Research progress on animal model of hepatocellular carcinoma_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

WANG Nana ¹ ,  FENG Chunlin ^1,2

1. Department of Hepatobiliary Surgery, The Third Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, P. R. China;
2. Zunyi Medical and Pharmaceutical College, Zunyi, Guizhou 563000, P. R. China;

Corresponding author：

FENG Chunlin, Email: 2084438832@qq.com

Keywords：

hepatocellular carcinoma; animal model; review

DOI：

10.7507/1007-9424.202204007

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To summarize the application research progress of animal models of hepatocellular carcinoma at home and abroad in recent years. Method The relevant literature on animal models of hepatocellular carcinoma at home and abroad in recent years was reviewed. Results At present, the common animal models of hepatocellular carcinoma mainly included spontaneous animal model, induced animal model, gene modified animal model, transplanted animal model, and humanized animal model. The etiology, pathogenesis, and pathophysiological changes of various animal models were different. The selection of animal models of hepatocellular carcinoma depended on the type and purpose of research. Conclusions Various animal models of hepatocellular carcinoma have their own advantages and disadvantages. Researchers should choose different animal models according to their own research purposes to achieve the expected experimental purposes, so that more valuable research results of animal models of hepatocellular carcinoma can be applied to clinical practice, and finally these research results can be truly applied to diagnosis and treatment of hepatocellular carcinoma.

Citation： WANG Nana, FENG Chunlin. Research progress on animal model of hepatocellular carcinoma. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2022, 29(10): 1376-1382. doi: 10.7507/1007-9424.202204007 Copy

