The Background and History of Human Gene Therapy and Advances in the Study of Gene Therapy of Human Hepatocellular Carcinoma_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

HUANG Jianzhao ¹ , GU Hongguang ¹ , XIA Shuisheng ²

Department of Hepatobiliary Surgery, Daping Hospital and the Research Institute of Surgery, The Third Military Medical University, Chongqing 400042, China;

Corresponding author：

Keywords：

Gene therapy; Hepatocellular carcinoma

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ObjectiveTo know the background of human gene therapy and the advances in gene therapy study of human hepatocellular carcinoma (HCC). MethodsThe related literatures were reviewed. ResultsAs a substitute measure gene therapy was of great superiority and had got a good result in the clinical study of treatment of human genetic diseases. But it was mainly limited to the study of preclinical phase when it was used to the treatment of tumor. As a carrier of gene transfer， the newly modified retrovirus might have superiority in the study of gene therapy of HCC when compared with other viruses such as adenovirus and adenoassociated virus (AAV). The genes TK,p53 and p16 etc. had been used to the study of therapy of HCC and had some good results.ConclusionThe future of human gene therapy is optimistic, but there is a long way to go when gene therapy is widely used in the clinical study of treatment of HCC.

Citation： HUANG Jianzhao,GU Hongguang,XIA Shuisheng. The Background and History of Human Gene Therapy and Advances in the Study of Gene Therapy of Human Hepatocellular Carcinoma. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2003, 10(1): 83-85. doi: Copy

1.	Thompson L. The first kids with new genes[J].Time, 1993；141(23)∶ 50.
2.	Human gene marker/therapy clinical protocols(complete updated listings) [J].Human Gene Therapy, 2000; 11(18)∶2543.
3.	Bilbao R, Gerolami R, Bralet MP， et al. Transduction efficacy, antitumoral effect, and toxicity of adenovirusmediated herpes simplex virus thymidine kinase/ganciclovir therapy of hepatocellular carcinoma: the woodchuck animal model[J]. Cancer Gene Ther， 2000; 7(5)∶657.
4.	Drozdzik M, Qian C, Xie X, et al. Combined gene therapy with suicide gene and interleukin12 is more efficient than therapy with one gene alone in a murine model of hepatocellular carcinoma[J]. J Hepatol， 2000; 32(2)∶279.
5.	Harada Y, Iwai M, Tanaka S， et al. Highly efficient suicide gene expression in hepatocellular carcinoma cells by epsteinbarr virusbased plasmid vectors combined with polyamidoamine dendrimer[J].Cancer Gene Ther， 2000; 7(1)∶27.
6.	Kuriyama S, Mitoro A, Yamazaki M， et al. Comparison of gene therapy with the herpes simplex virus thymidine kinase gene and the bacterial cytosine deaminase gene for the treatment of hepatocellular carcinoma[J]. Scand J Gastroenterol， 1999; 34(10)∶1033.
7.	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.
8.	Bao JJ, Zhang WW, Kuo MT. Adenoviral delivery of recombinant DNA into transgenic mice bearing hepatocellular carcinomas[J]. Hum Gene Ther， 1996; 7(3)∶355.
9.	Choi JY, Park YM, Byun BH， et al. Adenovirusmediated p53 tumor suppressor gene therapy against subcutaneous HuH7 hepatoma cell line nodule of nude mice[J].J Korean Med Sci， 1999; 14(3)∶271.
10.	Bui LA, Butterfield LH, Kim JY， et al. In vivo therapy of hepatocellular carcinoma with a tumorspecific adenoviral vector expressing interleukin2[J]. Hum Gene Ther， 1997; 8(18)∶2173.
11.	He P, Tang ZY, Liu BB， et al. The targeted expression of the human interleukin2/interferon alpha2b fused gene in alphafetoproteinexpressing hepatocellular carcinoma cells[J].J Cancer Res Clin Oncol， 1999; 125(2)∶77.
12.	Kuriyama S, Masui K, Kikukawa M， et al. Complete cure of established murine hepatocellular carcinoma is achievable by repeated injections of retroviruses carrying the herpes simplex virus thymidine kinase gene[J]. Gene Ther， 1999; 6(4)∶525.
13.	Peng D, Qian C, Sun Y， et al. Transduction of hepatocellular carcinoma (HCC) using recombinant adenoassociated virus (rAAV): in vitro and in vivo effects of genotoxic agents[J]. J Hepatol， 2000; 32(6)∶975.
14.	Gerolami R, Cardoso J, Lewin M, et al. Evaluation of HSVtk gene therapy in a rat model of chemically induced hepatocellular carcinoma by intratumoral and intrahepatic artery routes[J].Cancer Res， 2000; 60(4)∶993.
15.	Ohguchi A, 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 carcinona in gene therapy[J].Hepatology， 1998; 27(2)∶599.
16.	Huang JZ, Shen WL, Li B, et al. Molecular and immunohistochemical study of the inactivation of the p16 gene in primary heptocellular carcinoma[J]. CMJ， 2000； 113（10）∶889.
17.	Jin M, Piao Z, Kim NG， et al. p16 is a major inactivation target in hepatocellular carcinoma[J].Cancer， 2000; 89(1)∶60.
18.	Lehrman S. Virus treatment questioned after gene therapy death[J]. Nature， 1999; 401(6753)∶517.
19.	Xiao W, Chirmule N, Schnell MA， et al. Route of administration determines induction of Tcellindependent humoral responses to adenoassociated virus vectors [J]. Mol Ther， 2000; 1(4)∶323.
20.	Peng D, Qian C, Sun Y， et al. Transduction of hepatocellular carcinoma (HCC) using recombinant adenoassociated virus (rAAV): in vitro and in vivo effects of genotoxic agents[J].J Hepatol， 2000; 32(6)∶975.
21.	Naviaux RK, Costanzi E, Haas M， et al. The pCL vector system: rapid production of helperfree， hightiter, recombinant retroviruses[J]. J Virol， 1996; 70(8)∶5701.

