DEN诱发大鼠肝癌组织中CD117及CD133的表达及意义
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摘要
目的探讨CD117蛋白及CD133蛋白在DEN诱发大鼠肝癌组织中的表达及意义。
     方法将20只大鼠随机分为正常组(n=6)、模型组(n=14)。模型组大鼠连续饮用95ug/ml的二乙基亚硝胺(DEN)溶液4周后,改饮用灭菌自来水4周,再继续饮用含95ug/ml的DEN溶液。于造模后14周和18周处死大鼠,取肝组织标本进行病理检查、免疫组化采用SP法,观察CD117及CD133的表达情况。
     结果
     1.正常组肝细胞排列正常,无变性、坏死。模型组14周3/6只发生肝细胞癌,18周5/6只发生肝细胞癌。
     2.正常组在中央静脉、大血管周围及肝实质内可见少量CD117阳性细胞分布,阳性细胞数20±2.4/10~3个:模型组14周癌症及癌症周围组织内阳性细胞数111±16.3/10~3个;18周阳性细胞数94±11.1/10~3个,与正常组比较P<0.01。
     3.正常组在汇管区及中央静脉为中心可见少量CD133阳性细胞,阳性细胞数17±1.4/10~3:模型组14周癌症周围组织内阳性细胞数65±8.0/10~3,18周阳性细胞数88±13.4/10~3,与正常组比较P<0.01。
     4.正常组、模型组肝组织内均可见少量CD117和CD133共同表达的阳性细胞。
     结论
     1.大鼠肝硬化肝癌组织中存在CD117和CD133表达的卵圆细胞,并与肝硬化及肝癌的发生有关。
     2大鼠肝细胞癌发生发展的不同时期存在不同类型的卵圆细胞。
Objective To explore expression and significance.CD117 and CD133 in DEN-induced rat hepatocellular carcinoma.
     Methods A total 20 rats were randomly divided into normal group(n=6) and model group(n=14).95ug/ml diethylnitrosamine(DEN) was administrated to the model rats for four weeks,then they were continued to drink tap water that have sterilized for 4 weeks,after the 4 weeks the model groups continue to be consumed with the 95ug/ml Diethylnitrosamine(DEN).The model groups were killed after 14 weeks and 18 weeks,the pathological examination and immunohistochemical SP method were executed in the rats liver of the surgical excision,and the expression CD117 and CD133 Protein was observed.
     Results1.Liver cells were normal with no degeneration and necrosis in the normal group of rats.3/6 in the rat model of hepatocellular carcinoma occurred in 14 weeks of the group and 5/6 in the rat model of hepatocellular carcinoma occurred in 18 weeks of the group.
     2.A small number of positive cells that was expressed by CD117 could be seen around the central vein,large blood vessels and in the liver parenchyma in the rats liver tissues,the number of positive cells was 20±2.4/10~3.The number of positive cells was 111±16.3/10~3 in 14-week group;and the number of positive cells was 94±11.1/10~3 in 18-week group,there was extremely significant difference between Model group and normal group(P<0.01).
     3.A small number of positive cells that was expressed by CD133 could be seen in the portal area and around the central vein in rat liver,the number of positive cells was 17±1.4/10~3.The number of positive cells was 65±8.0/10~3 in 14-week group;and the number of positive cells was 88±13.4/10~3 in 18-week group,there was extremely significant difference between Model group and normal group(P<0.01).
     4.There were co-expressions of positive cells in a small number of organizations both the normal and model group liver tissue.
     Conclusion
     1 There are oval cells co-expression of CD117 and CD133 in rats with liver cirrhosis and hepatocellular carcinoma,the oval cells are related with the occurrence of liver cirrhosis and liver cancer.
     2 There are different types of oval cells in hepatocellular carcinoma development at different stages in rats.
引文
[1]蒋润德,李春海.从肝脏的组织再生理解肝细胞癌的产生,中华肝胆外科杂志.2002,8(6):323-328
    [2]Sell S.Is there a liver stem cell? Cancer Res.1990,50:3 811-3 815
    [3]Petersen BE,Women WC,Patrene KD,et al.Bone marrow as a potential source of hepatic oval cells.Science,1999,284:1 168-1 170
    [4]Evarts RP,Nagy P,Nakastsukas H,et al.In vivo differentiation of rat liver oval cells into hepatocytes.Cancers Res,1989,49:1 541-1 547
    [5]Fujio K,Evarts RP,Hu Z,et al.Expression of stem cell factor and its receptor,c-kit,during liver regeneration from putative stem cells in adult rat.Lab Invest,1994,70:511-516
    [6]Omori M,Omori N,Evarts RP.et al.Coexpression of fit-3 lig and / fit-3 and SCF / c-kit signal transduction system in bile-duct-ligated SI and W mice.Am J Pathol,1997,150:1 179-1 187
    [7]Reya T,Morrison SJ,Clarke MF,et al.Stem cells,cancer.And cancer stem cells.Nature,2001,414:105-111
    [8]Bonnet D,Dick JE.Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell.Nature Med,1997,3:730-737.
    [9]Al-Hajj M,Wicha MS,Benito-Hernandez A,et al.Prospective identifcation of tumorigenic breast cancer cells.Proc Natl Acad sci U S A,2003,100:3 983-3 988
    [10]Singh SK,Clarke ID,Terasaki M,et al.Identification of a cancer stem cell in human brain tumors.Cancer Res,2003,63:5 821-5 828
    [11]Kim CF,Jackson EL,Woolfenden AE,et al.Identification of bronchioalvelar stem cells in normal lung and lung cancer,Cell,2005,121:823-835
    [12]Collins AT,Berry PA,Hyde C,et al.Prospective identification of tumorigenic prostate cancer stem cells.Cancer Res,2005,65:10 946-10 951
    [13]Li C,Heidt DG,Dalcrba P,ct al.Identification of pancreatic cancer stem cells. Cancer Res, 2007, 67: 1030-1037
    
