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Mouse Model for Hepatocellular Carcinoma and Cholangiocarcinoma Originated from Mature Hepatocytes

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Hepatic Stem Cells

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1905))

Abstract

Liver cancer consists of two main histological subtypes, hepatocellular carcinoma and cholangiocarcinoma, both of which have poor prognosis. Therefore, in searching for new therapeutic targets, adequate mouse models to develop and validate therapeutic strategies are urgently needed. Although there are mouse models of liver cancer, each model has shortcomings. To overcome these shortcomings, a mouse model using a hydrodynamic tail vein injection and the Sleeping Beauty transposon was developed. By inducing stable expression of oncogenes in mouse hepatocytes in vivo, the model can easily induce liver cancer with specific characteristics that depend on the oncogenes used to induce carcinogenesis. Here, we describe the details of the methods to induce hepatocellular carcinoma or cholangiocarcinoma from mouse hepatocytes.

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References

  1. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136(5):E359–E386. https://doi.org/10.1002/ijc.29210

    Article  CAS  PubMed  Google Scholar 

  2. Altekruse SF, Henley SJ, Cucinelli JE, McGlynn KA (2014) Changing hepatocellular carcinoma incidence and liver cancer mortality rates in the United States. Am J Gastroenterol 109(4):542–553. https://doi.org/10.1038/ajg.2014.11

    Article  PubMed  PubMed Central  Google Scholar 

  3. El-Serag HB, Kanwal F (2014) Epidemiology of hepatocellular carcinoma in the United States: where are we? Where do we go? Hepatology 60(5):1767–1775. https://doi.org/10.1002/hep.27222

    Article  PubMed  Google Scholar 

  4. Razumilava N, Gores GJ (2014) Cholangiocarcinoma. Lancet 383(9935):2168–2179. https://doi.org/10.1016/S0140-6736(13)61903-0

    Article  PubMed  PubMed Central  Google Scholar 

  5. Palmer WC, Patel T (2012) Are common factors involved in the pathogenesis of primary liver cancers? A meta-analysis of risk factors for intrahepatic cholangiocarcinoma. J Hepatol 57(1):69–76. https://doi.org/10.1016/j.jhep.2012.02.022

    Article  PubMed  PubMed Central  Google Scholar 

  6. Forner A, Reig M, Bruix J (2018) Hepatocellular carcinoma. Lancet 391:1301–1314. https://doi.org/10.1016/s0140-6736(18)30010-2

    Article  PubMed  Google Scholar 

  7. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, Schwartz M, Porta C, Zeuzem S, Bolondi L, Greten TF, Galle PR, Seitz JF, Borbath I, Haussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, Bruix J, SHARP Investigators Study Group (2008) Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359(4):378–390. https://doi.org/10.1056/NEJMoa0708857

    Article  CAS  PubMed  Google Scholar 

  8. Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, Luo R, Feng J, Ye S, Yang TS, Xu J, Sun Y, Liang H, Liu J, Wang J, Tak WY, Pan H, Burock K, Zou J, Voliotis D, Guan Z (2009) Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol 10(1):25–34. https://doi.org/10.1016/S1470-2045(08)70285-7

    Article  CAS  PubMed  Google Scholar 

  9. Inuzuka T, Nishikawa H, Sekikawa A, Takeda H, Henmi S, Sakamoto A, Saito S, Kita R, Kimura T, Osaki Y, Kudo M (2011) Complete response of advanced hepatocellular carcinoma with multiple lung metastases treated with sorafenib: a case report. Oncology 81(Suppl 1):152–157. https://doi.org/10.1159/000333279

    Article  PubMed  Google Scholar 

  10. Valle J, Wasan H, Palmer DH, Cunningham D, Anthoney A, Maraveyas A, Madhusudan S, Iveson T, Hughes S, Pereira SP, Roughton M, Bridgewater J, ABC Trial Investigators (2010) Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med 362(14):1273–1281. https://doi.org/10.1056/NEJMoa0908721

