原发性肝癌的发生机制及中西医治疗研究进展
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摘要
<正>原发性肝癌是我国乃至世界上最常见、最具有危害性的恶性肿瘤之一。世界卫生组织国际癌症研究署发布的2015年全球癌症报告显示,全球肝癌死亡人数约为75.1万,我国每年约有38.3万人死于肝癌,占全球肝癌死亡总数的51%~([1])。近年来肝癌发病率和死亡率呈上升趋势,严重威胁人类生命健康~([2])。目前,肝癌的5年生存率大约为14%~([3]);由于起病隐匿,肝癌被发现时多处于中晚期,并且大部分常合并肝硬化,同时伴有肝功能异常,此时手术治疗或化学栓塞
引文
[1] 魏矿荣,彭侠彪,梁智恒,等.全球肝癌流行概况[J].中国肿瘤,2015,24(8):621-630.
[2] 陈万青.从肿瘤登记数据看中国恶性肿瘤的发病特点和趋势[J].中华健康管理学杂志,2016,10(4):249-252.
[3] Siegel R,Ward E,Brawley O,et al.Cancer statistics,2011:the impact of eliminating socioeconomic and racial disparities on premature cancer deaths[J].CA Cancer J Clin,2011,61(4):212-236.
[4] 董孟佳,许尤琪,方祯.中药复方治疗肝癌机理的实验研究进展[J].环球中医药,2017,10(10):1270-1273.
[5] Baecker A,Liu X,La Vecchia C,et al.Worldwide incidence of hepatocellular carcinoma cases attributable to major risk factors[J].Eur J Cancer Prev,2018,27(3):205-212.
[6] Chen CJ,Yang HI,Su J,et al.Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level[J].JAMA,2006,295(1):65-73.
[7] Lee MH,Yang HI,Lu SN,et al.Hepatitis C virus seromarkers and subsequent risk of hepatocellular carcinoma:long-term predictors from a community-based cohort study[J].J Clin Oncol,2010,28(30):4587-4593.
[8] Tian S,Hui X,Fan Z,et al.Suppression of hepatocellular carcinoma proliferation and hepatitis B surface antigen secretion with interferon-λ1 or PEG-interferon-λ1[J].FASEB J,2014,28(8):3528-3539.
[9] Bruix J,Sherman M.Management of hepatocellular carcinoma:an update[J].Hepatology,2011,53(3):1020-1022.
[10] 赵淑芬,刘卓环,罗美华,等.吸烟对原发性肝癌患者凝血功能的影响[J].中国实用医药,2016,11(35):50-52.
[11] 时培岑,李巍.肥胖对肝癌发生发展的影响及其作用机制[J].临床肝胆病杂志,2017,33(10):2004-2008.
[12] 梁静,韩涛.糖尿病与原发性肝癌:危险因素还是致病病因?[J].临床肝胆病杂志,2017,33(4):757-762.
[13] Huang J,Zheng DL,Qin FS,et al.Genetic and epigenetic silencing of SCARA5 may contribute to human hepatocellular carcinoma by activating FAK signaling[J].J Clin Invest,2010,120(1):223-241.
[14] 陈业盛,孙志为,孟春城,等.原发性肝癌分子生物学机制和相关分子靶向药物的研究进展[J].世界华人消化杂志,2015,23(6):914-924.
[15] Zhao M,He HW,Sun HX,et al.Dual knockdown of N-ras and epiregulin synergistically suppressed the growth of human hepatoma cells[J].Biochem Biophys Res Commun,2009,387(2):239-244.
[16] Jeon YE,Lee SC,Paik SS,et al.Histology-directed matrix-assisted laser desorption/ionization analysis reveals tissue origin and p53 status of primary liver cancers[J].Pathol Int,2011,61(8):449-455.
[17] Efroni S,Meerzaman D,Schaefer CF,et al.Systems analysis utilising pathway interactions identifies sonic hedgehog pathway as a primary biomarker and oncogenic target in hepatocellular carcinoma[J].IET Syst Biol,2013,7(6):243-251.
