贝伐单抗在肝癌治疗中的应用现状及进展
Bevacizumab: Current Approach in the Treatment of Hepatocellular Carcinoma

作者: 钱坤 * , 钱骏 :;

关键词: 贝伐单抗肝癌生物疗法介入治疗Bevacizumab Hepatocellular Carcinoma Biotherapy Interventional Therapy

摘要:
随着肝癌生物疗法的不断发展,抗血管生成药–贝伐单抗已用于临床中晚期肝癌的分子靶向性治疗。贝伐单抗作为一种人工合成针对血管内皮生长因子(vascular endothelial growth factor ,VEGF)重组人源化单克隆IgG1抗体,可高效结合VEGF并防止其与肿瘤血管内皮细胞表面的受体(Flt-1和KDR)结合,进而精准抑制肿瘤血管内皮细胞增殖和肿瘤血管的新生。肝癌是一种预后较差的富血管性肿瘤,新生血管的形成与肝癌的发生发展有着密切的关系。大量临床实验(包括人体、动物和细胞水平实验)已经证实贝伐单抗及联合其他疗法靶向性治疗肝癌的有效性。本文将贝伐单抗用于肝癌治疗的应用现状及用于综合性介入治疗肝癌的可行性进行综述。
With the continuous development of biotherapy, anti-angiogenesis drug-bevacizumab has become clinical molecular targeted therapy for live cancer, a first-line treatment for patients with advanced hepatocellular carcinoma. Bevacizumab (Avastin; Genentech Inc, South San Francisco, CA), a recombinant humanized monoclonal antibody that targets VEGF, it’s efficiently combination of VEGF can prevent VEGF combined with tumor vascular endothelial cell surface receptors (Flt-1 and KDR), thus inhibits cell proliferation and angiogenesis of the tumor. Hepatocellular carcinoma (HCC) is a vascular tumor with poor prognosis, and closely related to angiogenesis. Currently, numerous of studies confirmed the efficacy and tolerability of be-vacizumab in HCC. This review attempts to summarize the progress of bevacizumab in HCC and raises new possibilities of interventional therapy in the treatment of hepatocellular carcinoma with the help of Bevaci-zumab.

文章引用: 钱坤 , 钱骏 (2011) 贝伐单抗在肝癌治疗中的应用现状及进展。 医学诊断, 1, 1-5. doi: 10.12677/md.2011.11001

参考文献

[1] A. Maataoui, J. Qian, D. Vossoughi, et al. Transarterial che- moembolization alone and in combination with other therapies: A comparative study in an animal HCC model. European Radiology, 2005, 15(1): 127-133.

[2] H. X. Chen, R. E. Gore-Langton, and B. D. Cheson. Current clinical trials of the anti-VEGF monoclonal antibody bevaci- zumab. Oncology, 2001, 15(8): 1017.

[3] Anonymous. Bevacizumab Anti-VEGF monoclonal antibody, avastin, rhumab-VEGF. Drugs in R&D, 2002, 3(1): 28-30.

[4] A. Le Querrec, D. Duval, and G. Tobelem. Tumour angiogenesis. Bailliere’s Clinical Haematology 1993, 6: 711-730.

[5] M. Fernandez, D. Semela, J. Bruix, et al. Angiogenesis in liver disease. Journal of Hepatology, 2009, 50(3): 604-620.

[6] X. M. Li, Z. Y. Tang, G. Zhou, et al. Significance of vascular endothelial growth factor mRNA expression in invasion and metastasis of hepatocellular carcinoma. Journal of Experimental Clinical Cancer Research, 1998, 17(1): 13-17.

[7] M. Mise, S. Arii, H. Higashituji, et al. Clinical significance of vascular endothelial growth factor and basic fibroblast growth factor gene expression in liver tumor. Hepatology, 1996, 23(3): 455-464.

[8] R. Pang, R. T. P. Poon. Angiogenesis and antiangiogenic therapy in hepatocellular carcinoma. Cancer Letters, 2006, 242(2): 151-167.

[9] R. P. Guo, C. Zhong, M. Shi, et al. Clinical value of apoptosis and angiogenesis factors in estimating the prognosis of hepatocellular carcinoma. Journal of Cancer Research and Clinical Oncology, 2006, 132(9): 547-555.

[10] D. R. Senger, S. J. Galli, A. M. Dvorak, et al. Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science, 1983, 219(4587): 983-985.

[11] N. Ferrara, W. J. Henzel. Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells. Biochemical Biophysical Research Communication, 1989, 161(2): 851-858.

[12] N. Ferrara. Vascular endothelial growth factor: basic science and clinical progress. Endocrine Review, 2004, 25(4): 581-611.

