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Article

The synergistic effect of DZ‑NEP, panobinostat and temozolomide reduces clonogenicity and induces apoptosis in glioblastoma cells

  • Authors:
    • Javier De La Rosa
    • Alejandro Urdiciain
    • Idoya Zazpe
    • María V. Zelaya
    • Bárbara Meléndez
    • Juan A. Rey
    • Miguel A. Idoate
    • Javier S. Castresana
  • View Affiliations / Copyright

    Affiliations: Department of Biochemistry and Genetics, University of Navarra School of Sciences, 31008 Pamplona, Spain, Department of Neurosurgery, Hospital Complex of Navarra, 31008 Pamplona, Spain, Department of Pathology, Hospital Complex of Navarra, 31008 Pamplona, Spain, Molecular Pathology Research Unit, Department of Pathology, Virgen de la Salud Hospital, 45005 Toledo, Spain, IdiPaz Research Unit, La Paz University Hospital, 28046 Madrid, Spain, Department of Pathology, University of Navarra Clinic, 31008 Pamplona, Spain
  • Pages: 283-300
    |
    Published online on: October 30, 2019
       https://doi.org/10.3892/ijo.2019.4905
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Abstract

Current treatment against glioblastoma consists of surgical resection followed by temozolomide, with or without combined radiotherapy. Glioblastoma frequently acquires resistance to chemotherapy and/or radiotherapy. Novel therapeutic approaches are thus required. The inhibition of enhancer of zeste homolog 2 (EZH2; a histone methylase) and histone deacetylases (HDACs) are possible epigenetic treatments. Temozolomide, 3‑deazaneplanocin A (DZ‑Nep; an EZH2 inhibitor) and panobinostat (an HDAC inhibitor) were tested in regular and temozolomide‑resistant glioblastoma cells to confirm whether the compounds could behave in a synergistic, additive or antagonistic manner. A total of six commercial cell lines, two temozolomide‑induced resistant cell lines and two primary cultures derived from glioblastoma samples were used. Cell lines were exposed to single treatments of the drugs in addition to all possible two‑ and three‑drug combinations. Colony formation assays, synergistic assays and reverse transcription‑quantitative PCR analysis of apoptosis‑associated genes were performed. The highest synergistic combination was DZ‑Nep + panobinostat. Triple treatment was also synergistic. Reduced clonogenicity and increased apoptosis were both induced. It was concluded that the therapeutic potential of the combination of these three drugs in glioblastoma was evident and should be further explored.
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View References

1 

Veliz I, Loo Y, Castillo O, Karachaliou N, Nigro O and Rosell R: Advances and challenges in the molecular biology and treatment of glioblastoma-is there any hope for the future? Ann Transl Med. 3:72015.PubMed/NCBI

2 

Verhaak RG, Hoadley KA, Purdom E, Wang V, Qi Y, Wilkerson MD, Miller CR, Ding L, Golub T, Mesirov JP, et al Cancer Genome Atlas Research Network: Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell. 17:98–110. 2010. View Article : Google Scholar : PubMed/NCBI

3 

Fan TY, Wang H, Xiang P, Liu YW, Li HZ, Lei BX, Yu M and Qi ST: Inhibition of EZH2 reverses chemotherapeutic drug TMZ chemosensitivity in glioblastoma. Int J Clin Exp Pathol. 7:6662–6670. 2014.PubMed/NCBI

4 

Network CGAR; Cancer Genome Atlas Research Network: Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature. 455:1061–1068. 2008. View Article : Google Scholar : PubMed/NCBI

5 

Lo HW: EGFR-targeted therapy in malignant glioma: Novel aspects and mechanisms of drug resistance. Curr Mol Pharmacol. 3:37–52. 2010. View Article : Google Scholar

6 

Quick A, Patel D, Hadziahmetovic M, Chakravarti A and Mehta M: Current therapeutic paradigms in glioblastoma. Rev Recent Clin Trials. 5:14–27. 2010. View Article : Google Scholar : PubMed/NCBI

7 

Eyüpoglu IY and Savaskan NE: Epigenetics in Brain Tumors: HDACs Take Center Stage. Curr Neuropharmacol. 14:48–54. 2016. View Article : Google Scholar :

