Hepatocellular carcinoma stem cells: Origins and roles in hepatocarcinogenesis and disease progression

Frontiers in Bioscience - Elite

Volumn 4 E, Issue 3, 2012, Pages 1157-1169

  Shen, Yi ^a   Cao, Deliang ^a  

^a SOUTHERN ILLINOIS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Bone marrow cell; Cancer stem cells; Cancer therapy; Hedgehog signaling; Hepatic progenitor cell; Hepatocarcinogenesis; Hepatocellular Carcinoma; Hepatocyte; Liver development; Liver regeneration; Oval cell; Review; VEGF angiogenic signaling; Wnt betacatenin pathway

Indexed keywords

AEG 35156; BETA CATENIN; BEVACIZUMAB; BRIVANIB; CAPECITABINE; CD133 ANTIGEN; CEDIRANIB; CETUXIMAB; EPITHELIAL CELL ADHESION MOLECULE; ERLOTINIB; GEFITINIB; GEMCITABINE; LAPATINIB; LINIFANIB; LINSITINIB; SORAFENIB; SUNITINIB; THY 1 ANTIGEN; TIVANTINIB; VATALANIB;

ANGIOGENESIS; ARTICLE; CANCER GROWTH; CANCER STEM CELL; CARCINOGENICITY; CELL DEDIFFERENTIATION; CELL REGENERATION; CELL TRANSFORMATION; DRUG TARGETING; HEMATOPOIETIC STEM CELL; HUMAN; LIVER CARCINOGENESIS; LIVER CELL CARCINOMA; LIVER DEVELOPMENT; LIVER REGENERATION; NONHUMAN; WNT SIGNALING PATHWAY; DISEASE COURSE; LIVER TUMOR; PATHOLOGY; REVIEW;

ERINACEIDAE;

CARCINOMA, HEPATOCELLULAR; CELL TRANSFORMATION, NEOPLASTIC; DISEASE PROGRESSION; HUMANS; LIVER NEOPLASMS; NEOPLASTIC STEM CELLS;

EID: 84859577135     PISSN: 19450494     EISSN: 19450508     Source Type: Journal    
DOI: None     Document Type: Article

References (146)

1. S. Y. Yi and K. J. Nan: Tumor-initiating stem cells in liver cancer. Cancer Biol Ther, 7 (3), 325-30 (2008)
2. M. J. Thun, J. O. DeLancey, M. M. Center, A. Jemal and E. M. Ward: The global burden of cancer: priorities for prevention. Carcinogenesis, 31 (1), 100-10
3. R. N. Aravalli, C. J. Steer, M. B. Sahin and E. N. Cressman: Stem cell origins and animal models of hepatocellular carcinoma. Dig Dis Sci, 55 (5), 1241-50 4. T. K. Lee, A. Castilho, S. Ma and I. O. Ng: Liver cancer stem cells: implications for a new therapeutic target. Liver Int, 29 (7), 955-65 (2009)
4. Amal Samy Ibrahim: Cancer Incidence in Four Member Countries (Cyprus, Egypt, Israel, and Jordan) of the Middle East Cancer Consortium (MECC) Compared with US SEER. In: Cancer Incidence in Four Member Countries (Cyprus, Egypt, Israel, and Jordan) of the Middle East Cancer Consortium (MECC) Compared with US SEER. Ed E. B. Freedman LS, Ries LAG, Young JL (eds). NIH
5. J. W. Kung, I. S. Currie, S. J. Forbes and J. A. Ross: Liver development, regeneration, and carcinogenesis. J Biomed Biotechnol, 2010, 984248
6. L. Mishra, T. Banker, J. Murray, S. Byers, A. Thenappan, A. R. He, K. Shetty, L. Johnson and E. P. Reddy: Liver stem cells and hepatocellular carcinoma. Hepatology, 49 (1), 318-29 (2009)
7. K. D. Tremblay and K. S. Zaret: Distinct populations of endoderm cells converge to generate the embryonic liver bud and ventral foregut tissues. Dev Biol, 280 (1), 87-99 (2005) (Pubitemid 40342744)
8. F. Lemaigre and K. S. Zaret: Liver development update: new embryo models, cell lineage control, and morphogenesis. Curr Opin Genet Dev, 14 (5), 582-90 (2004) (Pubitemid 39360307)
9. R. Zhao and S. A. Duncan: Embryonic development of the liver. Hepatology, 41 (5), 956-67 (2005) (Pubitemid 40593901)
10. J. U. Marquardt, V. M. Factor and S. S. Thorgeirsson: Epigenetic regulation of cancer stem cells in liver cancer: current concepts and clinical implications. J Hepatol, 53 (3), 568-77
11. S. L. Friedman: Evolving challenges in hepatic fibrosis. Nat Rev Gastroenterol Hepatol, 7 (8), 425-36
12. G. M. Zou: Cancer initiating cells or cancer stem cells in the gastrointestinal tract and liver. J Cell Physiol, 217 (3), 598-604 (2008)
13. A. Suzuki, Y. Zheng, R. Kondo, M. Kusakabe, Y. Takada, K. Fukao, H. Nakauchi and H. Taniguchi: Flowcytometric separation and enrichment of hepatic progenitor cells in the developing mouse liver. Hepatology, 32 (6), 1230-9 (2000)
14. J. E. Allain, I. Dagher, D. Mahieu-Caputo, N. Loux, M. Andreoletti, K. Westerman, P. Briand, D. Franco, P. Leboulch and A. Weber: Immortalization of a primate bipotent epithelial liver stem cell. Proc Natl Acad Sci U S A, 99 (6), 3639-44 (2002)
