. Dig Dis Sci 2009; 54 (7): 1500–7. DOI: 10.1007/s10620-008-0507-4
16. Gaschler MM, Stockwell BR. Lipid peroxidation in cell death. Biochem Biophys Res Commun 2017; 482 (3): 419–25. DOI: 10.1016/j.bbrc.2016.10.086
17. Manda-Handzlik A, Demkow U. Neutrophils: The Role of Oxidative and Nitrosative Stress in Health and Disease. Adv Exp Med Biol 2015; 857: 51–60. DOI: 10.1007/5584_2015_117
18. Iinuma S, Naito Y, Yoshikawa T et al. In vitro studies indicating antioxidative properties of rebamipide. Dig Dis Sci 1998; 43 (9 Suppl.): 35S–39S.
19. Yoshikawa T, Naito Y, Tanigawa T, Kondo M. Free radical scavenging activity of the novel anti-ulcer agent rebamipide studied by electron spin resonance. Arzneimittelforschung 1993; 43 (3): 363–6.
20. Naito Y, Yoshikawa T, Tanigawa T et al. Hydroxyl radical scavenging by rebamipide and related compounds: electron paramagnetic resonance study. Free Radic Biol Med 1995; 18 (1): 117–23. DOI: 10.1016/0891-5849(94)00110-6
21. Sakurai K, Sasabe H, Koga T, Konishi T. Mechanism of hydroxyl radical scavenging by rebamipide: identification of mono-hydroxylated rebamipide as a major reaction product. Free Radic Res 2004; 38 (5): 487–94. DOI: 10.1080/1071576042000209808
22. Kim CD, Kim YK, Lee SH, Hong KW. Rebamipide inhibits neutrophil adhesion to hypoxia/reoxygenation-stimulated endothelial cells via nuclear factor-kappaB-dependent pathway. J Pharmacol Exp Ther 2000; 294 (3): 864–9.
23. Farhadi A, Keshavarzian A, Fitzpatrick LR et al. Modulatory effects of plasma and colonic milieu of patients with ulcerative colitis on neutrophil reactive oxygen species production in presence of a novel antioxidant, rebamipide. Dig Dis Sci 2002; 47 (6): 1342–8. DOI: 10.1023/a:1015382800434
24. Hahm KB, Park IS, Kim YS et al. Role of rebamipide on induction of heat-shock proteins and protection against reactive oxygen metabolite-mediated cell damage in cultured gastric mucosal cells. Free Radic Biol Med 1997; 22 (4): 711–6. DOI: 10.1016/s0891-5849(96)00406-6
25. Kim HK, Kim JI, Kim JK et al. Preventive effects of rebamipide on NSAID-induced gastric mucosal injury and reduction of gastric mucosal blood flow in healthy volunteers. Dig Dis Sci 2007; 52 (8): 1776–82. DOI: 10.1007/s10620-006-9367-y
26. Farré R, Vicario M. Abnormal Barrier Function in Gastrointestinal Disorders. Handb Exp Pharmacol 2017; 239: 193–217.
27. Zihni C, Mills C, Matter K, Balda MS. Tight junctions: from simple barriers to multifunctional molecular gates. Nat Rev Mol Cell Biol 2016; 17 (9): 564–80.
28. Piche T. Tight junctions and IBS – the link between epithelial permeability, low-grade inflammation, and symptom generation? Neurogastroenterol Motil 2014; 26 (3): 296–302.
29. 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. DOI: 10.3109/00365521.2013.828772
30. Thakre-Nighot M, Blikslager AT. Indomethacin induces increase in gastric epithelial tight junction permeability via redistribution of occludin and activation of p38 MAPK in MKN-28 Cells. Tissue Barriers 2016; 4 (3): e1187325. DOI: 10.1080/21688370.2016.1187325
31. Андреев Д.Н. Роль нарушения проницаемости слизистой оболочки кишечника в генезе функциональных заболеваний желудочно-кишечного тракта. Consilium Medicum. 2019; 21 (8): 29–34. DOI: 10.26442/20751753.2019.8.190539
[Andreev D.N. The role of alterations in permeability of the intestinal mucosa in the genesis of functional gastrointestinal disorders. Consilium Medicum. 2019; 21 (8): 29–34. DOI: 10.26442/20751753.2019.8.190539 (in Russian).]
