Pharmacological efficacy and potential of the use of nitazoxanide, a thiazolide drug with a wide spectrum of action

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Abstract

The article is devoted to the possibility and prospects of using nitazoxanide in a wide range of diseases. Based on literature data, the authors evaluate the pharmacological effectiveness and substantiate the potential of using nitazoxanide in bacterial, helminthic, protean, viral and oncological diseases. This information is of interest and can be used to decide on the need to conduct clinical trials of nitazoxanide in Russia. A systematic search for current information was conducted in four databases until December 1, 2023: PubMed, EMBASE, Web of Science and Cochrane Library. The work included preclinical studies in vitro and in vivo, as well as randomized clinical trials comparing the pharmacological effectiveness of nitazoxanide and placebo. The broad-spectrum thiazolide drug nitazoxanide has antibacterial, antiprotozoal, anthelmintic, antiviral and antitumor activity. This is achieved through its pharmacological properties, namely: regulation of the cell cycle, apoptosis, cell proliferation and migration; activation of innate immunity; influence on the synthesis and activation of cell proteins, some of which are links in cellular signaling pathways; binding to proteins of viruses, bacteria, protozoa and helminths with disruption of their vital functions; immunomodulating effect by regulating the activity of pro- and anti-inflammatory cytokines. The article systematizes and summarizes current information on the pharmacodynamics of nitazoxanide, as well as the results of preclinical and clinical studies of the drug, and discusses further prospects.

About the authors

Vladimir V. Rusanovsky

Saint Petersburg State Pediatric Medical University

Email: rusvv2058@mail.ru
ORCID iD: 0000-0002-0432-7946
SPIN-code: 7010-4530
Scopus Author ID: 57444102200

MD, Dr. Sci. (Medicine), Professor

Russian Federation, Saint Petersburg

Anastasia A. Savelyeva

Saint Petersburg State Pediatric Medical University

Email: a.a.savel1999@gmail.ru
ORCID iD: 0009-0009-4997-4045
Russian Federation, Saint Petersburg

Zara G. Tadtaeva

Saint Petersburg State Pediatric Medical University

Email: tadtaeva2003@mail.ru
ORCID iD: 0000-0002-5809-1457
SPIN-code: 6086-0169
Scopus Author ID: 57222536682

MD, Dr. Sci. (Medicine)

Russian Federation, Saint Petersburg

Egor S. Astudin

Saint Petersburg State Pediatric Medical University

Email: astudin-egor.ru@yandex.ru
ORCID iD: 0009-0002-6890-5634
Russian Federation, Saint Petersburg

Alexandr E. Krivoshein

Saint Petersburg State Pediatric Medical University

Author for correspondence.
Email: krivoshein20@mail.ru
ORCID iD: 0000-0002-4714-1180
Russian Federation, Saint Petersburg

Alexandr A. Akimov

Saint Petersburg State Pediatric Medical University

Email: laboremus_07@mail.ru
SPIN-code: 4176-2536

MD, Cand. Sci. (Medicine)

Russian Federation, Saint Petersburg

Natalia A. Kuritsina

Saint Petersburg State Pediatric Medical University

Email: bely25193@yandex.ru
ORCID iD: 0000-0002-0200-5097
SPIN-code: 4361-7365
Scopus Author ID: 57202789667

Cand. Sci. (Biology)