15. S. V. Perryman and K. G. Sylvester: Repair and regeneration: opportunities for carcinogenesis from tissue stem cells. J Cell Mol Med, 10 (2), 292-308 (2006) (Pubitemid 44870180)
16. S. Ma, K. W. Chan and X. Y. Guan: In search of liver cancer stem cells. Stem Cell Rev, 4 (3), 179-92 (2008)
17. P. A. Beachy, S. S. Karhadkar and D. M. Berman: Tissue repair and stem cell renewal in carcinogenesis. Nature, 432 (7015), 324-31 (2004) (Pubitemid 39551660)
18. G. K. Michalopoulos: Liver regeneration. J Cell Physiol, 213 (2), 286-300 (2007) (Pubitemid 47509705)
19. B. A. Schotanus, T. S. van den Ingh, L. C. Penning, J. Rothuizen, T. A. Roskams and B. Spee: Cross-species immunohistochemical investigation of the activation of the liver progenitor cell niche in different types of liver disease. Liver Int, 29 (8), 1241-52 (2009)
20. K. S. Zaret and M. Grompe: Generation and regeneration of cells of the liver and pancreas. Science, 322 (5907), 1490-4 (2008)
21. J. I. Leu, M. A. Crissey and R. Taub: Massive hepatic apoptosis associated with TGF-beta1 activation after Fas ligand treatment of IGF binding protein-1-deficient mice. J Clin Invest, 111 (1), 129-39 (2003) (Pubitemid 36134856)
22. R. Malik, C. Selden and H. Hodgson: The role of nonparenchymal cells in liver growth. Semin Cell Dev Biol, 13 (6), 425-31 (2002) (Pubitemid 36027147)
23. Z. Dong, H. Wei, R. Sun and Z. Tian: The roles of innate immune cells in liver injury and regeneration. Cell Mol Immunol, 4 (4), 241-52 (2007)
24. R. M. Rai, S. Q. Yang, C. McClain, C. L. Karp, A. S. Klein and A. M. Diehl: Kupffer cell depletion by gadolinium chloride enhances liver regeneration after partial hepatectomy in rats. Am J Physiol, 270 (6 Pt 1), G909-18 (1996)
25. T. Takeishi, K. Hirano, T. Kobayashi, G. Hasegawa, K. Hatakeyama and M. Naito: The role of Kupffer cells in liver regeneration. Arch Histol Cytol, 62 (5), 413-22 (1999) (Pubitemid 30095568)
26. K. Akita, M. Okuno, M. Enya, S. Imai, H. Moriwaki, N. Kawada, Y. Suzuki and S. Kojima: Impaired liver regeneration in mice by lipopolysaccharide via TNFalpha/ kallikrein-mediated activation of latent TGF-beta. Gastroenterology, 123 (1), 352-64 (2002) (Pubitemid 34747555)
27. H. Hayashi, K. Nabeshima, M. Hamasaki, Y. Yamashita, T. Shirakusa and H. Iwasaki: Presence of microsatellite lesions with colorectal liver metastases correlate with intrahepatic recurrence after surgical resection. Oncol Rep, 21 (3), 601-7 (2009)
28. E. K. Abdalla, J. N. Vauthey, L. M. Ellis, V. Ellis, R. Pollock, K. R. Broglio, K. Hess and S. A. Curley: Recurrence and outcomes following hepatic resection, radiofrequency ablation, and combined resection/ablation for colorectal liver metastases. Ann Surg, 239 (6), 818-25; discussion 825-7 (2004)
29. T. A. Aloia, J. N. Vauthey, E. M. Loyer, D. Ribero, T. M. Pawlik, S. H. Wei, S. A. Curley, D. Zorzi and E. K. Abdalla: Solitary colorectal liver metastasis: resection determines outcome. Arch Surg, 141 (5), 460-6; discussion 466-7 (2006)
30. M. C. de Jong, C. Pulitano, D. Ribero, J. Strub, G. Mentha, R. D. Schulick, M. A. Choti, L. Aldrighetti, L. Capussotti and T. M. Pawlik: Rates and patterns of recurrence following curative intent surgery for colorectal liver metastasis: an international multi-institutional analysis of 1669 patients. Ann Surg, 250 (3), 440-8 (2009)
31. A. L. Gleisner, M. A. Choti, L. Assumpcao, H. Nathan, R. D. Schulick and T. M. Pawlik: Colorectal liver metastases: recurrence and survival following hepatic resection, radiofrequency ablation, and combined resectionradiofrequency ablation. Arch Surg, 143 (12), 1204-12 (2008)
32. P. Hohenberger, P. Schlag, V. Schwarz and C. Herfarth: Tumor recurrence and options for further treatment after resection of liver metastases in patients with colorectal cancer. J Surg Oncol, 44 (4), 245-51 (1990) (Pubitemid 20269902)
33. D. Elias, T. De Baere, A. Roche, Mducreux, J. Leclere and P. Lasser: During liver regeneration following right portal embolization the growth rate of liver metastases is more rapid than that of the liver parenchyma. Br J Surg, 86 (6), 784-8 (1999) (Pubitemid 29271944)
