肾癌基因治疗研究进展_West China Medical Journal

Authors：

谢礼波 ,  卢一平

Corresponding author：

卢一平, Email: peterxielibo@163.com

Keywords：

肾癌; 基因治疗; 研究进展

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【摘要】　肾癌是泌尿系统最常见的恶性肿瘤之一，近年来有不断上升的趋势。将近一半的肾癌患者首次就诊时已属晚期或有远处转移，约50%的患者术后复发或转移。肾癌的治疗目前仍以手术为主，放射治疗及化学疗法效果均不佳，生物治疗逐渐展露优势，其中，随着新的肾癌相关基因的发现，基因治疗已成为近年来肾癌研究的热点。应用于肾癌的基因治疗方法目前有干扰增殖基因表达、修复抑癌基因、控制凋亡调控基因的表达、转基因免疫产物抑癌疗法、自杀基因疗法及基因治疗联合化学疗法等等。这些方法虽然目前发展不甚成熟，但却为肾癌生物治疗提供了新的契机。

Citation： 谢礼波,卢一平. 肾癌基因治疗研究进展. West China Medical Journal, 2011, 26(3): 471-475. doi: Copy

1.	鲍镇美. 肾癌的生物治疗[J]. 实用肿瘤杂志, 2000, 15(1): 7-8.
2.	赵国志, 郑少斌. 肾癌的基因治疗进展[J]. 广东医学, 2008, 29(4): 527-529.
3.	Brummelkamp TR, Bemards R, Agami R. A system for stable expression of short interfering RNA in mammalian cells[J]. Science, 2002, 296(5): 550-553.
4.	郑骏年, 陈家存, 孙晓青, 等. Ki67基因短发夹状RNA表达载体对肾癌细胞生长的抑制作用[J]. 中华实验外科杂志, 2006, 23(6): 744-746.
5.	徐斌, 胡自力. RNA 干扰技术特异性抑制肾癌survivin 表达的实验研究[J]. 重庆医科大学学报, 2008, 33(9): 1080-1083.
6.	Wiesener MS, Munchenhagen PM, Berger I, et al. Constitutive activation of hypoxia-inducible genes related to overexpression of hypoxia-inducible factor-1 alpha in clear cell renal carcinomas[J]. Cancer Res, 2001, 61(3): 5215-5222.
7.	Datta K, Sundberg C, Karumanchi SA, et al. The 104-123 amino acid sequence of the beta-domain of von Hippel-Lindau gene product is sufficient to inhibit renal tumor growth and invasion[J]. Cancer Res, 2001, 61(5): 1768-1775.
8.	Amato K, Robert J. Inhibition of DNA methylation by antisense oligonucleotide MG98 as cancer therapy[J]. Clin Genitourin Canc, 2007, 7(5): 422-426.
9.	Yano T, Fujimoto E, Hagiwara H. Connexin 32 as an anti-invasive and anti-metastatic gene in renal cell carcinoma[J]. Biol Pharm Bull, 2006, 29(10): 1991-1994.
10.	van Oosten RL, Earel JK, Griffith TS. Enhancement of Ad5-TRAIL cytotoxicity against renal cell carcinoma with histone deacetylase inhibitors[J]. Cancer Gene Ther, 2006, 13(5): 628-632.
11.	Xu K, Ding Q, Fang Z, et al. Silencing of HIF-1α suppresses tumorigenicity of renal cell carcinoma through induction of apoptosis[J]. Cancer Gene Ther, 2010, 17(3): 212-222.
12.	Bui MH. Carbonic anhydrase IX is an independent predictor of survival in advanced renal clear cell carcinoma: implications for prognosis and therapy[J]. Clin Cancer Res, 2002, 11(3): 2145-2151.
13.	Lamers CJ, Sleijfer S, Vulto AG, et al. Treatment of metastatic renal cell carcinoma with autologous t-lymphocytes genetically retargeted against carbonic anhydrase Ⅸ: first clinical experience[J]. J Clin Oncol, 2006, 24(13): 20-22.
14.	Lamers CJ, Langeveld SL, Groot-van Ruijven CM, et al. Gene-modified T cells for adoptive immunotherapy of renal cell cancer maintain transgene-specific immune functions in vivo[J]. Cancer Immunol Immunother, 2007, 56: 1875-1883.
