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Unconjugated bilirubin is a novel prognostic biomarker for
nasopharyngeal carcinoma and inhibits its metastasis via
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on September 25, 2015; DOI: 10.1158/1940-6207.CAPR-15-0257
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on September 25, 2015; DOI: 10.1158/1940-6207.CAPR-15-0257
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on September 25, 2015; DOI: 10.1158/1940-6207.CAPR-15-0257
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on September 25, 2015; DOI: 10.1158/1940-6207.CAPR-15-0257
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on September 25, 2015; DOI: 10.1158/1940-6207.CAPR-15-0257
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on September 25, 2015; DOI: 10.1158/1940-6207.CAPR-15-0257
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on September 25, 2015; DOI: 10.1158/1940-6207.CAPR-15-0257
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on September 25, 2015; DOI: 10.1158/1940-6207.CAPR-15-0257
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on September 25, 2015; DOI: 10.1158/1940-6207.CAPR-15-0257
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on September 25, 2015; DOI: 10.1158/1940-6207.CAPR-15-0257
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on September 25, 2015; DOI: 10.1158/1940-6207.CAPR-15-0257
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on September 25, 2015; DOI: 10.1158/1940-6207.CAPR-15-0257
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on September 25, 2015; DOI: 10.1158/1940-6207.CAPR-15-0257
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on September 25, 2015; DOI: 10.1158/1940-6207.CAPR-15-0257
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on September 25, 2015; DOI: 10.1158/1940-6207.CAPR-15-0257
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on September 25, 2015; DOI: 10.1158/1940-6207.CAPR-15-0257
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on September 25, 2015; DOI: 10.1158/1940-6207.CAPR-15-0257
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on September 25, 2015; DOI: 10.1158/1940-6207.CAPR-15-0257
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on September 25, 2015; DOI: 10.1158/1940-6207.CAPR-15-0257
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on September 25, 2015; DOI: 10.1158/1940-6207.CAPR-15-0257
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on September 25, 2015; DOI: 10.1158/1940-6207.CAPR-15-0257
2. Wei WI, Sham JS. Nasopharyngeal carcinoma. Lancet 2005;365: 2041–54. 3. Razak AR, Siu LL, Liu FF, Ito E, O’Sullivan B, Chan K. Nasopharyngeal carcinoma: the next challenges. European Journal of cancer 2010;46: 1967-78. 4. Lee AWM, Poon YF, Foo W, Law SC, Cheung FK, Chan DK, et al. Retrospective analysis of 5037 patients with nasopharyngeal carcinoma treated during 1976–1985: overall survival and patterns of failure. International Journal of Radiation Oncology* Biology* Physics 1992;23: 261-70. 5. Chan ATC. Nasopharyngeal carcinoma. Annals of Oncology 2010;21: vii308-vii312. 6. Stocker R, Yamamoto Y, McDonagh A, Glazer A, Ames B. Bilirubin is an antioxidant of possible physiological importance. Science 1987;235 : 1043–6. 7. Kimm H, Yun JE, Jo J, Jee SH. Low serum bilirubin level as an independent predictor of stroke incidence: a prospective study in Korean men and women. Stroke 2009;40: 3422–7. 8. Ishizaka N, Ishizaka Y, Takahashi E, Yamakado M, Hashimoto H. High serum bilirubin level is inversely associated with the presence of carotid plaque. Stroke 2001;32: 580–83. 9. Schwertner HA, Vitek L. Gilbert syndrome, UGT1A1*28 allele, and cardiovascular disease risk: possible protective effects and therapeutic applications of bilirubin. Atherosclerosis 2008;198: 1–11. 10. Schwertner HA, Jackson WG, Tolan G. Association of low serum concentration of bilirubin with increased risk of coronary artery disease. Clin Chem 1994;40: 18–23. 11. Ko GT, Chan JC, Woo J, Lau E, Yeung VT, Chow CC, et al. Serum bilirubin and cardiovascular risk factors in a Chinese population. J Cardiovasc Risk 1996;3: 459–63. 12. Perlstein TS, Pande RL, Beckman JA, Creager MA. Serum total bilirubin level and prevalent lower-extremity peripheral arterial disease: National Health and Nutrition Examination Survey (NHANES) 1999 to 2004. Arterioscler Thromb Vasc Biol 2008;28: 166–72. 13. Horsfall LJ, Rait G, Walters K, Swallow DM, Pereira SP, Nazareth I, et al. Serum bilirubin and risk of respiratory disease and death. JAMA 2011;305: 691-7. 14. Ioannou GN, Liou IW, Weiss NS. Serum bilirubin and colorectal cancer risk: a population-based cohort study. Aliment Pharmacol Ther 2006;23: 1637–42. 15. Zucker SD, Horn PS, Sherman KE. Serum bilirubin levels in the U.S. population: gender effect and inverse correlation with colorectal cancer. Hepatology 2004;40: 827-35. 16. Jirásková A, Novotný J, Novotný L, Vodicka P, Pardini B, Naccarati A, et al. Association of serum bilirubin and promoter variations in HMOX1 and UGT1A1 genes with sporadic colorectal cancer. International journal of cancer 2012;131: 1549-55. 17. Wagner KH, Wallner M, Molzer C, Gazzin S, Bulmer AC, Tiribelli C, et al. Looking to the horizon: the role of bilirubin in the development and prevention of age-related chronic diseases. Clinical Science 2015;129: 1-25. 18. Fridovich I. The biology of oxygen radicals. Science 1978;201: 875–80. 19. Waris G, Ahsan H. Reactive oxygen species: role in the development of cancer and various chronic conditions. Journal of carcinogenesis 2006;5: 14. 20. Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB. Oxidative stress, inflammation, and cancer: how are they linked?. Free Radical Biology and Medicine 2010;49: 1603-16. 21. Storz P. Reactive oxygen species in tumor progression. Front Biosci 2005;10: 1881-96. 22. Westermarck J. Kahari VM. Regulation of matrix metalloproteinase expression in tumor invasion. FASEB J 1999;13: 781–92. 23. Deryugina EI, Quigley JP. Matrix metalloproteinases and tumor metastasis. Cancer and Metastasis Reviews 2006;25: 9-34.
