Vascular Endothelial Growth Factor Is a Promising Therapeutic Target for the Treatment of Clear Cell Carcinoma of the Ovary

被引:75
作者
Mabuchi, Seiji [1 ]
Kawase, Chiaki [1 ]
Altomare, Deborah A. [4 ]
Morishige, Kenichirou [1 ]
Hayashi, Masami [1 ]
Sawada, Kenjiro [1 ]
Ito, Kimihiko [7 ]
Terai, Yoshito [3 ]
Nishio, Yukihiro [2 ]
Klein-Szanto, Andres J. [5 ]
Burger, Robert A. [4 ,6 ]
Ohmichi, Masahide [3 ]
Testa, Joseph R.
Kimura, Tadashi [1 ]
机构
[1] Osaka Univ, Grad Sch Med, Dept Obstet & Gynecol, Suita, Osaka 5650871, Japan
[2] Osaka Police Hosp, Dept Obstet & Gynecol, Osaka, Japan
[3] Osaka Med Coll, Dept Obstet & Gynecol, Osaka, Japan
[4] Fox Chase Canc Ctr, Womens Canc Program, Philadelphia, PA 19111 USA
[5] Fox Chase Canc Ctr, Canc Genet & Signaling Program, Philadelphia, PA 19111 USA
[6] Fox Chase Canc Ctr, Dept Surg, Philadelphia, PA 19111 USA
[7] Kansai Rosai Hosp, Dept Obstet & Gynecol, Amagasaki, Hyogo, Japan
关键词
GYNECOLOGIC-ONCOLOGY-GROUP; IN-VITRO; PHASE-II; ANTITUMOR-ACTIVITY; TUMOR-GROWTH; CANCER; EXPRESSION; INHIBITION; ANGIOGENESIS; BEVACIZUMAB;
D O I
10.1158/1535-7163.MCT-10-0169
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
This study examines the role of vascular endothelial growth factor (VEGF) as a therapeutic target in clear cell carcinoma (CCC) of the ovary, which has been regarded as a chemoresistant histologic 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 CCC cells (RMG1-CR and KOC7C-CR), compared with 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 cell-derived (RMG1 and KOC7C) and cisplatin-refractory CCC cell-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. Mol Cancer Ther; 9(8); 2411-22. (C) 2010 AACR.
引用
收藏
页码:2411 / 2422
页数:12
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