Russian Federation, Saint Petersburg

References

  1. Patent US 3950351. 1976 Apr 13. Rossignol JF, Cavier R. New derivatives of 2-benzamido-5-nitro thiazoles. Phavic Sprl, assignee.
  2. Smart T. NTZ trials for cryptosporidiosis. GMHC Treat Issues. 1995;9(9):14.
  3. Rossignol JF, Maisonneuve H. Nitazoxanide in the treatment of Taenia saginata and Hymenolepis nana infections. Am J Trop Med Hyg. 1984;33(3):511–512. doi: 10.4269/ajtmh.1984.33.511
  4. Roehr B. Another failed promise? NTZ gets the nix. J Int Assoc Physicians AIDS Care. 1998;4(8):26–29.
  5. Diaz E, Mondragon J, Ramirez E, Bernal R. Epidemiology and control of intestinal parasites with nitazoxanide in children in Mexico. Am J Trop Med Hyg. 2003;68(4):384–385.
  6. Lateef M, Zargar SA, Khan AR, et al. Successful treatment of niclosamide- and praziquantel-resistant beef tapeworm infection with nitazoxanide. Int J Infect Dis. 2008;12(1):80–82. doi: 10.1016/j.ijid.2007.04.017
  7. Rafiullah F, Kanwal S, Majeed UM, et al. Successful use of nitazoxanide in the treatment of recurrent Clostridium difficile infection. BMJ Case Rep. 2011;2011:bcr0420114123. doi: 10.1136/bcr.04.2011.4123
  8. Laxminarayan R, Duse A, Wattal C, et al. Antibiotic resistance-the need for global solutions. Lancet Infect Dis. 2013;13(12):1057–1098. doi: 10.1016/S1473-3099(13)70318-9
  9. Rodriguez-Morales AJ, Martinez-Pulgarin DF, Muñoz-Urbano M, et al. Bibliometric assessment of the global scientific production of nitazoxanide. Cureus. 2017;9(5): e1204. doi: 10.7759/cureus.1204
  10. Hemphill A, Mueller J, Esposito M. Nitazoxanide, a broad-spectrum thiazolide anti-infective agent for the treatment of gastrointestinal infections. Expert Opin Pharmacother. 2006;7(7):953–964. doi: 10.1517/14656566.7.7.953
  11. Di Santo N, Ehrisman J. A functional perspective of nitazoxanide as a potential anticancer drug. Mutat Res. 2014;768:16–21. doi: 10.1016/j.mrfmmm.2014.05.005
  12. alinia.com [internet]. Alinia (nitazoxanide) [cited 10 oct. 2023]. Available from: https://www.alinia.com/healthcare-professionals/
  13. Shakya A, Bhat HR, Ghosh SK. Update on nitazoxanide: a multifunctional chemotherapeutic agent. Curr Drug Discov Technol. 2018;15(3):201–213. doi: 10.2174/1570163814666170727130003
  14. Cedillo-Rivera R, Chávez B, González-Robles A, et al. In vitro effect of nitazoxanide against Entamoeba histolytica, Giardia intestinalis and Trichomonas vaginalis trophozoites. J Eukaryot Microbiol. 2002;49(3):201–208. doi: 10.1111/j.1550-7408.2002.tb00523.x
  15. Hashan MR, Elhusseiny KM, Huu-Hoai L, et al. Effect of nitazoxanide on diarrhea: A systematic review and network meta-analysis of randomized controlled trials. Acta Trop. 2020;210:105603. doi: 10.1016/j.actatropica.2020.105603
  16. Moron-Soto M, Gutierrez L, Sumano H, et al. Efficacy of nitazoxanide to treat natural Giardia infections in dogs. Parasit Vectors. 2017;10(1):52. doi: 10.1186/s13071-017-1998-7
  17. Bailey JM, Erramouspe J. Nitazoxanide treatment for giardiasis and cryptosporidiosis in children. Ann Pharmacother. 2004;38(4): 634–640. doi: 10.1345/aph.1D451
  18. Doumbo O, Rossignol JF, Pichard E, et al. Nitazoxanide in the treatment of cryptosporidial diarrhea and other intestinal parasitic infections associated with acquired immunodeficiency syndrome in tropical Africa. Am J Trop Med Hyg. 1997;56(6):637–639. doi: 10.4269/ajtmh.1997.56.637
