五种蛋白在家族聚集性与非家族聚集性肝癌表达的比对
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摘要
目的①研究p53、p21、p16、c-myc、cyclinD1在家族聚集性与非家族聚集性肝癌中的表达差异②探讨该五种蛋白中是否存在与家族聚集性肝癌具有密切相关性的蛋白。
方法用免疫组化Maxvision~(TM)法检测43例肝癌患者癌及癌旁石蜡切片组织中p53、p21、p16、c-myc、cyclinD1蛋白的表达情况。
结果①本组43例癌组织中p53、p21、p16、c-myc、cyclinD1的阳性表达率分别为53.49/%(23/43)、25.58/%(11/43)、39.53/%(17/43)、51.16/%(22/43)、44.19/%(19/43);在癌旁肝组织的阳性表达率分别为6.98/%(3/43)、60.47/%(26/43)、62.79/%(27/43)、30.23/%(13/43)、23.26/%(10/43)。五种蛋白在肝癌与癌旁组织的表达差异有统计学意义(P＜0.05)。
②分组进行检测时发现,癌组织中p53、p21、p16、c-myc、cyclinD1在FH组的阳性表达率分别为55.56%(5/9)、22.22%(2/9)、55.56%(5/9)、44.44%(4/9)、44.44%(4/9),在NFH组的阳性表达率分别为52.94%(18/34)、26.47%(9/34)、35.29%(12/34)、52.94%(18/34)、15/34(44.12%)。癌组织中p53、p21、p16、c-myc、cyclinD1在FH组与NFH组间的阳性表达率比较均无统计学意义(P＞0.05)。
③癌旁组织p53、p21、p16、c-myc、cyclinD1在FH组的表达率分别为11.11%(1/9)、66.67%(6/9)、44.44%(4/9)、66.67%(6/9)、11.11%(1/9),在NFH组的表达阳性率分别5.88%(2/34)、58.82%(20/34)、67.65%(23/34)、20.59%(7/34)、26.47%(9/34)。p53、p21、p16、cyclinD1在FH组与NFH组间的表达阳性率比较均无统计学意义(P＞0.05)。而C-myc在FH组的表达阳性率明显高于NFH组,χ~2值为5.145(P＜0.05)。
结论①p53、p21、p16、cyclinD1可能与肝癌的家族聚集性发病无明显相关性。②c-myc可能与肝癌的家族聚集性发病有密切相关性。
Objective①TO investigate the expression of p53,p21,p16,c-myc, cyclinD1 protein between familial hepatocellular carcinoma and non-familial hepatocellular carcinoma。②TO explore sensitive protein of familial hepatocellular carcinoma
Methods Detecting the expression of p53、p21、p16、c-myc、cyclinD1 protein in 43 HCC patients including 9 familial aggregation HCC and 34 non-familial HCC using immunohistochemistry.
Results①The positive expression rate of p53,p21,p16,c-myc and cyclinD1 protein in the hepatocellular carcinoma tissue was 53.49/%(23/43), 25.58/%(11/43),39.53/%(17/43),51.16/%(22/43),44.19/%(19/43)。The positive expression rate of p53,p21,p16,c-myc and cyclinD1 protein in surrounding carcinoma tissue was 6.98/%(3/43),60.47/%(26/43),62.79/% (27/43),30.23/%(13/43),23.26/%(10/43)。There was significant difference of the five protein between carcinoma tissue and surrounding carcinoma tissue (p＜0.05)。
②The expression rate of p53,p21,p16,c-myc,cyclinD1 protein in carcinoma tissue was 55.56%(5/9),22.22%(2/9),55.56%(5/9),44.44%(4/9), 44.44%(4/9)in FH group。The expression rate of p53,p21,p16,c-myc, cyclinD1 protein in carcinoma tissue was 52.94%(18/34),26.47%(9/34), 35.29%(12/34),52.94%(18/34),15/34(44.12%)in NFH group。They were all no significant difference between FH and NFH(P＞0.05)。
③The expression rate of p53,p21,p16,c-myc,cyclinD1 in surrounding carcinoma tissue was 11.11%(1/9),66.67%(6/9),44.44%(4/9),66.67%(6/9), 11.11%(1/9)in FH group。The expression rate of p53,p21,p16,c-myc, cyclinD1 in surrounding carcinoma tissue was 5.88%(2/34),58.82%(20/34), 67.65%(23/34),20.59%(7/34),26.47%(9/34)in NFH group~ There was no significant difference in p53,p21,p16,cyclinD1 expression between FH group and NFH group(P＞0.05)。But,there was significant difference in c-myc expression between the two group(P＜0.05).