    Article  CAS  PubMed  Google Scholar 

  11. Heindryckx F, Colle I, Van Vlierberghe H (2009) Experimental mouse models for hepatocellular carcinoma research. Int J Exp Pathol 90(4):367–386. https://doi.org/10.1111/j.1365-2613.2009.00656.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Chen X, Calvisi DF (2014) Hydrodynamic transfection for generation of novel mouse models for liver cancer research. Am J Pathol 184(4):912–923. https://doi.org/10.1016/j.ajpath.2013.12.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Landgraf M, McGovern JA, Friedl P, Hutmacher DW (2018) Rational design of mouse models for cancer research. Trends Biotechnol 36:242–251. https://doi.org/10.1016/j.tibtech.2017.12.001

    Article  CAS  PubMed  Google Scholar 

  14. Liu F, Song Y, Liu D (1999) Hydrodynamics-based transfection in animals by systemic administration of plasmid DNA. Gene Ther 6(7):1258–1266. https://doi.org/10.1038/sj.gt.3300947

    Article  CAS  PubMed  Google Scholar 

  15. Zhang G, Budker V, Wolff JA (1999) High levels of foreign gene expression in hepatocytes after tail vein injections of naked plasmid DNA. Hum Gene Ther 10(10):1735–1737. https://doi.org/10.1089/10430349950017734

    Article  CAS  PubMed  Google Scholar 

  16. Yokoo T, Kamimura K, Abe H, Kobayashi Y, Kanefuji T, Ogawa K, Goto R, Oda M, Suda T, Terai S (2016) Liver-targeted hydrodynamic gene therapy: Recent advances in the technique. World J Gastroenterol 22(40):8862–8868. https://doi.org/10.3748/wjg.v22.i40.8862

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Suda T, Liu D (2007) Hydrodynamic gene delivery: its principles and applications. Mol Ther 15(12):2063–2069. https://doi.org/10.1038/sj.mt.6300314

    Article  CAS  PubMed  Google Scholar 

  18. Sawyer GJ, Rela M, Davenport M, Whitehorne M, Zhang X, Fabre JW (2009) Hydrodynamic gene delivery to the liver: theoretical and practical issues for clinical application. Curr Gene Ther 9(2):128–135

    Article  CAS  PubMed  Google Scholar 

  19. Bonamassa B, Hai L, Liu D (2011) Hydrodynamic gene delivery and its applications in pharmaceutical research. Pharm Res 28(4):694–701. https://doi.org/10.1007/s11095-010-0338-9