  19. Li J, Kuang H, Zhan X. Nitazoxanide in the treatment of intestinal parasitic infections in children: a systematic review and meta-analysis. Indian J Pediatr. 2020;87(1):17–25. doi: 10.1007/s12098-019-03098-w
  20. Rossignol JF, Ayoub A, Ayers MS. Treatment of diarrhea caused by Giardia intestinalis and Entamoeba histolytica or E. dispar: a randomized, double-blind, placebo-controlled study of nitazoxanide. J Infect Dis. 2001;184(3):381–384. doi: 10.1086/322038
  21. Rossignol JF, Kabil SM, El-Gohary Y, Younis AM. Nitazoxanide in the treatment of amoebiasis. Trans R Soc Trop Med Hyg. 2007;101(10):1025–1031. doi: 10.1016/j.trstmh.2007.04.001
  22. Goel V, Jain A, Sharma G, et al. Evaluating the efficacy of nitazoxanide in uncomplicated amebic liver abscess. Indian J Gastroenterol. 2021;40(3):272–280. doi: 10.1007/s12664-020-01132-w
  23. SmirnovLP, Borvinskaya EV, Sukhovskaya IV, Kochneva AA. Glutathione s-transferases in helminths. Trudy KarNTs RAN. 2015;(11):3–14. EDN: VBCYRT doi: 10.17076/eb213 (In Russ.)
  24. Halloran DM. Database of glutamate-gated chloride (GluCl) subunits across 125 nematode species: patterns of gene accretion and sequence diversification. G3 (Bethesda). 2022;12(2):jkab438. doi: 10.1093/g3journal/jkab438
  25. El-Saber Batiha G, Alqahtani A, Ilesanmi OB, et al. Avermectin derivatives, pharmacokinetics, therapeutic and toxic dosages, mechanism of action, and their biological effects. Pharmaceuticals (Basel). 2020;13(8):196. doi: 10.3390/ph13080196
  26. Chero JC, Saito M, Bustos JA, et al. Hymenolepis nana infection: symptoms and response to nitazoxanide in field conditions. Trans R Soc Trop Med Hyg. 2007;101(2):203–205. doi: 10.1016/j.trstmh.2006.04.004
  27. Hu Y, Ellis BL, Yiu YY, et al. An extensive comparison of the effect of anthelmintic classes on diverse nematodes. PLoS One. 2013;8(7): e70702. doi: 10.1371/journal.pone.0070702
  28. Pyzocha N, Cuda A. Common intestinal parasites. Amer Fam Physician. 2023;108(5):487–493. PMID: 37983700.
  29. Pérez-Molina JA, Díaz-Menéndez M, Gallego JI, et al. Evaluation of nitazoxanide for the treatment of disseminated cystic echinococcosis: report of five cases and literature review. Am J Trop Med Hyg. 2011;84(2):351–356. doi: 10.4269/ajtmh.2011.10-0513
  30. Hoffman PS, Sisson G, Croxen MA, et al. Antiparasitic drug nitazoxanide inhibits the pyruvate oxidoreductases of Helicobacter pylori, selected anaerobic bacteria and parasites, and Campylobacter jejuni. Antimicrob Agents Chemother. 2007;51(3):868–876. doi: 10.1128/AAC.01159-06
  31. Shamir ER, Warthan M, Brown SP, et al. Nitazoxanide inhibits biofilm production and hemagglutination by enteroaggregative Escherichia coli strains by blocking assembly of AafA fimbriae. Antimicrob Agents Chemother. 2010;54(4):1526–1533. doi: 10.1128/AAC.01279-09
  32. de Carvalho LP, Darby CM, Rhee KY, Nathan C. Nitazoxanide disrupts membrane potential and intrabacterial PH homeostasis of mycobacterium tuberculosis. ACS Med Chem Lett. 2011;2(11):849–854. doi: 10.1021/ml200157f
  33. Busch A, Waksman G. Chaperone-usher pathways: diversity and pilus assembly mechanism. Philos Trans R Soc Lond B Biol Sci. 2012;367(1592):1112–1122. doi: 10.1098/rstb.2011.0206