Conclusion①p53,p21,p16 and cyclinDt might to be not related to the familial aggregation HCC。②c-myc might to be related to the familial aggregation HCC。
方法用免疫组化Maxvision~(TM)法检测43例肝癌患者癌及癌旁石蜡切片组织中p53、p21、p16、c-myc、cyclinD1蛋白的表达情况。
结果①本组43例癌组织中p53、p21、p16、c-myc、cyclinD1的阳性表达率分别为53.49/%(23/43)、25.58/%(11/43)、39.53/%(17/43)、51.16/%(22/43)、44.19/%(19/43);在癌旁肝组织的阳性表达率分别为6.98/%(3/43)、60.47/%(26/43)、62.79/%(27/43)、30.23/%(13/43)、23.26/%(10/43)。五种蛋白在肝癌与癌旁组织的表达差异有统计学意义(P＜0.05)。
②分组进行检测时发现,癌组织中p53、p21、p16、c-myc、cyclinD1在FH组的阳性表达率分别为55.56%(5/9)、22.22%(2/9)、55.56%(5/9)、44.44%(4/9)、44.44%(4/9),在NFH组的阳性表达率分别为52.94%(18/34)、26.47%(9/34)、35.29%(12/34)、52.94%(18/34)、15/34(44.12%)。癌组织中p53、p21、p16、c-myc、cyclinD1在FH组与NFH组间的阳性表达率比较均无统计学意义(P＞0.05)。
③癌旁组织p53、p21、p16、c-myc、cyclinD1在FH组的表达率分别为11.11%(1/9)、66.67%(6/9)、44.44%(4/9)、66.67%(6/9)、11.11%(1/9),在NFH组的表达阳性率分别5.88%(2/34)、58.82%(20/34)、67.65%(23/34)、20.59%(7/34)、26.47%(9/34)。p53、p21、p16、cyclinD1在FH组与NFH组间的表达阳性率比较均无统计学意义(P＞0.05)。而C-myc在FH组的表达阳性率明显高于NFH组,χ~2值为5.145(P＜0.05)。
结论①p53、p21、p16、cyclinD1可能与肝癌的家族聚集性发病无明显相关性。②c-myc可能与肝癌的家族聚集性发病有密切相关性。
Objective①TO investigate the expression of p53,p21,p16,c-myc, cyclinD1 protein between familial hepatocellular carcinoma and non-familial hepatocellular carcinoma。②TO explore sensitive protein of familial hepatocellular carcinoma
Methods Detecting the expression of p53、p21、p16、c-myc、cyclinD1 protein in 43 HCC patients including 9 familial aggregation HCC and 34 non-familial HCC using immunohistochemistry.
Results①The positive expression rate of p53,p21,p16,c-myc and cyclinD1 protein in the hepatocellular carcinoma tissue was 53.49/%(23/43), 25.58/%(11/43),39.53/%(17/43),51.16/%(22/43),44.19/%(19/43)。The positive expression rate of p53,p21,p16,c-myc and cyclinD1 protein in surrounding carcinoma tissue was 6.98/%(3/43),60.47/%(26/43),62.79/% (27/43),30.23/%(13/43),23.26/%(10/43)。There was significant difference of the five protein between carcinoma tissue and surrounding carcinoma tissue (p＜0.05)。
②The expression rate of p53,p21,p16,c-myc,cyclinD1 protein in carcinoma tissue was 55.56%(5/9),22.22%(2/9),55.56%(5/9),44.44%(4/9), 44.44%(4/9)in FH group。The expression rate of p53,p21,p16,c-myc, cyclinD1 protein in carcinoma tissue was 52.94%(18/34),26.47%(9/34), 35.29%(12/34),52.94%(18/34),15/34(44.12%)in NFH group。They were all no significant difference between FH and NFH(P＞0.05)。
③The expression rate of p53,p21,p16,c-myc,cyclinD1 in surrounding carcinoma tissue was 11.11%(1/9),66.67%(6/9),44.44%(4/9),66.67%(6/9), 11.11%(1/9)in FH group。The expression rate of p53,p21,p16,c-myc, cyclinD1 in surrounding carcinoma tissue was 5.88%(2/34),58.82%(20/34), 67.65%(23/34),20.59%(7/34),26.47%(9/34)in NFH group~ There was no significant difference in p53,p21,p16,cyclinD1 expression between FH group and NFH group(P＞0.05)。But,there was significant difference in c-myc expression between the two group(P＜0.05).
Conclusion①p53,p21,p16 and cyclinDt might to be not related to the familial aggregation HCC。②c-myc might to be related to the familial aggregation HCC。
引文
[1]Gottlieb TM,Oren M.p53 in growth control and neoplasia.[J]Biochim Biophys Acta,1996,1287(2-3):77-102.
[2]Qin L F,Ng I O,Fan S T,et al.p21/WAF1,p53 and PCNA expression and p53 mutation status in hepatocellular carcinoma[J].Int J Cancer,1998,79(4):424-428.
[3]Zarkowska T,Mittmacht S.Differential phosphorylation of the Retinoblasto ma protain by G1/S cyclin-dependent kinases[J].J Biol Chem.1997,272(19):12738-12746.
[4]Weihrauch M,Benicke M,Lehnert G,et al.Frequent K-ras-2 mutations and p16(INK4A)methylation in hepatocellular carcinomas in workers exposed to vinyl chloride[J].Br J Cancer,2001,84(7):982-989.
[5]Dang CV,Lewis BC.Role of oncogenic transcription factor c-myc in cell cycle regulation,apoptosis and metabolism[J].J Biomed Sci,1997,4(6):269-278.