34. G. J. van der Bij, S. J. Oosterling, S. Meijer, R. H. Beelen and M. van Egmond: Therapeutic potential of Kupffer cells in prevention of liver metastases outgrowth. Immunobiology, 210 (2-4), 259-65 (2005) (Pubitemid 41025167)
35. W. G. Jiang, D. Lloyds, M. C. Puntis, T. Nakamura and M. B. Hallett: Regulation of spreading and growth of colon cancer cells by hepatocyte growth factor. Clin Exp Metastasis, 11 (3), 235-42 (1993) (Pubitemid 23138522)
36. W. G. Jiang, M. B. Hallett and M. C. Puntis: Hepatocyte growth factor/scatter factor, liver regeneration and cancer metastasis. Br J Surg, 80 (11), 1368-73 (1993) (Pubitemid 23345088)
37. D. S. Grant, H. K. Kleinman, I. D. Goldberg, M. M. Bhargava, B. J. Nickoloff, J. L. Kinsella, P. Polverini and E. M. Rosen: Scatter factor induces blood vessel formation in vivo. Proc Natl Acad Sci U S A, 90 (5), 1937-41 (1993) (Pubitemid 23069972)
38. G. D. Slooter, R. L. Marquet, J. Jeekel and J. N. Ijzermans: Tumour growth stimulation after partial hepatectomy can be reduced by treatment with tumour necrosis factor alpha. Br J Surg, 82 (1), 129-32 (1995)
39. G. Heuff, H. S. Oldenburg, H. Boutkan, J. J. Visser, R. H. Beelen, N. Van Rooijen, C. D. Dijkstra and S. Meyer: Enhanced tumour growth in the rat liver after selective elimination of Kupffer cells. Cancer Immunol Immunother, 37 (2), 125-30 (1993) (Pubitemid 23175048)
40. M. H. Castillo, R. J. Doerr, N. Paolini, S. Cohen and M. Goldrosen: Hepatectomy prolongs survival of mice with induced liver metastases. Arch Surg, 124 (2), 167-9 (1989) (Pubitemid 19059738)
41. R. Doerr, M. Castillo, P. Evans, N. Paolini, M. Goldrosen and S. A. Cohen: Partial hepatectomy augments the liver's antitumor response. Arch Surg, 124 (2), 170-4 (1989)
42. S. Sell and H. L. Leffert: Liver cancer stem cells. J Clin Oncol, 26 (17), 2800-5 (2008)
43. S. Murashima, M. Tanaka, M. Haramaki, S. Yutani, Y. Nakashima, K. Harada, T. Ide, R. Kumashiro and M. Sata: A decrease in AFP level related to administration of interferon in patients with chronic hepatitis C and a high level of AFP. Dig Dis Sci, 51 (4), 808-12 (2006)
44. S. L. Han, X. L. Wu, Z. R. Jia and P. F. Wang: Adult hepatic cavernous haemangioma with highly elevated alpha-fetoprotein. Hong Kong Med J, 16 (5), 400-2
45. A. A. Mhanni, B. N. Chodirker, J. A. Evans, S. Menticouglou, N. Wiseman, N. MacDonald and A. E. Chudley: Fetal hepatic haemangioendothelioma: a new association with elevated maternal serum alpha-fetoprotein. Prenat Diagn, 20 (5), 432-5 (2000)
46. S. Sell: Cellular origin of cancer: dedifferentiation or stem cell maturation arrest? Environ Health Perspect, 101 Suppl 5, 15-26 (1993) (Pubitemid 24096320)
47. S. Sell and G. B. Pierce: Maturation arrest of stem cell differentiation is a common pathway for the cellular origin of teratocarcinomas and epithelial cancers. Lab Invest, 70 (1), 6-22 (1994) (Pubitemid 24080100)
48. H. C. Pitot: The natural history of neoplastic development: the relation of experimental models to human cancer. Cancer, 49 (6), 1206-11 (1982) (Pubitemid 12187824)
49. E. Scherer: Neoplastic progression in experimental hepatocarcinogenesis. Biochim Biophys Acta, 738 (4), 219-36 (1984) (Pubitemid 15151931)
50. P. Bannasch, H. J. Hacker, F. Klimek and D. Mayer: Hepatocellular glycogenosis and related pattern of enzymatic changes during hepatocarcinogenesis. Adv Enzyme Regul, 22, 97-121 (1984)
51. K. Aterman: Hepatic neoplasia: reflections and ruminations. Virchows Arch, 427 (1), 1-18 (1995)
52. S. Sell: Mouse models to study the interaction of risk factors for human liver cancer. Cancer Res, 63 (22), 7553-62 (2003) (Pubitemid 37466672)
53. H. Ishikawa, K. Nakao, K. Matsumoto, D. Nishimura, T. Ichikawa, K. Hamasaki and K. Eguchi: Bone marrow engraftment in a rodent model of chemical carcinogenesis but no role in the histogenesis of hepatocellular carcinoma. Gut, 53 (6), 884-9 (2004) (Pubitemid 38662141)
