• 四川大學華西醫(yī)院普通外科（成都610041）;

目的介紹目前關于肝癌基因治療靶向性研究的進展。方法采用文獻回顧的方式對肝癌基因治療研究中采用的組織特異性載體系統以及細胞特異性基因表達調控系統等相關文獻進行了綜述。結果合成的DNA轉運系統和經修飾的病毒載體體外轉染靶細胞后，可獲得顯著表達。目的基因細胞特異性表達主要是以甲胎蛋白或白蛋白基因的轉錄調控元件為基礎，體外實驗顯示出較強的作用靶向性。其它基因治療策略也顯示了很好的應用前景。結論尋找更具特異性和普遍性的肝癌抗原是解決基因治療靶向性的關鍵。根據疾病和患者的具體情況選擇合適的基因轉運系統和調控元件是未來基因治療的方向。

引用本文： 趙永恒,綜述嚴律南,審校. 肝癌基因治療的靶向性研究進展. 中國普外基礎與臨床雜志, 2002, 9(6): 445-447. doi: 復制

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8. Mohr L, Schauer JI, Boutin RH, et al. Targeted gene transfer to hepatocellular carcinoma cells in vitro using a novel monoclonal antibodybased gene delivery system [J]. Hepatology, 1999; 29(1)∶82.
9. Moradpour D, Compagnon B, Wilson BE, et al. Specific targeting of human hepatocellular carcinoma cells by immunoliposomes in vitro [J]. Hepatology, 1995; 22(5)∶1527.
10. Cotten M, LangleRouault F, Kirlappos H, et al. Transferrinpolycationmediated introduction of DNA into human leukemic cells: stimulation by agents that affect the survival of transfected DNA or modulate transferrin receptor levels [J]. Proc Natl Acad Sci USA, 1990; 87(11)∶4033.
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14. Zern MA, Kresina TF. Hepatic drug delivery and gene therapy [J]. Hepatology, 1997; 25(2)∶484.
15. Somia NV, Zoppe M, Verma IM. Generation of targeted retroviral vectors by using singlechain variable fragment: an approach to in vivo gene delivery [J]. Proc Natl Acad Sci USA,1995; 92(16)∶7570.
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24. Vollmer CM Jr, Eilber FC, Butterfield LH, et al. Alphafetoproteinspecific genetic immunotherapy for hepatocellular carcinoma [J]. Cancer Res,1999; 59(13)∶3064.
25. Gordon EM, Liu PX, Chen ZH, et al. Inhibition of metastatic tumor growth in nude mice by portal vein infusions of matrixtargeted retroviral vectors bearing a cytocidal cyclin G1 construct [J]. Cancer Res, 2000; 60(13)∶3343.
  1. 1. Zhang G, Budker V, Wolff JA. High levels of foreign gene expression in hepatocytes after tail vein injections of naked plasmid DNA [J]. Hum Gen Ther, 1999; 10(10)∶1735.
  2. 2. Sharon N, Lis H. Lectins as cell recognition molecules [J]. Science, 1989; 246(4927)∶227.
  3. 3. Han J, Il Yeom Y. Specific gene transfer mediated by galactossylated polyLlysine into hepatoma cells [J]. Int J Pharm, 2000; 202(1-2)∶51.
  4. 4. Park JU, Ishihara T, Kano A, et al. Preparation of dendritic graft coplymer consisting of poly（llysine） and arabinogalactan as a hepatocyte specific DNA carrier [J]. Prep Biochem Biotechnol, 1999;29(4)∶353.
  5. 5. Junbo H, Li Q, Zaide W, et al. Receptormediated interlukin2 gene transfer into human hepatoma cells [J]. Int J Mol Med, 1999; 3(6)∶601.
  6. 6. Takahashi H, Ozturk M, Wilson B, et al. In vivo expression of two novel tumorassociated antigens and their use in immunolocalization of human hepatocellular carcinoma [J]. Hepatology, 1989; 9(4)∶625.
  7. 7. Wilson B, Qzuturk M, Takahashi H, et al. Cell surface changes associated with transformation of human hepatocytes to the malignant phenotype [J]. Proc Natl Acad Sci USA, 1988; 85(9)∶3140.
  8. 8. Mohr L, Schauer JI, Boutin RH, et al. Targeted gene transfer to hepatocellular carcinoma cells in vitro using a novel monoclonal antibodybased gene delivery system [J]. Hepatology, 1999; 29(1)∶82.
  9. 9. Moradpour D, Compagnon B, Wilson BE, et al. Specific targeting of human hepatocellular carcinoma cells by immunoliposomes in vitro [J]. Hepatology, 1995; 22(5)∶1527.
