Vascular endothelial growth factor is a promising therapeutic target for the treatment of clear cell carcinoma of the ovary.
Vascular endothelial growth factor is a promising therapeutic target for the treatment of clear cell carcinoma of the ovary.
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DOI：
10.1158/1535-7163.mct-10-0169
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发表时间：
2010-08
影响因子：
5.7
通讯作者：
Kimura T
中科院分区：
文献类型：
--
作者：
Mabuchi S;Kawase C;Altomare DA;Morishige K;Hayashi M;Sawada K;Ito K;Terai Y;Nishio Y;Klein-Szanto AJ;Burger RA;Ohmichi M;Testa JR;Kimura T
本研究探讨了VEGF作为卵巢透明细胞癌（CCC）治疗靶点的作用，CCC被认为是一种耐药的组织学亚型。免疫组化分析98例原发性卵巢癌组织芯片显示，VEGF在早期和晚期卵巢CCC中均强表达。在早期CCC中，VEGF水平高的患者的生存期明显短于VEGF水平低的患者。体外实验显示，在顺铂存在下，与相应的亲本细胞（RMG 1和KOC 7 C）相比，VEGF在顺铂难治性人透明细胞癌细胞（RMG 1-CR和KOC 7 C-CR）中的表达显著更高。由于抑制肿瘤血管生成，贝伐珠单抗体内治疗显著抑制了亲代CCC细胞衍生（RMG 1和KOC 7 C）和顺铂难治性CCC细胞衍生（RMG 1-CR和KOC 7 C-CR）肿瘤的生长。目前的研究结果表明，VEGF是频繁表达，并可能是一个有前途的治疗目标，在CCC的管理。贝伐珠单抗不仅可以作为一线治疗，而且可以作为既往接受过顺铂治疗的复发性疾病患者的二线治疗。
This study examined the role of VEGF as a therapeutic target in clear cell carcinoma (CCC) of the ovary, which has been regarded as a chemoresistant histological subtype. Immunohistochemical analysis using tissue microarrays of 98 primary ovarian cancers revealed that VEGF was strongly expressed both in early stage and advanced stage CCC of the ovary. In early stage CCCs, patients who had tumors with high levels of VEGF had significantly shorter survival than those with low levels of VEGF. In vitro experiments revealed that VEGF expression was significantly higher in cisplatin-refractory human clear cell carcinoma cells (RMG1-CR and KOC7C-CR), compared to the respective parental cells (RMG1 and KOC7C) in the presence of cisplatin. In vivo treatment with bevacizumab markedly inhibited the growth of both parental CCC cells-derived (RMG1 and KOC7C) and cisplatin-refractory CCC cells-derived (RMG1-CR and KOC7C-CR) tumors as a result of inhibition of tumor angiogenesis. The results of the current study indicate that VEGF is frequently expressed and can be a promising therapeutic target in the management of CCC. Bevacizumab may be efficacious not only as a first-line treatment but also as a second-line treatment of recurrent disease in patients previously treated with cisplatin.