54. J. Gournay, I. Auvigne, V. Pichard, C. Ligeza, M. P. Bralet and N. Ferry: In vivo cell lineage analysis during chemical hepatocarcinogenesis in rats using retroviralmediated gene transfer: evidence for dedifferentiation of mature hepatocytes. Lab Invest, 82 (6), 781-8 (2002) (Pubitemid 34633828)
55. M. P. Bralet, V. Pichard and N. Ferry: Demonstration of direct lineage between hepatocytes and hepatocellular carcinoma in diethylnitrosamine-treated rats. Hepatology, 36 (3), 623-30 (2002) (Pubitemid 34977172)
56. V. M. Craddock: Effect of a single treatment with the alkylating carcinogens dimethynitrosamine, diethylnitrosamine and methyl methanesulphonate, on liver regenerating after partial hepatectomy. I. Test for induction of liver carcinomas. Chem Biol Interact, 10 (5), 313-21 (1975)
57. C. C. Hsia, S. S. Thorgeirsson and E. Tabor: Expression of hepatitis B surface and core antigens and transforming growth factor-alpha in "oval cells" of the liver in patients with hepatocellular carcinoma. J Med Virol, 43 (3), 216-21 (1994) (Pubitemid 24227589)
58. L. Libbrecht: Hepatic progenitor cells in human liver tumor development. World J Gastroenterol, 12 (39), 6261-5 (2006) (Pubitemid 44712404)
59. B. Knight, J. E. Tirnitz-Parker and J. K. Olynyk: C-kit inhibition by imatinib mesylate attenuates progenitor cell expansion and inhibits liver tumor formation in mice. Gastroenterology, 135 (3), 969-79, 979 e1 (2008)
60. D. C. Hixson, J. Brown, A. C. McBride and S. Affigne: Differentiation status of rat ductal cells and ethionineinduced hepatic carcinomas defined with surface-reactive monoclonal antibodies. Exp Mol Pathol, 68 (3), 152-69 (2000) (Pubitemid 30337516)
61. E. Lagasse, H. Connors, M. Al-Dhalimy, M. Reitsma, M. Dohse, L. Osborne, X. Wang, M. Finegold, I. L. Weissman and M. Grompe: Purified hematopoietic stem cells can differentiate into hepatocytes in vivo. Nat Med, 6 (11), 1229-34 (2000)
62. R. E. Schwartz, M. Reyes, L. Koodie, Y. Jiang, M. Blackstad, T. Lund, T. Lenvik, S. Johnson, W. S. Hu and C. M. Verfaillie: Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte-like cells. J Clin Invest, 109 (10), 1291-302 (2002) (Pubitemid 34546893)
63. Y. Sato, H. Araki, J. Kato, K. Nakamura, Y. Kawano, M. Kobune, T. Sato, K. Miyanishi, T. Takayama, M. Takahashi, R. Takimoto, S. Iyama, T. Matsunaga, S. Ohtani, A. Matsuura, H. Hamada and Y. Niitsu: Human mesenchymal stem cells xenografted directly to rat liver are differentiated into human hepatocytes without fusion. Blood, 106 (2), 756-63 (2005) (Pubitemid 40981278)
64. S. Snykers, T. Vanhaecke, P. Papeleu, A. Luttun, Y. Jiang, Y. Vander Heyden, C. Verfaillie and V. Rogiers: Sequential exposure to cytokines reflecting embryogenesis: the key for in vitro differentiation of adult bone marrow stem cells into functional hepatocyte-like cells. Toxicol Sci, 94 (2), 330-41; discussion 235-9 (2006) (Pubitemid 44817149)
65. S. Y. Ong, H. Dai and K. W. Leong: Hepatic differentiation potential of commercially available human mesenchymal stem cells. Tissue Eng, 12 (12), 3477-85 (2006) (Pubitemid 46037170)
66. S. Oyagi, M. Hirose, M. Kojima, M. Okuyama, M. Kawase, T. Nakamura, H. Ohgushi and K. Yagi: Therapeutic effect of transplanting HGF-treated bone marrow mesenchymal cells into CCl4-injured rats. J Hepatol, 44 (4), 742-8 (2006)
67. D. C. Zhao, J. X. Lei, R. Chen, W. H. Yu, X. M. Zhang, S. N. Li and P. Xiang: Bone marrow-derived mesenchymal stem cells protect against experimental liver fibrosis in rats. World J Gastroenterol, 11 (22), 3431-40 (2005) (Pubitemid 40873250)
68. P. A. Farazi and R. A. DePinho: Hepatocellular carcinoma pathogenesis: from genes to environment. Nat Rev Cancer, 6 (9), 674-87 (2006) (Pubitemid 44286000)
69. L. Libbrecht, V. Desmet and T. Roskams: Preneoplastic lesions in human hepatocarcinogenesis. Liver Int, 25 (1), 16-27 (2005) (Pubitemid 40298240)
70. S. Watanabe, K. Okita, T. Harada, T. Kodama, Y. Numa, T. Takemoto and T. Takahashi: Morphologic studies of the liver cell dysplasia. Cancer, 51 (12), 2197-205 (1983) (Pubitemid 13106843)
71. B. Le Bail, P. H. Bernard, J. Carles, C. Balabaud and P. Bioulac-Sage: Prevalence of liver cell dysplasia and association with HCC in a series of 100 cirrhotic liver explants. J Hepatol, 27 (5), 835-42 (1997) (Pubitemid 27454827)