8 

Ferreira WA, Pinheiro DR, Costa Junior CA, Rodrigues-Antunes S, Araújo MD, Leão Barros MB, Teixeira AC, Faro TA, Burbano RR, Oliveira EH, et al: An update on the epigenetics of glioblastomas. Epigenomics. 8:1289–1305. 2016. View Article : Google Scholar : PubMed/NCBI

9 

Gusyatiner O and Hegi ME: Glioma epigenetics: From subclassification to novel treatment options. Semin Cancer Biol. 51:50–58. 2018. View Article : Google Scholar

10 

Kreth S, Thon N and Kreth FW: Epigenetics in human gliomas. Cancer Lett. 342:185–192. 2014. View Article : Google Scholar

11 

Yong RL and Tsankova NM: Emerging interplay of genetics and epigenetics in gliomas: A new hope for targeted therapy. Semin Pediatr Neurol. 22:14–22. 2015. View Article : Google Scholar : PubMed/NCBI

12 

Chen J, Zhang M, Zhang X, Fan L, Liu P, Yu L, Cao X, Qiu S and Xu Y: EZH2 inhibitor DZNep modulates microglial activation and protects against ischaemic brain injury after experimental stroke. Eur J Pharmacol. 857:1724522019. View Article : Google Scholar : PubMed/NCBI

13 

Atadja P: Development of the pan-DAC inhibitor panobinostat (LBH589): Successes and challenges. Cancer Lett. 280:233–241. 2009. View Article : Google Scholar : PubMed/NCBI

14 

Gall Trošelj K, Novak Kujundzic R and Ugarkovic D: Polycomb repressive complex's evolutionary conserved function: The role of EZH2 status and cellular background. Clin Epigenetics. 8:552016. View Article : Google Scholar

15 

Rao ZY, Cai MY, Yang GF, He LR, Mai SJ, Hua WF, Liao YJ, Deng HX, Chen YC, Guan XY, et al: EZH2 supports ovarian carcinoma cell invasion and/or metastasis via regulation of TGF-beta1 and is a predictor of outcome in ovarian carcinoma patients. Carcinogenesis. 31:1576–1583. 2010. View Article : Google Scholar : PubMed/NCBI

16 

Li K, Liu C, Zhou B, Bi L, Huang H, Lin T and Xu K: Role of EZH2 in the growth of prostate cancer stem cells isolated from LNCaP cells. Int J Mol Sci. 14:11981–11993. 2013. View Article : Google Scholar : PubMed/NCBI

17 

Zhang Y, Yu X, Chen L, Zhang Z and Feng S: EZH2 overexpression is associated with poor prognosis in patients with glioma. Oncotarget. 8:565–573. 2017.

18 

Crea F, Fornaro L, Bocci G, Sun L, Farrar WL, Falcone A and Danesi R: EZH2 inhibition: Targeting the crossroad of tumor invasion and angiogenesis. Cancer Metastasis Rev. 31:753–761. 2012. View Article : Google Scholar : PubMed/NCBI

19 

Hayden A, Johnson PW, Packham G and Crabb SJ: S-adenosylhomocysteine hydrolase inhibition by 3-deazaneplanocin A analogues induces anti-cancer effects in breast cancer cell lines and synergy with both histone deacetylase and HER2 inhibition. Breast Cancer Res Treat. 127:109–119. 2011. View Article : Google Scholar

20 

Kemp CD, Rao M, Xi S, Inchauste S, Mani H, Fetsch P, Filie A, Zhang M, Hong JA, Walker RL, et al: Polycomb repressor complex-2 is a novel target for mesothelioma therapy. Clin Cancer Res. 18:77–90. 2012. View Article : Google Scholar

21 

Suvà ML, Riggi N, Janiszewska M, Radovanovic I, Provero P, Stehle JC, Baumer K, Le Bitoux MA, Marino D, Cironi L, et al: EZH2 is essential for glioblastoma cancer stem cell maintenance. Cancer Res. 69:9211–9218. 2009. View Article : Google Scholar : PubMed/NCBI

