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Anti-tumor and anti-metastasis efficacy of E6201, a MEK1 inhibitor, in preclinical models of triple-negative breast cancer

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Breast Cancer Research and Treatment Aims and scope Submit manuscript

A Correction to this article was published on 15 April 2019

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Abstract

Purpose

Triple-negative breast cancer (TNBC) lacks the receptor targets estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2, and thus, it does not respond to receptor-targeted treatments. TNBC has higher recurrence, metastasis, and mortality rates than other subtypes of breast cancer. Mounting data suggest that the MAPK (also known as RAS-RAF-MEK-ERK) pathway is an important therapeutic target in TNBC.

Methods

To evaluate anti-tumor and anti-metastasis efficacy of E6201, we used cell proliferation assay, soft agar assay, cell cycle assay, Annexin V staining assay, immunoblotting analysis, immunohistochemistry, migration assay, invasion assay, mammary fat pad xenograft, and experimental and spontaneous metastasis xenograft models. We also evaluated the anti-tumor efficacy of E6201 plus CDK4/6 inhibitor, mTOR inhibitor, or ATR inhibitor.

Results

E6201 inhibited TNBC cell colony formation, migration, and invasion in a dose-dependent manner. E6201 induced G1 cell cycle arrest and apoptosis. E6201 inhibited TNBC xenograft growth and inhibited TNBC lung metastasis and improved mouse survival in experimental metastasis and spontaneous metastasis assays. Immunohistochemical staining demonstrated that E6201 decreased the metastatic burden in the lung and decreased phosphorylated ERK expression in a dose-dependent manner. Combination of E6201 with CDK4/6 inhibitor or mTOR inhibitor enhanced E6201’s in vitro anti-tumor efficacy.

Conclusion

These results indicate that E6201 exhibits anti-tumor efficacy against TNBC in vitro and anti-metastasis efficacy against TNBC in vivo. These results provide a rationale for further clinical development of E6201 as a MAPK-pathway-targeted therapy for TNBC.

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Change history

  • 15 April 2019

    Unfortunately in the original publication of the article, the author’s funding support has been mentioned incorrectly. The correct funding statement should read as “This work was supported by the Morgan Welch Inflammatory Breast Cancer Research Program, the State of Texas Rare and Aggressive Breast Cancer Research Program, MD Anderson’s Cancer Center Support Grant (P30CA016672, used the Characterized Cell Line Core Facility and Flow Cytometry and Cellular Imaging Facility), and Spirita Oncology, LLC.”

    The first affiliations was incorrect in the original article. The correct information is given below.

References

  1. Ismail-Khan R, Bui MM (2010) A review of triple-negative breast cancer. Cancer Control 17(3):173–176

    Article  PubMed  Google Scholar 

  2. Brouckaert O, Wildiers H, Floris G, Neven P (2012) Update on triple-negative breast cancer: prognosis and management strategies. Int J Womens Health 4:511–520

    PubMed  PubMed Central  Google Scholar 

  3. Dent R, Trudeau M, Pritchard KI, Hanna WM, Kahn HK, Sawka CA et al (2007) Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res 13(15 Pt 1):4429–4434

    Article  PubMed  Google Scholar 

  4. Santarpia L, Lippman SM, El-Naggar AK (2012) Targeting the MAPK-RAS-RAF signaling pathway in cancer therapy. Expert Opin Ther Targets 16(1):103–119

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Eroglu Z, Ribas A (2016) Combination therapy with BRAF and MEK inhibitors for melanoma: latest evidence and place in therapy. Ther Adv Med Oncol 8(1):48–56

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Tran KA, Cheng MY, Mitra A, Ogawa H, Shi VY, Olney LP et al (2016) MEK inhibitors and their potential in the treatment of advanced melanoma: the advantages of combination therapy. Drug Des Dev Ther 10:43–52

    CAS  Google Scholar 

  7. Yang Y, Liu YH, Sun X, Yu MW, Yang L, Cheng PY et al (2017) Risk of peripheral edema in cancer patients treated with MEK inhibitors: a systematic review and meta-analysis of clinical trials. Curr Med Res Opin 33(9):1663–1675

    Article  CAS  PubMed  Google Scholar 

  8. Bartholomeusz C, Xie X, Pitner MK, Kondo K, Dadbin A, Lee J et al (2015) MEK inhibitor selumetinib (AZD6244; ARRY-142886) prevents lung metastasis in a triple-negative breast cancer xenograft model. Mol Cancer Ther 14(12):2773–2781