  10. 10. Cotten M, LangleRouault F, Kirlappos H, et al. Transferrinpolycationmediated introduction of DNA into human leukemic cells: stimulation by agents that affect the survival of transfected DNA or modulate transferrin receptor levels [J]. Proc Natl Acad Sci USA, 1990; 87(11)∶4033.
  11. 11. Curiel DT, Agarwal S, Wagner E, et al. Adenovirus enhancement of transferrinpolylysinemediated gne delivery [J]. Proc Natl Acad Sci USA, 1991; 88(19)∶8850.
  12. 12. Moradpour D, Schauer JI, Zurawski VR, et al. Efficient gene transfer into mammalian cells with cholesterylspermidine [J]. Biochem Biophys Res Commun, 1996; 221(1)∶82.
  13. 13. Plank C , Mechtler K, Szoka FC Jr, et al. Activation of the complement system by synthetic DNA complexes: a potential barrier for intravenous gene delivery [J]. Hum Gene Ther, 1996; 7(12)∶1437.
  14. 14. Zern MA, Kresina TF. Hepatic drug delivery and gene therapy [J]. Hepatology, 1997; 25(2)∶484.
  15. 15. Somia NV, Zoppe M, Verma IM. Generation of targeted retroviral vectors by using singlechain variable fragment: an approach to in vivo gene delivery [J]. Proc Natl Acad Sci USA,1995; 92(16)∶7570.
  16. 16. Yang Y, Nunes FA, Bernencsi K, et al. Cellular immunity to viral antigens limits E1deleted adenovirus for gene therapy [J]. Proc Natl Acad Sci USA, 1994; 91(10)∶4407.
  17. 17. Engelhardt JF, Ye X, Doranz B, et al.Ablation of E2A in recombinant adenoviruses improves transgene persistence and decreases inflammatory response in mouse liver [J]. Proc Natl Acad Sci USA, 1994; 91(13)∶6196.
  18. 18. Ruoslahti E. Alphafetoprotein in cancer and fetal development [J] Adv Cancer Res,1979; 29∶275.
  19. 19. Xu GW, Sun ZT, Forrester K, et al. Tissuespecific growth suppression and chemosensitivity promotion in human hepatocellular carcinoma cells by retroviralmediated transfer of the wildtype P53 gene [J]. Hepatology, 1996; 24(5)∶1264.
  20. 20. Ido A, Nakata K, Kato Y, et al. Gene therapy for hepatoma cells using a retrovirus vector carring herpes simplex virus thymidine kinase gene under the control of human alphafetoprotein gene promoter [J]. Cancer Res, 1995; 55(14)∶3105.
  21. 21. Kanai F, Shiratori Y, Yoshida Y, et al. Gene therapy for alphafetoproteinproducing human hepatoma cells by adenovirusmediated transfer of the herpes simplex virus thymidine kinase gene [J]. Hepatology, 1996; 23(6)∶1359.
  22. 22. Su H, Lu R, Chang JC, et al. Tissuespecific expression of herpes simplex virus thymidine kinase gene delivered by adenoassociated virus inhibits the growth of human hepatocellular carcinoma in athymic mice [J]. Proc Natl Acad Sci USA, 1997; 94(25)∶13891.
  23. 23. Ohguchi S, Nakatsukasa H, Higashi T, et al. Expression of αfetoprotein and albumin genes in human hepatocellular carcinomas: limitations in the application of the genes for targeting human hepatocellular carcinoma in gene therapy [J]. Hepatology, 1998; 27(2)∶599.
  24. 24. Vollmer CM Jr, Eilber FC, Butterfield LH, et al. Alphafetoproteinspecific genetic immunotherapy for hepatocellular carcinoma [J]. Cancer Res,1999; 59(13)∶3064.
  25. 25. Gordon EM, Liu PX, Chen ZH, et al. Inhibition of metastatic tumor growth in nude mice by portal vein infusions of matrixtargeted retroviral vectors bearing a cytocidal cyclin G1 construct [J]. Cancer Res, 2000; 60(13)∶3343.