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on September 25, 2015; DOI: 10.1158/1940-6207.CAPR-15-0257
24. Qian CN, Berghuis B, Tsarfaty G, Bruch M, Kort EJ, Ditlev J, et al. Preparing the “soil”: the primary tumor induces vasculature reorganization in the sentinel lymph node before the arrival of metastatic cancer cells. Cancer research 2006;66: 10365-76. 25. Li XJ, Ong CK, Cao Y, Cao Y, Xiang YQ, Shao JY, et al. Serglycin is a theranostic target in nasopharyngeal carcinoma that promotes metastasis. Cancer research 2011;71: 3162-72. 26. Liang Y, Zhong Z, Huang Y, Deng W, Cao J, Tsao G, et al. Stem-like cancer cells are inducible by inc.reasing genomic instability in cancer cells. Journal of Biological Chemistry 2010;285: 4931-40. 27. Deng CC, Liang Y, Wu MS, Feng FT, Hu WR, Chen LZ, et al. Nigericin selectively targets cancer stem cells in nasopharyngeal carcinoma. The international journal of biochemistry & cell biology 2013;45: 1997-2006. 28. Rao P, Suzuki R, Mizobuchi S, Yamaguchi T, Sasaguri S. Bilirubin exhibits a novel anti-cancer effect on human adenocarcinoma. Biochemical and biophysical research communications 2006;342: 1279-83. 29. Keshavan P, Schwemberger S J, Smith D L H, Babcock GF, Zucker SD. Unconjugated bilirubin induces apoptosis in colon cancer cells by triggering mitochondrial depolarization. International journal of cancer 2004;112: 433-45. 30. Egeblad M, Werb Z. New functions for the matrix metalloproteinases in cancer progression. Nature Reviews Cancer 2002;2: 161-74. 31. Sebolt-Leopold JS, Herrera R. Targeting the mitogen-activated protein kinase cascade to treat cancer. Nature Reviews Cancer 2004;4: 937-947. 32. Tochhawng L, Deng S, Pervaiz S, Yap CT. Redox regulation of cancer cell migration and invasion. Mitochondrion 2013;13: 246-53. 33. Lucey JF. Neonatal jaundice and phototherapy. Pediatr Clin North Am 1972;19: 827–39. 34. Gourley GR. Bilirubin metabolism and kernicterus. Adv Pediatr 1997;44: 173–229. 35. Hansen TWR, Mathiesen SBW, Walaas SI. Bilirubin has widespread inhibitory effects on protein phosphorylation. Pediatric research 1996;39: 1072-77. 36. Ching S, Ingram D, Hahnel R, Beilby J, Rossi E. Serum levels of micronutrients, antioxidants and total antioxidant status predict risk of breast cancer in a case control study. J Nutr 2002;132: 303-06. 37. Temme EH, Zhang J, Schouten EG, Kesteloot H. Serum bilirubin and 10-year mortality risk in a Belgian population. Cancer Causes Control 2001;12: 887-94. 38. Bernhard K, Ritzel G, Steiner KU. On a biological significance of bile pigments: bilirubin and biliverdin as antioxidants for vitamin A and essential fatty acids [in German]. Helv Chim Acta 1954;37: 306–13. 39. Beer H, Bernhard K. The effect of bilirubin and vitamin E on the oxidation of unsaturated fatty acids by ultraviolet irradiation [in German]. Chimia 1959;13: 291–2. 40. Stocker R, Glazer AN, Ames BN. Antioxidant activity of albumin-bound bilirubin. Proc Natl Acad Sci U S A 1987;84: 5918-22. 41. Baranano DE, Rao M, Ferris CD, Snyder SH. Biliverdin reductase: a major physiologic cytoprotectant. Proc Natl Acad Sci U S A 2002;99: 16093-8. 42. Fidler IJ. The pathogenesis of cancer metastasis: the 'seed and soil' hypothesis revisited. Nature Reviews Cancer 2003;3: 453-458. 43. Valastyan S, Weinberg RA. Tumor metastasis: molecular insights and evolving paradigms. Cell 2011;147: 275-92.
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on September 25, 2015; DOI: 10.1158/1940-6207.CAPR-15-0257
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on September 25, 2015; DOI: 10.1158/1940-6207.CAPR-15-0257
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on September 25, 2015; DOI: 10.1158/1940-6207.CAPR-15-0257
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on September 25, 2015; DOI: 10.1158/1940-6207.CAPR-15-0257
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on September 25, 2015; DOI: 10.1158/1940-6207.CAPR-15-0257
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on September 25, 2015; DOI: 10.1158/1940-6207.CAPR-15-0257
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on September 25, 2015; DOI: 10.1158/1940-6207.CAPR-15-0257
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on September 25, 2015; DOI: 10.1158/1940-6207.CAPR-15-0257
Published OnlineFirst September 25, 2015.Cancer Prev Res Cheng-Cheng Deng, Miao Xu, Jing Li, et al. anti-oxidation activitynasopharyngeal carcinoma and inhibits its metastasis via Unconjugated bilirubin is a novel prognostic biomarker for
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Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on September 25, 2015; DOI: 10.1158/1940-6207.CAPR-15-0257