1.	Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2021, 71(3): 209-249.
2.	Janevska D, Chaloska-Ivanova V, Janevski V. Hepatocellular carcinoma: risk factors, diagnosis and treatment. Open Access Maced J Med Sci, 2015, 3(4): 732-736.
3.	Gu CY, Lee TKW. Preclinical mouse models of hepatocellular carcinoma: An overview and update. Exp Cell Res, 2022, 412(2): 113042. doi: 10.1016/j.yexcr.2022.113042.
4.	夏猛, 孙玉浩, 王萌, 等. 原发性肝癌常见动物模型的研究进展. 临床肝胆病杂志, 2021, 37(8): 1938-1942.
5.	Uehara T, Pogribny IP, Rusyn I. The DEN and CCl₄-induced mouse model of fibrosis and inflammation-associated hepatocellular carcinoma. Curr Protoc, 2021, 1(8): e211. doi: 10.1002/cpz1.211.
6.	Macek Jilkova Z, Kurma K, Decaens T. Animal models of hepatocellular carcinoma: the role of immune system and tumor microenvironment. Cancers (Basel), 2019, 11(10): 1487. doi: 10.3390/cancers11101487.
7.	Zhang HE, Henderson JM, Gorrell MD. Animal models for hepatocellular carcinoma. Biochim Biophys Acta Mol Basis Dis, 2019, 1865(5): 993-1002.
8.	Henderson JM, Polak N, Chen J, et al. Multiple liver insults synergize to accelerate experimental hepatocellular carcinoma. Sci Rep, 2018, 8(1): 10283. doi: 10.1038/s41598-018-28486-8.
9.	Xin B, Cui Y, Wang Y, et al. Combined use of alcohol in conventional chemical-induced mouse liver cancer model improves the simulation of clinical characteristics of human hepatocellular carcinoma. Oncol Lett, 2017, 14(4): 4722-4728.
10.	Yan J, Caviglia JM, Schwabe RF. Animal models of HCC—When injury meets mutation. J Hepatol, 2017, S0168-8278(17)32197-9. doi: 10.1016/j.jhep.2017.07.023.
11.	吕建军, 李耀庭, 周舒雅, 等. 建立原代小鼠肝细胞体外模型用于致癌物作用机制研究. 药物分析杂志, 2016, 36(10): 1785-1797.
12.	Blidisel A, Marcovici I, Coricovac D, et al. Experimental models of hepatocellular carcinoma-a preclinical perspective. Cancers (Basel), 2021, 13(15): 3651. doi: 10.3390/cancers13153651.
13.	Romualdo GR, Prata GB, da Silva TC, et al. Fibrosis-associated hepatocarcinogenesis revisited: Establishing standard medium-term chemically-induced male and female models. PLoS One, 2018, 13(9): e0203879. doi: 10.1371/journal.pone.0203879.
14.	Ding YF, Wu ZH, Wei YJ, et al. Hepatic inflammation-fibrosis-cancer axis in the rat hepatocellular carcinoma induced by diethylnitrosamine. J Cancer Res Clin Oncol, 2017, 143(5): 821-834.
15.	Lee JS, Chu IS, Mikaelyan A, et al. Application of comparative functional genomics to identify best-fit mouse models to study human cancer. Nat Genet, 2004, 36(12): 1306-1311.
16.	Dow M, Pyke RM, Tsui BY, et al. Integrative genomic analysis of mouse and human hepatocellular carcinoma. Proc Natl Acad Sci U S A, 2018, 115(42): E9879-E9888. doi: 10.1073/pnas.1811029115.
17.	Connor F, Rayner TF, Aitken SJ, et al. Mutational landscape of a chemically-induced mouse model of liver cancer. J Hepatol, 2018, 69(4): 840-850.
18.	Schulien I, Hasselblatt P. Diethylnitrosamine-induced liver tumorigenesis in mice. Methods Cell Biol, 2021, 163: 137-152.