[6]Su JJ,Ban KC,Li Y etal.Alteration of p53 and p21 during hepatocarcinogenesis in tree shrews.[J].World J Gastroenterol 2004;10(24):3559-3563。
[7]Wagayama H,Shiraki K,Sugimoto K,et al。High expression of p21WAF1/CIP1 is correlated with human hepatocellular carcinoma in patients with hepatitis C virus-associated chronic liver diseases[J]。Hum Pathol.2002;33(4):429-434
[8]Fukai K,Yokosuka O,Imazeki F etal.Methylation status of p14ARF,p15INK4b,and p16INK4a genes in human hepatocellular carcinoma[J].Liver Int.2005;25(6):1209-1216.
[9]Niu ZS,Li BK,Wang M.Expression of p53 and C-myc genes and its clinical relevance in the hepatocellular carcinomatous and pericarcinomatous tissues.[J]World J Gastroenterol.2002 Oct;8(5):822-826
[10]朱斌,姚晓平,杨甲梅等.原发性肝细胞癌中细胞周期G1期相关基因cyclinD1的表达及其临床病理学意义[J].肝胆外科杂志.1999,7(3)214-216。
[11]龚惠民,陈建国.启东肝癌家族聚集现象初析.中华肿瘤学杂志,1985,7(6):408-410
[12]李国坚,梁任祥,韦忠亮.TTV感染及复制与原发性肝癌家庭聚集性关系研究[J].广西医科大学学报,2007,24(1)1-3.
[13]丁保国,樊冬梅,王飞霞等。不良精神因素、家族史及肝脏疾病史与肝.[J]中国慢性病预防与控制.2003,11(1)3-4.
[14]丁建华,李苏平,高长明等.泰兴市全人群肝癌病例对照研究[J].中国肿瘤.2001,10(2)103-104.
[15]孙安龙,贾庆良,李勤等.重庆市原发性肝癌的危险因素[J]中国肿瘤。2000,9(3)123-124.
[16]Bresalier R S,Ho S B,Schoeppner H L et al.Enhanced Sialylation of mucin-associated carbohydrate structures in human colon cancer metas tasis.Gastroenterology.1996,110(5):1354-1367.
[17]许良中,杨文涛.免疫组化结果的判断标准[J].中国癌症杂志.1996,6(4)229-231.
[18]朱波,欧超,罗元等.CyclinD1、c-myc和p53的表达与肝细胞癌生物学行为关系[J].中国肿瘤临床,2006,3(2)67-70.
[19]张梅芳,云径平,苏曙光等.原发性肝细胞癌组织中p53和p21及MDM2蛋白的表达及其临床意义.[J]中华肿瘤防治杂志.2007,14(15)1121-1124.
[20]孟芝兰,叶大雄,宋晓华等.肝细胞癌p16蛋白的表达及DNA含量分析[J]. 临床肝胆病杂志,2003,19(03).154-155.
[21]Hui AM,Shi YZ,LiX,et al.Loss of p16INK4 Protein Alone and Together with Loss of Retinoblastoma Protein Correlate with Hepatocellular Carcinoma Progression.[J]Cancer Lett,2000,154(1):93-99.
[22]Matsuda Y,Ichida T,Mastuzawa J,et al.p16INK4 is Inactivated by Extensive CpG Methylation in Human Hepatocellular Carcinoma.[J]Gastroenterology,1999,116(2):394-400.
[23]朱忠超,龚昭,刘彦.肝癌细胞中端粒酶逆转录酶与c-myc表达的关系[J].临床外科杂志2007,15(3)174-175.
[24]杨建民,卜保国,高晋华.肝细胞癌组织中P16、P21蛋白表达的临床病理意义[J].重庆医学,2003,32(9)1172-1173.
[25]Koskinas J,Petraki K,Kavantzas N,etal Hepatic expression of the proliferative marker Ki-67 and p53 protein in HBV or HCV cirrhosis in relation to dysplastic liver cell changes and hepatocellular carcinoma.J Viral Hepat.2005;12(6):635-641.
[26]冯震博;何如昆;吕自力等p21和增殖细胞核抗原在肝硬化组织中的表达及其与肝细胞不典型增生的关系中华肝脏病杂志,2000,6,343-345.
[27]Azechi H,Nishida N,Fukuda Y,etal Disruption of the p16/cyclin D1/retinoblastoma protein pathway in the majority of human hepatocellular carcinomas.Oncology.2001;60(4):346-354.
[28]Takahashi Y,Kawate S,Watanabe M,etal Amplification of c-myc and cyclin D1 genes in primary and metastatic carcinomas of the liver.Pathol Int.2007;57(7):437-442
[29]孙燕翔,陈崇稼,周汉高等.c-myc和p53在大肠腺瘤与大肠癌中的表达.华人消化杂志,1998;6(12):1054-1056.
[30]史宪杰,李开宗,窦科峰等.原发性肝细胞癌组织中c-myc和p53基因的表 达及意义[J].世界华人消化杂志.1999,7(6)549-549.
[31]胡少辉,张志伟,陈孝平.skp2,C-myc在肝细胞肝癌中的表达及其意义[J].中国普通外科杂志.2006,15(1)45-48.