    [14]Bapat SA, Mali AM, Koppikar CB, et al. Stem and progenitor-like cells contribute to the aggressive behavior of human epithelial ovarian cancer. Cancer Res, 2005, 65: 3 025-3 029
    
    [15]Haraguchi N, Utsunomiya T, Inoue H, et al. Characterization of a side population of cancer cells from human gastrointestinal system. Stem cells, 2006. 24: 506-513.
    
    [16]Kondo T, Setoguchi T, Taga Persistence of a small subpopulation of cancer stem. like ceils in the C6 glioma cell line. Proc Natl Acad Sci U S A, 2004, 101: 781-786.
    
    [17] Suetsugu A, Nagaki M, Aoki H, et al. Characterization of CD133+ hepatocellular carcinoma cells as cancer stem / progenitor cells. Biochem Biophys Res Commun, 2006, 351(4): 820-824
    
    [18]Ma S, Chan KW, Hu L, et al. Identification and characterization of tumorigenic liver cancer stem / progenitor cells. Gastroenterology, 2007, 132(7):2 542-2 556
    
    [19] Suarcz-Rodriguez R, Belkind-Gerson J. Cultured nestin-positive cells from postnatal mouse small bowell differentiate exvivo into neurons, glia, and smooth muscle. Stem Cells, 2004; 22: 1373-1385
    
    [20] Maulik G Bharti A Khan E Broderick RJ Kijima T. Salgia R. Modulation of c-Kit / SCF pathway leads to alterations in Topoisomerase-I activity in small cell lung cancer. J Environ Pathol Toxicof Oncol, 2004; 23: 237-2351
    
    [21] Miyazaki M, Masaka T, Akiyama I, Nakashima E, Sakaguchi M , Huh NH. Propagation of adult rat bone marrow-derived Hepatocyte-like cells by serial passages in vitro. Cell Transplant, 2004; 13: 385-391
    
    [22]Schonfeldt V, Wistuba J, Schlatt S. Notch-1, c-kit an d GFR alpha-1 are developmentally regulated markers for premeiotic germ cells. Cytogenet Genome Res, 2004; 105: 235-239
    