  34. Bailey MA, Na H, Duthie MS, et al. Nitazoxanide is active against Mycobacterium leprae. PLoS One. 2017;12(8):e0184107. doi: 10.1371/journal.pone.0184107
  35. Glal KAM, Abd-Elsalam SM, Mostafa TM. Nitazoxanide versus rifaximin in preventing the recurrence of hepatic encephalopathy: A randomized double-blind controlled trial. J Hepatobiliary Pancreat Sci. 2021;28(10):812–824. doi: 10.1002/jhbp.947
  36. Musher DM, Logan N, Hamill RJ, et al. Nitazoxanide for the treatment of Clostridium difficile colitis. Clin Infect Dis. 2006;43(4): 421–427. doi: 10.1086/506351
  37. Musher DM, Logan N, Mehendiratta V, et al. Clostridium difficile colitis that fails conventional metronidazole therapy: response to nitazoxanide. J Antimicrob Chemother. 2007;59(4):705–710. doi: 10.1093/jac/dkl553
  38. Lanata CF, Franco M. Nitazoxanide for rotavirus diarrhoea? Lancet. 2006;368(9530):100–101. doi: 10.1016/S0140-6736(06)68981-2
  39. Guevara B, Cogdill AG. Helicobacter pylori: A review of current diagnostic and management strategies. Dig Dis Sci. 2020;65(7): 1917–1931. doi: 10.1007/s10620-020-06193-7
  40. Abd-Elsalam S, Kobtan A, El-Kalla F, et al. A 2-week Nitazoxanide-based quadruple treatment as a rescue therapy for Helicobacter pylori eradication: A single center experience. Medicine (Baltimore). 2016;95(24): e3879. doi: 10.1097/MD.0000000000003879
  41. Shawky D, Salamah AM, Abd-Elsalam SM, et al. Nitazoxanide-based therapeutic regimen as a novel treatment for Helicobacter pylori infection in children and adolescents: a randomized trial. Eur Rev Med Pharmacol Sci. 2022;26(9):3132–3137. doi: 10.26355/eurrev_202205_28730
  42. Rossignol JF, El-Gohary YM. Nitazoxanide in the treatment of viral gastroenteritis: a randomized double-blind placebo-controlled clinical trial. Aliment Pharmacol Ther. 2006;24(10):1423–1430. doi: 10.1111/j.1365-2036.2006.03128.x
  43. Teran CG, Teran-Escalera CN, Villarroel P. Nitazoxanide vs. probiotics for the treatment of acute rotavirus diarrhea in children: a randomized, single-blind, controlled trial in Bolivian children. Int J Infect Dis. 2009;13(4):518–523. doi: 10.1016/j.ijid.2008.09.014
  44. Dang W, Xu L, Ma B, et al. Nitazoxanide inhibits human norovirus replication and synergizes with ribavirin by activation of cellular antiviral response. Antimicrob Agents Chemother. 2018;62(11): e00707–e00718. doi: 10.1128/aac. 00707-18
  45. Siddiq DM, Koo HL, Adachi JA, Viola GM. Norovirus gastroenteritis successfully treated with nitazoxanide. J Infect. 2011;63(5): 394–397. doi: 10.1016/j.jinf.2011.08.002
  46. Haubrich K, Gantt S, Blydt-Hansen T. Successful treatment of chronic norovirus gastroenteritis with nitazoxanide in a pediatric kidney transplant recipient. Pediatr Transplant. 2018;22(4):e13186. doi: 10.1111/petr.13186
  47. Morris J, Morris C. Nitazoxanide is effective therapy for norovirus gastroenteritis after chemotherapy and hematopoietic stem cell transplantation (HSCT). Biol Blood Marrow Transplant. 2015;21(2):S255–S256. doi: 10.1016/j.bbmt.2014.11.405
  48. Hargest V, Sharp B, Livingston B, et al. Astrovirus replication is inhibited by nitazoxanide in vitro and in vivo. J Virol. 2020;94(5): e01706–e0119. doi: 10.1128/JVI.01706-19
  49. Esquer Garrigos Z, Barth D, Hamdi AM, et al. Nitazoxanide is a therapeutic option for adenovirus-related enteritis in immunocompromised adults. Antimicrob Agents Chemother. 2018;62(12): e01937–e01118. doi: 10.1128/AAC.01937-18