[18] Jeng KS,Sheen IS,Jeng WJ,et al.Activation of the sonic hedgehog signaling pathway occurs in the CD133 positive cells of mouse liver cancer Hepa 1-6 cells[J].Onco Targets Ther,2013,6:1047-1055.
[19] Lai EC,Lau WY.The continuing challenge of hepatic cancer in Asia[J].Surgeon,2005,3(3):210-215.
[20] Lau WY,Lai EC.Hepatocellular carcinoma:current management and recent advances[J].Hepatobiliary Pancreat Dis Int,2008,7(3):237-257.
[21] Zheng SS,Xu X,Wu J,et al.Liver transplantation for hepatocellular carcinoma:Hangzhou experiences[J].Transplantation,2008,85(12):1726-1732.
[22] Fan J,Yang GS,Fu ZR,et al.Liver transplantation outcomes in 1,078 hepatocellular carcinoma patients:a multi-center experience in Shanghai,China[J].J Cancer Res Clin Oncol,2009,135(10):1403-1412.
[23] Hasegawa K,Aoki T,Ishizawa T,et al.Comparison of the therapeutic outcomes between surgical resection and percutaneous ablation for small hepatocellular carcinoma[J].Ann Surg Oncol,2014,21(Suppl 3):S348-S355.
[24] Lencioni R,de Baere T,Soulen MC,et al.Lipiodol transarterial chemoembolization for hepatocellular carcinoma:a systematic review of efficacy and safety data[J].Hepatology,2016,64(1):106-116.
[25] Zeng ZC,Tang ZY,Fan J,et al.A comparison of chemoembolization combination with and without radiotherapy for unresectable hepatocellular carcinoma[J].Cancer J,2004,10(5):307-316.
[26] Zhou LY,Zeng ZC,Fan J,et al.Radiotherapy treatment of adrenal gland metastases from hepatocellular carcinoma:clinical features and prognostic factors[J].BMC Cancer,2014,14:878.
[27] 程树群,吴孟超,陈汉,等.胸腺肽α1对原发性肝癌术后复发的影响[J].中华肝胆外科杂志,2004,10(9):592-593.
[28] Lee JH,Lee JH,Lim YS,et al.Adjuvant immunotherapy with autologous cytokine-induced killer cells for hepatocellular carcinoma[J].Gastroenterology,2015,148(7):1383-1391.
[29] 阎涛,毕新宇,方仪,等.槐耳颗粒对原发性肝癌患者术后长期生存的影响[J].中华肝胆外科杂志,2012,18(2):99-102.
[30] 高继良.肝复乐方剂治疗晚期原发性肝癌的前瞻性、随机对照临床研究[J].中国中药杂志,2014,39(12):2367-2369.
[31] Ling CQ,Yue XQ,Ling C.Three advantages of using traditional Chinese medicine to prevent and treat tumor[J].J Integr Med,2014,12(4):331-335.
[32] Chen XZ,Cao ZY,Li JN,et al.Ethyl acetate extract from Jiedu Xiaozheng Yin inhibits the proliferation of human hepatocellular carcinoma cells by suppressing polycomb gene product Bmi1 and Wnt/β-catenin signaling[J].Oncol Rep,2014,32(6):2710-2718.
[33] Cao Z,Chen X,Lin W,et al.Jiedu Xiaozheng Yin decoction inhibits hepatoma cell proliferation by inducing apoptosis via the mitochondrial-mediated pathway[J].Mol Med Rep,2015,12(2):2800-2806.
[34] 张怡,周荣耀,钟薏,等.补肾健脾方含药血清对人肝癌细胞株SMMC-7721细胞增殖和细胞凋亡的影响[J].上海中医药大学学报,2013,27(3):77-81.
[35] 罗春蕾,顾怡中,钟薏,等.六味地黄丸抑制移植性原发性肝癌小鼠肿瘤生长的实验研究[J].河北中医,2015,37(10):1519-1522,1531.