15.	Lamers CHJ, Sleijfer S, Willemsen RA, et al. Adoptive immuno-gene therapy of cancer with single chain antibody [scFv(Ig)] gene modified T lymphocytes[J]. J Biol Reg Homeos Ag, 2004, (18): 134-140.
16.	Kawai K, Tani K, Yamashita N, et al. Advanced renal cell carcinoma treated with granulocyte-macrophage colony-stimulating factor gene therapy: a clinical course of the first Japanese experience[J]. Int J Urol, 2002, 9: 462-466.
17.	赖海标, 吴松, 钟希文, 等. 重组腺病毒介导survivin 基因转染树突状细胞对肾细胞癌的免疫效应[J]. 中国肿瘤生物治疗杂志, 2008, 15(4): 331-335.
18.	Zhang Y, Luo CL, He BC, et al. Exosomes derived from IL-12-anchored renal cancer cells increase induction of specific antitumor response in vitro: a novel vaccine for renal cell carcinoma[J]. Int J Oncol, 2010, 36(1): 133-140.
19.	Calanis E, Burch PA, Richardson L, et al. Intratumoral administration of a 1, 2-dimyristyloxypropyl-3-dimthylhydro-xyethyl ammonium bromide/dioleoylphosphatidylethanolamine fomulation of the human interleukin-2 gene in the treatment of metastatic renal cell carcinoma[J]. Cancer, 2004, 101(11): 2557-2566.
20.	Budryk M, Wilczynska U, Szary J, et al. Direct transfer of IL-12 gene into growing renca tumors[J]. Acta Biochim Pol, 2000, 47(2): 386-391.
21.	Geiger JD. Vaccination of pediatric solid tumor patients specific T cells and mediate tumor regression[J]. Cancer Res, 2001, 61: 8513-8519.
22.	张世睿, 王禾, 秦卫军, 等. DOX-GA3对pG转染人肾癌GRC-1细胞的体外杀伤作用[J]. 第四军医大学学报, 2005, 26(24): 2212-2214.
23.	赵国志, 郑少斌, 谭万龙, 等. 腺病毒介导胞嘧啶脱氨酶基因联合α-IFN治疗肾癌的实验观察[J]. 第四军医大学学报, 2008, 29(8): 726-729.
24.	Pulkkanen KJ, Parkkinen JJ, Laukkanen JM, et al. HSV-tk gene therapy for human renal cell carcinoma in nude mice[J]. Cancer Gene Ther, 2001, 8(7): 529-536.
25.	Pulkkanen KJ, Laukkanen JM, Fuxe J, et al. The combination of HSV-tk and endostatin gene therapy eradicates orthotopic human renal cell carcinomas in nude mice[J]. Cancer Gene Ther, 2002, 9(11): 908-916.
26.	冯峰. PinX1基因在肾癌组织和细胞中的表达和生物学意义[D]. 北京: 中国人民解放军军医进修学院, 2007.
27.	Lin PY, Fosmire SP, Park SH, et al. Attenuation of PTEN increases p2 1 stability and cytosolic, localization in kidney cancer cells: a potential mechanism of apoptosis resistance[J]. Mol Cancer, 2007, 6: 16.
28.	刘军叶, 郭鹞, 郭国祯. HIF依赖性表达的自杀基因抑制肾细胞癌生长的实验研究[J]. 现代肿瘤医学, 2006, 14(1): 536-539.
29.	Mellon MJ, Bae KH, Steding CE, et al. Suppression of renal cell carcinoma growth and metastasis with sustained antiangiogenic: gene therapy[J]. Human Gene Ther, 2008, 19(5): 487-495.
30.	潘周辉, 杨太森. 人反义血管内皮生长因子基因载体构建及对肾细胞癌血管内皮生长因子表达的影响[J]. 中国组织工程研究与临床康复, 2008, 12(2): 262-265.
31.	Tavares TS, Nanus D, Yang XJ, et al. Gene microarray analysis of human renal cell carcinoma; the effects of HDAC inhibition and retinoid treatment[J]. Canc Bio Ther, 2008, 7(10): 1607-1618.
32.	Nelson NJ. Faux chromosomes hit the street, hold real promise for gene therapy[J]. JNCI, 1997, 89(13): 908-910.