[32]刘平果、钟德玝、扬竹林。原发性肝癌组织中C-myc癌基因、Ki-67抗原的表达与意义[J].中华肝胆外科杂志.1999,5(1)32-34.
[33]王可新,胡三元,靳斌等.hTERT及c-myc在肝癌组织中的表达及其意义[J].中国普通外科杂志.2007,16(3)279-281.
[1]Lau WY.Primary hepatocellular carcinoma[M].In:Blumgart LH &Fong Y.(2ndeds.)Surgery of the Liver and Biliary Tract VolumeⅡ,2000:1423-1450.
[2]Bosch FX,Ribes J,Diaz M,et al.Primary liver Cancer:world wide incidence and trends[J].Gastroenterology,2004,127(Suppl):S5216.
[3]Lai EC,Lau WY.The continuing challenge of hepatic cancer in Asia[J].Surgeon,2005,3(3):210-215.
[4]龚惠民,陈建国.启东肝癌家族聚集现象初析.中华肿瘤学杂志,1985,7(6):408-410
[5]李国坚,梁任祥,韦忠亮.TTV感染及复制与原发性肝癌家庭聚集性关系研究[J].广西医科大学学报,2007,24(1)1-3.
[6]丁保国,樊冬梅,王飞霞等。不良精神因素、家族史及肝脏疾病史与肝.[J]中国慢性病预防与控制.2003,11(1)3-4。
[7]丁建华,李苏平,高长明等.泰兴市全人群肝癌病例对照研究[J].中国肿瘤.2001,10(2)103-104。
[8]孙安龙,贾庆良,李勤等。重庆市原发性肝癌的危险因素[J]中国肿瘤。2000,9(3)123-124.
[9]Gottlieb TM,Oren M.p53 in growth control and neoplasia.[J]Biochim Biophys Acta,1996,1287(2-3):77-102.
[10]Qin L F,Ng I O,Fan S T,et al.p21/WAF1,p53 and PCNA expression and p53 mutation status in hepatocellular carcinoma[J].Int J Cancer,1998,79(4):424-428.
[11]Zarkowska T,Mittmacht S.Differential phosphorylation of the retinoblastoma protain by G1/S cyclin-dependent kinases[J].J Biol Chem.1997,272(19):12738-12746.
[12]Weihrauch M,Benicke M,Lehnert G,etal.Frequent K-ras-2 mutations and p16(INK4A)methylation in hepatocellular carcinomas in workers exposed to vinyl chloride[J].Br J Cancer,2001,84(7):982-989.
[13]Dang CV,Lewis Be.Role of oncogenic transcription factor c-myc in cell cycle regulation,apoptosis and metabolism[J].J Biomed Sci,1997,4(6):269-278.
[14]Su JJ,Ban KC,Li Y etal.Alteration of p53 and p21 during hepatocarcinogenesis in tree shrews.[J].World J Gastroenterol 2004;10(24):3559-3563.
[15]Wagayama H,Shiraki K,Sugimoto K,et al。High expression of p21WAF1/CIP1 is correlated with human hepatocellular carcinoma in patients with hepatitis C virus-associated chronic liver diseases[J]。Hum Pathol.2002;33(4):429-434
[16]Fukai K,Yokosuka O,Imazeki F etal.Methylation status of p14ARF,p15INK4b,and p16INK4a genes in human hepatocellular carcinoma[J].Liver Int.2005;25(6):1209-1216.
[17]Niu ZS,Li BK,Wang M.Expression of p53 and C-myc genes and its clinical relevance in the hepatocellular carcinomatous and pericarcinomatous tissues.[J]World J Gastroenterol.2002 Oct;8(5):822-826
[18]朱斌,姚晓平,杨甲梅等.原发性肝细胞癌中细胞周期G1期相关基因CyclinD1的表达及其临床病理学意义[J].肝胆外科杂志.1999,7(3)214-216。
[19]刘合代,丁罡,张明,等原发性肝细胞肝癌的家族聚集性研究[J]中国优生与遗传杂志.2007,15(1).110-112.
[20]肖开银,黎乐群,彭民浩等.家族聚集性肝癌101例家族史和临床分析.广西医科大学学报.2005,22(2)224-226.
[21]吴燕,刘耳,张宝初.不同地区原发性肝癌患者家族史分析[J].华人消化杂志,1998,6(2):178-179.
[22]程兵,门伯媛,徐慧文等.原发性肝癌遗传流行病学研究-遗传因素与遗传模式分析、遗传度计算[J].中华肝脏病杂志,1996,4(1):36-36.
[23]蔡琳,易应南.福建省原发性肝癌遗传因素分析[J].中国公共卫生学报,1997,16(6):335-337.
[24]李苏平,丁建华,吴建中,等.泰兴市肝癌的分离比及遗传度估算[J肿瘤防治杂志,2001,8(6):570-572.
[25]邓伟.广西肝癌高发区谷胱苷肽基因多态性与肝癌家族聚集性关系的研究,[D],广西医科大学,2006.
[1]Bresalier R S,Ho S B,Schoeppner H L et al.Enhanced Sialylation of mucin-associated carbohydrate structures in human colon cancer metastasis.Gastroenterology.1996,110(5):1354-1367.