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Lee J, Galloway R, Grandjean G, Jacob J, Humphries J, Bartholomeusz C et al (2015) Comprehensive two- and three-dimensional RNAi screening identifies PI3K inhibition as a complement to MEK inhibitor AS703026 for combination treatment of triple-negative breast cancer. J Cancer 6(12):1306–1319

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Muramoto K, Goto M, Inoue Y, Ishii N, Chiba K, Kuboi Y et al (2010) E6201, a novel kinase inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase-1 and mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase-1: in vivo effects on cutaneous inflammatory responses by topical administration. J Pharmacol Exp Ther 335(1):23–31

    Article  CAS  PubMed  Google Scholar 

  11. Ikemori-Kawada M, Inoue A, Goto M, Wang YJ, Kawakami Y (2012) Docking simulation study and kinase selectivity of f152A1 and its analogs. J Chem Inf Model 52(8):2059–2068

    Article  CAS  PubMed  Google Scholar 

  12. Byron SA, Loch DC, Wellens CL, Wortmann A, Wu J, Wang J et al (2012) Sensitivity to the MEK inhibitor E6201 in melanoma cells is associated with mutant BRAF and wildtype PTEN status. Mol Cancer 11:75

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Gampa G, Kim M, Cook-Rostie N, Laramy JK, Sarkaria JN, Paradiso L et al (2018) Brain distribution of a novel MEK inhibitor E6201: implications in the treatment of melanoma brain metastases. Drug Metab Dispos 46(5):658–666

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Tibes R, Borad MJ, Dutcus CE, Reyderman L, Feit K, Eisen A et al (2018) Safety, pharmacokinetics, and preliminary efficacy of E6201 in patients with advanced solid tumours, including melanoma: results of a phase 1 study. Br J Cancer 118(12):1580–1585

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Zhang W, Borthakur G, Gao C, Chen Y, Mu H, Ruvolo VR et al (2016) The dual MEK/FLT3 inhibitor E6201 exerts cytotoxic activity against acute myeloid leukemia cells harboring resistance-conferring FLT3 mutations. Cancer Res 76(6):1528–1537

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Carragher NO, Frame MC (2004) Focal adhesion and actin dynamics: a place where kinases and proteases meet to promote invasion. Trends Cell Biol 14(5):241–249

    Article  CAS  PubMed  Google Scholar 

  17. Wallace EM, Lyssikatos JP, Yeh T, Winkler JD, Koch K (2005) Progress towards therapeutic small molecule MEK inhibitors for use in cancer therapy. Curr Top Med Chem 5(2):215–229

    Article  CAS  PubMed  Google Scholar 

  18. Mitchell C, Yacoub A, Hossein H, Martin AP, Bareford MD, Eulitt P et al (2010) Inhibition of MCL-1 in breast cancer cells promotes cell death in vitro and in vivo. Cancer Biol Ther 10(9):903–917. https://doi.org/10.4161/cbt.10.9.13273

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Chetoui N, Sylla K, Gagnon-Houde JV, Alcaide-Loridan C, Charron D, Al-Daccak R et al (2008) Down-regulation of mcl-1 by small interfering RNA sensitizes resistant melanoma cells to fas-mediated apoptosis. Mol Cancer Res 6(1):42–52. https://doi.org/10.1158/1541-7786.MCR-07-0080

    Article  CAS  PubMed  Google Scholar 

  20. Konopleva M, Milella M, Ruvolo P, Watts JC, Ricciardi MR, Korchin B et al (2012) MEK inhibition enhances ABT-737-induced leukemia cell apoptosis via prevention of ERK-activated MCL-1 induction and modulation of MCL-1/BIM complex. Leukemia 26(4):778–787. https://doi.org/10.1038/leu.2011.287

    Article  CAS  PubMed  Google Scholar 

  21. Hermanson DL, Das SG, Li Y, Xing C (2013) Overexpression of Mcl-1 confers multidrug resistance, whereas topoisomerase IIbeta downregulation introduces mitoxantrone-specific drug resistance in acute myeloid leukemia. Mol Pharmacol 84(2):236–243. https://doi.org/10.1124/mol.113.086140