[36] 牛静秀,应简子,吴晓静,等.温化胶囊对人肝癌细胞株Bel-7402凋亡的作用[J].生物医学工程与临床,2015,19(3):305-308.
[37] 黄跃英,李洪生,张晓明,等.扶正抑瘤方对肝癌细胞运动及侵袭能力影响的实验研究[J].现代预防医学,2014,41(14):2604-2606.
[38] 史国军,山广志,邱慧颖.健脾柔肝汤对肝癌小鼠癌组织VEGF及MVD表达影响的研究[J].中国中医药科技,2014,21(6):627-629.
[39] 卜凡儒,张超,蒋树龙.化痰祛瘀方含药血清对肝癌细胞血管内皮生长因子的调控作用研究[J].新中医,2013,45(9):154-156.
[40] 崔佳,朱成功,赵莹莹,等.解氏肝癌2号方对肝癌H22荷瘤小鼠作用的研究[J].现代中西医结合杂志,2014,23(33):3655-3657,3661.
[41] 陈嘉璐,李湧健,张晓迪,等.四逆汤上调p53蛋白表达诱导肝癌细胞凋亡研究[J].中华中医药杂志,2013,28(2):548-551.
[42] 吴婷婷,吴伟忠,高东梅,等.补肾健脾方抑制裸鼠高转移原位肝癌切除术后肿瘤复发以及对索拉非尼的增效减毒作用[J].上海中医药杂志,2015,49(9):63-66,76.
[43] Wang N,Feng Y,Tan HY,et al.Inhibition of eukaryotic elongation factor-2 confers to tumor suppression by a herbal formulation Huanglian-Jiedu decoction in human hepatocellular carcinoma[J].J Ethnopharmacol,2015,164:309-318.
[44] Boye A,Wu C,Jiang Y,et al.Compound Astragalus and Salvia miltiorrhiza extracts modulate MAPK-regulated TGF-β/Smad signaling in hepatocellular carcinoma by multi-target mechanism[J].J Ethnopharmacol,2015,169:219-228.
[45] Zhang YH,Wang Y,Yusufali AH,et al.Cytotoxic genes from traditional Chinese medicine inhibit tumor growth both in vitro and in vivo[J].J Integr Med,2014,12(6):483-494.
[46] Zhao CQ,Zhou Y,Ping J,et al.Traditional Chinese medicine for treatment of liver diseases:progress,challenges and opportunities[J].J Integr Med,2014,12(5):401-408.
[2] 陈万青.从肿瘤登记数据看中国恶性肿瘤的发病特点和趋势[J].中华健康管理学杂志,2016,10(4):249-252.
[3] Siegel R,Ward E,Brawley O,et al.Cancer statistics,2011:the impact of eliminating socioeconomic and racial disparities on premature cancer deaths[J].CA Cancer J Clin,2011,61(4):212-236.
[4] 董孟佳,许尤琪,方祯.中药复方治疗肝癌机理的实验研究进展[J].环球中医药,2017,10(10):1270-1273.
[5] Baecker A,Liu X,La Vecchia C,et al.Worldwide incidence of hepatocellular carcinoma cases attributable to major risk factors[J].Eur J Cancer Prev,2018,27(3):205-212.
[6] Chen CJ,Yang HI,Su J,et al.Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level[J].JAMA,2006,295(1):65-73.
[7] Lee MH,Yang HI,Lu SN,et al.Hepatitis C virus seromarkers and subsequent risk of hepatocellular carcinoma:long-term predictors from a community-based cohort study[J].J Clin Oncol,2010,28(30):4587-4593.
[8] Tian S,Hui X,Fan Z,et al.Suppression of hepatocellular carcinoma proliferation and hepatitis B surface antigen secretion with interferon-λ1 or PEG-interferon-λ1[J].FASEB J,2014,28(8):3528-3539.
[9] Bruix J,Sherman M.Management of hepatocellular carcinoma:an update[J].Hepatology,2011,53(3):1020-1022.