22 

Crea F, Hurt EM, Mathews LA, Cabarcas SM, Sun L, Marquez VE, Danesi R and Farrar WL: Pharmacologic disruption of Polycomb Repressive Complex 2 inhibits tumorigenicity and tumor progression in prostate cancer. Mol Cancer. 10:402011. View Article : Google Scholar : PubMed/NCBI

23 

Chiba T, Suzuki E, Negishi M, Saraya A, Miyagi S, Konuma T, Tanaka S, Tada M, Kanai F, Imazeki F, et al: 3-Deazaneplanocin A is a promising therapeutic agent for the eradication of tumor-initiating hepatocellular carcinoma cells. Int J Cancer. 130:2557–2567. 2012. View Article : Google Scholar

24 

Smits M, Mir SE, Nilsson RJ, van der Stoop PM, Niers JM, Marquez VE, Cloos J, Breakefield XO, Krichevsky AM, Noske DP, et al: Down-regulation of miR-101 in endothelial cells promotes blood vessel formation through reduced repression of EZH2. PLoS One. 6:e162822011. View Article : Google Scholar : PubMed/NCBI

25 

Yamagishi M and Uchimaru K: Targeting EZH2 in cancer therapy. Curr Opin Oncol. 29:375–381. 2017. View Article : Google Scholar : PubMed/NCBI

26 

Yan KS, Lin CY, Liao TW, Peng CM, Lee SC, Liu YJ, Chan WP and Chou RH: EZH2 in Cancer Progression and Potential Application in Cancer Therapy: A Friend or Foe? Int J Mol Sci. 18:182017. View Article : Google Scholar

27 

Kim KH and Roberts CW: Targeting EZH2 in cancer. Nat Med. 22:128–134. 2016. View Article : Google Scholar : PubMed/NCBI

28 

Yu C, Friday BB, Yang L, Atadja P, Wigle D, Sarkaria J and Adjei AA: Mitochondrial Bax translocation partially mediates synergistic cytotoxicity between histone deacetylase inhibitors and proteasome inhibitors in glioma cells. Neuro Oncol. 10:309–319. 2008. View Article : Google Scholar : PubMed/NCBI

29 

Berghauser Pont LM, Kleijn A, Kloezeman JJ, van den Bossche W, Kaufmann JK, de Vrij J, Leenstra S, Dirven CM and Lamfers ML: The HDAC Inhibitors Scriptaid and LBH589 Combined with the Oncolytic Virus Delta24-RGD Exert Enhanced Anti-Tumor Efficacy in Patient-Derived Glioblastoma Cells. PLoS One. 10:e01270582015. View Article : Google Scholar : PubMed/NCBI

30 

Lee EQ, Reardon DA, Schiff D, Drappatz J, Muzikansky A, Grimm SA, Norden AD, Nayak L, Beroukhim R, Rinne ML, et al: Phase II study of panobinostat in combination with bevacizumab for recurrent glioblastoma and anaplastic glioma. Neuro Oncol. 17:862–867. 2015. View Article : Google Scholar : PubMed/NCBI

31 

Pont LM, Naipal K, Kloezeman JJ, Venkatesan S, van den Bent M, van Gent DC, Dirven CM, Kanaar R, Lamfers ML and Leenstra S: DNA damage response and anti-apoptotic proteins predict radiosensitization efficacy of HDAC inhibitors SAHA and LBH589 in patient-derived glioblastoma cells. Cancer Lett. 356(2 Pt B): 525–535. 2015. View Article : Google Scholar

32 

Singleton WG, Collins AM, Bienemann AS, Killick-Cole CL, Haynes HR, Asby DJ, Butts CP, Wyatt MJ, Barua NU and Gill SS: Convection enhanced delivery of panobinostat (LBH589)-loaded pluronic nano-micelles prolongs survival in the F98 rat glioma model. Int J Nanomedicine. 12:1385–1399. 2017. View Article : Google Scholar : PubMed/NCBI

33 

Yao ZG, Li WH, Hua F, Cheng HX, Zhao MQ, Sun XC, Qin YJ and Li JM: LBH589 Inhibits Glioblastoma Growth and Angiogenesis Through Suppression of HIF-1α Expression. J Neuropathol Exp Neurol. 76:1000–1007. 2017. View Article : Google Scholar : PubMed/NCBI

34 

Li Y and Seto E: HDACs and HDAC Inhibitors in Cancer Development and Therapy. Cold Spring. Harb Perspect Med. 6:62016.