[2]许良中,杨文涛.免疫组化结果的判断标准[J].中国癌症杂志.1996,6(4)229-231.
[3]李国坚,梁任祥,韦忠亮.TTV感染及复制与原发性肝癌家庭聚集性关系研究[J].广西医科大学学报,2007,24(1)1-3.
[4]朱波,欧超,罗元等.CyclinDl、c-myc和p53的表达与肝细胞癌生物学行为关系[J].中国肿瘤临床,2006,3(2)67-70.
[5]朱斌,姚晓平,杨甲梅等.原发性肝细胞癌中细胞周期G1期相关基因CyclinD1的表达及其临床病理学意义[J].肝胆外科杂志.1999,7(3)214-216。
[6]朱忠超,龚昭,刘彦.肝癌细胞中端粒酶逆转录酶与c-myc表达的关系[J].临床外科杂志2007,15(3)174-175.
[7]杨建民,卜保国,高晋华.肝细胞癌组织中P16、P21蛋白表达的临床病理意 义[J].重庆医学,2003,32(9)1172-1173.
[8]孟芝兰,叶大雄,宋晓华等.肝细胞癌p16蛋白的表达及DNA含量分析[J].临床肝胆病杂志,2003,19(03).154-155。
[9]史宪杰,李开宗,窦科峰等.原发性肝细胞癌组织中c-myc和p53基因的表达及意义[J].世界华人消化杂志.1999,7(6)549-549.
[10]胡少辉,张志伟,陈孝平.skp2。C-myc在肝细胞肝癌中的表达及其意义[J].中国普通外科杂志.2006,15(1)45-48.
1 施益民,鲁常青,陈同钰,等.脑转移瘤肿中mtp53、二磷酸核苷激酶/nm23-H1的表达和临床意义[J].中华试验外科杂志,2007,17(4):322-323.
2 Bargonetti J,Manfredi JJ.Multiple roles of the tumor suppressor p53[J].CurrOp in Oncol,2002,14(1):86-91.
3 Tokino T,Nakamura Y.The role of p532target genes in human cancer[J].Oncology/Hematology,2000,33(1):1-6.
4 Vogelstein 13,Kinzler KW.P53 function and dysfunction[J].Cell,1992,70(8):523-526.
5 Prives C,Hall PA.The p53 pathway[J].J Pathol,1999,187(1):112-126.
6 Gu ZM,Flemington C,Chittenden T,et al.A p53 response gene involved in growth suppression and apop tosis[J].Mol Cell Biol,2000,20(1):233-241.
7 Vogelstein B,Lane D,Levine AJ.Surfing the p53 network[J].Nature,2000,408(6810):307-310.
8 虞朝辉,李岚,历有明,等.胃癌组织芯片p53、p16及环氧合酶-2表达的研究[J].中华内科杂志,2006,45(8):658-660.
9 冯云,张小伯,李原,等.早期喉癌人乳头状瘤病毒感染和p53、p16、nm23蛋白表达及端粒酶激活相关性分析[J].中日友好医院学报,2004,18(3):158-162.
10 王峰,王水,宣卓琦,等.乳腺癌细胞中p53、C-erbB-2、p21-WAF1和CDK4的表达及临床意义[J].南京医科大学学报,2007,27(1):70-73.
11 方志文,牟召霞,王新艳,等.p53与c2myc和cyclin B1在卵巢上皮性癌组织中的表达及意义[J].中华肿瘤防治杂志,2007,14(4):284-286
12 Roth JA,Nquyen D,Lawrence DD,et al.Retrovirus-mediated wild type p53gene transfer to tumors of patients with lung cancer[J].Nature Medicine,1996,2(9):985-991.
13 鲁建国,林晨,黄志强,等.腺病毒介导的p16和p53的联合应用对胆管癌细胞QBC939的生长抑制作用[J].解放军医学杂志,2001,26(6):393-395.
14 陈世晞,陈骏,徐卫东,等.动脉灌注p53基因治疗晚期肝癌的初步临床应用[J].介入放射学杂志,2007,16(2):127-129.
15 肖绍文,刘长清,孙艳,等.重组人p53基因联合放疗、热疗治疗晚期软组织肉瘤的临床观察[J].中国肿瘤临床,2007,34(2):65-67.
16 张开通,戚晓东,黄灵,等.重组p53腺病毒联合中药治疗小鼠腹水瘤的疗效[J].中国肿瘤生物治疗杂志,2006,13(6):466-468.
17 赵玫,范云霞,张洵,等.mtP53稳定性与化疗敏感性关系[J].中华医学研究杂志,2003,3(4):292-294.
[2]Qin L F,Ng I O,Fan S T,et al.p21/WAF1,p53 and PCNA expression and p53 mutation status in hepatocellular carcinoma[J].Int J Cancer,1998,79(4):424-428.
[3]Zarkowska T,Mittmacht S.Differential phosphorylation of the Retinoblasto ma protain by G1/S cyclin-dependent kinases[J].J Biol Chem.1997,272(19):12738-12746.