    Article  CAS  PubMed  Google Scholar 

  20. Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, Devon K, Dewar K, Doyle M, FitzHugh W, Funke R, Gage D, Harris K, Heaford A, Howland J, Kann L, Lehoczky J, LeVine R, McEwan P, McKernan K, Meldrim J, Mesirov JP, Miranda C, Morris W, Naylor J, Raymond C, Rosetti M, Santos R, Sheridan A, Sougnez C, Stange-Thomann Y, Stojanovic N, Subramanian A, Wyman D, Rogers J, Sulston J, Ainscough R, Beck S, Bentley D, Burton J, Clee C, Carter N, Coulson A, Deadman R, Deloukas P, Dunham A, Dunham I, Durbin R, French L, Grafham D, Gregory S, Hubbard T, Humphray S, Hunt A, Jones M, Lloyd C, McMurray A, Matthews L, Mercer S, Milne S, Mullikin JC, Mungall A, Plumb R, Ross M, Shownkeen R, Sims S, Waterston RH, Wilson RK, Hillier LW, McPherson JD, Marra MA, Mardis ER, Fulton LA, Chinwalla AT, Pepin KH, Gish WR, Chissoe SL, Wendl MC, Delehaunty KD, Miner TL, Delehaunty A, Kramer JB, Cook LL, Fulton RS, Johnson DL, Minx PJ, Clifton SW, Hawkins T, Branscomb E, Predki P, Richardson P, Wenning S, Slezak T, Doggett N, Cheng JF, Olsen A, Lucas S, Elkin C, Uberbacher E, Frazier M, Gibbs RA, Muzny DM, Scherer SE, Bouck JB, Sodergren EJ, Worley KC, Rives CM, Gorrell JH, Metzker ML, Naylor SL, Kucherlapati RS, Nelson DL, Weinstock GM, Sakaki Y, Fujiyama A, Hattori M, Yada T, Toyoda A, Itoh T, Kawagoe C, Watanabe H, Totoki Y, Taylor T, Weissenbach J, Heilig R, Saurin W, Artiguenave F, Brottier P, Bruls T, Pelletier E, Robert C, Wincker P, Smith DR, Doucette-Stamm L, Rubenfield M, Weinstock K, Lee HM, Dubois J, Rosenthal A, Platzer M, Nyakatura G, Taudien S, Rump A, Yang H, Yu J, Wang J, Huang G, Gu J, Hood L, Rowen L, Madan A, Qin S, Davis RW, Federspiel NA, Abola AP, Proctor MJ, Myers RM, Schmutz J, Dickson M, Grimwood J, Cox DR, Olson MV, Kaul R, Raymond C, Shimizu N, Kawasaki K, Minoshima S, Evans GA, Athanasiou M, Schultz R, Roe BA, Chen F, Pan H, Ramser J, Lehrach H, Reinhardt R, McCombie WR, de la Bastide M, Dedhia N, Blocker H, Hornischer K, Nordsiek G, Agarwala R, Aravind L, Bailey JA, Bateman A, Batzoglou S, Birney E, Bork P, Brown DG, Burge CB, Cerutti L, Chen HC, Church D, Clamp M, Copley RR, Doerks T, Eddy SR, Eichler EE, Furey TS, Galagan J, Gilbert JG, Harmon C, Hayashizaki Y, Haussler D, Hermjakob H, Hokamp K, Jang W, Johnson LS, Jones TA, Kasif S, Kaspryzk A, Kennedy S, Kent WJ, Kitts P, Koonin EV, Korf I, Kulp D, Lancet D, Lowe TM, McLysaght A, Mikkelsen T, Moran JV, Mulder N, Pollara VJ, Ponting CP, Schuler G, Schultz J, Slater G, Smit AF, Stupka E, Szustakowki J, Thierry-Mieg D, Thierry-Mieg J, Wagner L, Wallis J, Wheeler R, Williams A, Wolf YI, Wolfe KH, Yang SP, Yeh RF, Collins F, Guyer MS, Peterson J, Felsenfeld A, Wetterstrand KA, Patrinos A, Morgan MJ, de Jong P, Catanese JJ, Osoegawa K, Shizuya H, Choi S, Chen YJ, Szustakowki J, International Human Genome Sequencing Consortium (2001) Initial sequencing and analysis of the human genome. Nature 409(6822):860–921. https://doi.org/10.1038/35057062

    Article  CAS  PubMed  Google Scholar 

  21. Ivics Z, Hackett PB, Plasterk RH, Izsvak Z (1997) Molecular reconstruction of Sleeping Beauty, a Tc1-like transposon from fish, and its transposition in human cells. Cell 91(4):501–510

    Article  CAS  PubMed  Google Scholar 

  22. Izsvak Z, Ivics Z (2004) Sleeping beauty transposition: biology and applications for molecular therapy. Mol Ther 9(2):147–156. https://doi.org/10.1016/j.ymthe.2003.11.009

    Article  CAS  PubMed  Google Scholar 

  23. Marquardt JU, Andersen JB, Thorgeirsson SS (2015) Functional and genetic deconstruction of the cellular origin in liver cancer. Nat Rev Cancer 15(11):653–667. https://doi.org/10.1038/nrc4017

    Article  CAS  PubMed  Google Scholar 

  24. Sell S (2002) Cellular origin of hepatocellular carcinomas. Semin Cell Dev Biol 13(6):419–424

    Article  PubMed  Google Scholar 

  25. Oikawa T (2016) Cancer Stem cells and their cellular origins in primary liver and biliary tract cancers. Hepatology 64(2):645–651. https://doi.org/10.1002/hep.28485

    Article  PubMed  Google Scholar 

  26. Sekiya S, Suzuki A (2012) Intrahepatic cholangiocarcinoma can arise from Notch-mediated conversion of hepatocytes. J Clin Invest 122(11):3914–3918. https://doi.org/10.1172/JCI63065