35 

De Souza C and Chatterji BP: HDAC Inhibitors as Novel Anti-Cancer Therapeutics. Recent Patents Anticancer Drug Discov. 10:145–162. 2015. View Article : Google Scholar

36 

Turtoi A, Peixoto P, Castronovo V and Bellahcène A: Histone deacetylases and cancer-associated angiogenesis: Current understanding of the biology and clinical perspectives. Crit Rev Oncog. 20:119–137. 2015. View Article : Google Scholar : PubMed/NCBI

37 

Aum DJ, Kim DH, Beaumont TL, Leuthardt EC, Dunn GP and Kim AH: Molecular and cellular heterogeneity: The hallmark of glioblastoma. Neurosurg Focus. 37:E112014. View Article : Google Scholar : PubMed/NCBI

38 

Friedmann-Morvinski D: Glioblastoma heterogeneity and cancer cell plasticity. Crit Rev Oncog. 19:327–336. 2014. View Article : Google Scholar : PubMed/NCBI

39 

Greco WR, Bravo G and Parsons JC: The search for synergy: A critical review from a response surface perspective. Pharmacol Rev. 47:331–385. 1995.PubMed/NCBI

40 

Goldin A and Mantel N: The employment of combinations of drugs in the chemotherapy of neoplasia: A review. Cancer Res. 17:635–654. 1957.PubMed/NCBI

41 

Chou TC and Talalay P: Quantitative analysis of dose-effect relationships: The combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul. 22:27–55. 1984. View Article : Google Scholar : PubMed/NCBI

42 

Berenbaum MC: Synergy, additivism and antagonism in immunosuppression. A critical review Clin Exp Immunol. 28:1–18. 1977.

43 

Loewe S: Marginal notes on the quantitative pharmacology of combined drugs. Arzneimittelforschung. 9:449–456. 1959.In German. PubMed/NCBI

44 

Chou TC: Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies. Pharmacol Rev. 58:621–681. 2006. View Article : Google Scholar : PubMed/NCBI

45 

Foucquier J and Guedj M: Analysis of drug combinations: Current methodological landscape. Pharmacol Res Perspect. 3:e001492015. View Article : Google Scholar : PubMed/NCBI

46 

Chou TC: Drug combination studies and their synergy quantification using the Chou-Talalay method. Cancer Res. 70:440–446. 2010. View Article : Google Scholar : PubMed/NCBI

47 

Chou T and Martin N: CompuSyn Software for Drug Combinations and for General Dose Effect Analysis. ComboSyn, Inc.; Paramus, NJ: 2007

48 

Johannessen TC, Hasan-Olive MM, Zhu H, Denisova O, Grudic A, Latif MA, Saed H, Varughese JK, Røsland GV, Yang N, et al: Thioridazine inhibits autophagy and sensitizes glioblastoma cells to temozolomide. Int J Cancer. 144:1735–1745. 2019. View Article : Google Scholar

49 

Smits M, Nilsson J, Mir SE, van der Stoop PM, Hulleman E, Niers JM, de Witt Hamer PC, Marquez VE, Cloos J, Krichevsky AM, et al: miR-101 is down-regulated in glioblastoma resulting in EZH2-induced proliferation, migration, and angiogenesis. Oncotarget. 1:710–720. 2010. View Article : Google Scholar

50 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)). Method Methods. 25:402–408. 2001. View Article : Google Scholar

51 

Lee SY: Temozolomide resistance in glioblastoma multiforme. Genes Dis. 3:198–210. 2016. View Article : Google Scholar : PubMed/NCBI

52 

Fiskus W, Rao R, Balusu R, Ganguly S, Tao J, Sotomayor E, Mudunuru U, Smith JE, Hembruff SL, Atadja P, et al: Superior efficacy of a combined epigenetic therapy against human mantle cell lymphoma cells. Clin Cancer Res. 18:6227–6238. 2012. View Article : Google Scholar : PubMed/NCBI