32. Gweon TG, Park JH, Kim BW et al; Incheon and Western Kyonggi Gastrointestinal Study. Additive Effects of Rebamipide Plus Proton Pump Inhibitors on the Expression of Tight Junction Proteins in a Rat Model of Gastro-Esophageal Reflux Disease. Gut Liver 2018; 12 (1): 46–50. DOI: 10.5009/gnl17078
33. Suzuki T, Yoshida N, Nakabe N et al. Prophylactic effect of rebamipide on aspirin-induced gastric lesions and disruption of tight junctional protein zonula occludens-1 distribution. J Pharmacol Sci 2008; 106 (3): 469–77. DOI: 10.1254/jphs.fp0071422
34. Shim S, Jang HS, Myung HW et al. Rebamipide ameliorates radiation-induced intestinal injury in a mouse model. Toxicol Appl Pharmacol 2017; 329: 40–7. DOI: 10.1016/j.taap.2017.05.012
35. Jang H, Park S, Lee J et al. Rebamipide alleviates radiation-induced colitis through improvement of goblet cell differentiation in mice. J Gastroenterol Hepatol 2018; 33 (4): 878–86. DOI: 10.1111/jgh.14021
36. Маев И.В., Андреев Д.Н. Инфекция Helicobacter pylori и ассоциированные заболевания. М.: Ремедиум, 2018.
[Maev I.V., Andreev D.N. Helicobacter pylori infection and associated diseases. Moscow: Remedium, 2018 (in Russian).]
37. Malfertheiner P, Venerito M, Schulz C. Helicobacter pylori Infection: New Facts in Clinical Management. Curr Treat Options Gastroenterol 2018; 16 (4): 605–15. DOI: 10.1007/s11938-018-0209-8
38. Hooi JKY, Lai WY, Ng WK et al. Global Prevalence of Helicobacter pylori Infection: Systematic Review and Meta-Analysis. Gastroenterology 2017; 153 (2): 420–9. DOI: 10.1053/j.gastro.2017.04.022
39. Zamani M, Ebrahimtabar F, Zamani V et al. Systematic review with meta-analysis: the worldwide prevalence of Helicobacter pylori infection. Aliment Pharmacol Ther 2018; 47 (7): 868–76. DOI: 10.1111/apt.14561
40. Coelho E, Magalhães A, Dinis-Ribeiro M, Reis CA. Mecanismos Moleculares de Adesão e Colonização da Mucosa Gástrica pela Helicobacter pylori e suas Implicações Clínicas [Molecular Mechanisms for Adhesion and Colonization of Human Gastric Mucosa by Helicobacter pylori and its Clinical Implications]. Acta Med Port 2016; 29 (7–8): 476–83. DOI: 10.20344/amp.6651
41. Bonsor DA, Sundberg EJ. Roles of Adhesion to Epithelial Cells in Gastric Colonization by Helicobacter pylori. Adv Exp Med Biol 2019; 1149: 57–75. DOI: 10.1007/5584_2019_359
42. Asahi M, Azuma T, Ito S et al. Helicobacter pylori CagA protein can be tyrosine phosphorylated in gastric epithelial cells. J Exp Med 2000; 191 (4): 593–602. DOI: 10.1084/jem.191.4.593
43. Hayashi S, Sugiyama T, Amano K et al. Effect of rebamipide, a novel antiulcer agent, on Helicobacter pylori adhesion to gastric epithelial cells. Antimicrob Agents Chemother 1998; 42 (8): 1895–9.
44. Lee KH, Kim JY, Kim WK et al. Protective effect of rebamipide against Helicobacter pylori-CagA-induced effects on gastric epithelial cells. Dig Dis Sci 2011; 56 (2): 441–8. DOI: 10.1007/s10620-010-1299-x
45. Masamune A, Yoshida M, Sakai Y, Shimosegawa T. Rebamipide inhibits ceramide-induced interleukin-8 production in Kato III human gastric cancer cells. J Pharmacol Exp Ther 2001; 298 (2): 485–92.
46. Aihara M, Azuma A, Takizawa H et al. Molecular analysis of suppression of interleukin-8 production by rebamipide in Helicobacter pylori-stimulated gastric cancer cell lines. Dig Dis Sci 1998; 43 (9 Suppl.): 174S–180S.