72. P. P. Anthony, C. L. Vogel and L. F. Barker: Liver cell dysplasia: a premalignant condition. J Clin Pathol, 26 (3), 217-23 (1973)
73. M. Roncalli, M. Borzio, B. Brando, G. Colloredo and E. Servida: Abnormal DNA content in liver-cell dysplasia: a flow cytometric study. Int J Cancer, 44 (2), 204-7 (1989) (Pubitemid 19217202)
74. R. M. Thomas, J. J. Berman, R. A. Yetter, G. W. Moore and G. M. Hutchins: Liver cell dysplasia: a DNA aneuploid lesion with distinct morphologic features. Hum Pathol, 23 (5), 496-503 (1992)
75. E. Santoni-Rugiu, P. Nagy, M. R. Jensen, V. M. Factor and S. S. Thorgeirsson: Evolution of neoplastic development in the liver of transgenic mice co-expressing c-myc and transforming growth factor-alpha. Am J Pathol, 149 (2), 407-28 (1996) (Pubitemid 26256330)
76. R. G. Lee, A. C. Tsamandas and A. J. Demetris: Large cell change (liver cell dysplasia) and hepatocellular carcinoma in cirrhosis: matched case-control study, pathological analysis, and pathogenetic hypothesis. Hepatology, 26 (6), 1415-22 (1997) (Pubitemid 27520005)
77. A. Eguchi, O. Nakashima, S. Okudaira, S. Sugihara and M. Kojiro: Adenomatous hyperplasia in the vicinity of small hepatocellular carcinoma. Hepatology, 15 (5), 843-8 (1992)
78. K. Kaji, T. Terada and Y. Nakanuma: Frequent occurrence of hepatocellular carcinoma in cirrhotic livers after surgical resection of atypical adenomatous hyperplasia (borderline hepatocellular lesion): a follow-up study. Am J Gastroenterol, 89 (6), 903-8 (1994) (Pubitemid 24165918)
79. Terminology of nodular hepatocellular lesions. International Working Party. Hepatology, 22 (3), 983-93 (1995)
80. M. Maggioni, G. Coggi, B. Cassani, P. Bianchi, S. Romagnoli, A. Mandelli, M. Borzio, P. Colombo and M. Roncalli: Molecular changes in hepatocellular dysplastic nodules on microdissected liver biopsies. Hepatology, 32 (5), 942-6 (2000)
81. L. Tornillo, V. Carafa, G. Sauter, H. Moch, E. Minola, M. Gambacorta, R. Vecchione, L. Bianchi and L. M. Terracciano: Chromosomal alterations in hepatocellular nodules by comparative genomic hybridization: high-grade dysplastic nodules represent early stages of hepatocellular carcinoma. Lab Invest, 82 (5), 547-53 (2002) (Pubitemid 34522367)
82. M. Roncalli, E. Roz, G. Coggi, M. G. Di Rocco, P. Bossi, E. Minola, M. Gambacorta and M. Borzio: The vascular profile of regenerative and dysplastic nodules of the cirrhotic liver: mplications for diagnosis and classification. Hepatology, 30 (5), 1174-8 (1999) (Pubitemid 29510855)
83. G. E. Rines: Virchow, Rudolf. In: Encyclopedia Americana. Ed G. E. Rines. (1917-1920)
84. R. Derosa: (Rudolf Virchow and Karl Marx. on an Unpublished Letter by Kugelmann to Marx About Virchow (1868)). Virchows Arch Pathol Anat Physiol Klin Med, 337, 593-5 (1964)
85. C. T. Jordan, M. L. Guzman and M. Noble: Cancer stem cells. N Engl J Med, 355 (12), 1253-61 (2006) (Pubitemid 44427449)
86. E. A. Conner, E. R. Lemmer, M. Omori, P. J. Wirth, V. M. Factor and S. S. Thorgeirsson: Dual functions of E2F-1 in a transgenic mouse model of liver carcinogenesis. Oncogene, 19 (44), 5054-62 (2000)
87. S. S. Thorgeirsson and E. Santoni-Rugiu: Transgenic mouse models in carcinogenesis: interaction of c-myc with transforming growth factor alpha and hepatocyte growth factor in hepatocarcinogenesis. Br J Clin Pharmacol, 42 (1), 43-52 (1996) (Pubitemid 26230053)
88. M. V. Frolov and N. J. Dyson: Molecular mechanisms of E2F-dependent activation and pRB-mediated repression. J Cell Sci, 117 (Pt 11), 2173-81 (2004) (Pubitemid 38807486)
89. R. Taub: Liver regeneration: from myth to mechanism. Nat Rev Mol Cell Biol, 5 (10), 836-47 (2004)
90. L. M. Brandriet: Intrapreneurial/entrepreneurial roles for nurses in long-term care. Seize the opportunity to be nontraditional. J Gerontol Nurs, 18 (12), 9-14 (1992)
91. H. Okabe, S. Satoh, T. Kato, O. Kitahara, R. Yanagawa, Y. Yamaoka, T. Tsunoda, Y. Furukawa and Y. Nakamura: Genome-wide analysis of gene expression in human hepatocellular carcinomas using cDNA microarray: identification of genes involved in viral carcinogenesis and tumor progression. Cancer Res, 61 (5), 2129-37 (2001) (Pubitemid 32692038)