  50. Rossignol JF. Thiazolides: a new class of antiviral drugs. Expert Opin Drug Metab Toxicol. 2009;5(6):667–674. doi: 10.1517/17425250902988487
  51. Korba BE, Elazar M, Lui P, et al. Potential for hepatitis C virus resistance to nitazoxanide or tizoxanide. Antimicrob Agents Chemother. 2008;52(11):4069–4071. doi: 10.1128/AAC.00078-08
  52. Ashiru O, Howe JD, Butters TD. Nitazoxanide, an antiviral thiazolide, depletes ATP-sensitive intracellular Ca(2+) stores. Virology. 2014;462–463:135–148. doi: 10.1016/j.virol.2014.05.015
  53. Sekiba K, Otsuka M, Funato K, et al. HBx-induced degradation of Smc5/6 complex impairs homologous recombination-mediated repair of damaged DNA. J Hepatol. 2022;76(1):53–62. doi: 10.1016/j.jhep.2021.08.010
  54. Schollmeier A, Glitscher M, Hildt E. Relevance of hbx for hepatitis B virus-associated pathogenesis. Int J Mol Sci. 2023;24(5):4964. doi: 10.3390/ijms24054964
  55. Sekiba K, Otsuka M, Ohno M, et al. Inhibition of HBV transcription from CCCDNA with nitazoxanide by targeting the HBX-DDB1 interaction. Cell Mol Gastroenterol Hepatol. 2019;7(2):297–312. doi: 10.1016/j.jcmgh.2018.10.010
  56. Nikolova K, Gluud C, Grevstad B, Jakobsen JC. Nitazoxanide for chronic hepatitis C. Cochrane Database Syst Rev. 2014;(4):CD009182. doi: 10.1002/14651858.CD009182.pub2
  57. Shehab HM, Elbaz TM, Deraz DM. Nitazoxanide plus pegylated interferon and ribavirin in the treatment of genotype 4 chronic hepatitis C, a randomized controlled trial. Liver Int. 2014;34(2):259–265. doi: 10.1111/liv.12267
  58. Kolozsi WZ, El-Gohary M, Keeffe MB, et al. Treatment of chronic hepatitis B (CHB) with nitazoxanide (Ntz) alone or Ntz plus adefovir (ADV) for two years with loss of hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HbsAg). Am J Gastroenterol. 2008;103: S150–S151. doi: 10.14309/00000434-200809001-00390
  59. Rossignol JF, Bréchot C. A pilot clinical trial of nitazoxanide in the treatment of chronic hepatitis B. Hepatol Commun. 2019;3(6): 744–747. doi: 10.1002/hep4.1339
  60. Jasenosky LD, Cadena C, Mire CE, et al. The FDA-approved oral drug nitazoxanide amplifies host antiviral responses and inhibits Ebola virus. iScience. 2019;19:1279–1290. doi: 10.1016/j.isci.2019.07.003
  61. Matsumiya T, Stafforini DM. Function and regulation of retinoic acid-inducible gene-I. Crit Rev Immunol. 2010;30(6):489–513. doi: 10.1615/critrevimmunol.v30.i6.10
  62. Zou PF, Tang JC, Li Y, et al. MAVS splicing variants associated with TRAF3 and TRAF6 in NF-κB and IRF3 signaling pathway in large yellow croaker Larimichthys crocea. Dev Comp Immunol. 2021;121:104076. doi: 10.1016/j.dci.2021.104076
  63. Tilmanis D, van Baalen C, Oh DY, et al. The susceptibility of circulating human influenza viruses to tizoxanide, the active metabolite of nitazoxanide. Antiviral Res. 2017;147:142–148. doi: 10.1016/j.antiviral.2017.10.002
  64. Haffizulla J, Hartman A, Hoppers M, et al.; US Nitazoxanide Influenza Clinical Study Group. Effect of nitazoxanide in adults and adolescents with acute uncomplicated influenza: a double-blind, randomised, placebo-controlled, phase 2b/3 trial. Lancet Infect Dis. 2014;14(7):609–618. doi: 10.1016/S1473-3099(14)70717-0