    [23] Potti A Ganti AK Foster H, Knox S,Hebert BJ, Tendulkar K, et al. Immunohistochemical detection of HER-2 / neu, c-kit(CD117) and vascular endothelial growth factor(VEGF) over expression in soft tissue sarcomas. Anticancer Res,2004;24:333-337
    [24]Yin S,Li J,Hu C,et al.CD133 positive hepatocelular carcinoma cells possess high capacity for tumorigenicity.Int J Cancer,2007,120(7):1 444-1 450
    [25]钟晓刚,何生,殷舞,等.成体肝干细胞向肝癌细胞趋向性迁移的体外实验.中华肝脏病杂志,2005,13(9):644-647
    [26]Yoshiji H,Yoshii J,Ikenaka Y,et al.Inhibition of renninangto tensm system attenuates liver enzyme-altered preneoplastic lesions and fibrosis develolpment in rats.J Hepatal,2002,37(1):22-30
    [27]Fukumasu H,Avanzo J L,Heidor R,et al.Protective efects of guarana(Paullinia cupana Mart.var.Sorbilis) against DEN-induced DNA damage on mouse liver.Food Chem Toxicol,2006,44(6):862-867
    [28]Qian Y,Ling CQ.Preventive effect of Ganfujian granule on experimental hepatocarcinoma in rats.Gast roenterol,2004,10(5):755
    [29]Hitoshi,Mitsuhiko M.Detection of serum and intrahepatic hepatocyte growth factor during DEN-induced carcinogenesis in the rat.Hepatol Resea,2002,24(3):385
    [30]杨富春,郑树森,蒋天安.改良法大鼠原发性肝癌模型的建立.中华医学杂志,2004,84:2 018-2 019
    [31]Barajas M,Mzzolini G,Gennove G,et al.Gene therapy of orthotopic hepatocellular carenoma in rats using adenovirus coding for intedeukin 12.Hepatology,2001,33:52-61
    [32]Jin YH,Clark AB,Slebos RJ,et al.Cadmium is a mutagen that acts by inhibiting mismatch repair.Nat Genet,2003,34:326-329
    [33]BE Petersen,W C Bowen,KD Patrene,et al.Science,1999:284:1168-1170
    [34]Theise ND,Nimmakayalu M,Gardner R,et al.Hepatology,2000:32(1):11-16
    [35]龚加庆,方驰华,李雅等.卵圆细胞参与实验性肝癌形成过程的研究.中华外科杂志,2004,42(5):291-295.
    [36]肖家诚,朱延波,朱上林,等.肝细胞肝癌中卵圆细胞的组织学与超微结构研究.临床与实验病理学杂志,2000,16(2)177-179
    [37]Olempska M,Eisenach PA,Ammerpohl O,et al.Detection of tumor stem cell markers in pancreatic carcinoma ceIl lines.Hepatobiliary Pancreat Dis lnt,2007,6(1):92-97
    [38]Singh SK,Hawkins C,Clarke ID,et al.Identification of human brain tumour initiating cells.Nature,2004,432:396-401
    [39]Collins AT,Berry PA,Hyde C,et al.Prospective identification of tumorigenic prostate cancer stem cells.Cancer Res,2005,65:10 946-10 951
    [40]Yin A H,Miraglia S,Zanjani E D.et al.AC133.a novel marker for human hematopoietic stem and progenitor cells.Blood,1997,90(12):5 002-5 012
    [41]Peichev M,Naiyer AJ,Pereira D,et al.Expression of VEGFR-2 and AC 133by circulating human CD34+ cells identifies a population of functional endothelial precursors.Blood,2000,95:952-958
    [42]Reyes M,Dudek A,Jahagirdar B,et al.Origin of endothelial progenitors in human postnatal bone marrow.J Clin Invest,2002,109(3):337-346