92. X. Wang, E. Quail, N. J. Hung, Y. Tan, H. Ye and R. H. Costa: Increased levels of forkhead box M1B transcription factor in transgenic mouse hepatocytes prevent age-related proliferation defects in regenerating liver. Proc Natl Acad Sci U S A, 98 (20), 11468-73 (2001) (Pubitemid 32928752)
93. M. L. Major, R. Lepe and R. H. Costa: Forkhead box M1B transcriptional activity requires binding of Cdk-cyclin complexes for phosphorylation-dependent recruitment of p300/CBP coactivators. Mol Cell Biol, 24 (7), 2649-61 (2004)
94. S. M. Gollin: Mechanisms leading to chromosomal instability. Semin Cancer Biol, 15 (1), 33-42 (2005) (Pubitemid 40018526)
95. A. Saeki, S. Tamura, N. Ito, S. Kiso, Y. Matsuda, I. Yabuuchi, S. Kawata and Y. Matsuzawa: Frequent impairment of the spindle assembly checkpoint in hepatocellular carcinoma. Cancer, 94 (7), 2047-54 (2002) (Pubitemid 34270059)
96. M. W. Smith, Z. N. Yue, G. K. Geiss, N. Y. Sadovnikova, V. S. Carter, L. Boix, C. A. Lazaro, G. B. Rosenberg, R. E. Bumgarner, N. Fausto, J. Bruix and M. G. Katze: Identification of novel tumor markers in hepatitis C virus-associated hepatocellular carcinoma. Cancer Res, 63 (4), 859-64 (2003) (Pubitemid 36231988)
97. C. T. Yu, J. M. Hsu, Y. C. Lee, A. P. Tsou, C. K. Chou and C. Y. Huang: Phosphorylation and stabilization of HURP by Aurora-A: implication of HURP as a transforming target of Aurora-A. Mol Cell Biol, 25 (14), 5789-800 (2005)
98. N. C. Teoh, Y. Y. Dan, K. Swisshelm, S. Lehman, J. H. Wright, J. Haque, Y. Gu and N. Fausto: Defective DNA strand break repair causes chromosomal instability and accelerates liver carcinogenesis in mice. Hepatology, 47 (6), 2078-88 (2008) (Pubitemid 351945574)
99. S. N. Huang and F. V. Chisari: Strong, sustained hepatocellular proliferation precedes hepatocarcinogenesis in hepatitis B surface antigen transgenic mice. Hepatology, 21 (3), 620-6 (1995)
100. N. Nishida, Y. Fukuda, H. Kokuryu, J. Toguchida, D. W. Yandell, M. Ikenega, H. Imura and K. Ishizaki: Role and mutational heterogeneity of the p53 gene in hepatocellular carcinoma. Cancer Res, 53 (2), 368-72 (1993) (Pubitemid 23031851)
101. K. Minouchi, S. Kaneko and K. Kobayashi: Mutation of p53 gene in regenerative nodules in cirrhotic liver. J Hepatol, 37 (2), 231-9 (2002) (Pubitemid 34833085)
102. S. Ma, K. W. Chan, L. Hu, T. K. Lee, J. Y. Wo, I. O. Ng, B. J. Zheng and X. Y. Guan: Identification and characterization of tumorigenic liver cancer stem/progenitor cells. Gastroenterology, 132 (7), 2542-56 (2007) (Pubitemid 46890873)
103. A. Suetsugu, M. Nagaki, H. Aoki, T. Motohashi, T. Kunisada and H. Moriwaki: Characterization of CD133+ hepatocellular carcinoma cells as cancer stem/progenitor cells. Biochem Biophys Res Commun, 351 (4), 820-4 (2006) (Pubitemid 44715858)
104. S. Ma, T. K. Lee, B. J. Zheng, K. W. Chan and X. Y. Guan: CD133+ HCC cancer stem cells confer chemoresistance by preferential expression of the Akt/PKB survival pathway. Oncogene, 27 (12), 1749-58 (2008) (Pubitemid 351380265)
105. D. E. Bergsagel and F. A. Valeriote: Growth characteristics of a mouse plasma cell tumor. Cancer Res, 28 (11), 2187-96 (1968)
106. Z. F. Yang, D. W. Ho, M. N. Ng, C. K. Lau, W. C. Yu, P. Ngai, P. W. Chu, C. T. Lam, R. T. Poon and S. T. Fan: Significance of CD90+ cancer stem cells in human liver cancer. Cancer Cell, 13 (2), 153-66 (2008) (Pubitemid 351163165)
107. Z. F. Yang, P. Ngai, D. W. Ho, W. C. Yu, M. N. Ng, C. K. Lau, M. L. Li, K. H. Tam, C. T. Lam, R. T. Poon and S. T. Fan: Identification of local and circulating cancer stem cells in human liver cancer. Hepatology, 47 (3), 919-28 (2008) (Pubitemid 351449683)
108. T. Yamashita, J. Ji, A. Budhu, M. Forgues, W. Yang, H. Y. Wang, H. Jia, Q. Ye, L. X. Qin, E. Wauthier, L. M. Reid, H. Minato, M. Honda, S. Kaneko, Z. Y. Tang and X. W. Wang: EpCAM-positive hepatocellular carcinoma cells are tumor-initiating cells with stem/progenitor cell features. Gastroenterology, 136 (3), 1012-24 (2009)