53 

Fiskus W, Wang Y, Sreekumar A, Buckley KM, Shi H, Jillella A, Ustun C, Rao R, Fernandez P, Chen J, et al: Combined epigenetic therapy with the histone methyltransferase EZH2 inhibitor 3-deazaneplanocin A and the histone deacetylase inhibitor panobinostat against human AML cells. Blood. 114:2733–2743. 2009. View Article : Google Scholar : PubMed/NCBI

54 

Takashina T, Kinoshita I, Kikuchi J, Shimizu Y, Sakakibara-Konishi J, Oizumi S, Nishimura M and Dosaka-Akita H: Combined inhibition of EZH2 and histone deacetylases as a potential epigenetics therapy for non-small-cell lung cancer cells. Cancer Sci. 107:955–962. 2016. View Article : Google Scholar : PubMed/NCBI

55 

Ding L, Chen S, Liu P, Pan Y, Zhong J, Regan KM, Wang L, Yu C, Rizzardi A, Cheng L, et al: CBP loss cooperates with PTEN haploinsufficiency to drive prostate cancer: Implications for epigenetic therapy. Cancer Res. 74:2050–2061. 2014. View Article : Google Scholar : PubMed/NCBI

56 

Çıtışlı V, Dodurga Y, Eroğlu C, Seçme M, Avcı CB and Şatıroğlu-Tufan NL: Temozolomide may induce cell cycle arrest by interacting with URG4/URGCP in SH-SY5Y neuroblastoma cells. Tumour Biol. 36:6765–6772. 2015. View Article : Google Scholar

57 

Pawlowska E, Szczepanska J, Szatkowska M and Blasiak J: An Interplay between Senescence, Apoptosis and Autophagy in Glioblastoma Multiforme-Role in Pathogenesis and Therapeutic Perspective. Int J Mol Sci. 19:32018. View Article : Google Scholar

58 

Perazzoli G, Prados J, Ortiz R, Caba O, Cabeza L, Berdasco M, Gónzalez B and Melguizo C: Temozolomide Resistance in Glioblastoma Cell Lines: Implication of MGMT, MMR, P-Glycoprotein and CD133 Expression. PLoS One. 10:e01401312015. View Article : Google Scholar : PubMed/NCBI

59 

Dong J, Meng X, Li S, Chen Q, Shi L, Jiang C and Cai J: Risk of adverse vascular events in patients with malignant glioma treated with bevacizumab plus irinotecan: A systematic review and meta-analysis. World Neurosurg. 130:e236–e243. 2019. View Article : Google Scholar : PubMed/NCBI

60 

Zhang R, Banik NL and Ray SK: Differential sensitivity of human glioblastoma LN18 (PTEN-positive) and A172 (PTEN-negative) cells to Taxol for apoptosis. Brain Res. 1239:216–225. 2008. View Article : Google Scholar : PubMed/NCBI

61 

Patyka M, Sharifi Z, Petrecca K, Mansure J, Jean-Claude B and Sabri S: Sensitivity to PRIMA-1MET is associated with decreased MGMT in human glioblastoma cells and glioblastoma stem cells irrespective of p53 status. Oncotarget. 7:60245–60269. 2016. View Article : Google Scholar : PubMed/NCBI

62 

Koul D, Wang S, Wu S, Saito N, Zheng S, Gao F, Kaul I, Setoguchi M, Nakayama K, Koyama K, et al: Preclinical therapeutic efficacy of a novel blood-brain barrier-penetrant dual PI3K/mTOR inhibitor with preferential response in PI3K/PTEN mutant glioma. Oncotarget. 8:21741–21753. 2017. View Article : Google Scholar : PubMed/NCBI

63 

Hill VK, Kim JS, James CD and Waldman T: Correction of PTEN mutations in glioblastoma cell lines via AAV-mediated gene editing. PLoS One. 12:e01766832017. View Article : Google Scholar : PubMed/NCBI