[4]Weihrauch M,Benicke M,Lehnert G,et al.Frequent K-ras-2 mutations and p16(INK4A)methylation in hepatocellular carcinomas in workers exposed to vinyl chloride[J].Br J Cancer,2001,84(7):982-989.
[5]Dang CV,Lewis BC.Role of oncogenic transcription factor c-myc in cell cycle regulation,apoptosis and metabolism[J].J Biomed Sci,1997,4(6):269-278.
[6]Su JJ,Ban KC,Li Y etal.Alteration of p53 and p21 during hepatocarcinogenesis in tree shrews.[J].World J Gastroenterol 2004;10(24):3559-3563。
[7]Wagayama H,Shiraki K,Sugimoto K,et al。High expression of p21WAF1/CIP1 is correlated with human hepatocellular carcinoma in patients with hepatitis C virus-associated chronic liver diseases[J]。Hum Pathol.2002;33(4):429-434
[8]Fukai K,Yokosuka O,Imazeki F etal.Methylation status of p14ARF,p15INK4b,and p16INK4a genes in human hepatocellular carcinoma[J].Liver Int.2005;25(6):1209-1216.
[9]Niu ZS,Li BK,Wang M.Expression of p53 and C-myc genes and its clinical relevance in the hepatocellular carcinomatous and pericarcinomatous tissues.[J]World J Gastroenterol.2002 Oct;8(5):822-826
[10]朱斌,姚晓平,杨甲梅等.原发性肝细胞癌中细胞周期G1期相关基因cyclinD1的表达及其临床病理学意义[J].肝胆外科杂志.1999,7(3)214-216。
[11]龚惠民,陈建国.启东肝癌家族聚集现象初析.中华肿瘤学杂志,1985,7(6):408-410
[12]李国坚,梁任祥,韦忠亮.TTV感染及复制与原发性肝癌家庭聚集性关系研究[J].广西医科大学学报,2007,24(1)1-3.
[13]丁保国,樊冬梅,王飞霞等。不良精神因素、家族史及肝脏疾病史与肝.[J]中国慢性病预防与控制.2003,11(1)3-4.
[14]丁建华,李苏平,高长明等.泰兴市全人群肝癌病例对照研究[J].中国肿瘤.2001,10(2)103-104.
[15]孙安龙,贾庆良,李勤等.重庆市原发性肝癌的危险因素[J]中国肿瘤。2000,9(3)123-124.
[16]Bresalier R S,Ho S B,Schoeppner H L et al.Enhanced Sialylation of mucin-associated carbohydrate structures in human colon cancer metas tasis.Gastroenterology.1996,110(5):1354-1367.
[17]许良中,杨文涛.免疫组化结果的判断标准[J].中国癌症杂志.1996,6(4)229-231.
[18]朱波,欧超,罗元等.CyclinD1、c-myc和p53的表达与肝细胞癌生物学行为关系[J].中国肿瘤临床,2006,3(2)67-70.
[19]张梅芳,云径平,苏曙光等.原发性肝细胞癌组织中p53和p21及MDM2蛋白的表达及其临床意义.[J]中华肿瘤防治杂志.2007,14(15)1121-1124.
[20]孟芝兰,叶大雄,宋晓华等.肝细胞癌p16蛋白的表达及DNA含量分析[J]. 临床肝胆病杂志,2003,19(03).154-155.
[21]Hui AM,Shi YZ,LiX,et al.Loss of p16INK4 Protein Alone and Together with Loss of Retinoblastoma Protein Correlate with Hepatocellular Carcinoma Progression.[J]Cancer Lett,2000,154(1):93-99.
[22]Matsuda Y,Ichida T,Mastuzawa J,et al.p16INK4 is Inactivated by Extensive CpG Methylation in Human Hepatocellular Carcinoma.[J]Gastroenterology,1999,116(2):394-400.
[23]朱忠超,龚昭,刘彦.肝癌细胞中端粒酶逆转录酶与c-myc表达的关系[J].临床外科杂志2007,15(3)174-175.
[24]杨建民,卜保国,高晋华.肝细胞癌组织中P16、P21蛋白表达的临床病理意义[J].重庆医学,2003,32(9)1172-1173.
[25]Koskinas J,Petraki K,Kavantzas N,etal Hepatic expression of the proliferative marker Ki-67 and p53 protein in HBV or HCV cirrhosis in relation to dysplastic liver cell changes and hepatocellular carcinoma.J Viral Hepat.2005;12(6):635-641.
[26]冯震博;何如昆;吕自力等p21和增殖细胞核抗原在肝硬化组织中的表达及其与肝细胞不典型增生的关系中华肝脏病杂志,2000,6,343-345.
[27]Azechi H,Nishida N,Fukuda Y,etal Disruption of the p16/cyclin D1/retinoblastoma protein pathway in the majority of human hepatocellular carcinomas.Oncology.2001;60(4):346-354.
[28]Takahashi Y,Kawate S,Watanabe M,etal Amplification of c-myc and cyclin D1 genes in primary and metastatic carcinomas of the liver.Pathol Int.2007;57(7):437-442
[29]孙燕翔,陈崇稼,周汉高等.c-myc和p53在大肠腺瘤与大肠癌中的表达.华人消化杂志,1998;6(12):1054-1056.