109. T. Yamashita, M. Forgues, W. Wang, J. W. Kim, Q. Ye, H. Jia, A. Budhu, K. A. Zanetti, Y. Chen, L. X. Qin, Z. Y. Tang and X. W. Wang: EpCAM and alpha-fetoprotein expression defines novel prognostic subtypes of hepatocellular carcinoma. Cancer Res, 68 (5), 1451-61 (2008) (Pubitemid 351346853)
110. E. Bugianesi: Review article: steatosis, the metabolic syndrome and cancer. Aliment Pharmacol Ther, 22 Suppl 2, 40-3 (2005) (Pubitemid 41564381)
111. S. S. Thorgeirsson, J. S. Lee and J. W. Grisham: Molecular prognostication of liver cancer: end of the beginning. J Hepatol, 44 (4), 798-805 (2006)
112. X. W. Wang, S. P. Hussain, T. I. Huo, C. G. Wu, M. Forgues, L. J. Hofseth, C. Brechot and C. C. Harris: Molecular pathogenesis of human hepatocellular carcinoma. Toxicology, 181-182, 43-7 (2002) (Pubitemid 36015671)
113. A. Villanueva, P. Newell, D. Y. Chiang, S. L. Friedman and J. M. Llovet: Genomics and signaling pathways in hepatocellular carcinoma. Semin Liver Dis, 27 (1), 55-76 (2007)
114. J. U. Marquardt and S. S. Thorgeirsson: Stem cells in hepatocarcinogenesis: evidence from genomic data. Semin Liver Dis, 30 (1), 26-34
115. A. W. Duncan, C. Dorrell and M. Grompe: Stem cells and liver regeneration. Gastroenterology, 137 (2), 466-81 (2009)
116. W. Yang, H. X. Yan, L. Chen, Q. Liu, Y. Q. He, L. X. Yu, S. H. Zhang, D. D. Huang, L. Tang, X. N. Kong, C. Chen, S. Q. Liu, M. C. Wu and H. Y. Wang: Wnt/betacatenin signaling contributes to activation of normal and tumorigenic liver progenitor cells. Cancer Res, 68 (11), 4287-95 (2008)
117. C. M. Shachaf, A. M. Kopelman, C. Arvanitis, A. Karlsson, S. Beer, S. Mandl, M. H. Bachmann, A. D. Borowsky, B. Ruebner, R. D. Cardiff, Q. Yang, J. M. Bishop, C. H. Contag and D. W. Felsher: MYC inactivation uncovers pluripotent differentiation and tumour dormancy in hepatocellular cancer. Nature, 431 (7012), 1112-7 (2004) (Pubitemid 39472236)
118. D. Semela and J. F. Dufour: Angiogenesis and hepatocellular carcinoma. J Hepatol, 41 (5), 864-80 (2004) (Pubitemid 39434320)
119. J. Folkman: Fundamental concepts of the angiogenic process. Curr Mol Med, 3 (7), 643-51 (2003) (Pubitemid 37236406)
120. L. R. Roberts and G. J. Gores: Emerging drugs for hepatocellular carcinoma. Expert Opin Emerg Drugs, 11 (3), 469-87 (2006) (Pubitemid 44386371)
121. M. Papetti and I. M. Herman: Mechanisms of normal and tumor-derived angiogenesis. Am J Physiol Cell Physiol, 282 (5), C947-70 (2002) (Pubitemid 34663101)
122. L. R. Roberts and G. J. Gores: Hepatocellular carcinoma: molecular pathways and new therapeutic targets. Semin Liver Dis, 25 (2), 212-25 (2005) (Pubitemid 40781073)
123. R. T. Poon, C. Lau, W. C. Yu, S. T. Fan and J. Wong: High serum levels of vascular endothelial growth factor predict poor response to transarterial chemoembolization in hepatocellular carcinoma: a prospective study. Oncol Rep, 11 (5), 1077-84 (2004)
124. Y. Chao, C. P. Li, G. Y. Chau, C. P. Chen, K. L. King, W. Y. Lui, S. H. Yen, F. Y. Chang, W. K. Chan and S. D. Lee: Prognostic significance of vascular endothelial growth factor, basic fibroblast growth factor, and angiogenin in patients with resectable hepatocellular carcinoma after surgery. Ann Surg Oncol, 10 (4), 355-62 (2003) (Pubitemid 40486931)
125. N. Barker and H. Clevers: Mining the Wnt pathway for cancer therapeutics. Nat Rev Drug Discov, 5 (12), 997-1014 (2006) (Pubitemid 44835127)
126. R. T. Moon, A. D. Kohn, G. V. De Ferrari and A. Kaykas: WNT and beta-catenin signalling: diseases and therapies. Nat Rev Genet, 5 (9), 691-701 (2004) (Pubitemid 39150127)
127. K. S. Zaret: Genetic programming of liver and pancreas progenitors: lessons for stem-cell differentiation. Nat Rev Genet, 9 (5), 329-40 (2008) (Pubitemid 351556060)
128. R. H. Giles, J. H. van Es and H. Clevers: Caught up in a Wnt storm: Wnt signaling in cancer. Biochim Biophys Acta, 1653 (1), 1-24 (2003) (Pubitemid 36627817)
129. S. Inagawa, M. Itabashi, S. Adachi, T. Kawamoto, M. Hori, J. Shimazaki, F. Yoshimi and K. Fukao: Expression and prognostic roles of beta-catenin in hepatocellular carcinoma: correlation with tumor progression and postoperative survival. Clin Cancer Res, 8 (2), 450-6 (2002) (Pubitemid 34193964)