47. Choi KW, Lee YC, Chung IS et al. Effect of rebamipide in treatment of Helicobacter pylori-associated duodenal ulcer: attenuation of chemokine expression and nitrosative damage. Dig Dis Sci 2002; 47 (2): 283–91. DOI: 10.1023/a:1013753602149
48. Bray F, Ferlay J, Soerjomataram I et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68 (6): 394–424. DOI: 10.3322/caac.21492
49. Rawla P, Barsouk A. Epidemiology of gastric cancer: global trends, risk factors and prevention. Prz Gastroenterol 2019; 14 (1): 26–38. DOI: 10.5114/pg.2018.80001
50. Carcas LP. Gastric cancer review. J Carcinog 2014; 13: 14. DOI: 10.4103/1477-3163.146506
51. Graham DY. Helicobacter pylori update: gastric cancer, reliable therapy, and possible benefits. Gastroenterology 2015; 148 (4): 719–31.e3. DOI: 10.1053/j.gastro.2015.01.040
52. Matos JI, de Sousa HA, Marcos-Pinto R, Dinis-Ribeiro M. Helicobacter pylori CagA and VacA genotypes and gastric phenotype: a meta-analysis. Eur J Gastroenterol Hepatol 2013; 25 (12): 1431–41. DOI: 10.1097/MEG.0b013e328364b53e
53. Min DS. A Potential Efficacy of Rebamipide as Anti-gastric Cancer Drug. J Life Sci 2016; 26 (10): 1214–7. DOI: 10.5352/JLS.2016.26.10.1214
54. Haruma K, Ito M, Kido S et al. Long-term rebamipide therapy improves Helicobacter pylori-associated chronic gastritis. Dig Dis Sci 2002; 47 (4): 862–7. DOI: 10.1023/a:1014716822702
55. Kamada T, Sato M, Tokutomi T et al. Rebamipide improves chronic inflammation in the lesser curvature of the corpus after Helicobacter pylori eradication: a multicenter study. Biomed Res Int 2015; 2015: 865146. DOI: 10.1155/2015/865146
56. Kang DW, Min G, Park DY et al. Rebamipide-induced downregulation of phospholipase D inhibits inflammation and proliferation in gastric cancer cells. Exp Mol Med 2010; 42 (8): 555–64. DOI: 10.3858/emm.2010.42.8.056
57. Kang DW, Noh YN, Hwang WC et al. Rebamipide attenuates Helicobacter pylori CagA-induced self-renewal capacity via modulation of b-catenin signaling axis in gastric cancer-initiating cells. Biochem Pharmacol 2016; 113: 36–44. DOI: 10.1016/j.bcp.2016.06.003

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1. Naito Y, Yoshikawa T. Rebamipide: a gastrointestinal protective drug with pleiotropic activities. Expert Rev Gastroenterol Hepatol 2010; 4 (3): 261–70.
2. Zvyaglova M.Yu., Knyazev O.V., Parfenov A.I. Pharmacological and clinical feature of rebamipide: new therapeutic targets. Therapeutic Archive. 2020; 92 (2): 104–11. DOI: 10.26442/00403660.2020.02.000569 (in Russian).
3. Arakawa T, Higuchi K, Fujiwara Y et al. 15th anniversary of rebamipide: looking ahead to the new mechanisms and new applications. Dig Dis Sci 2005; 50 (Suppl. 1): S3–S11. DOI: 10.1007/s10620-005-2800-9
4. Genta RM. Review article: the role of rebamipide in the management of inflammatory disease of the gastrointestinal tract. Aliment Pharmacol Ther 2003; 18 (Suppl. 1): 8–13. DOI: 10.1046/j.1365-2036.18.s1.5.x
5. Arakawa T, Kobayashi K, Yoshikawa T, Tarnawski A. Rebamipide: overview of its mechanisms of action and efficacy in mucosal protection and ulcer healing. Dig Dis Sci 1998; 43 (9 Suppl.): 5S–13S.
6. Miller SB. Prostaglandins in health and disease: an overview. Semin Arthritis Rheum 2006; 36 (1): 37–49. DOI: 10.1016/j.semarthrit.2006.03.005
7. Cryer B. Mucosal defense and repair. Role of prostaglandins in the stomach and duodenum. Gastroenterol Clin North Am 2001; 30 (4): 877–vi. DOI: 10.1016/s0889-8553(05)70218-1
8. Wallace JL. Prostaglandins, NSAIDs, and gastric mucosal protection: why doesn't the stomach digest itself? Physiol Rev 2008; 88 (4): 1547–65. DOI: 10.1152/physrev.00004.2008
9. Maev I.V., Samsonov A.A., Andreev D.N. Gastropatii, indutsirovannye nesteroidnymi protivovospalitel'nymi sredstvami: patogeneticheski obosnovannye podkhody k profilaktike i terapii. Farmateka. 2016; 2: 49–54 (in Russian).