[10] 赵淑芬,刘卓环,罗美华,等.吸烟对原发性肝癌患者凝血功能的影响[J].中国实用医药,2016,11(35):50-52.
[11] 时培岑,李巍.肥胖对肝癌发生发展的影响及其作用机制[J].临床肝胆病杂志,2017,33(10):2004-2008.
[12] 梁静,韩涛.糖尿病与原发性肝癌:危险因素还是致病病因?[J].临床肝胆病杂志,2017,33(4):757-762.
[13] Huang J,Zheng DL,Qin FS,et al.Genetic and epigenetic silencing of SCARA5 may contribute to human hepatocellular carcinoma by activating FAK signaling[J].J Clin Invest,2010,120(1):223-241.
[14] 陈业盛,孙志为,孟春城,等.原发性肝癌分子生物学机制和相关分子靶向药物的研究进展[J].世界华人消化杂志,2015,23(6):914-924.
[15] Zhao M,He HW,Sun HX,et al.Dual knockdown of N-ras and epiregulin synergistically suppressed the growth of human hepatoma cells[J].Biochem Biophys Res Commun,2009,387(2):239-244.
[16] Jeon YE,Lee SC,Paik SS,et al.Histology-directed matrix-assisted laser desorption/ionization analysis reveals tissue origin and p53 status of primary liver cancers[J].Pathol Int,2011,61(8):449-455.
[17] Efroni S,Meerzaman D,Schaefer CF,et al.Systems analysis utilising pathway interactions identifies sonic hedgehog pathway as a primary biomarker and oncogenic target in hepatocellular carcinoma[J].IET Syst Biol,2013,7(6):243-251.
[18] Jeng KS,Sheen IS,Jeng WJ,et al.Activation of the sonic hedgehog signaling pathway occurs in the CD133 positive cells of mouse liver cancer Hepa 1-6 cells[J].Onco Targets Ther,2013,6:1047-1055.
[19] Lai EC,Lau WY.The continuing challenge of hepatic cancer in Asia[J].Surgeon,2005,3(3):210-215.
[20] Lau WY,Lai EC.Hepatocellular carcinoma:current management and recent advances[J].Hepatobiliary Pancreat Dis Int,2008,7(3):237-257.
[21] Zheng SS,Xu X,Wu J,et al.Liver transplantation for hepatocellular carcinoma:Hangzhou experiences[J].Transplantation,2008,85(12):1726-1732.
[22] Fan J,Yang GS,Fu ZR,et al.Liver transplantation outcomes in 1,078 hepatocellular carcinoma patients:a multi-center experience in Shanghai,China[J].J Cancer Res Clin Oncol,2009,135(10):1403-1412.
[23] Hasegawa K,Aoki T,Ishizawa T,et al.Comparison of the therapeutic outcomes between surgical resection and percutaneous ablation for small hepatocellular carcinoma[J].Ann Surg Oncol,2014,21(Suppl 3):S348-S355.
[24] Lencioni R,de Baere T,Soulen MC,et al.Lipiodol transarterial chemoembolization for hepatocellular carcinoma:a systematic review of efficacy and safety data[J].Hepatology,2016,64(1):106-116.
[25] Zeng ZC,Tang ZY,Fan J,et al.A comparison of chemoembolization combination with and without radiotherapy for unresectable hepatocellular carcinoma[J].Cancer J,2004,10(5):307-316.
[26] Zhou LY,Zeng ZC,Fan J,et al.Radiotherapy treatment of adrenal gland metastases from hepatocellular carcinoma:clinical features and prognostic factors[J].BMC Cancer,2014,14:878.
[27] 程树群,吴孟超,陈汉,等.胸腺肽α1对原发性肝癌术后复发的影响[J].中华肝胆外科杂志,2004,10(9):592-593.
[28] Lee JH,Lee JH,Lim YS,et al.Adjuvant immunotherapy with autologous cytokine-induced killer cells for hepatocellular carcinoma[J].Gastroenterology,2015,148(7):1383-1391.