19.	Qi X, Schepers E, Avella D, et al. An oncogenic hepatocyte-induced orthotopic mouse model of hepatocellular cancer arising in the setting of hepatic inflammation and fibrosis. J Vis Exp, 2019, (151): 10.3791/59368. doi: 10.3791/59368.
20.	Ju HL, Han KH, Lee JD, et al. Transgenic mouse models generated by hydrodynamic transfection for genetic studies of liver cancer and preclinical testing of anti-cancer therapy. Int J Cancer, 2016, 138(7): 1601-1608.
21.	Brown ZJ, Heinrich B, Greten TF. Mouse models of hepatocellular carcinoma: an overview and highlights for immunotherapy research. Nat Rev Gastroenterol Hepatol, 2018, 15(9): 536-554.
22.	Nakayama J, Gong Z. Transgenic zebrafish for modeling hepatocellular carcinoma. MedComm (2020), 2020, 1(2): 140-156.
23.	Nakayama J, Lu JW, Makinoshima H, et al. A novel zebrafish model of metastasis identifies the HSD11β1 inhibitor adrenosterone as a suppressor of epithelial-mesenchymal transition and metastatic dissemination. Mol Cancer Res, 2020, 18(3): 477-487.
24.	Lee AQ, Li Y, Gong Z. Inducible liver cancer models in transgenic zebrafish to investigate cancer biology. Cancers (Basel), 2021, 13(20): 5148. doi: 10.3390/cancers13205148.
25.	Nakayama J, Makinoshima H. Zebrafish-based screening models for the identification of anti-metastatic drugs. Molecules, 2020, 25(10): 2407. doi: 10.3390/molecules25102407.
26.	Wrighton PJ, Oderberg IM, Goessling W. There is something fishy about liver cancer: zebrafish models of hepatocellular carcinoma. Cell Mol Gastroenterol Hepatol, 2019, 8(3): 347-363.
27.	Cigliano A, Pilo MG, Li L, et al. Deregulated c-Myc requires a functional HSF1 for experimental and human hepatocarcinogenesis. Oncotarget, 2017, 8(53): 90638-90650.
28.	Liu YT, Tseng TC, Soong RS, et al. A novel spontaneous hepatocellular carcinoma mouse model for studying T-cell exhaustion in the tumor microenvironment. J Immunother Cancer, 2018, 6(1): 144. doi: 10.1186/s40425-018-0462-3.
29.	Kersten K, de Visser KE, van Miltenburg MH, et al. Genetically engineered mouse models in oncology research and cancer medicine. EMBO Mol Med, 2017, 9(2): 137-153.
30.	Hassan SA, Schmithals C, von Harten M, et al. Time-dependent changes in proliferation, DNA damage and clock gene expression in hepatocellular carcinoma and healthy liver of a transgenic mouse model. Int J Cancer, 2021, 148(1): 226-237.
31.	Cho K, Ro SW, Seo SH, et al. Genetically engineered mouse models for liver cancer. Cancers (Basel), 2019, 12(1): 14. doi: 10.3390/cancers12010014.
32.	Chung SI, Moon H, Kim DY, et al. Development of a transgenic mouse model of hepatocellular carcinoma with a liver fibrosis background. BMC Gastroenterol, 2016, 16: 13. doi: 10.1186/s12876-016-0423-6.
33.	Li E, Lin L, Chen CW, et al. Mouse models for immunotherapy in hepatocellular carcinoma. Cancers (Basel), 2019, 11(11): 1800. doi: 10.3390/cancers11111800.
34.	雷会霞, 苗明三. 基于数据挖掘的肝癌动物模型应用分析. 中药药理与临床, 2022, 38(3): 186-190.
35.	Bresnahan E, Ramadori P, Heikenwalder M, et al. Novel patient-derived preclinical models of liver cancer. J Hepatol, 2020, 72(2): 239-249.