1. Thompson L. The first kids with new genes[J].Time, 1993；141(23)∶ 50.
2. Human gene marker/therapy clinical protocols(complete updated listings) [J].Human Gene Therapy, 2000; 11(18)∶2543.
3. Bilbao R, Gerolami R, Bralet MP， et al. Transduction efficacy, antitumoral effect, and toxicity of adenovirusmediated herpes simplex virus thymidine kinase/ganciclovir therapy of hepatocellular carcinoma: the woodchuck animal model[J]. Cancer Gene Ther， 2000; 7(5)∶657.
4. Drozdzik M, Qian C, Xie X, et al. Combined gene therapy with suicide gene and interleukin12 is more efficient than therapy with one gene alone in a murine model of hepatocellular carcinoma[J]. J Hepatol， 2000; 32(2)∶279.
5. Harada Y, Iwai M, Tanaka S， et al. Highly efficient suicide gene expression in hepatocellular carcinoma cells by epsteinbarr virusbased plasmid vectors combined with polyamidoamine dendrimer[J].Cancer Gene Ther， 2000; 7(1)∶27.
6. Kuriyama S, Mitoro A, Yamazaki M， et al. Comparison of gene therapy with the herpes simplex virus thymidine kinase gene and the bacterial cytosine deaminase gene for the treatment of hepatocellular carcinoma[J]. Scand J Gastroenterol， 1999; 34(10)∶1033.
7. 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.
8. Bao JJ, Zhang WW, Kuo MT. Adenoviral delivery of recombinant DNA into transgenic mice bearing hepatocellular carcinomas[J]. Hum Gene Ther， 1996; 7(3)∶355.
9. Choi JY, Park YM, Byun BH， et al. Adenovirusmediated p53 tumor suppressor gene therapy against subcutaneous HuH7 hepatoma cell line nodule of nude mice[J].J Korean Med Sci， 1999; 14(3)∶271.
10. Bui LA, Butterfield LH, Kim JY， et al. In vivo therapy of hepatocellular carcinoma with a tumorspecific adenoviral vector expressing interleukin2[J]. Hum Gene Ther， 1997; 8(18)∶2173.
11. He P, Tang ZY, Liu BB， et al. The targeted expression of the human interleukin2/interferon alpha2b fused gene in alphafetoproteinexpressing hepatocellular carcinoma cells[J].J Cancer Res Clin Oncol， 1999; 125(2)∶77.
12. Kuriyama S, Masui K, Kikukawa M， et al. Complete cure of established murine hepatocellular carcinoma is achievable by repeated injections of retroviruses carrying the herpes simplex virus thymidine kinase gene[J]. Gene Ther， 1999; 6(4)∶525.
13. Peng D, Qian C, Sun Y， et al. Transduction of hepatocellular carcinoma (HCC) using recombinant adenoassociated virus (rAAV): in vitro and in vivo effects of genotoxic agents[J]. J Hepatol， 2000; 32(6)∶975.
14. Gerolami R, Cardoso J, Lewin M, et al. Evaluation of HSVtk gene therapy in a rat model of chemically induced hepatocellular carcinoma by intratumoral and intrahepatic artery routes[J].Cancer Res， 2000; 60(4)∶993.
15. Ohguchi A, 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 carcinona in gene therapy[J].Hepatology， 1998; 27(2)∶599.
16. Huang JZ, Shen WL, Li B, et al. Molecular and immunohistochemical study of the inactivation of the p16 gene in primary heptocellular carcinoma[J]. CMJ， 2000； 113（10）∶889.
17. Jin M, Piao Z, Kim NG， et al. p16 is a major inactivation target in hepatocellular carcinoma[J].Cancer， 2000; 89(1)∶60.
18. Lehrman S. Virus treatment questioned after gene therapy death[J]. Nature， 1999; 401(6753)∶517.
19. Xiao W, Chirmule N, Schnell MA， et al. Route of administration determines induction of Tcellindependent humoral responses to adenoassociated virus vectors [J]. Mol Ther， 2000; 1(4)∶323.
20. Peng D, Qian C, Sun Y， et al. Transduction of hepatocellular carcinoma (HCC) using recombinant adenoassociated virus (rAAV): in vitro and in vivo effects of genotoxic agents[J].J Hepatol， 2000; 32(6)∶975.
21. Naviaux RK, Costanzi E, Haas M， et al. The pCL vector system: rapid production of helperfree， hightiter, recombinant retroviruses[J]. J Virol， 1996; 70(8)∶5701.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

The Background and History of Human Gene Therapy and Advances in the Study of Gene Therapy of Human Hepatocellular Carcinoma

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