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Wu H, Schiff DS, Lin Y, Neboori HJ, Goyal S, Feng Z et al (2014) Ionizing radiation sensitizes breast cancer cells to Bcl-2 inhibitor, ABT-737, through regulating Mcl-1. Radiat Res 182(6):618–625. https://doi.org/10.1667/RR13856.1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Kawakami H, Huang S, Pal K, Dutta SK, Mukhopadhyay D, Sinicrope FA (2016) Mutant BRAF upregulates MCL-1 to confer apoptosis resistance that is reversed by MCL-1 antagonism and cobimetinib in colorectal cancer. Mol Cancer Ther 15(12):3015–3027. https://doi.org/10.1158/1535-7163.mct-16-0017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Bartholomeusz C, Xie X, Pitner MK, Kondo K, Dadbin A, Lee J et al (2015) MEK inhibitor selumetinib (AZD6244; ARRY-142886) prevents lung metastasis in a triple-negative breast cancer xenograft model. Mol Cancer Ther. https://doi.org/10.1158/1535-7163.mct-15-0243

    Article  PubMed  PubMed Central  Google Scholar 

  25. Arthur JS, Ley SC (2013) Mitogen-activated protein kinases in innate immunity. Nat Rev Immunol 13(9):679–692. https://doi.org/10.1038/nri3495

    Article  CAS  PubMed  Google Scholar 

  26. ClinicalTrials.gov (2019) Search of: MEK inhibitor|interventional studies|breast cancer—list results—ClinicalTrials.gov. https://clinicaltrials.gov/ct2/results?cond=breast+cancer&term=MEK+inhibitor&type=Intr&rslt=&age_v=&gndr=&intr=&titles=&outc=&spons=&lead=&id=&cntry=&state=&city=&dist=&locn=&strd_s=&strd_e=&prcd_s=&prcd_e=&sfpd_s=&sfpd_e=&lupd_s=&lupd_e=&sort=

  27. Cheng Y, Tian H (2017) Current Development status of MEK inhibitors. Molecules 22(10):1551

    Article  CAS  PubMed Central  Google Scholar 

  28. Albanell J, Elvin JA, Ali SM, Schrock AB, Chung J, Vergilio J-A et al (2017) BRAF: an emerging target for triple-negative breast cancer. J Clin Oncol 35(15_suppl):1099–1099

    Article  Google Scholar 

  29. Rimawi MF, Shetty PB, Weiss HL, Schiff R, Osborne CK, Chamness GC et al (2010) Epidermal growth factor receptor expression in breast cancer association with biologic phenotype and clinical outcomes. Cancer 116(5):1234–1242

    Article  PubMed  PubMed Central  Google Scholar 

  30. Law JH, Habibi G, Hu K, Masoudi H, Wang MY, Stratford AL et al (2008) Phosphorylated insulin-like growth factor-i/insulin receptor is present in all breast cancer subtypes and is related to poor survival. Cancer Res 68(24):10238–10246

    Article  CAS  PubMed  Google Scholar 

  31. Verbeek BS, Vroom TM, Adriaansen-Slot SS, Ottenhoff-Kalff AE, Geertzema JG, Hennipman A et al (1996) c-Src protein expression is increased in human breast cancer. An immunohistochemical and biochemical analysis. J Pathol 180(4):383–388

    Article  CAS  PubMed  Google Scholar 

  32. Maiello MR, D’Alessio A, Bevilacqua S, Gallo M, Normanno N, De Luca A (2015) EGFR and MEK blockade in triple negative breast cancer cells. J Cell Biochem 116(12):2778–2785

    Article  CAS  PubMed  Google Scholar 

  33. Nakai K, Hung MC, Yamaguchi H (2016) A perspective on anti-EGFR therapies targeting triple-negative breast cancer. Am J Cancer Res 6(8):1609–1623

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Bartholomeusz C, Oishi T, Saso H, Akar U, Liu P, Kondo K et al (2012) MEK1/2 inhibitor selumetinib (AZD6244) inhibits growth of ovarian clear cell carcinoma in a PEA-15-dependent manner in a mouse xenograft model. Mol Cancer Ther 11(2):360–369

    Article  CAS  PubMed  Google Scholar 

  35. Chen X, Zheng Z, Chen L, Zheng H (2017) MAPK, NFkappaB, and VEGF signaling pathways regulate breast cancer liver metastasis. Oncotarget 8(60):101452–101460

    PubMed  PubMed Central  Google Scholar 

  36. Shao GL, Wang MC, Fan XL, Zhong L, Ji SF, Sang G et al (2018) Correlation between Raf/MEK/ERK signaling pathway and clinicopathological features and prognosis for patients with breast cancer having axillary Lymph node metastasis. Technol Cancer Res Treat. https://doi.org/10.1177/1533034617754024

