肝癌动物模型建立的研究进展
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摘要
肝癌是严重威胁我国居民健康的常见恶性肿瘤之一,明确肝癌的发病机制,生物学特性及实现对肝癌的防治是我国医学工作者面临的主要问题。由于肝脏本身的结构特点,在肝脏早期病变时患者无明显症状,一般患者察觉时大多数病情已是中晚期,失去了最佳手术时机,所以早期检测并诊断肝癌是一个亟待解决的重要问题。目前肝癌的治疗方法主要以外科手术、化疗联合放疗、基因靶向治疗为主,但是仍然没有找到完全治愈肝癌的有效方法。针对疾病治疗研究方法的实施都需要动物实验进行模拟,所以建立一个模拟人肝癌的动物模型对于研究本病至关重要。
Liver cancer is one of the common malignant tumors that seriously threaten the health of Chinese residents.It is a major problem for Chinese medical workers to determine the pathogenesis of liver cancer,biological characteristics and the prevention and control of hepatocellular carcinoma. Due to the structural characteristics of liver,there is often no obvious symptom during the early stage,that most diagnosed patients are already in advanced stages,missing the optimum surgery time. Therefore,early detection and diagnosis of liver cancer is an important issue to be solved urgently. At present,the treatment of liver cancer is mainly based on surgery,chemotherapy combined with radiotherapy and gene-targeted therapy,but there is still no effective way to completely cure liver cancer. There are etiological and disease prevention research methods for the treatment of diseases. So it is essential to establish animal models of human hepatocellular carcinoma models for the study of treatment of the disease.
Liver cancer is one of the common malignant tumors that seriously threaten the health of Chinese residents.It is a major problem for Chinese medical workers to determine the pathogenesis of liver cancer,biological characteristics and the prevention and control of hepatocellular carcinoma. Due to the structural characteristics of liver,there is often no obvious symptom during the early stage,that most diagnosed patients are already in advanced stages,missing the optimum surgery time. Therefore,early detection and diagnosis of liver cancer is an important issue to be solved urgently. At present,the treatment of liver cancer is mainly based on surgery,chemotherapy combined with radiotherapy and gene-targeted therapy,but there is still no effective way to completely cure liver cancer. There are etiological and disease prevention research methods for the treatment of diseases. So it is essential to establish animal models of human hepatocellular carcinoma models for the study of treatment of the disease.
引文
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[26]Song MS,Salmena L,Pandolfi PP.The functions and regulation of the PTEN tumour suppressor[J].Nat Rev Mol Cell Biol,2012,13(5):283-296.
[27]Hollander MC,Blumenthal GM,Dennis PA.PTEN loss in the continuum of common cancers,rare syndromes and mouse models[J].Nat Rev Cancer,2011,11(4):289-301.
[28]Bettermann K,Vucur M,Haybaeck J,et al.TAK1 suppresses a NEMO-dependent but NF-kappa B-independent pathway to liver cancer[J].Cancer Cell,2010,17(5):481-496.
[29]Inokuchi S,Aoyama T,Miura K,et al.Disruption of TAK1 in hepatocytes causes hepatic injury,inflammation,fibrosis,and carcinogenesis[J].Proc Natl Acad Sci U S A,2010,107(2):844-849.
[30]Caviglia JM,Schwabe RF.Mouse models of liver cancer[J].Methods Mol Biol,2015,1267:165-183.
[31]Katzenellenbogen M,Mizrahi L,Pappo O,et al.Molecular mechanisms of liver carcinogenesis in the mdr2-knockout mice[J].Mol Cancer Res,2007,5(11):1159-1170.
[32]Lu JW,Ho YJ,Yang YJ,et al.Zebrafish as a disease model for studying human hepatocellular carcinoma[J].World J Gastroenterol,2015,21(42):12042-12058.
[33]He L,Tian DA,Li PY,et al.Mouse models of liver cancer:Progress and recommendations[J].Oncotarget,2015,6(27):23306-23322.
[2]陶莹,于玮,王珏,等.裸鼠人肝癌原位移植瘤模型的建立[J].北京医学,2012,34(12):1065-1067.
[3]陈爽,谢艳,王春晖,等.奥曲肽致裸鼠肝癌原位移植瘤坏死的实验研究[J].癌症,2009,28(7):673-678.
[4]田树红,王日超,邢桂兰,等.裸小鼠肝癌原位移植模型的建立[J].中国实验动物学报,2016,24(3):239-242.
[5]侯杰,罗兰,焦成斌,等.H22昆明鼠肝癌原位模型的建立[J].黑龙江医药科学,2015,38(1):78-79.
[6]Zhao GJ,Xu LX,Chu ES,et al.Establishment of an orthotopic transplantation tumor model of hepatocellular carcinoma in mice[J].World J Gastroenterol,2012,18(47):7087-7092.
[7]White SB,Chen J,Gordon AC,et al.Percutaneous ultrasound guided implantation of VX2 for creation of a rabbit hepatic tumor model[J].PLo S One,2015,10(4):e0123888.
[8]Lee JK,Chung YH,Song BC,et al.Recurrences of hepatocellular carcinoma following initial remission by transcatheter arterial chemoembolization[J].J Gastroenterol Hepatol,2002,17(1):52-58.