64 

Muñoz J, Inda MM, Lázcoz P, Zazpe I, Fan X, Alfaro J, Tuñón T, Rey JA and Castresana JS: Promoter Methylation of RASSF1A Associates to Adult Secondary Glioblastomas and Pediatric Glioblastomas. ISRN Neurol. 2012:5765782012. View Article : Google Scholar : PubMed/NCBI

65 

de la Rosa J, Urdiciain A, Aznar-Morales JJ, Meléndez B, Rey JA, Idoate MA and Castresana JS: Panobinostat and its combination with 3-deazaneplanocin-A induce apoptosis and inhibit In vitro tumorigenesis and metastasis in GOS-3 glioblastoma cell lines. Cancer Transl Med. 4:39–47. 2018. View Article : Google Scholar

66 

Forget KJ, Tremblay G and Roucou X: p53 Aggregates penetrate cells and induce the co-aggregation of intracellular p53. PLoS One. 8:e692422013. View Article : Google Scholar : PubMed/NCBI

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De La Rosa J, Urdiciain A, Zazpe I, Zelaya MV, Meléndez B, Rey JA, Idoate MA and Castresana JS: The synergistic effect of DZ‑NEP, panobinostat and temozolomide reduces clonogenicity and induces apoptosis in glioblastoma cells. Int J Oncol 56: 283-300, 2020.
APA
De La Rosa, J., Urdiciain, A., Zazpe, I., Zelaya, M.V., Meléndez, B., Rey, J.A. ... Castresana, J.S. (2020). The synergistic effect of DZ‑NEP, panobinostat and temozolomide reduces clonogenicity and induces apoptosis in glioblastoma cells. International Journal of Oncology, 56, 283-300. https://doi.org/10.3892/ijo.2019.4905
MLA
De La Rosa, J., Urdiciain, A., Zazpe, I., Zelaya, M. V., Meléndez, B., Rey, J. A., Idoate, M. A., Castresana, J. S."The synergistic effect of DZ‑NEP, panobinostat and temozolomide reduces clonogenicity and induces apoptosis in glioblastoma cells". International Journal of Oncology 56.1 (2020): 283-300.
Chicago
De La Rosa, J., Urdiciain, A., Zazpe, I., Zelaya, M. V., Meléndez, B., Rey, J. A., Idoate, M. A., Castresana, J. S."The synergistic effect of DZ‑NEP, panobinostat and temozolomide reduces clonogenicity and induces apoptosis in glioblastoma cells". International Journal of Oncology 56, no. 1 (2020): 283-300. https://doi.org/10.3892/ijo.2019.4905
Copy and paste a formatted citation
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Spandidos Publications style
De La Rosa J, Urdiciain A, Zazpe I, Zelaya MV, Meléndez B, Rey JA, Idoate MA and Castresana JS: The synergistic effect of DZ‑NEP, panobinostat and temozolomide reduces clonogenicity and induces apoptosis in glioblastoma cells. Int J Oncol 56: 283-300, 2020.
APA
De La Rosa, J., Urdiciain, A., Zazpe, I., Zelaya, M.V., Meléndez, B., Rey, J.A. ... Castresana, J.S. (2020). The synergistic effect of DZ‑NEP, panobinostat and temozolomide reduces clonogenicity and induces apoptosis in glioblastoma cells. International Journal of Oncology, 56, 283-300. https://doi.org/10.3892/ijo.2019.4905
MLA
De La Rosa, J., Urdiciain, A., Zazpe, I., Zelaya, M. V., Meléndez, B., Rey, J. A., Idoate, M. A., Castresana, J. S."The synergistic effect of DZ‑NEP, panobinostat and temozolomide reduces clonogenicity and induces apoptosis in glioblastoma cells". International Journal of Oncology 56.1 (2020): 283-300.
Chicago
De La Rosa, J., Urdiciain, A., Zazpe, I., Zelaya, M. V., Meléndez, B., Rey, J. A., Idoate, M. A., Castresana, J. S."The synergistic effect of DZ‑NEP, panobinostat and temozolomide reduces clonogenicity and induces apoptosis in glioblastoma cells". International Journal of Oncology 56, no. 1 (2020): 283-300. https://doi.org/10.3892/ijo.2019.4905
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