1. 　鲍镇美. 肾癌的生物治疗[J]. 实用肿瘤杂志, 2000, 15(1): 7-8.
2. 　赵国志, 郑少斌. 肾癌的基因治疗进展[J]. 广东医学, 2008, 29(4): 527-529.
3. 　Brummelkamp TR, Bemards R, Agami R. A system for stable expression of short interfering RNA in mammalian cells[J]. Science, 2002, 296(5): 550-553.
4. 　郑骏年, 陈家存, 孙晓青, 等. Ki67基因短发夹状RNA表达载体对肾癌细胞生长的抑制作用[J]. 中华实验外科杂志, 2006, 23(6): 744-746.
5. 　徐斌, 胡自力. RNA 干扰技术特异性抑制肾癌survivin 表达的实验研究[J]. 重庆医科大学学报, 2008, 33(9): 1080-1083.
6. 　Wiesener MS, Munchenhagen PM, Berger I, et al. Constitutive activation of hypoxia-inducible genes related to overexpression of hypoxia-inducible factor-1 alpha in clear cell renal carcinomas[J]. Cancer Res, 2001, 61(3): 5215-5222.
7. 　Datta K, Sundberg C, Karumanchi SA, et al. The 104-123 amino acid sequence of the beta-domain of von Hippel-Lindau gene product is sufficient to inhibit renal tumor growth and invasion[J]. Cancer Res, 2001, 61(5): 1768-1775.
8. 　Amato K, Robert J. Inhibition of DNA methylation by antisense oligonucleotide MG98 as cancer therapy[J]. Clin Genitourin Canc, 2007, 7(5): 422-426.
9. 　Yano T, Fujimoto E, Hagiwara H. Connexin 32 as an anti-invasive and anti-metastatic gene in renal cell carcinoma[J]. Biol Pharm Bull, 2006, 29(10): 1991-1994.
10. 　van Oosten RL, Earel JK, Griffith TS. Enhancement of Ad5-TRAIL cytotoxicity against renal cell carcinoma with histone deacetylase inhibitors[J]. Cancer Gene Ther, 2006, 13(5): 628-632.
11. 　Xu K, Ding Q, Fang Z, et al. Silencing of HIF-1α suppresses tumorigenicity of renal cell carcinoma through induction of apoptosis[J]. Cancer Gene Ther, 2010, 17(3): 212-222.
12. 　Bui MH. Carbonic anhydrase IX is an independent predictor of survival in advanced renal clear cell carcinoma: implications for prognosis and therapy[J]. Clin Cancer Res, 2002, 11(3): 2145-2151.
13. 　Lamers CJ, Sleijfer S, Vulto AG, et al. Treatment of metastatic renal cell carcinoma with autologous t-lymphocytes genetically retargeted against carbonic anhydrase Ⅸ: first clinical experience[J]. J Clin Oncol, 2006, 24(13): 20-22.
14. 　Lamers CJ, Langeveld SL, Groot-van Ruijven CM, et al. Gene-modified T cells for adoptive immunotherapy of renal cell cancer maintain transgene-specific immune functions in vivo[J]. Cancer Immunol Immunother, 2007, 56: 1875-1883.
15. 　Lamers CHJ, Sleijfer S, Willemsen RA, et al. Adoptive immuno-gene therapy of cancer with single chain antibody [scFv(Ig)] gene modified T lymphocytes[J]. J Biol Reg Homeos Ag, 2004, (18): 134-140.
16. 　Kawai K, Tani K, Yamashita N, et al. Advanced renal cell carcinoma treated with granulocyte-macrophage colony-stimulating factor gene therapy: a clinical course of the first Japanese experience[J]. Int J Urol, 2002, 9: 462-466.