    [43]Gehling UM,Ergun S,Schumacher U,et al.In vitro differentiation of endothelial cells from AC133- positive progenitor Cells.Blood,2000,95(10):3 106-3112
    [44]Sugimoto K,Adachi Y,Moriyama K,et al.Growth Factor,2001;19(4):219-31
    [45]Fujio K,Evarts RP,Hu Z,et al,Lab Invest,1994 Apr:70(4):511
    [46]Fujio K,Hu Z,Evarts RP,et al.Exp Cell Res,1996 May 1:224(2):243-2502007,132(7):2 542-2 556
    [47]Song W,Li H,Tao K,Li R,Expression and clinical significance of the stem cell marker CD133 in hepatocellular carcinoma.Int J Clin Pract,2008,62(8):1 212-1 218
    [48]王花,李雯,汪谦.CD133在肝细胞癌、胰腺癌研究中的进展.中华普通外科学文献,2008,2(3):48-50
    [1]袁立超,党双锁,程延安.肝癌的靶向治疗.世界最新医学信息文摘,2003.2(6):881-883
    [2]卞修武.肿瘤动物模型.魏泓.四川:四川科学技术出版社,2001
    [3]徐静,李旭.肝癌动物模型的建立.实用肝脏病杂志,2005,8(2):116-118
    [4]马曾辰.可供临床研究的常用鼠肝癌模型.国外医学肿瘤学分册,1982,1(1):13
    [5]郑杰,武忠弼,阮幼冰等.二乙基亚硝胺诱发大鼠肝癌过程中三种基因的原位表达.中华病理学杂志,1995,24(5):309-311
    [6]吴细丕.实验动物与肿瘤的研究.北京:中国医药科技出版社.2000:176
    [7]马曾辰,汤钊猷,余业勤等.供临床研究用的鼠肝癌模型-几种大鼠肝癌模型的比较及裸鼠人肝癌移植的初步观察,癌症.1983.2(4):236-237
    [8]高进.肿瘤学基础与研究方法.北京:人民卫生出版社,1999
    [9]谢胜学,许戈良.诱导性大鼠肝癌模型进展.肝胆外科杂志,2007,(15)3:237-239
    [10]Okubo H,Moriyama M,Tanaka N,et al.Detection of serum and intrahepatic hepatocyte growth factor during DEN-induced carcinogenesis in the rat.Hepatol Res,2002,24(4):385-394
    [11]Fukumasu H,Avanzo J L,Heidor R,et al.Protective effects of guarana(Paullinia cupana Mart.var.Sorbilis)against DEN-induced DNA damage on mouse liver.Food Chem Toxicol,2006,44(6):862-867
    [12]杨富春,郑树森,蒋天安.改良法大鼠原发性肝癌模型的建立.中华医学杂志,2004,84:2 018-2 019
    [13]Yoshiji H,Yoshii J,Ikenaka Y,et al.Inhibition of renninangto tensm system attenuates liver enzyme-altered preneoplastic lesions and fibrosis develolpment in rats.J Hepatal,2002,37(1):22-30
    [14]Qian Y,Ling CQ.Preventive effect of Ganfujian granule on experimental ?hepatocarcinoma in rats.Gast roenterol,2004,10(5):755
    [15]Hitoshi,Mitsuhiko M.Detection of serum and intrahepatic hepatocyte growth factor during DEN-induced carcinogenesis in the rat.Hepatol Resea,2002,24(3):385
    [16]Nakatani T,Roy G,Fujimoto N,et al.Sex hormone dependency of diethylnitrosamine-induced liver tumors in mice and chemoprevention by leuprorelin.Jpn J Cancer Res,2001,92(3):249-256
    [17]周光兴,杨俊华等.性别对二乙基亚硝胺诱发Wistar大鼠肝癌的影响.中国实验动物学杂志,1994.4(1):1-5
    [18]周传香,高文信.癌基因skp2与肿瘤关系研究进展.国外医学口腔医学分册,2003,30(6):438-440
    [19]Zhang H,Kobayashi R,Galaktionov K,et al.pl9Skp1 and p45Skp2 are essential elements of the cyclin A-CDK2 S phase kinase.Cell,1995,82(6):915-925
    [20]郑祥毅,丁伟,谢立平等.Skp2和p27KIP1在前列腺癌组织中的表达与临床病理特征的相关性研究.癌症,2004,23(2):215-218
    [21]张嘉宁,顾为望等.大鼠肝癌模型的建立及影像学表现.中国实验动物学杂志,1999,9(2):98-101
    [22]敖红,黄爱民,等.IVC中大鼠肝脏诱癌模型的建立.上海实验动物科学,2004,24(4):243-244
    [23]杨富春,郑树森等.改良法大鼠原发性肝癌模型的建立.中华医学杂志,2004,84(23):2 018-2 019