    Article  PubMed  PubMed Central  Google Scholar 

  37. Torres-Adorno AM, Lee J, Kogawa T, Ordentlich P, Tripathy D, Lim B et al (2017) Histone deacetylase inhibitor enhances the efficacy of MEK inhibitor through NOXA-mediated MCL1 degradation in triple-negative and inflammatory breast cancer. Clin Cancer Res 23(16):4780–4792

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Jing J, Greshock J, Holbrook JD, Gilmartin A, Zhang X, McNeil E et al (2012) Comprehensive predictive biomarker analysis for MEK inhibitor GSK1120212. Mol Cancer Ther 11(3):720–729

    Article  CAS  PubMed  Google Scholar 

  39. Nagaria TS, Shi C, Leduc C, Hoskin V, Sikdar S, Sangrar W et al (2017) Combined targeting of Raf and Mek synergistically inhibits tumorigenesis in triple negative breast cancer model systems. Oncotarget 8(46):80804–80819

    Article  PubMed  PubMed Central  Google Scholar 

  40. Sato N, Wakabayashi M, Nakatsuji M, Kashiwagura H, Shimoji N, Sakamoto S et al (2017) MEK and PI3K catalytic activity as predictor of the response to molecularly targeted agents in triple-negative breast cancer. Biochem Biophys Res Commun 489(4):484–489

    Article  CAS  PubMed  Google Scholar 

  41. Duncan JS, Whittle MC, Nakamura K, Abell AN, Midland AA, Zawistowski JS et al (2012) Dynamic reprogramming of the kinome in response to targeted MEK inhibition in triple-negative breast cancer. Cell 149(2):307–321

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Mirzoeva OK, Das D, Heiser LM, Bhattacharya S, Siwak D, Gendelman R et al (2009) Basal subtype and MAPK/ERK kinase (MEK)-phosphoinositide 3-kinase feedback signaling determine susceptibility of breast cancer cells to MEK inhibition. Cancer Res 69(2):565–572

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Adjei AA, Cohen RB, Franklin W, Morris C, Wilson D, Molina JR et al (2008) Phase I pharmacokinetic and pharmacodynamic study of the oral, small-molecule mitogen-activated protein kinase kinase 1/2 inhibitor AZD6244 (ARRY-142886) in patients with advanced cancers. J Clin Oncol 26(13):2139–2146

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Rinehart J, Adjei AA, Lorusso PM, Waterhouse D, Hecht JR, Natale RB et al (2004) Multicenter phase II study of the oral MEK inhibitor, CI-1040, in patients with advanced non-small-cell lung, breast, colon, and pancreatic cancer. J Clin Oncol 22(22):4456–4462

    Article  CAS  PubMed  Google Scholar 

  45. Hoeflich KP, O’Brien C, Boyd Z, Cavet G, Guerrero S, Jung K et al (2009) In vivo antitumor activity of MEK and phosphatidylinositol 3-kinase inhibitors in basal-like breast cancer models. Clin Cancer Res 15(14):4649–4664

    Article  CAS  PubMed  Google Scholar 

  46. Leung EY, Kim JE, Askarian-Amiri M, Rewcastle GW, Finlay GJ, Baguley BC (2014) Relationships between signaling pathway usage and sensitivity to a pathway inhibitor: examination of trametinib responses in cultured breast cancer lines. PLoS ONE 9(8):e105792

    Article  PubMed  PubMed Central  Google Scholar 

  47. Van Swearingen AED, Sambade MJ, Siegel MB, Sud S, McNeill RS, Bevill SM et al (2017) Combined kinase inhibitors of MEK1/2 and either PI3K or PDGFR are efficacious in intracranial triple-negative breast cancer. Neuro Oncol 19(11):1481–1493

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Corcoran RB, Andre T, Atreya CE, Schellens JHM, Yoshino T, Bendell JC et al (2018) Combined BRAF, EGFR, and MEK Inhibition in patients with BRAF(V600E)-mutant colorectal cancer. Cancer Discov 8(4):428–443

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Gaudio E, Tarantelli C, Kwee I, Barassi C, Bernasconi E, Rinaldi A et al (2016) Combination of the MEK inhibitor pimasertib with BTK or PI3K-delta inhibitors is active in preclinical models of aggressive lymphomas. Ann Oncol 27(6):1123–1128

    Article  CAS  PubMed  Google Scholar 

  50. Lee MS, Helms TL, Feng N, Gay J, Chang QE, Tian F et al (2016) Efficacy of the combination of MEK and CDK4/6 inhibitors in vitro and in vivo in KRAS mutant colorectal cancer models. Oncotarget 7(26):39595–39608