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Fan B, Malato Y, Calvisi DF, Naqvi S, Razumilava N, Ribback S, Gores GJ, Dombrowski F, Evert M, Chen X, Willenbring H (2012) Cholangiocarcinomas can originate from hepatocytes in mice. J Clin Invest 122(8):2911–2915. https://doi.org/10.1172/JCI63212

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Yamamoto M, Xin B, Watanabe K, Ooshio T, Fujii K, Chen X, Okada Y, Abe H, Taguchi Y, Miyokawa N, Furukawa H, Nishikawa Y (2017) Oncogenic determination of a broad spectrum of phenotypes of hepatocyte-derived mouse liver tumors. Am J Pathol 187:2711–2725. https://doi.org/10.1016/j.ajpath.2017.07.022

    Article  CAS  PubMed  Google Scholar 

  29. Li X, Tao J, Cigliano A, Sini M, Calderaro J, Azoulay D, Wang C, Liu Y, Jiang L, Evert K, Demartis MI, Ribback S, Utpatel K, Dombrowski F, Evert M, Calvisi DF, Chen X (2015) Co-activation of PIK3CA and Yap promotes development of hepatocellular and cholangiocellular tumors in mouse and human liver. Oncotarget 6(12):10102–10115. https://doi.org/10.18632/oncotarget.3546

    Article  PubMed  PubMed Central  Google Scholar 

  30. Lee CH, Chang CJ, Lin YJ, Yeh CN, Chen MF, Hsieh SY (2009) Viral hepatitis-associated intrahepatic cholangiocarcinoma shares common disease processes with hepatocellular carcinoma. Br J Cancer 100(11):1765–1770. https://doi.org/10.1038/sj.bjc.6605063

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Fujimoto A, Furuta M, Totoki Y, Tsunoda T, Kato M, Shiraishi Y, Tanaka H, Taniguchi H, Kawakami Y, Ueno M, Gotoh K, Ariizumi S, Wardell CP, Hayami S, Nakamura T, Aikata H, Arihiro K, Boroevich KA, Abe T, Nakano K, Maejima K, Sasaki-Oku A, Ohsawa A, Shibuya T, Nakamura H, Hama N, Hosoda F, Arai Y, Ohashi S, Urushidate T, Nagae G, Yamamoto S, Ueda H, Tatsuno K, Ojima H, Hiraoka N, Okusaka T, Kubo M, Marubashi S, Yamada T, Hirano S, Yamamoto M, Ohdan H, Shimada K, Ishikawa O, Yamaue H, Chayama K, Miyano S, Aburatani H, Shibata T, Nakagawa H (2016) Whole-genome mutational landscape and characterization of noncoding and structural mutations in liver cancer. Nat Genet 48(5):500–509. https://doi.org/10.1038/ng.3547

    Article  CAS  PubMed  Google Scholar 

  32. Kim MJ, Ahituv N (2013) The hydrodynamic tail vein assay as a tool for the study of liver promoters and enhancers. Methods Mol Biol 1015:279–289. https://doi.org/10.1007/978-1-62703-435-7_18

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Butash KA, Natarajan P, Young A, Fox DK (2000) Reexamination of the effect of endotoxin on cell proliferation and transfection efficiency. BioTechniques 29(3):610–614, 616, 618–619

    Article  CAS  PubMed  Google Scholar 

  34. Xin B, Yamamoto M, Fujii K, Ooshio T, Chen X, Okada Y, Watanabe K, Miyokawa N, Furukawa H, Nishikawa Y (2017) Critical role of Myc activation in mouse hepatocarcinogenesis induced by the activation of AKT and RAS pathways. Oncogene 36(36):5087–5097. https://doi.org/10.1038/onc.2017.114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Mendez-Lucas A, Li X, Hu J, Che L, Song X, Jia J, Wang J, Xie C, Driscoll PC, Tschaharganeh DF, Calvisi DF, Yuneva M, Chen X (2017) Glucose catabolism in liver tumors induced by c-MYC can be sustained by various PKM1/PKM2 ratios and pyruvate kinase activities. Cancer Res 77(16):4355–4364. https://doi.org/10.1158/0008-5472.CAN-17-0498