10. Tarnawski AS, Chai J, Pai R, Chiou SK. Rebamipide activates genes encoding angiogenic growth factors and Cox2 and stimulates angiogenesis: a key to its ulcer healing action? Dig Dis Sci 2004; 49 (2): 202–9.
DOI: 10.1023/b:ddas.0000017439.60943.5c
11. Sun WH, Tsuji S, Tsujii M et al. Induction of cyclooxygenase-2 in rat gastric mucosa by rebamipide, a mucoprotective agent. J Pharmacol Exp Ther 2000; 295 (2): 447–52.
12. Murata H, Yabe Y, Tsuji S et al. Gastro-protective agent rebamipide induces cyclooxygenease-2 (COX-2)
in gastric epithelial cells. Dig Dis Sci 2005; 50 (Suppl. 1): S70–5. DOI: 10.1007/s10620-005-2809-0
13. Suetsugu H, Ishihara S, Moriyama N et al. Effect of rebamipide on prostaglandin EP4 receptor gene expression in rat gastric mucosa. J Lab Clin Med 2000; 136 (1): 50–7. DOI: 10.1067/mlc.2000.107303
14. Tanigawa T, Watanabe T, Ohkawa F et al. Rebamipide, a mucoprotective drug, inhibits NSAIDs-induced gastric mucosal injury: possible involvement of the downregulation of 15-hydroxyprostaglandin dehydrogenase. J Clin Biochem Nutr 2011; 48 (2): 149–53. DOI: 10.3164/jcbn.10-75
15. Iijima K, Ichikawa T, Okada S et al. Rebamipide, a cytoprotective drug, increases gastric mucus secretion in human: evaluations with endoscopic gastrin test. Dig Dis Sci 2009; 54 (7): 1500–7. DOI: 10.1007/s10620-008-0507-4
16. Gaschler MM, Stockwell BR. Lipid peroxidation in cell death. Biochem Biophys Res Commun 2017; 482 (3): 419–25. DOI: 10.1016/j.bbrc.2016.10.086
17. Manda-Handzlik A, Demkow U. Neutrophils: The Role of Oxidative and Nitrosative Stress in Health and Disease. Adv Exp Med Biol 2015; 857: 51–60. DOI: 10.1007/5584_2015_117
18. Iinuma S, Naito Y, Yoshikawa T et al. In vitro studies indicating antioxidative properties of rebamipide. Dig Dis Sci 1998; 43 (9 Suppl.): 35S–39S.
19. Yoshikawa T, Naito Y, Tanigawa T, Kondo M. Free radical scavenging activity of the novel anti-ulcer agent rebamipide studied by electron spin resonance. Arzneimittelforschung 1993; 43 (3): 363–6.
20. Naito Y, Yoshikawa T, Tanigawa T et al. Hydroxyl radical scavenging by rebamipide and related compounds: electron paramagnetic resonance study. Free Radic Biol Med 1995; 18 (1): 117–23. DOI: 10.1016/0891-5849(94)00110-6
21. Sakurai K, Sasabe H, Koga T, Konishi T. Mechanism of hydroxyl radical scavenging by rebamipide: identification of mono-hydroxylated rebamipide as a major reaction product. Free Radic Res 2004; 38 (5): 487–94. DOI: 10.1080/1071576042000209808
22. Kim CD, Kim YK, Lee SH, Hong KW. Rebamipide inhibits neutrophil adhesion to hypoxia/reoxygenation-stimulated endothelial cells via nuclear factor-kappaB-dependent pathway. J Pharmacol Exp Ther 2000; 294 (3): 864–9.