[29] 阎涛,毕新宇,方仪,等.槐耳颗粒对原发性肝癌患者术后长期生存的影响[J].中华肝胆外科杂志,2012,18(2):99-102.
[30] 高继良.肝复乐方剂治疗晚期原发性肝癌的前瞻性、随机对照临床研究[J].中国中药杂志,2014,39(12):2367-2369.
[31] Ling CQ,Yue XQ,Ling C.Three advantages of using traditional Chinese medicine to prevent and treat tumor[J].J Integr Med,2014,12(4):331-335.
[32] Chen XZ,Cao ZY,Li JN,et al.Ethyl acetate extract from Jiedu Xiaozheng Yin inhibits the proliferation of human hepatocellular carcinoma cells by suppressing polycomb gene product Bmi1 and Wnt/β-catenin signaling[J].Oncol Rep,2014,32(6):2710-2718.
[33] Cao Z,Chen X,Lin W,et al.Jiedu Xiaozheng Yin decoction inhibits hepatoma cell proliferation by inducing apoptosis via the mitochondrial-mediated pathway[J].Mol Med Rep,2015,12(2):2800-2806.
[34] 张怡,周荣耀,钟薏,等.补肾健脾方含药血清对人肝癌细胞株SMMC-7721细胞增殖和细胞凋亡的影响[J].上海中医药大学学报,2013,27(3):77-81.
[35] 罗春蕾,顾怡中,钟薏,等.六味地黄丸抑制移植性原发性肝癌小鼠肿瘤生长的实验研究[J].河北中医,2015,37(10):1519-1522,1531.
[36] 牛静秀,应简子,吴晓静,等.温化胶囊对人肝癌细胞株Bel-7402凋亡的作用[J].生物医学工程与临床,2015,19(3):305-308.
[37] 黄跃英,李洪生,张晓明,等.扶正抑瘤方对肝癌细胞运动及侵袭能力影响的实验研究[J].现代预防医学,2014,41(14):2604-2606.
[38] 史国军,山广志,邱慧颖.健脾柔肝汤对肝癌小鼠癌组织VEGF及MVD表达影响的研究[J].中国中医药科技,2014,21(6):627-629.
[39] 卜凡儒,张超,蒋树龙.化痰祛瘀方含药血清对肝癌细胞血管内皮生长因子的调控作用研究[J].新中医,2013,45(9):154-156.
[40] 崔佳,朱成功,赵莹莹,等.解氏肝癌2号方对肝癌H22荷瘤小鼠作用的研究[J].现代中西医结合杂志,2014,23(33):3655-3657,3661.
[41] 陈嘉璐,李湧健,张晓迪,等.四逆汤上调p53蛋白表达诱导肝癌细胞凋亡研究[J].中华中医药杂志,2013,28(2):548-551.
[42] 吴婷婷,吴伟忠,高东梅,等.补肾健脾方抑制裸鼠高转移原位肝癌切除术后肿瘤复发以及对索拉非尼的增效减毒作用[J].上海中医药杂志,2015,49(9):63-66,76.
[43] Wang N,Feng Y,Tan HY,et al.Inhibition of eukaryotic elongation factor-2 confers to tumor suppression by a herbal formulation Huanglian-Jiedu decoction in human hepatocellular carcinoma[J].J Ethnopharmacol,2015,164:309-318.
[44] Boye A,Wu C,Jiang Y,et al.Compound Astragalus and Salvia miltiorrhiza extracts modulate MAPK-regulated TGF-β/Smad signaling in hepatocellular carcinoma by multi-target mechanism[J].J Ethnopharmacol,2015,169:219-228.
[45] Zhang YH,Wang Y,Yusufali AH,et al.Cytotoxic genes from traditional Chinese medicine inhibit tumor growth both in vitro and in vivo[J].J Integr Med,2014,12(6):483-494.
[46] Zhao CQ,Zhou Y,Ping J,et al.Traditional Chinese medicine for treatment of liver diseases:progress,challenges and opportunities[J].J Integr Med,2014,12(5):401-408.