130. M. Branda and J. R. Wands: Signal transduction cascades and hepatitis B and C related hepatocellular carcinoma. Hepatology, 43 (5), 891-902 (2006) (Pubitemid 43724611)
131. P. Merle, S. de la Monte, M. Kim, M. Herrmann, S. Tanaka, A. Von Dem Bussche, M. C. Kew, C. Trepo and J. R. Wands: Functional consequences of frizzled-7 receptor overexpression in human hepatocellular carcinoma. Gastroenterology, 127 (4), 1110-22 (2004) (Pubitemid 39345880)
132. E. U. Bieler, D. Nagel and E. J. De Bruin: Comparative determination of total serum thyroxine. Radio-immunoassay and protein-binding assay. S Afr Med J, 49 (17), 712-4 (1975)
133. K. Quint, S. Stintzing, B. Alinger, C. Hauser-Kronberger, O. Dietze, S. Gahr, E. G. Hahn, M. Ocker and D. Neureiter: The expression pattern of PDX-1, SHH, Patched and Gli-1 is associated with pathological and clinical features in human pancreatic cancer. Pancreatology, 9 (1-2), 116-26 (2009)
134. J. K. Sicklick, Y. X. Li, A. Jayaraman, R. Kannangai, Y. Qi, P. Vivekanandan, J. W. Ludlow, K. Owzar, W. Chen, M. S. Torbenson and A. M. Diehl: Dysregulation of the Hedgehog pathway in human hepatocarcinogenesis. Carcinogenesis, 27 (4), 748-57 (2006)
135. S. Huang, J. He, X. Zhang, Y. Bian, L. Yang, G. Xie, K. Zhang, W. Tang, A. A. Stelter, Q. Wang, H. Zhang and J. Xie: Activation of the hedgehog pathway in human hepatocellular carcinomas. Carcinogenesis, 27 (7), 1334-40 (2006) (Pubitemid 43985408)
136. J. Li, X. Zhao, L. Chen, H. Guo, F. Lv, K. Jia, K. Yv, F. Wang, C. Li, J. Qian, C. Zheng and Y. Zuo: Safety and pharmacokinetics of novel selective vascular endothelial growth factor receptor-2 inhibitor YN968D1 in patients with advanced malignancies. BMC Cancer, 10, 529
137. T. Yau, P. Chan, R. Pang, K. Ng, S. T. Fan and R. T. Poon: Phase 1-2 trial of PTK787/ZK222584 combined with intravenous doxorubicin for treatment of patients with advanced hepatocellular carcinoma: implication for antiangiogenic approach to hepatocellular carcinoma. Cancer, 116 (21), 5022-9
138. W. Sun, D. Sohal, D. G. Haller, K. Mykulowycz, M. Rosen, M. C. Soulen, M. Caparro, U. R. Teitelbaum, B. Giantonio, P. J. O'Dwyer, A. Shaked, R. Reddy and K. Olthoff: Phase 2 trial of bevacizumab, capecitabine, and oxaliplatin in treatment of advanced hepatocellular carcinoma. Cancer
139. V. Beljanski, C. S. Lewis and C. D. Smith: Antitumor activity of Sphingosine Kinase 2 inhibitor ABC294640 and sorafenib in hepatocellular carcinoma xenografts. Cancer Biol Ther, 11 (5)
140. R. Sacco, I. Bargellini, G. Giannelli, M. Bertini, E. Bozzi, E. Altomare, V. Battaglia, A. Romano, M. Bertoni, A. Capria, G. Bresci and C. Bartolozzi: Complete response for advanced liver cancer during sorafenib therapy: Case Report. BMC Gastroenterol, 11 (1), 4
141. R. J. Gilbertson and J. N. Rich: Making a tumour's bed: glioblastoma stem cells and the vascular niche. Nat Rev Cancer, 7 (10), 733-6 (2007) (Pubitemid 47463683)
142. Y. Gokmen-Polar and K. D. Miller: Redefining the target again: chemotherapeutics as vascular disrupting agents? Cancer Cell, 14 (3), 195-6 (2008)
143. J. M. Llovet, A. Burroughs and J. Bruix: Hepatocellular carcinoma. Lancet, 362 (9399), 1907-17 (2003) (Pubitemid 37518510)
144. M. F. Clarke, J. E. Dick, P. B. Dirks, C. J. Eaves, C. H. Jamieson, D. L. Jones, J. Visvader, I. L. Weissman and G. M. Wahl: Cancer stem cells-perspectives on current status and future directions: AACR Workshop on cancer stem cells. Cancer Res, 66 (19), 9339-44 (2006) (Pubitemid 44623625)
145. C. Yin, Y. Lin, X. Zhang, Y. X. Chen, X. Zeng, H. Y. Yue, J. L. Hou, X. Deng, J. P. Zhang, Z. G. Han and W. F. Xie: Differentiation therapy of hepatocellular carcinoma in mice with recombinant adenovirus carrying hepatocyte nuclear factor-4alpha gene. Hepatology, 48 (5), 1528-39 (2008)
146. C. H. Sukowati, N. Rosso, L. S. Croce and C. Tiribelli: Hepatic cancer stem cells and drug resistance: Relevance in targeted therapies for hepatocellular carcinoma. World J Hepatol, 2 (3), 114-26 (2010)