The Advances in Target Gene Therapy of Liver Cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

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Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041;

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Liver cancer Gene therapy Target

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Objective To review the advances of target gene therapy of liver cancer. MethodsWe analyze and compare the tissuespecific carrier system or cellspecific gene expressing system from current researches of liver cancer gene therapy. ResultsArtificial synthetic DNA transfer system and modified viral vectors could efficiently transfect target cells and get highlevel expression. The ciselements of alpha fetal protein or albumin gene have been often adopted in the regulation of therapeutic gene and have shown their effectiveness. Some other gene therapy strategies also promised a good future. Conclusion Searching for more specific and universal liver cancer antigens is the key to improve the target gene therapy efficiency. The individual situation is the basis to select the best transfer system or regulatory elements in the future.

Citation： ZHAO Yongheng,YAN Lnan.. The Advances in Target Gene Therapy of Liver Cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2002, 9(6): 445-447. doi: Copy

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.	Sharon N, Lis H. Lectins as cell recognition molecules [J]. Science, 1989; 246(4927)∶227.
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.	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.	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.	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.	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.	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.
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.	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.	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.	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.
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.	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.	Ruoslahti E. Alphafetoprotein in cancer and fetal development [J] Adv Cancer Res,1979; 29∶275.
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.	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.	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.	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.	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.	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. 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. Sharon N, Lis H. Lectins as cell recognition molecules [J]. Science, 1989; 246(4927)∶227.
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. 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. 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. 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. 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. 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.
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. 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. 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. 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.
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. 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. Ruoslahti E. Alphafetoprotein in cancer and fetal development [J] Adv Cancer Res,1979; 29∶275.
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. 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. 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. 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. 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. 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.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

The Advances in Target Gene Therapy of Liver Cancer

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