36.	罗晓琴, 丁冠茗, 郑旭, 等. 小鼠肝癌原位移植性肿瘤动物模型的改良. 中国比较医学杂志, 2021, 31(6): 16-22.
37.	Wu T, Heuillard E, Lindner V, et al. Multimodal imaging of a humanized orthotopic model of hepatocellular carcinoma in immunodeficient mice. Sci Rep, 2016, 6: 35230. doi: 10.1038/srep35230.
38.	Kim KJ, Kim JH, Lee SJ, et al. Radiation improves antitumor effect of immune checkpoint inhibitor in murine hepatocellular carcinoma model. Oncotarget, 2017, 8(25): 41242-41255.
39.	朱瑞敏, 李宝亮, 路亚岚, 等. 肝细胞癌原位与皮下PDX模型的方法学比较分析研究. 中国实验动物学报, 2021, 29(4): 512-518.
40.	卢东诚, 覃沁怡, 雷荣娥, 等. 尾静脉注射法建立胰腺癌血行转移小鼠动物模型. 广东医学, 2018, 39(18): 2732-2736, 2740.
41.	Bresnahan E, Lindblad KE, Ruiz de Galarreta M, et al. Mouse models of oncoimmunology in hepatocellular carcinoma. Clin Cancer Res, 2020, 26(20): 5276-5286.
42.	Ou DL, Lin YY, Hsu CL, et al. Development of a PD-L1-expressing orthotopic liver cancer model: implications for immunotherapy for hepatocellular carcinoma. Liver Cancer, 2019, 8(3): 155-171.
43.	Zhao W, Zhang L, Xu Y, et al. Hepatic stellate cells promote tumor progression by enhancement of immunosuppressive cells in an orthotopic liver tumor mouse model. Lab Invest, 2014, 94(2): 182-191.
44.	Romualdo GR, Leroy K, Costa CJS, et al. In vivo and in vitro models of hepatocellular carcinoma: current strategies for translational modeling. Cancers (Basel), 2021, 13(21): 5583. doi: 10.3390/cancers13215583.
45.	Xu W, Zhao ZY, An QM, et al. Comprehensive comparison of patient-derived xenograft models in hepatocellular carcinoma and metastatic liver cancer. Int J Med Sci, 2020, 17(18): 3073-3081.
46.	Wu Y, Wang J, Zheng X, et al. Establishment and preclinical therapy of patient-derived hepatocellular carcinoma xenograft model. Immunol Lett, 2020, 223: 33-43.
47.	Blumer T, Fofana I, Matter MS, et al. Hepatocellular carcinoma xenografts established from needle biopsies preserve the characteristics of the originating tumors. Hepatol Commun, 2019, 3(7): 971-986.
48.	Gao H, Korn JM, Ferretti S, et al. High-throughput screening using patient-derived tumor xenografts to predict clinical trial drug response. Nat Med, 2015, 21(11): 1318-1325.
49.	Morton JJ, Bird G, Refaeli Y, et al. Humanized mouse xenograft models: narrowing the tumor-microenvironment gap. Cancer Res, 2016, 76(21): 6153-6158.
50.	Choi Y, Lee S, Kim K, et al. Studying cancer immunotherapy using patient-derived xenografts (PDXs) in humanized mice. Exp Mol Med, 2018, 50(8): 1-9.
51.	Cogels MM, Rouas R, Ghanem GE, et al. Humanized mice as a valuable pre-clinical model for cancer immunotherapy research. Front Oncol, 2021, 11: 784947. doi: 10.3389/fonc.2021.784947.
52.	Jin KT, Du WL, Lan HR, et al. Development of humanized mouse with patient-derived xenografts for cancer immunotherapy studies: A comprehensive review. Cancer Sci, 2021, 112(7): 2592-2606.
53.	Yaguchi T, Kobayashi A, Inozume T, et al. Human PBMC-transferred murine MHC class Ⅰ/Ⅱ-deficient NOG mice enable long-term evaluation of human immune responses. Cell Mol Immunol, 2018, 15(11): 953-962.

1. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2021, 71(3): 209-249.
2. Janevska D, Chaloska-Ivanova V, Janevski V. Hepatocellular carcinoma: risk factors, diagnosis and treatment. Open Access Maced J Med Sci, 2015, 3(4): 732-736.
3. Gu CY, Lee TKW. Preclinical mouse models of hepatocellular carcinoma: An overview and update. Exp Cell Res, 2022, 412(2): 113042. doi: 10.1016/j.yexcr.2022.113042.
4. 夏猛, 孙玉浩, 王萌, 等. 原发性肝癌常见动物模型的研究进展. 临床肝胆病杂志, 2021, 37(8): 1938-1942.
5. Uehara T, Pogribny IP, Rusyn I. The DEN and CCl₄-induced mouse model of fibrosis and inflammation-associated hepatocellular carcinoma. Curr Protoc, 2021, 1(8): e211. doi: 10.1002/cpz1.211.
6. Macek Jilkova Z, Kurma K, Decaens T. Animal models of hepatocellular carcinoma: the role of immune system and tumor microenvironment. Cancers (Basel), 2019, 11(10): 1487. doi: 10.3390/cancers11101487.
7. Zhang HE, Henderson JM, Gorrell MD. Animal models for hepatocellular carcinoma. Biochim Biophys Acta Mol Basis Dis, 2019, 1865(5): 993-1002.
8. Henderson JM, Polak N, Chen J, et al. Multiple liver insults synergize to accelerate experimental hepatocellular carcinoma. Sci Rep, 2018, 8(1): 10283. doi: 10.1038/s41598-018-28486-8.
9. Xin B, Cui Y, Wang Y, et al. Combined use of alcohol in conventional chemical-induced mouse liver cancer model improves the simulation of clinical characteristics of human hepatocellular carcinoma. Oncol Lett, 2017, 14(4): 4722-4728.
10. Yan J, Caviglia JM, Schwabe RF. Animal models of HCC—When injury meets mutation. J Hepatol, 2017, S0168-8278(17)32197-9. doi: 10.1016/j.jhep.2017.07.023.
11. 吕建军, 李耀庭, 周舒雅, 等. 建立原代小鼠肝细胞体外模型用于致癌物作用机制研究. 药物分析杂志, 2016, 36(10): 1785-1797.
12. Blidisel A, Marcovici I, Coricovac D, et al. Experimental models of hepatocellular carcinoma-a preclinical perspective. Cancers (Basel), 2021, 13(15): 3651. doi: 10.3390/cancers13153651.
13. Romualdo GR, Prata GB, da Silva TC, et al. Fibrosis-associated hepatocarcinogenesis revisited: Establishing standard medium-term chemically-induced male and female models. PLoS One, 2018, 13(9): e0203879. doi: 10.1371/journal.pone.0203879.
14. Ding YF, Wu ZH, Wei YJ, et al. Hepatic inflammation-fibrosis-cancer axis in the rat hepatocellular carcinoma induced by diethylnitrosamine. J Cancer Res Clin Oncol, 2017, 143(5): 821-834.
15. Lee JS, Chu IS, Mikaelyan A, et al. Application of comparative functional genomics to identify best-fit mouse models to study human cancer. Nat Genet, 2004, 36(12): 1306-1311.
16. Dow M, Pyke RM, Tsui BY, et al. Integrative genomic analysis of mouse and human hepatocellular carcinoma. Proc Natl Acad Sci U S A, 2018, 115(42): E9879-E9888. doi: 10.1073/pnas.1811029115.
17. Connor F, Rayner TF, Aitken SJ, et al. Mutational landscape of a chemically-induced mouse model of liver cancer. J Hepatol, 2018, 69(4): 840-850.
18. Schulien I, Hasselblatt P. Diethylnitrosamine-induced liver tumorigenesis in mice. Methods Cell Biol, 2021, 163: 137-152.
19. Qi X, Schepers E, Avella D, et al. An oncogenic hepatocyte-induced orthotopic mouse model of hepatocellular cancer arising in the setting of hepatic inflammation and fibrosis. J Vis Exp, 2019, (151): 10.3791/59368. doi: 10.3791/59368.
20. Ju HL, Han KH, Lee JD, et al. Transgenic mouse models generated by hydrodynamic transfection for genetic studies of liver cancer and preclinical testing of anti-cancer therapy. Int J Cancer, 2016, 138(7): 1601-1608.
21. Brown ZJ, Heinrich B, Greten TF. Mouse models of hepatocellular carcinoma: an overview and highlights for immunotherapy research. Nat Rev Gastroenterol Hepatol, 2018, 15(9): 536-554.
22. Nakayama J, Gong Z. Transgenic zebrafish for modeling hepatocellular carcinoma. MedComm (2020), 2020, 1(2): 140-156.
23. Nakayama J, Lu JW, Makinoshima H, et al. A novel zebrafish model of metastasis identifies the HSD11β1 inhibitor adrenosterone as a suppressor of epithelial-mesenchymal transition and metastatic dissemination. Mol Cancer Res, 2020, 18(3): 477-487.
24. Lee AQ, Li Y, Gong Z. Inducible liver cancer models in transgenic zebrafish to investigate cancer biology. Cancers (Basel), 2021, 13(20): 5148. doi: 10.3390/cancers13205148.
25. Nakayama J, Makinoshima H. Zebrafish-based screening models for the identification of anti-metastatic drugs. Molecules, 2020, 25(10): 2407. doi: 10.3390/molecules25102407.
26. Wrighton PJ, Oderberg IM, Goessling W. There is something fishy about liver cancer: zebrafish models of hepatocellular carcinoma. Cell Mol Gastroenterol Hepatol, 2019, 8(3): 347-363.
27. Cigliano A, Pilo MG, Li L, et al. Deregulated c-Myc requires a functional HSF1 for experimental and human hepatocarcinogenesis. Oncotarget, 2017, 8(53): 90638-90650.