[9]Ogawa K,Nakanishi H,Takeshita F,et al.Establishment of rat hepatocellular carcinoma cell lines with differing metastatic potential in nude mice[J].Int J Cancer,2001,91(6):797-802.
[10]Soares KC,Foley K,Olino K,et al.A preclinical murine model of hepatic metastases[J].J Vis Exp,2014(91):51677.
[11]Lee WY,Hong HK,Ham SK,et al.Comparison of colorectal cancer in differentially established liver metastasis models[J].Anticancer Res,2014,34(7):3321-3328.
[12]Limani P,Borgeaud N,Linecker M,et al.Selective portal vein injection for the design of syngeneic models of liver malignancy[J].Am J Physiol Gastrointest Liver Physiol,2016,310(9):G682-688.
[13]刘东璞,卢凤美,姚海涛,等.黄曲霉毒素B1诱导大鼠肝癌模型的建立[J].黑龙江医药科学,2012,35(6):47-48.
[14]李彦,李小弟,廖明.二乙基亚硝胺诱发大鼠肝纤维化-肝癌动物模型的建立[J].实验动物科学,2013,30(5):20-23.
[15]赵婉,梁荣感,徐庆.DEN诱导仓鼠肝癌模型的建立及其异种成瘤性[J].世界华人消化杂志,2014,22(31):4795-4799.
[16]信波,覃君慧,梁媛,等.BALB/c小鼠肝癌模型建立及其形态学特征分析[J].中华肿瘤防治杂志,2013,20(7):481-484.
[17]Woo LL,Egner PA,Belanger CL,et al.Aflatoxin B1-DNA adduct formation and mutagenicity in livers of neonatal male and female B6C3F1 mice[J].Toxicol Sci,2011,122(1):38-44.
[18]Mc Glynn KA,Hunter K,Le Voyer T,et al.Susceptibility to aflatoxin B1-related primary hepatocellular carcinoma in mice and humans[J].Cancer Res,2003,63(15):4594-4601.
[19]Villar S,Ortiz-Cuaran S,Abedi-Ardekani B,et al.Aflatoxininduced TP53 R249S mutation in hepatocellular carcinoma in Thailand:Association with tumors developing in the absence of liver cirrhosis[J].PLo S One,2012,7(6):e37707.
[20]Evarts RP,Nagy P,Marsden E,et al.A precursor-product relationship exists between oval cells and hepatocytes in rat liver[J].Carcinogenesis,1987,8(11):1737-1740.
[21]杨新宇,徐蓓蕾,沈芸.诱发性大鼠肝癌模型的建立[J].哈尔滨商业大学学报(自然科学版),2015,31(4):401-404.
[22]De Minicis S,Kisseleva T,Francis H,et al.Liver carcinogenesis:Rodent models of hepatocarcinoma and cholangiocarcinoma[J].Dig Liver Dis,2013,45(6):450-459.
[23]Naas T,Ghorbani M,Alvarez-Maya I,et al.Characterization of liver histopathology in a transgenic mouse model expressing genotype 1a hepatitis C virus core and envelope proteins 1 and 2[J].J Gen Virol,2005,86(Pt 8):2185-2196.
[24]Kamegaya Y,Hiasa Y,Zukerberg L,et al.Hepatitis C virus acts as a tumor accelerator by blocking apoptosis in a mouse model of hepatocarcinogenesis[J].Hepatology,2005,41(3):660-667.
[25]Kalra N,Kumar V.c-Fos is a mediator of the c-myc-induced apoptotic signaling in serum-deprived hepatoma cells via the p38mitogen-activated protein kinase pathway[J].J Biol Chem,2004,279(24):25313-25319.
[26]Song MS,Salmena L,Pandolfi PP.The functions and regulation of the PTEN tumour suppressor[J].Nat Rev Mol Cell Biol,2012,13(5):283-296.
[27]Hollander MC,Blumenthal GM,Dennis PA.PTEN loss in the continuum of common cancers,rare syndromes and mouse models[J].Nat Rev Cancer,2011,11(4):289-301.
[28]Bettermann K,Vucur M,Haybaeck J,et al.TAK1 suppresses a NEMO-dependent but NF-kappa B-independent pathway to liver cancer[J].Cancer Cell,2010,17(5):481-496.
[29]Inokuchi S,Aoyama T,Miura K,et al.Disruption of TAK1 in hepatocytes causes hepatic injury,inflammation,fibrosis,and carcinogenesis[J].Proc Natl Acad Sci U S A,2010,107(2):844-849.
[30]Caviglia JM,Schwabe RF.Mouse models of liver cancer[J].Methods Mol Biol,2015,1267:165-183.
[31]Katzenellenbogen M,Mizrahi L,Pappo O,et al.Molecular mechanisms of liver carcinogenesis in the mdr2-knockout mice[J].Mol Cancer Res,2007,5(11):1159-1170.
[32]Lu JW,Ho YJ,Yang YJ,et al.Zebrafish as a disease model for studying human hepatocellular carcinoma[J].World J Gastroenterol,2015,21(42):12042-12058.
[33]He L,Tian DA,Li PY,et al.Mouse models of liver cancer:Progress and recommendations[J].Oncotarget,2015,6(27):23306-23322.