  65. Piacentini S, La Frazia S, Riccio A, et al. Nitazoxanide inhibits paramyxovirus replication by targeting the Fusion protein folding: role of glycoprotein-specific thiol oxidoreductase ERp57. Sci Rep. 2018;8(1):10425. doi: 10.1038/s41598-018-28172-9
  66. Perelygina L, Hautala T, Seppänen M, et al. Inhibition of rubella virus replication by the broad-spectrum drug nitazoxanide in cell culture and in a patient with a primary immune deficiency. Antiviral Res. 2017;147:58–66. doi: 10.1016/j.antiviral.2017.09.019
  67. Gao G, Liu Y, Qu H, et al. Systematic identification of synergistic drug pairs targeting HIV. Nat Biotechnol. 2012;30(11):1125–1130. doi: 10.1038/nbt.2391
  68. Clerici M, Trabattoni D, Pacei M, et al. The anti-infective nitazoxanide shows strong immumodulating effects (155.21). J Immunol. 2011;186(S1):155.21. doi: 10.4049/jimmunol.186.Supp.155.21
  69. Purandare N, Gomez-Lopez N, Arenas-Hernandez M, et al. The MNRR1 activator nitazoxanide abrogates lipopolysaccharide-induced preterm birth in mice. Placenta. 2023;140:66–71. doi: 10.1016/j.placenta.2023.07.005
  70. Di Santo N, Ehrisman J. Research perspective: potential role of nitazoxanide in ovarian cancer treatment. Old drug, new purpose? Cancers (Basel). 2013;5(3):1163–1176. doi: 10.3390/cancers5031163
  71. Wang L, Wang X, Wang CC. Protein disulfide-isomerase, a folding catalyst and a redox-regulated chaperone. Free Radic Biol Med. 2015;83:305–313. doi: 10.1016/j.freeradbiomed.2015.02.007
  72. Read A, Schröder M. The unfolded protein response: an overview. Biology (Basel). 2021;10(5):384. doi: 10.3390/biology10050384
  73. Moenner M, Pluquet O, Bouchecareilh M, Chevet E. Integrated endoplasmic reticulum stress responses in cancer. Cancer Res. 2007;67(2):10631–10634. doi: 10.1158/0008-5472.CAN-07-1705
  74. Lovat PE, Corazzari M, Armstrong JL, et al. Increasing melanoma cell death using inhibitors of protein disulfide isomerases to abrogate survival responses to endoplasmic reticulum stress. Cancer Res. 2008;68(13):5363–5369. doi: 10.1158/0008-5472.CAN-08-0035
  75. Dickerhof N, Kleffmann T, Jack R, McCormick S. Bacitracin inhibits the reductive activity of protein disulfide isomerase by disulfide bond formation with free cysteines in the substrate-binding domain. FEBS J. 2011;278(12):2034–2043. doi: 10.1111/j.1742-4658.2011.08119.x
  76. Müller J, Naguleswaran A, Müller N, Hemphill A. Neospora caninum: Functional inhibition of protein disulfide isomerase by the broad-spectrum anti-parasitic drug nitazoxanide and other thiazolides. Exp Parasitol. 2008;118(1):80–88. doi: 10.1016/j.exppara.2007.06.008
  77. Lane D, Matte I, Rancourt C, Piché A. Prognostic significance of IL-6 and IL-8 ascites levels in ovarian cancer patients. BMC Cancer. 2011;11:210. doi: 10.1186/1471-2407-11-210
  78. Naugler WE, Karin M. The wolf in sheep' s clothing: The role of interleukin-6 in immunity, inflammation and cancer. Trends Mol Med. 2008;14(3):109–119. doi: 10.1016/j.molmed.2007.12.007
  79. Hong SK, Kim HJ, Song CS, et al. Nitazoxanide suppresses IL-6 production in LPS-stimulated mouse macrophages and TG-injected mice. Int Immunopharmacol. 2012;13(1):23–27. doi: 10.1016/j.intimp.2012.03.002
  80. Sun H, Ou T, Hu J, et al. Nitazoxanide impairs mitophagy flux through ROS-mediated mitophagy initiation and lysosomal dysfunction in bladder cancer. Biochem Pharmacol. 2021;190:114588. doi: 10.1016/j.bcp.2021.114588