28. Liu YT, Tseng TC, Soong RS, et al. A novel spontaneous hepatocellular carcinoma mouse model for studying T-cell exhaustion in the tumor microenvironment. J Immunother Cancer, 2018, 6(1): 144. doi: 10.1186/s40425-018-0462-3.
29. Kersten K, de Visser KE, van Miltenburg MH, et al. Genetically engineered mouse models in oncology research and cancer medicine. EMBO Mol Med, 2017, 9(2): 137-153.
30. Hassan SA, Schmithals C, von Harten M, et al. Time-dependent changes in proliferation, DNA damage and clock gene expression in hepatocellular carcinoma and healthy liver of a transgenic mouse model. Int J Cancer, 2021, 148(1): 226-237.
31. Cho K, Ro SW, Seo SH, et al. Genetically engineered mouse models for liver cancer. Cancers (Basel), 2019, 12(1): 14. doi: 10.3390/cancers12010014.
32. Chung SI, Moon H, Kim DY, et al. Development of a transgenic mouse model of hepatocellular carcinoma with a liver fibrosis background. BMC Gastroenterol, 2016, 16: 13. doi: 10.1186/s12876-016-0423-6.
33. Li E, Lin L, Chen CW, et al. Mouse models for immunotherapy in hepatocellular carcinoma. Cancers (Basel), 2019, 11(11): 1800. doi: 10.3390/cancers11111800.
34. 雷会霞, 苗明三. 基于数据挖掘的肝癌动物模型应用分析. 中药药理与临床, 2022, 38(3): 186-190.
35. Bresnahan E, Ramadori P, Heikenwalder M, et al. Novel patient-derived preclinical models of liver cancer. J Hepatol, 2020, 72(2): 239-249.
36. 罗晓琴, 丁冠茗, 郑旭, 等. 小鼠肝癌原位移植性肿瘤动物模型的改良. 中国比较医学杂志, 2021, 31(6): 16-22.
37. Wu T, Heuillard E, Lindner V, et al. Multimodal imaging of a humanized orthotopic model of hepatocellular carcinoma in immunodeficient mice. Sci Rep, 2016, 6: 35230. doi: 10.1038/srep35230.
38. Kim KJ, Kim JH, Lee SJ, et al. Radiation improves antitumor effect of immune checkpoint inhibitor in murine hepatocellular carcinoma model. Oncotarget, 2017, 8(25): 41242-41255.
39. 朱瑞敏, 李宝亮, 路亚岚, 等. 肝细胞癌原位与皮下PDX模型的方法学比较分析研究. 中国实验动物学报, 2021, 29(4): 512-518.
40. 卢东诚, 覃沁怡, 雷荣娥, 等. 尾静脉注射法建立胰腺癌血行转移小鼠动物模型. 广东医学, 2018, 39(18): 2732-2736, 2740.
41. Bresnahan E, Lindblad KE, Ruiz de Galarreta M, et al. Mouse models of oncoimmunology in hepatocellular carcinoma. Clin Cancer Res, 2020, 26(20): 5276-5286.
42. Ou DL, Lin YY, Hsu CL, et al. Development of a PD-L1-expressing orthotopic liver cancer model: implications for immunotherapy for hepatocellular carcinoma. Liver Cancer, 2019, 8(3): 155-171.
43. Zhao W, Zhang L, Xu Y, et al. Hepatic stellate cells promote tumor progression by enhancement of immunosuppressive cells in an orthotopic liver tumor mouse model. Lab Invest, 2014, 94(2): 182-191.
44. Romualdo GR, Leroy K, Costa CJS, et al. In vivo and in vitro models of hepatocellular carcinoma: current strategies for translational modeling. Cancers (Basel), 2021, 13(21): 5583. doi: 10.3390/cancers13215583.
45. Xu W, Zhao ZY, An QM, et al. Comprehensive comparison of patient-derived xenograft models in hepatocellular carcinoma and metastatic liver cancer. Int J Med Sci, 2020, 17(18): 3073-3081.
46. Wu Y, Wang J, Zheng X, et al. Establishment and preclinical therapy of patient-derived hepatocellular carcinoma xenograft model. Immunol Lett, 2020, 223: 33-43.
47. Blumer T, Fofana I, Matter MS, et al. Hepatocellular carcinoma xenografts established from needle biopsies preserve the characteristics of the originating tumors. Hepatol Commun, 2019, 3(7): 971-986.
48. Gao H, Korn JM, Ferretti S, et al. High-throughput screening using patient-derived tumor xenografts to predict clinical trial drug response. Nat Med, 2015, 21(11): 1318-1325.
49. Morton JJ, Bird G, Refaeli Y, et al. Humanized mouse xenograft models: narrowing the tumor-microenvironment gap. Cancer Res, 2016, 76(21): 6153-6158.
50. Choi Y, Lee S, Kim K, et al. Studying cancer immunotherapy using patient-derived xenografts (PDXs) in humanized mice. Exp Mol Med, 2018, 50(8): 1-9.
51. Cogels MM, Rouas R, Ghanem GE, et al. Humanized mice as a valuable pre-clinical model for cancer immunotherapy research. Front Oncol, 2021, 11: 784947. doi: 10.3389/fonc.2021.784947.
52. Jin KT, Du WL, Lan HR, et al. Development of humanized mouse with patient-derived xenografts for cancer immunotherapy studies: A comprehensive review. Cancer Sci, 2021, 112(7): 2592-2606.
53. Yaguchi T, Kobayashi A, Inozume T, et al. Human PBMC-transferred murine MHC class Ⅰ/Ⅱ-deficient NOG mice enable long-term evaluation of human immune responses. Cell Mol Immunol, 2018, 15(11): 953-962.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Research progress on animal model of hepatocellular carcinoma

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