[30]史宪杰,李开宗,窦科峰等.原发性肝细胞癌组织中c-myc和p53基因的表 达及意义[J].世界华人消化杂志.1999,7(6)549-549.
[31]胡少辉,张志伟,陈孝平.skp2,C-myc在肝细胞肝癌中的表达及其意义[J].中国普通外科杂志.2006,15(1)45-48.
[32]刘平果、钟德玝、扬竹林。原发性肝癌组织中C-myc癌基因、Ki-67抗原的表达与意义[J].中华肝胆外科杂志.1999,5(1)32-34.
[33]王可新,胡三元,靳斌等.hTERT及c-myc在肝癌组织中的表达及其意义[J].中国普通外科杂志.2007,16(3)279-281.
[1]Lau WY.Primary hepatocellular carcinoma[M].In:Blumgart LH &Fong Y.(2ndeds.)Surgery of the Liver and Biliary Tract VolumeⅡ,2000:1423-1450.
[2]Bosch FX,Ribes J,Diaz M,et al.Primary liver Cancer:world wide incidence and trends[J].Gastroenterology,2004,127(Suppl):S5216.
[3]Lai EC,Lau WY.The continuing challenge of hepatic cancer in Asia[J].Surgeon,2005,3(3):210-215.
[4]龚惠民,陈建国.启东肝癌家族聚集现象初析.中华肿瘤学杂志,1985,7(6):408-410
[5]李国坚,梁任祥,韦忠亮.TTV感染及复制与原发性肝癌家庭聚集性关系研究[J].广西医科大学学报,2007,24(1)1-3.
[6]丁保国,樊冬梅,王飞霞等。不良精神因素、家族史及肝脏疾病史与肝.[J]中国慢性病预防与控制.2003,11(1)3-4。
[7]丁建华,李苏平,高长明等.泰兴市全人群肝癌病例对照研究[J].中国肿瘤.2001,10(2)103-104。
[8]孙安龙,贾庆良,李勤等。重庆市原发性肝癌的危险因素[J]中国肿瘤。2000,9(3)123-124.
[9]Gottlieb TM,Oren M.p53 in growth control and neoplasia.[J]Biochim Biophys Acta,1996,1287(2-3):77-102.
[10]Qin L F,Ng I O,Fan S T,et al.p21/WAF1,p53 and PCNA expression and p53 mutation status in hepatocellular carcinoma[J].Int J Cancer,1998,79(4):424-428.
[11]Zarkowska T,Mittmacht S.Differential phosphorylation of the retinoblastoma protain by G1/S cyclin-dependent kinases[J].J Biol Chem.1997,272(19):12738-12746.
[12]Weihrauch M,Benicke M,Lehnert G,etal.Frequent K-ras-2 mutations and p16(INK4A)methylation in hepatocellular carcinomas in workers exposed to vinyl chloride[J].Br J Cancer,2001,84(7):982-989.
[13]Dang CV,Lewis Be.Role of oncogenic transcription factor c-myc in cell cycle regulation,apoptosis and metabolism[J].J Biomed Sci,1997,4(6):269-278.
[14]Su JJ,Ban KC,Li Y etal.Alteration of p53 and p21 during hepatocarcinogenesis in tree shrews.[J].World J Gastroenterol 2004;10(24):3559-3563.
[15]Wagayama H,Shiraki K,Sugimoto K,et al。High expression of p21WAF1/CIP1 is correlated with human hepatocellular carcinoma in patients with hepatitis C virus-associated chronic liver diseases[J]。Hum Pathol.2002;33(4):429-434
[16]Fukai K,Yokosuka O,Imazeki F etal.Methylation status of p14ARF,p15INK4b,and p16INK4a genes in human hepatocellular carcinoma[J].Liver Int.2005;25(6):1209-1216.
[17]Niu ZS,Li BK,Wang M.Expression of p53 and C-myc genes and its clinical relevance in the hepatocellular carcinomatous and pericarcinomatous tissues.[J]World J Gastroenterol.2002 Oct;8(5):822-826
[18]朱斌,姚晓平,杨甲梅等.原发性肝细胞癌中细胞周期G1期相关基因CyclinD1的表达及其临床病理学意义[J].肝胆外科杂志.1999,7(3)214-216。
[19]刘合代,丁罡,张明,等原发性肝细胞肝癌的家族聚集性研究[J]中国优生与遗传杂志.2007,15(1).110-112.
[20]肖开银,黎乐群,彭民浩等.家族聚集性肝癌101例家族史和临床分析.广西医科大学学报.2005,22(2)224-226.
[21]吴燕,刘耳,张宝初.不同地区原发性肝癌患者家族史分析[J].华人消化杂志,1998,6(2):178-179.
[22]程兵,门伯媛,徐慧文等.原发性肝癌遗传流行病学研究-遗传因素与遗传模式分析、遗传度计算[J].中华肝脏病杂志,1996,4(1):36-36.
[23]蔡琳,易应南.福建省原发性肝癌遗传因素分析[J].中国公共卫生学报,1997,16(6):335-337.