    [24]Takeuchi Y,Sugimoto M,Ochiai K,et al.Expression of glycoprotein in rat hepatooarcinogenesis by diethylnitrosamine and the modulation by anticancer drugs.Hepatol Res,2002,2(2):107-118
    [25]周峥珍,章宗籍等.DEN诱发大鼠肝癌模型的实验病理研究.昆明医学院学报,2005,(3):15-19
    [26]程延安,袁利超,等.间断小剂量DEN诱发大鼠肝癌模型研究.肿瘤防治杂志,2005,12(11):806-808
    [27]顾性初,钱培丽。等.应用大鼠中期肝癌实验研究DEN和2-AAF的促癌作 用.中国药理学.2001.17(3):289-292
    [28]李岩,白成勇,刘同慎等.二乙基亚硝胺诱发大鼠肝癌模型的建立及病理学改变.滨州医学院学报,2007,30(6):401-406
    [29]张志敏,王阁,杨志祥等间歇给药对DEN诱发大鼠肝癌模型的影响研究.重庆医学,2007(36)20:2 035-2 037
    [30]姜幼纯,董奇男,肖邦良等.非坏死剂量二乙基亚硝胺诱发大鼠肝癌模型的研究.华西医科大学学报,2001,32(4):555-558,628
    [31]张新立,史景泉,卞修武.DEN诱发大鼠肝癌变的病理形态与细胞增殖活性的定量研究.第三军医大学学报,2001,23(3):304-307
    [32]Qiu C,Shan L,Yu M,et al.Deregulation of the cyclin D1 / Cdk4 retinoblastoma pathway in rat mammary gland carcinomas induced by the flood-derived carcinogen 2-amino-1-methyl-6-phenylimidazo(4,5-b) pyridine.Cancer Res,2003,63(18):5674
    [33]Wallace DC.Mitochondrial diseases in man and mouse.Science,1999,283(5407):1482
    [34]Hiroko Yoshino,Mitsuru Futakuchi,Young-Man Cho,et al.Modification of an in vivo lung metastasis model of hepatecellular carcinoma by low dose N-nitrosomorpholine and diethylnitrosamine[J].Clinical & Experimental Metastasis,2005,22:41-47
    [35]谢胜学,许戈良.DEN联合NMOR诱导建立具有转移潜能的肝癌模型.中华消化外科杂志.2008.7(1):46-48
    [36]赵鲁笳,刘小北,郭宏伟,3-Me-DAB诱发大鼠肝癌模型的建立与病理研究.中国实验诊断学,2004,8(3):243-245
    [37]姜幼纯,董奇男,肖邦良,等.非坏死计量二乙基亚硝胺诱发大鼠肝癌模型的研究.华西医科大学学报,2001,32(4)555-558,628
    [38]王晓明,王宝恩,王泰龄等.实验性肝细胞癌癌变过程中嗜碱性小细胞病灶的癌变趋势.中华肝脏病杂志,2006,14(7):495-498
    [39]Chae HB,Jang LC,Park SM,et al.An experimental model of hepatic fibrosis induced by alcohol and CCl_4:Can the lipopolysaccharide prevent liver induced by alcohol and CCl_4[J]Tachan Kan.Hakhoe Chi,2002,8(2):173-178.
    [40]阎丽,柳婧美,乔伟等.肝硬化基础上大鼠肝癌模型的建立.第四军医大学学报,2007,28(13)1181-1182
    [41]李浩.中医药结合肝动脉化疗栓塞治疗中晚期原发性肝癌的研究进展.现代中西医结合杂志,2006,15(2):261-262
    [42]楼琦,金晓音,周莎桑.大鼠肝癌模型肝动脉缺血预处理后的介入技术.浙江省医学科学院学报,2007,(68):23-24
    [43]凌昌全,李琦,刘晓华,等.经动脉灌注蜂毒素-聚乳酸/羟乙酸微球治疗大鼠肝肿瘤[J].世界华人消化杂志,2003,11(7):900-903
    [44]顾伟,沈婕,翟枫.大鼠移植性肝癌模型生物学行为与分期的初步探讨.中西医结合学报,2005,3(2):136-138
    [45]Tancredi T,McCuskey PA,Kan Z,et al.Changes in rat liver microcirculation after experimental hepatic arterial embolization:comparison of different embolic agents.Radiology,1999,211(1):177-181
    [46]宋祥福,吕喆,刘欣.两种方式接种肝癌模型的比较.中国比较医学杂志,2007,17(2):96-98
    [47]李琦,孟庆莉,彭永海等.大鼠移植性肝癌模型的制作.第二军医大学学报,2002,(23):1074
    [48]Ogawa K,Yokokawa K,Tomoyori T,et al.Induction of gammaslutamyl transpeptidase-positive altered hepatocytic lesions by combination of transplacental-initiation and poatanal-selection,Int J Cancer,1982,29(3):333-336.
    [49]褚成静 钟华 何芳.二乙亚硝胺诱发大鼠肝癌模型的研究现状.农垦医学,2003,25(4):281-283

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