    Article  PubMed  PubMed Central  Google Scholar 

  51. Zhao H, Cui K, Nie F, Wang L, Brandl MB, Jin G et al (2012) The effect of mTOR inhibition alone or combined with MEK inhibitors on brain metastasis: an in vivo analysis in triple-negative breast cancer models. Breast Cancer Res Treat 131(2):425–436

    Article  CAS  PubMed  Google Scholar 

  52. Balko JM, Giltnane JM, Wang K, Schwarz LJ, Young CD, Cook RS et al (2014) Molecular profiling of the residual disease of triple-negative breast cancers after neoadjuvant chemotherapy identifies actionable therapeutic targets. Cancer Discov 4(2):232–245

    Article  CAS  PubMed  Google Scholar 

  53. Brufsky A, Miles D, Zvirbule Z, Eniu A, Lopez-Miranda E, Seo JH et al (2018) Abstract P5-21-01: Cobimetinib combined with paclitaxel as first-line treatment for patients with advanced triple-negative breast cancer (COLET study): Primary analysis of cohort I. Cancer Research. SABCS17-P5-21-01

  54. Chumsri S, Polley M-Y, Anderson SL, O’Sullivan CCM, Colon-Otero G, Knutson KL et al (2018) Phase I/II trial of pembrolizumab in combination with binimetinib in unresectable locally advanced or metastatic triple negative breast cancer. J Clin Oncol 36(5_suppl):TPS17–TPS17

    Article  Google Scholar 

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Acknowledgements

We thank Sunita Patterson and Stephanie Deming of the Department of Scientific Publications at MD Anderson Cancer Center for editing the manuscript.

Funding

This work was supported by the Morgan Welch Inflammatory Breast Cancer Research Program, the State of Texas Rare and Aggressive Breast Cancer Research Program, the National Institutes of Health/National Cancer Institute (Grant CA123318), MD Anderson’s Cancer Center Support Grant (P30CA016672, used the Characterized Cell Line Core Facility and Flow Cytometry and Cellular Imaging Facility), and Spirita Oncology, LLC.

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Authors and Affiliations

  1. Section of Translational Breast Cancer Research, Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Jangsoon Lee, Bora Lim, Troy Pearson, Kuicheon Choi, Jon A. Fuson, Chandra Bartholomeusz, Debu Tripathy & Naoto T. Ueno

  2. Spirita Oncology, LLC, Natick, MA, USA

    Linda J. Paradiso & Thomas Myers

  3. Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Unit 1354, 1515 Holcombe Boulevard, Houston, TX, 77030-4009, USA

    Jangsoon Lee, Bora Lim, Chandra Bartholomeusz & Naoto T. Ueno

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Correspondence to Naoto T. Ueno.

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Conflict of interest

Naoto T. Ueno has a research agreement with Spirita Oncology, LLC. Linda J. Paradiso and Thomas Myers are employees of Spirita Oncology, LLC. All other authors declare no potential conflicts of interest.

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Animal studies and procedures were approved by The University of Texas MD Anderson Cancer Center Animal Care and Use Committee. Protocol #: 00000968-RN02 (approval date 5/1/2015, expiration date 4/22/2021).

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Supplemental Figure 1

. Anti-proliferation effect of MEK inhibitors in TNBC cell lines. TNBC cells were treated with selumetinib, pimasertib, or trametinib for 5 days, and viability was measured by using CellTiter-Blue and sulforhodamine-B assays. Data shown are representative of three experiments with similar results. Each point represents the mean of three independent experiments; error bars indicate standard deviation. Supplemental Figure 2. FLT3 inhibition does not affect TNBC cell proliferation, migration, or invasion. a Western blotting of cells treated with E6201 for the indicated times. b Proliferation assay. TNBC cell lines were treated with quizartinib for 5 days, and viability was measured by using CellTiter-Blue. c and d Migration and invasion assays. TNBC cells (1×105/well) were added into trans-wells with or without quizartinib for 6 hr (migration, c) or 24 hr (invasion, d). Migration and invasion were evaluated by using ImageJ software. Data shown are representative of three experiments with similar results; error bars indicate standard deviation. Supplementary material 1 (PPTX 1826 KB)

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Lee, J., Lim, B., Pearson, T. et al. Anti-tumor and anti-metastasis efficacy of E6201, a MEK1 inhibitor, in preclinical models of triple-negative breast cancer. Breast Cancer Res Treat 175, 339–351 (2019). https://doi.org/10.1007/s10549-019-05166-3

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