17. 　赖海标, 吴松, 钟希文, 等. 重组腺病毒介导survivin 基因转染树突状细胞对肾细胞癌的免疫效应[J]. 中国肿瘤生物治疗杂志, 2008, 15(4): 331-335.
18. 　Zhang Y, Luo CL, He BC, et al. Exosomes derived from IL-12-anchored renal cancer cells increase induction of specific antitumor response in vitro: a novel vaccine for renal cell carcinoma[J]. Int J Oncol, 2010, 36(1): 133-140.
19. 　Calanis E, Burch PA, Richardson L, et al. Intratumoral administration of a 1, 2-dimyristyloxypropyl-3-dimthylhydro-xyethyl ammonium bromide/dioleoylphosphatidylethanolamine fomulation of the human interleukin-2 gene in the treatment of metastatic renal cell carcinoma[J]. Cancer, 2004, 101(11): 2557-2566.
20. 　Budryk M, Wilczynska U, Szary J, et al. Direct transfer of IL-12 gene into growing renca tumors[J]. Acta Biochim Pol, 2000, 47(2): 386-391.
21. 　Geiger JD. Vaccination of pediatric solid tumor patients specific T cells and mediate tumor regression[J]. Cancer Res, 2001, 61: 8513-8519.
22. 　张世睿, 王禾, 秦卫军, 等. DOX-GA3对pG转染人肾癌GRC-1细胞的体外杀伤作用[J]. 第四军医大学学报, 2005, 26(24): 2212-2214.
23. 　赵国志, 郑少斌, 谭万龙, 等. 腺病毒介导胞嘧啶脱氨酶基因联合α-IFN治疗肾癌的实验观察[J]. 第四军医大学学报, 2008, 29(8): 726-729.
24. 　Pulkkanen KJ, Parkkinen JJ, Laukkanen JM, et al. HSV-tk gene therapy for human renal cell carcinoma in nude mice[J]. Cancer Gene Ther, 2001, 8(7): 529-536.
25. 　Pulkkanen KJ, Laukkanen JM, Fuxe J, et al. The combination of HSV-tk and endostatin gene therapy eradicates orthotopic human renal cell carcinomas in nude mice[J]. Cancer Gene Ther, 2002, 9(11): 908-916.
26. 　冯峰. PinX1基因在肾癌组织和细胞中的表达和生物学意义[D]. 北京: 中国人民解放军军医进修学院, 2007.
27. 　Lin PY, Fosmire SP, Park SH, et al. Attenuation of PTEN increases p2 1 stability and cytosolic, localization in kidney cancer cells: a potential mechanism of apoptosis resistance[J]. Mol Cancer, 2007, 6: 16.
28. 　刘军叶, 郭鹞, 郭国祯. HIF依赖性表达的自杀基因抑制肾细胞癌生长的实验研究[J]. 现代肿瘤医学, 2006, 14(1): 536-539.
29. 　Mellon MJ, Bae KH, Steding CE, et al. Suppression of renal cell carcinoma growth and metastasis with sustained antiangiogenic: gene therapy[J]. Human Gene Ther, 2008, 19(5): 487-495.
30. 　潘周辉, 杨太森. 人反义血管内皮生长因子基因载体构建及对肾细胞癌血管内皮生长因子表达的影响[J]. 中国组织工程研究与临床康复, 2008, 12(2): 262-265.
31. 　Tavares TS, Nanus D, Yang XJ, et al. Gene microarray analysis of human renal cell carcinoma; the effects of HDAC inhibition and retinoid treatment[J]. Canc Bio Ther, 2008, 7(10): 1607-1618.
32. 　Nelson NJ. Faux chromosomes hit the street, hold real promise for gene therapy[J]. JNCI, 1997, 89(13): 908-910.

West China Medical Journal

肾癌基因治疗研究进展

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