[13] M. Safran, W. G. Kaelin Jr. HIF hydroxylation and the mammalian oxygen-sensing pathway. The Journal of Clinical Investigation, 2003, 111(6): 779-783.

[14] Z. Von Marschall, A. Scholz, T. Cramer, et al. Effects of interferon alpha on vascular endothelial growth factor gene transcription and tumor angiogenesis. Journal of the National Cancer Institute, 2003, 95(6): 437-448.

[15] P. M. Lam, L. S. Po, L. P. Cheung, et al. The effect of exogenous estradiol treatment on the mRNA expression of vascular endothelial growth factor and its receptors in cultured human oviduct mucosal cells. Journal of Assisted Reproduction Genetics, 2005, 22(6): 251-255.

[16] V. A. Robb, G. J. Pepe, and E. D. Albrecht.Acute temporal regulation of placental vascular endothelial growth/permeability factor expression in baboons by estrogen. Biology of Reproduction, 2004, 71(5): 1694-1698.

[17] P. D. Collins, D. T. Connolly, and T. J. Williams. Characterization of the increase in vascular permeability induced by vascular permeability factor in vivo. British Journal of Pharmacology, 109(1): 195-199.

[18] Y. Ren, B. Cao, S. Law, et al. (2005) Hepatocyte growth factor promotes cancer cell migration and angiogenic factors expression: a prognostic marker of human esophageal squamous cell carcinomas. Clinical Cancer Research, 2005, 11: 6190-6197.

[19] L. Jussila, K. Alitalo. Vascular growth factors and lymphangiogenesis. Physiological Reviews, 2002, 82(3): 673-700.

[20] M. Volm, R. Koomagi, and J. Mattern. Prognostic value of vascular endothelial growth factor and its receptor Flt-1 in squa- mous cell lung cancer. International Journal of Cancer, 1997, 74(1): 64-68.

[21] H. Yoshiji, D. E. Gomez, M. Shibuya, and U. P. Thorgeirsson. Expression of vascular endothelial growth factor, its receptor, and other angiogenic factors in human breast cancer. Cancer Research, 1996, 56: 2013-2016.

[22] L. M. Ellis, Y. Takahashi, C. J. Fenoglio, K. R. Cleary, C. D. Bucana, and D. B. Evans. Vessel counts and vascular endothelial growth factor expression in pancreatic adenocarcinoma. European Journal of Cancer, 1998, 34(3): 337-340.

[23] M. Tomisawa, T. Tokunaga, Y. Oshika, T. Tsuchida, Y. Fukushima, H. Sato, H. Kijima, H. Yamazaki, Y. Ueyama, N. Tamaoki, and M. Nakamura. Expression pattern of vascular endothelial growth factor isoform is closely correlated with tumour stage and vascularisation in renal cell carcinoma. European Journal of Cancer, 35(1): 133-137.

[24] H. M. Sowter, A. N. Corps, A. L. Evans, D. E. Clark, D. S. Charnock-Jones, and S. K. Smith. Expression and localization of the vascular endothelial growth factor family in ovarian epithelial tumors. Labatory Investigation, 1997, 77(6): 607-614.

[25] O. N. El-Assal, A. Yamanoi, Y. Soda et al. Clinical significance of microvessel density and vascular endothelial growth factor expression in hepatocellular carcinoma and surrounding liver: Possible involvement of vascular endothelial growth factor in the angiogenesis of cirrhotic liver. Hepatology, 1998, 27(6): 1554- 1562.

[26] R. S. Warren, H. Yuan, M. R. Matli, N. A. Gillett, and N. Ferrara. Regulation by vascular endothelial growth factor of human colon cancer tumorigenesis in a mouse model of experimental liver metastasis. The Journal of Clinical Investigation, 1995, 95(4): 1789-1797.

[27] O. Melnyk, M. A. Shuman, and K. J. Kim. Vascular endothelial growth factor promotes tumor dissemination by a mechanism distinct from its effect on primary tumor growth. Cancer Research, 1996, 56: 921-924.

[28] P. Borgstrom, K. J. Hillan, P. Sriramarao, and N. Ferrara. Complete inhibition of angiogenesis and growth of microtumors by antivascular endothelial growth factor neutralizing antibody: novel concepts of angiostatic therapy from intravital videomicroscopy. Cancer Research, 1996, 56: 4032-4039.

[29] P. Borgstrom, M. A. Bourdon, K. J. Hillan, P. Sriramarao, and N. Ferrara. Neutralizing anti-vascular endothelial growth factor antibody completely inhibits angiogenesis and growth of human prostate carcinoma micro tumors in vivo. Prostate, 1998, 35(1): 1-10.