23. Farhadi A, Keshavarzian A, Fitzpatrick LR et al. Modulatory effects of plasma and colonic milieu of patients with ulcerative colitis on neutrophil reactive oxygen species production in presence of a novel antioxidant, rebamipide. Dig Dis Sci 2002; 47 (6): 1342–8. DOI: 10.1023/a:1015382800434
24. Hahm KB, Park IS, Kim YS et al. Role of rebamipide on induction of heat-shock proteins and protection against reactive oxygen metabolite-mediated cell damage in cultured gastric mucosal cells. Free Radic Biol Med 1997; 22 (4): 711–6. DOI: 10.1016/s0891-5849(96)00406-6
25. Kim HK, Kim JI, Kim JK et al. Preventive effects of rebamipide on NSAID-induced gastric mucosal injury and reduction of gastric mucosal blood flow in healthy volunteers. Dig Dis Sci 2007; 52 (8): 1776–82. DOI: 10.1007/s10620-006-9367-y
26. Farré R, Vicario M. Abnormal Barrier Function in Gastrointestinal Disorders. Handb Exp Pharmacol 2017; 239: 193–217.
27. Zihni C, Mills C, Matter K, Balda MS. Tight junctions: from simple barriers to multifunctional molecular gates. Nat Rev Mol Cell Biol 2016; 17 (9): 564–80.
28. Piche T. Tight junctions and IBS – the link between epithelial permeability, low-grade inflammation, and symptom generation? Neurogastroenterol Motil 2014; 26 (3): 296–302.
29. 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. DOI: 10.3109/00365521.2013.828772
30. Thakre-Nighot M, Blikslager AT. Indomethacin induces increase in gastric epithelial tight junction permeability via redistribution of occludin and activation of p38 MAPK in MKN-28 Cells. Tissue Barriers 2016; 4 (3): e1187325. DOI: 10.1080/21688370.2016.1187325
31. Andreev D.N. The role of alterations in permeability of the intestinal mucosa in the genesis of functional gastrointestinal disorders. Consilium Medicum. 2019; 21 (8): 29–34. DOI: 10.26442/20751753.2019.8.190539 (in Russian).
32. Gweon TG, Park JH, Kim BW et al; Incheon and Western Kyonggi Gastrointestinal Study. Additive Effects of Rebamipide Plus Proton Pump Inhibitors on the Expression of Tight Junction Proteins in a Rat Model of Gastro-Esophageal Reflux Disease. Gut Liver 2018; 12 (1): 46–50. DOI: 10.5009/gnl17078
33. Suzuki T, Yoshida N, Nakabe N et al. Prophylactic effect of rebamipide on aspirin-induced gastric lesions and disruption of tight junctional protein zonula occludens-1 distribution. J Pharmacol Sci 2008; 106 (3): 469–77. DOI: 10.1254/jphs.fp0071422
34. Shim S, Jang HS, Myung HW et al. Rebamipide ameliorates radiation-induced intestinal injury in a mouse model. Toxicol Appl Pharmacol 2017; 329: 40–7. DOI: 10.1016/j.taap.2017.05.012
35. Jang H, Park S, Lee J et al. Rebamipide alleviates radiation-induced colitis through improvement of goblet cell differentiation in mice. J Gastroenterol Hepatol 2018; 33 (4): 878–86. DOI: 10.1111/jgh.14021
36. Maev I.V., Andreev D.N. Helicobacter pylori infection and associated diseases. Moscow: Remedium, 2018 (in Russian).
37. Malfertheiner P, Venerito M, Schulz C. Helicobacter pylori Infection: New Facts in Clinical Management. Curr Treat Options Gastroenterol 2018; 16 (4): 605–15. DOI: 10.1007/s11938-018-0209-8
38. Hooi JKY, Lai WY, Ng WK et al. Global Prevalence of Helicobacter pylori Infection: Systematic Review and Meta-Analysis. Gastroenterology 2017; 153 (2): 420–9. DOI: 10.1053/j.gastro.2017.04.022
39. Zamani M, Ebrahimtabar F, Zamani V et al. Systematic review with meta-analysis: the worldwide prevalence of Helicobacter pylori infection. Aliment Pharmacol Ther 2018; 47 (7): 868–76. DOI: 10.1111/apt.14561
40. Coelho E, Magalhães A, Dinis-Ribeiro M, Reis CA. Mecanismos Moleculares de Adesão e Colonização da Mucosa Gástrica pela Helicobacter pylori e suas Implicações Clínicas [Molecular Mechanisms for Adhesion and Colonization of Human Gastric Mucosa by Helicobacter pylori and its Clinical Implications]. Acta Med Port 2016; 29 (7–8): 476–83. DOI: 10.20344/amp.6651
41. Bonsor DA, Sundberg EJ. Roles of Adhesion to Epithelial Cells in Gastric Colonization by Helicobacter pylori. Adv Exp Med Biol 2019; 1149: 57–75. DOI: 10.1007/5584_2019_359
42. Asahi M, Azuma T, Ito S et al. Helicobacter pylori CagA protein can be tyrosine phosphorylated in gastric epithelial cells. J Exp Med 2000; 191 (4): 593–602. DOI: 10.1084/jem.191.4.593
43. Hayashi S, Sugiyama T, Amano K et al. Effect of rebamipide, a novel antiulcer agent, on Helicobacter pylori adhesion to gastric epithelial cells. Antimicrob Agents Chemother 1998; 42 (8): 1895–9.