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Tao J, Zhang R, Singh S, Poddar M, Xu E, Oertel M, Chen X, Ganesh S, Abrams M, Monga SP (2017) Targeting beta-catenin in hepatocellular cancers induced by coexpression of mutant beta-catenin and K-Ras in mice. Hepatology 65(5):1581–1599. https://doi.org/10.1002/hep.28975

    Article  CAS  PubMed  Google Scholar 

  37. Tao J, Xu E, Zhao Y, Singh S, Li X, Couchy G, Chen X, Zucman-Rossi J, Chikina M, Monga SP (2016) Modeling a human hepatocellular carcinoma subset in mice through coexpression of met and point-mutant beta-catenin. Hepatology 64(5):1587–1605. https://doi.org/10.1002/hep.28601

    Article  CAS  PubMed  Google Scholar 

  38. Hu J, Che L, Li L, Pilo MG, Cigliano A, Ribback S, Li X, Latte G, Mela M, Evert M, Dombrowski F, Zheng G, Chen X, Calvisi DF (2016) Co-activation of AKT and c-Met triggers rapid hepatocellular carcinoma development via the mTORC1/FASN pathway in mice. Sci Rep 6:20484. https://doi.org/10.1038/srep20484

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Ho C, Wang C, Mattu S, Destefanis G, Ladu S, Delogu S, Armbruster J, Fan L, Lee SA, Jiang L, Dombrowski F, Evert M, Chen X, Calvisi DF (2012) AKT (v-akt murine thymoma viral oncogene homolog 1) and N-Ras (neuroblastoma ras viral oncogene homolog) coactivation in the mouse liver promotes rapid carcinogenesis by way of mTOR (mammalian target of rapamycin complex 1), FOXM1 (forkhead box M1)/SKP2, and c-Myc pathways. Hepatology 55(3):833–845. https://doi.org/10.1002/hep.24736

    Article  CAS  PubMed  Google Scholar 

  40. Wang C, Delogu S, Ho C, Lee SA, Gui B, Jiang L, Ladu S, Cigliano A, Dombrowski F, Evert M, Calvisi DF, Chen X (2012) Inactivation of Spry2 accelerates AKT-driven hepatocarcinogenesis via activation of MAPK and PKM2 pathways. J Hepatol 57(3):577–583. https://doi.org/10.1016/j.jhep.2012.04.026

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Stauffer JK, Scarzello AJ, Andersen JB, De Kluyver RL, Back TC, Weiss JM, Thorgeirsson SS, Wiltrout RH (2011) Coactivation of AKT and beta-catenin in mice rapidly induces formation of lipogenic liver tumors. Cancer Res 71(7):2718–2727. https://doi.org/10.1158/0008-5472.CAN-10-2705

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Calvisi DF, Wang C, Ho C, Ladu S, Lee SA, Mattu S, Destefanis G, Delogu S, Zimmermann A, Ericsson J, Brozzetti S, Staniscia T, Chen X, Dombrowski F, Evert M (2011) Increased lipogenesis, induced by AKT-mTORC1-RPS6 signaling, promotes development of human hepatocellular carcinoma. Gastroenterology 140(3):1071–1083. https://doi.org/10.1053/j.gastro.2010.12.006

    Article  CAS  PubMed  Google Scholar 

  43. Lee SA, Ladu S, Evert M, Dombrowski F, De Murtas V, Chen X, Calvisi DF (2010) Synergistic role of Sprouty2 inactivation and c-Met up-regulation in mouse and human hepatocarcinogenesis. Hepatology 52(2):506–517. https://doi.org/10.1002/hep.23681

    Article  CAS  PubMed  Google Scholar 

  44. Xu CR, Lee S, Ho C, Bommi P, Huang SA, Cheung ST, Dimri GP, Chen X (2009) Bmi1 functions as an oncogene independent of Ink4A/Arf repression in hepatic carcinogenesis. Mol Cancer Res 7(12):1937–1945. https://doi.org/10.1158/1541-7786.MCR-09-0333