[24]李苏平,丁建华,吴建中,等.泰兴市肝癌的分离比及遗传度估算[J肿瘤防治杂志,2001,8(6):570-572.
[25]邓伟.广西肝癌高发区谷胱苷肽基因多态性与肝癌家族聚集性关系的研究,[D],广西医科大学,2006.
[1]Bresalier R S,Ho S B,Schoeppner H L et al.Enhanced Sialylation of mucin-associated carbohydrate structures in human colon cancer metastasis.Gastroenterology.1996,110(5):1354-1367.
[2]许良中,杨文涛.免疫组化结果的判断标准[J].中国癌症杂志.1996,6(4)229-231.
[3]李国坚,梁任祥,韦忠亮.TTV感染及复制与原发性肝癌家庭聚集性关系研究[J].广西医科大学学报,2007,24(1)1-3.
[4]朱波,欧超,罗元等.CyclinDl、c-myc和p53的表达与肝细胞癌生物学行为关系[J].中国肿瘤临床,2006,3(2)67-70.
[5]朱斌,姚晓平,杨甲梅等.原发性肝细胞癌中细胞周期G1期相关基因CyclinD1的表达及其临床病理学意义[J].肝胆外科杂志.1999,7(3)214-216。
[6]朱忠超,龚昭,刘彦.肝癌细胞中端粒酶逆转录酶与c-myc表达的关系[J].临床外科杂志2007,15(3)174-175.
[7]杨建民,卜保国,高晋华.肝细胞癌组织中P16、P21蛋白表达的临床病理意 义[J].重庆医学,2003,32(9)1172-1173.
[8]孟芝兰,叶大雄,宋晓华等.肝细胞癌p16蛋白的表达及DNA含量分析[J].临床肝胆病杂志,2003,19(03).154-155。
[9]史宪杰,李开宗,窦科峰等.原发性肝细胞癌组织中c-myc和p53基因的表达及意义[J].世界华人消化杂志.1999,7(6)549-549.
[10]胡少辉,张志伟,陈孝平.skp2。C-myc在肝细胞肝癌中的表达及其意义[J].中国普通外科杂志.2006,15(1)45-48.
1 施益民,鲁常青,陈同钰,等.脑转移瘤肿中mtp53、二磷酸核苷激酶/nm23-H1的表达和临床意义[J].中华试验外科杂志,2007,17(4):322-323.
2 Bargonetti J,Manfredi JJ.Multiple roles of the tumor suppressor p53[J].CurrOp in Oncol,2002,14(1):86-91.
3 Tokino T,Nakamura Y.The role of p532target genes in human cancer[J].Oncology/Hematology,2000,33(1):1-6.
4 Vogelstein 13,Kinzler KW.P53 function and dysfunction[J].Cell,1992,70(8):523-526.
5 Prives C,Hall PA.The p53 pathway[J].J Pathol,1999,187(1):112-126.
6 Gu ZM,Flemington C,Chittenden T,et al.A p53 response gene involved in growth suppression and apop tosis[J].Mol Cell Biol,2000,20(1):233-241.
7 Vogelstein B,Lane D,Levine AJ.Surfing the p53 network[J].Nature,2000,408(6810):307-310.
8 虞朝辉,李岚,历有明,等.胃癌组织芯片p53、p16及环氧合酶-2表达的研究[J].中华内科杂志,2006,45(8):658-660.
9 冯云,张小伯,李原,等.早期喉癌人乳头状瘤病毒感染和p53、p16、nm23蛋白表达及端粒酶激活相关性分析[J].中日友好医院学报,2004,18(3):158-162.
10 王峰,王水,宣卓琦,等.乳腺癌细胞中p53、C-erbB-2、p21-WAF1和CDK4的表达及临床意义[J].南京医科大学学报,2007,27(1):70-73.
11 方志文,牟召霞,王新艳,等.p53与c2myc和cyclin B1在卵巢上皮性癌组织中的表达及意义[J].中华肿瘤防治杂志,2007,14(4):284-286
12 Roth JA,Nquyen D,Lawrence DD,et al.Retrovirus-mediated wild type p53gene transfer to tumors of patients with lung cancer[J].Nature Medicine,1996,2(9):985-991.
13 鲁建国,林晨,黄志强,等.腺病毒介导的p16和p53的联合应用对胆管癌细胞QBC939的生长抑制作用[J].解放军医学杂志,2001,26(6):393-395.
14 陈世晞,陈骏,徐卫东,等.动脉灌注p53基因治疗晚期肝癌的初步临床应用[J].介入放射学杂志,2007,16(2):127-129.
15 肖绍文,刘长清,孙艳,等.重组人p53基因联合放疗、热疗治疗晚期软组织肉瘤的临床观察[J].中国肿瘤临床,2007,34(2):65-67.
16 张开通,戚晓东,黄灵,等.重组p53腺病毒联合中药治疗小鼠腹水瘤的疗效[J].中国肿瘤生物治疗杂志,2006,13(6):466-468.
17 赵玫,范云霞,张洵,等.mtP53稳定性与化疗敏感性关系[J].中华医学研究杂志,2003,3(4):292-294.