TY - JOUR
T1 - Vascular endothelial growth factor is a promising therapeutic target for the treatment of clear cell carcinoma of the ovary
AU - Mabuchi, Seiji
AU - Kawase, Chiaki
AU - Altomare, Deborah A.
AU - Morishige, Kenichirou
AU - Hayashi, Masami
AU - Sawada, Kenjiro
AU - Ito, Kimihiko
AU - Terai, Yoshito
AU - Nishio, Yukihiro
AU - Klein-Szanto, Andres J.
AU - Burger, Robert A.
AU - Ohmichi, Masahide
AU - Testa, Joseph R.
AU - Kimura, Tadashi
N1 - (c) 2010 AACR.
PY - 2010/8
Y1 - 2010/8
N2 - 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.
AB - 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.
KW - Adenocarcinoma, Clear Cell/pathology
KW - Angiogenesis Inhibitors/pharmacology
KW - Animals
KW - Antibodies, Monoclonal, Humanized
KW - Antibodies, Monoclonal/pharmacology
KW - Bevacizumab
KW - Cell Line, Tumor
KW - Cell Proliferation/drug effects
KW - Cisplatin/pharmacology
KW - Cystadenocarcinoma, Serous/pathology
KW - Drug Resistance, Neoplasm/drug effects
KW - Female
KW - Humans
KW - Mice
KW - Mice, Nude
KW - Ovarian Neoplasms/pathology
KW - Vascular Endothelial Growth Factors/biosynthesis
KW - Xenograft Model Antitumor Assays
UR - https://www.scopus.com/pages/publications/77955498353
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=purepublist2023&SrcAuth=WosAPI&KeyUT=WOS:000280734200024&DestLinkType=FullRecord&DestApp=WOS
U2 - 10.1158/1535-7163.MCT-10-0169
DO - 10.1158/1535-7163.MCT-10-0169
M3 - Article
C2 - 20663925
SN - 1535-7163
VL - 9
SP - 2411
EP - 2422
JO - Molecular Cancer Therapeutics
JF - Molecular Cancer Therapeutics
IS - 8
ER -