44. Lee KH, Kim JY, Kim WK et al. Protective effect of rebamipide against Helicobacter pylori-CagA-induced effects on gastric epithelial cells. Dig Dis Sci 2011; 56 (2): 441–8. DOI: 10.1007/s10620-010-1299-x
45. Masamune A, Yoshida M, Sakai Y, Shimosegawa T. Rebamipide inhibits ceramide-induced interleukin-8 production in Kato III human gastric cancer cells. J Pharmacol Exp Ther 2001; 298 (2): 485–92.
46. Aihara M, Azuma A, Takizawa H et al. Molecular analysis of suppression of interleukin-8 production by rebamipide in Helicobacter pylori-stimulated gastric cancer cell lines. Dig Dis Sci 1998; 43 (9 Suppl.): 174S–180S.
47. Choi KW, Lee YC, Chung IS et al. Effect of rebamipide in treatment of Helicobacter pylori-associated duodenal ulcer: attenuation of chemokine expression and nitrosative damage. Dig Dis Sci 2002; 47 (2): 283–91. DOI: 10.1023/a:1013753602149
48. Bray F, Ferlay J, Soerjomataram I et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68 (6): 394–424. DOI: 10.3322/caac.21492
49. Rawla P, Barsouk A. Epidemiology of gastric cancer: global trends, risk factors and prevention. Prz Gastroenterol 2019; 14 (1): 26–38. DOI: 10.5114/pg.2018.80001
50. Carcas LP. Gastric cancer review. J Carcinog 2014; 13: 14. DOI: 10.4103/1477-3163.146506
51. Graham DY. Helicobacter pylori update: gastric cancer, reliable therapy, and possible benefits. Gastroenterology 2015; 148 (4): 719–31.e3. DOI: 10.1053/j.gastro.2015.01.040
52. Matos JI, de Sousa HA, Marcos-Pinto R, Dinis-Ribeiro M. Helicobacter pylori CagA and VacA genotypes and gastric phenotype: a meta-analysis. Eur J Gastroenterol Hepatol 2013; 25 (12): 1431–41. DOI: 10.1097/MEG.0b013e328364b53e
53. Min DS. A Potential Efficacy of Rebamipide as Anti-gastric Cancer Drug. J Life Sci 2016; 26 (10): 1214–7. DOI: 10.5352/JLS.2016.26.10.1214
54. Haruma K, Ito M, Kido S et al. Long-term rebamipide therapy improves Helicobacter pylori-associated chronic gastritis. Dig Dis Sci 2002; 47 (4): 862–7. DOI: 10.1023/a:1014716822702
55. Kamada T, Sato M, Tokutomi T et al. Rebamipide improves chronic inflammation in the lesser curvature of the corpus after Helicobacter pylori eradication: a multicenter study. Biomed Res Int 2015; 2015: 865146. DOI: 10.1155/2015/865146
56. Kang DW, Min G, Park DY et al. Rebamipide-induced downregulation of phospholipase D inhibits inflammation and proliferation in gastric cancer cells. Exp Mol Med 2010; 42 (8): 555–64. DOI: 10.3858/emm.2010.42.8.056
57. Kang DW, Noh YN, Hwang WC et al. Rebamipide attenuates Helicobacter pylori CagA-induced self-renewal capacity via modulation of b-catenin signaling axis in gastric cancer-initiating cells. Biochem Pharmacol 2016; 113: 36–44.
DOI: 10.1016/j.bcp.2016.06.003

Д.Н. Андреев*, А.К. Кулиева

ФГБОУ ВО «Московский государственный медико-стоматологический университет им. А.И. Евдокимова» Минздрава России, Москва, Россия
*dna-mit8@mail.ru

________________________________________________

Dmitrii N. Andreev*, Alla K. Kulieva

Yevdokimov Moscow State University of Medicine and Dentistry, Moscow, Russia
*dna-mit8@mail.ru