[30] K. J. Kim, B. Li, J. Winer, et al. Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature, 1993, 362: 841-844.

[31] R. S. Warren, H. Yuan, M. R. Matli, et al. Regulation by vascular endothelial growth factor of human colon cancer tumorigenesis in a mouse model of experimental liver metastasis. The Journal of Clinical Investigation, 1995, 95(4): 1789-1797.

[32] L. G. Presta, H. Chen, S. J. O’connor, et al. Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders. Cancer Research, 1997, 57: 4593-4599.

[33] R. K. Jain. Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science, 2005, 307(5706): 58- 62.

[34] A. X. Zhu, L. S. Blaszkowsky, D. P. Ryan, et al. Phase II study of gemcitabine and oxaliplatin in combination with bevacizumab in patients with advanced hepatocellular carcinoma. Journal of Clinical Oncology, 2006, 24(12): 1898-1903.

[35] N. Lassau, S. Koscielny, L. Chami et al. Advanced hepatocellular carcinoma: early evaluation of response to bevacizumab therapy at dynamic contrast-enhanced US with quantification—preliminary results. Radiology, 2011, 258: 291-300.

[36] A. B. Siegel, E. I. Cohen, A. Ocean et al. Phase II trial evaluating the clinical and biologic effects of bevacizumab in unresectable hepatocellular carcinoma. Journal of Clinical Oncology, 2008, 26(18): 2992-2998.

[37] C. H. Hsu, T. S. Yang, C. Hsu et al. Efficacy and tolerability of bevacizumab plus capecitabine as first-line therapy in patients with advanced hepatocellular carcinoma. British Journal of Cancer, 2010, 102(6): 981-986.

[38] L. C. Ong, I. C. Song, Y. Jin, et al. Effective inhibition of xenografts of hepatocellular carcinoma (HepG2) by rapamycin and bevacizumab in an intrahepatic model. Molecular Imaging and Biology, 2009, 11(5): 334-342.

[39] D. Semela, A. C. Piguet, M. Kolev, K. Schmitter, R. Hlushchuk, V. Djonov, et al. Vascular remodeling and antitumoral effects of mTOR inhibition in a rat model of hepatocellular carcinoma. Journal of Hepatology, 2007, 46(5): 840-848.

[40] Y. Q. Xiong, H. C. Sun, X. D. Zhu, et al. Bevacizumab enhances chemosensitivity of hepatocellular carcinoma to adriamycin related to inhibition of survivin expression. Journal of Cancer Research and Clinical Oncology, 2011, 137(3): 505-512.

[41] N. E. Kemeny, L. Schwartz, M. Gonen, et al. Treating primary liver cancer with hepatic arterial infusion of floxuridine and dexamethasone: does the addition of systemic bevacizumab improve results? Oncology, 2011, 80(3-4): 153-159.

[42] 郭子姮, 王杰军, 于观贞等. Bevacizumab抑制高转移性人肝癌原位移植瘤的淋巴管形成[J]. 肿瘤, 2006, 26(8): 4.

[43] 陈方国, 陈漪, 于观贞等. Bevacizumab抑制高转移性人肝癌原位移植瘤的血管形成[J]. 中国临床医学, 2006, 13(6): 2.

[44] 万骋, 崔斐, 陈斌等. 抗肿瘤血管生成药bevacizumab对VEGF促人肝癌细胞株HepG2增殖的阻断作用[J]. 第二军医大学学报, 2008, 29(6): 5.

[45] 张伟, 孙惠川, 熊宇泉等. 合用阿伐斯汀增强索拉非尼对肝癌生长转移的抑制作用[J]. 中华实验外科杂志, 2010, 27(2): 3.

[46] L. Rossi, F. Zoratto, A. Papa, et al. Current approach in the treatment of hepatocellular carcinoma. World Journal of Gastrointestinal Oncology, 2010, 2(9): 348-359.

[47] C. Wich, A. Agaimy, D. Strobel, et al. Sustained treatment response of metastatic hepatocellular carcinoma with bevacizumab and sorafenib. World Journal of Gastroenterology, 2010, 16(28): 3592-3596.

[48] 钱骏, 冯敢生. 原发性肝癌的综合介入治疗[J]. 中华肿瘤杂志, 2003, 25(5): 3.

[49] 李欣, 郑传胜, 冯敢生. 肿瘤血管生成及影像学在其中的应用[J]. 国外医学临床放射学分册, 2000, 23(5): 293-297.

[50] 曹玮, 王执民, 梁志会等. 血管生成抑制剂TNP-470与碘化油混合栓塞肝癌的实验研究[J]. 世界华人消化杂志, 2000, 8(6): 629-632.

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