  81. Ding WX, Yin XM. Mitophagy: mechanisms, pathophysiological roles, and analysis. Biol Chem. 2012;393(7):547–564. doi: 10.1515/hsz-2012-0119
  82. Ezeriņa D, Takano Y, Hanaoka K, et al. N-Acetyl cysteine functions as a fast-acting antioxidant by triggering intracellular H2S and sulfane sulfur production. Cell Chem Biol. 2018;25(4):447–459.e4. doi: 10.1016/j.chembiol.2018.01.011
  83. Mauthe M, Orhon I, Rocchi C, et al. Chloroquine inhibits autophagic flux by decreasing autophagosome-lysosome fusion. Autophagy. 2018;14(8):1435–1455. doi: 10.1080/15548627.2018.1474314
  84. Nguyen TT, Ung TT, Kim NH, Jung YD. Role of bile acids in colon carcinogenesis. World J Clin Cases. 2018;6(13):577–588. doi: 10.12998/wjcc.v6.i13.577
  85. NTZ Increases β-catenin Citrullination to Suppress WNT Signaling. Cancer Discov. 2018;8(1):OF19. doi: 10.1158/2159-8290.CD-RW2017-214
  86. Yu J, Yang K, Zheng J, et al. Synergistic tumor inhibition of colon cancer cells by nitazoxanide and obeticholic acid, a farnesoid X receptor ligand. Cancer Gene Ther. 2021;28(6):590–601. doi: 10.1038/s41417-020-00239-8
  87. Emran TB, Shahriar A, Mahmud AR, et al. Multidrug resistance in cancer: understanding molecular mechanisms, immunoprevention and therapeutic approaches. Front Oncol. 2022;12:891652. doi: 10.3389/fonc.2022.891652
  88. Hodges LM, Markova SM, Chinn LW, et al. Very important pharmacogene summary: ABCB1 (MDR1, P-glycoprotein). Pharmacogenet Genomics. 2011;21(3):152–161. doi: 10.1097/FPC.0b013e3283385a1c
  89. Cargnello M, Roux PP. Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases. Microbiol Mol Biol Rev. 2011;75(1):50–83. doi: 10.1128/MMBR.00031-10
  90. Hemmati-Dinarvand M, Ahmadvand H, Seghatoleslam A. Nitazoxanide and cancer drug resistance: targeting Wnt/β-catenin signaling pathway. Arch Med Res. 2022;53(3):263–270. doi: 10.1016/j.arcmed.2021.12.001
  91. Li H, Zeng J, Shen K. PI3K/AKT/mTOR signaling pathway as a therapeutic target for ovarian cancer. Arch Gynecol Obstet. 2014;290(6):1067–1078. doi: 10.1007/s00404-014-3377-3
  92. Ye C, Wei M, Huang H, et al. Nitazoxanide inhibits osteosarcoma cells growth and metastasis by suppressing AKT/mTOR and Wnt/β-catenin signaling pathways. Biol Chem. 2022;403(10): 929–943. doi: 10.1515/hsz-2022-0148
  93. Karlsson H, Fryknäs M, Senkowski W, et al. Selective radiosensitization by nitazoxanide of quiescent clonogenic colon cancer tumour cells. Oncol Lett. 2022;23(4):123. doi: 10.3892/ol.2022.13243
  94. Lü Z, Li X, Li K, et al. Nitazoxanide and related thiazolides induce cell death in cancer cells by targeting the 20S proteasome with novel binding modes. Biochem Pharmacol. 2022;197:114913. doi: 10.1016/j.bcp.2022.114913
  95. Coux O, Tanaka K, Goldberg AL. Structure and functions of the 20S and 26S proteasomes. Annu Rev Biochem. 1996;65:801–847. doi: 10.1146/annurev.bi.65.070196.004101
  96. Ghaleb AM, Nandan MO, Chanchevalap S, et al. Krüppel-like factors 4 and 5: the yin and yang regulators of cellular proliferation. Cell Res. 2005;15(2):92–96. doi: 10.1038/sj.cr.7290271
  97. MYBL2 MYB proto-oncogene like 2 [Homo sapiens (human)] Gene ID: 4605, updated on 10-Oct-2023
  98. Huang Q, Liu M, Zhang D, et al. Nitazoxanide inhibits acetylated KLF5-induced bone metastasis by modulating KLF5 function in prostate cancer. BMC Med. 2023;21(1):68. doi: 10.1186/s12916-023-02763-4