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Lee SA, Ho C, Roy R, Kosinski C, Patil MA, Tward AD, Fridlyand J, Chen X (2008) Integration of genomic analysis and in vivo transfection to identify sprouty 2 as a candidate tumor suppressor in liver cancer. Hepatology 47(4):1200–1210. https://doi.org/10.1002/hep.22169

    Article  CAS  PubMed  Google Scholar 

  46. Tward AD, Jones KD, Yant S, Cheung ST, Fan ST, Chen X, Kay MA, Wang R, Bishop JM (2007) Distinct pathways of genomic progression to benign and malignant tumors of the liver. Proc Natl Acad Sci U S A 104(37):14771–14776. https://doi.org/10.1073/pnas.0706578104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Patil MA, Lee SA, Macias E, Lam ET, Xu C, Jones KD, Ho C, Rodriguez-Puebla M, Chen X (2009) Role of cyclin D1 as a mediator of c-Met- and beta-catenin-induced hepatocarcinogenesis. Cancer Res 69(1):253–261. https://doi.org/10.1158/0008-5472.CAN-08-2514

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Zhang S, Song X, Cao D, Xu Z, Fan B, Che L, Hu J, Chen B, Dong M, Pilo MG, Cigliano A, Evert K, Ribback S, Dombrowski F, Pascale RM, Cossu A, Vidili G, Porcu A, Simile MM, Pes GM, Giannelli G, Gordan J, Wei L, Evert M, Cong W, Calvisi DF, Chen X (2017) Pan-mTOR inhibitor MLN0128 is effective against intrahepatic cholangiocarcinoma in mice. J Hepatol 67(6):1194–1203. https://doi.org/10.1016/j.jhep.2017.07.006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Carlson CM, Frandsen JL, Kirchhof N, McIvor RS, Largaespada DA (2005) Somatic integration of an oncogene-harboring Sleeping Beauty transposon models liver tumor development in the mouse. Proc Natl Acad Sci U S A 102(47):17059–17064. https://doi.org/10.1073/pnas.0502974102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Tao J, Calvisi DF, Ranganathan S, Cigliano A, Zhou L, Singh S, Jiang L, Fan B, Terracciano L, Armeanu-Ebinger S, Ribback S, Dombrowski F, Evert M, Chen X, Monga SPS (2014) Activation of beta-catenin and Yap1 in human hepatoblastoma and induction of hepatocarcinogenesis in mice. Gastroenterology 147(3):690–701. https://doi.org/10.1053/j.gastro.2014.05.004

    Article  CAS  PubMed  Google Scholar 

  51. Chow EK, Fan LL, Chen X, Bishop JM (2012) Oncogene-specific formation of chemoresistant murine hepatic cancer stem cells. Hepatology 56(4):1331–1341. https://doi.org/10.1002/hep.25776

    Article  CAS  PubMed  Google Scholar 

  52. Ju HL, Ahn SH, Kim DY, Baek S, Chung SI, Seong J, Han KH, Ro SW (2013) Investigation of oncogenic cooperation in simple liver-specific transgenic mouse models using noninvasive in vivo imaging. PLoS One 8(3):e59869. https://doi.org/10.1371/journal.pone.0059869

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Division of Tumor Pathology, Department of Pathology, Asahikawa Medical University, Asahikawa, Hokkaido, Japan

    Masahiro Yamamoto, Bing Xin & Yuji Nishikawa

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  1. Masahiro Yamamoto
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  2. Bing Xin
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  3. Yuji Nishikawa
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Correspondence to Masahiro Yamamoto .

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  1. Sapporo Medical University, Sapporo, Hokkaido, Japan

    Naoki Tanimizu

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Yamamoto, M., Xin, B., Nishikawa, Y. (2019). Mouse Model for Hepatocellular Carcinoma and Cholangiocarcinoma Originated from Mature Hepatocytes. In: Tanimizu, N. (eds) Hepatic Stem Cells . Methods in Molecular Biology, vol 1905. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-8961-4_20

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  • DOI: https://doi.org/10.1007/978-1-4939-8961-4_20

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