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Согласие на обработку персональных данных с помощью сервиса «Яндекс.Метрика»

1. Я (далее – «Пользователь» или «Субъект персональных данных»), осуществляя использование сайта https://journals.rcsi.science/ (далее – «Сайт»), подтверждая свою полную дееспособность даю согласие на обработку персональных данных с использованием средств автоматизации Оператору - федеральному государственному бюджетному учреждению «Российский центр научной информации» (РЦНИ), далее – «Оператор», расположенному по адресу: 119991, г. Москва, Ленинский просп., д.32А, со следующими условиями.

2. Категории обрабатываемых данных: файлы «cookies» (куки-файлы). Файлы «cookie» – это небольшой текстовый файл, который веб-сервер может хранить в браузере Пользователя. Данные файлы веб-сервер загружает на устройство Пользователя при посещении им Сайта. При каждом следующем посещении Пользователем Сайта «cookie» файлы отправляются на Сайт Оператора. Данные файлы позволяют Сайту распознавать устройство Пользователя. Содержимое такого файла может как относиться, так и не относиться к персональным данным, в зависимости от того, содержит ли такой файл персональные данные или содержит обезличенные технические данные.

3. Цель обработки персональных данных: анализ пользовательской активности с помощью сервиса «Яндекс.Метрика».

4. Категории субъектов персональных данных: все Пользователи Сайта, которые дали согласие на обработку файлов «cookie».

5. Способы обработки: сбор, запись, систематизация, накопление, хранение, уточнение (обновление, изменение), извлечение, использование, передача (доступ, предоставление), блокирование, удаление, уничтожение персональных данных.

6. Срок обработки и хранения: до получения от Субъекта персональных данных требования о прекращении обработки/отзыва согласия.

7. Способ отзыва: заявление об отзыве в письменном виде путём его направления на адрес электронной почты Оператора: info@rcsi.science или путем письменного обращения по юридическому адресу: 119991, г. Москва, Ленинский просп., д.32А

8. Субъект персональных данных вправе запретить своему оборудованию прием этих данных или ограничить прием этих данных. При отказе от получения таких данных или при ограничении приема данных некоторые функции Сайта могут работать некорректно. Субъект персональных данных обязуется сам настроить свое оборудование таким способом, чтобы оно обеспечивало адекватный его желаниям режим работы и уровень защиты данных файлов «cookie», Оператор не предоставляет технологических и правовых консультаций на темы подобного характера.

9. Порядок уничтожения персональных данных при достижении цели их обработки или при наступлении иных законных оснований определяется Оператором в соответствии с законодательством Российской Федерации.

10. Я согласен/согласна квалифицировать в качестве своей простой электронной подписи под настоящим Согласием и под Политикой обработки персональных данных выполнение мною следующего действия на сайте: https://journals.rcsi.science/ нажатие мною на интерфейсе с текстом: «Сайт использует сервис «Яндекс.Метрика» (который использует файлы «cookie») на элемент с текстом «Принять и продолжить».