Vascular endothelial growth factor is a promising therapeutic target for the treatment of clear cell carcinoma of the ovary

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 t...

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Veröffentlicht in:Molecular cancer therapeutics 2010-08, Vol.9 (8), p.2411-2422
Hauptverfasser: Mabuchi, Seiji, Kawase, Chiaki, Altomare, Deborah A, Morishige, Kenichirou, Hayashi, Masami, Sawada, Kenjiro, Ito, Kimihiko, Terai, Yoshito, Nishio, Yukihiro, Klein-Szanto, Andres J, Burger, Robert A, Ohmichi, Masahide, Testa, Joseph R, Kimura, Tadashi
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container_end_page 2422
container_issue 8
container_start_page 2411
container_title Molecular cancer therapeutics
container_volume 9
creator Mabuchi, Seiji
Kawase, Chiaki
Altomare, Deborah A
Morishige, Kenichirou
Hayashi, Masami
Sawada, Kenjiro
Ito, Kimihiko
Terai, Yoshito
Nishio, Yukihiro
Klein-Szanto, Andres J
Burger, Robert A
Ohmichi, Masahide
Testa, Joseph R
Kimura, Tadashi
description 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.
doi_str_mv 10.1158/1535-7163.MCT-10-0169
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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. 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Kawase, Chiaki ; Altomare, Deborah A ; Morishige, Kenichirou ; Hayashi, Masami ; Sawada, Kenjiro ; Ito, Kimihiko ; Terai, Yoshito ; Nishio, Yukihiro ; Klein-Szanto, Andres J ; Burger, Robert A ; Ohmichi, Masahide ; Testa, Joseph R ; Kimura, Tadashi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c421t-5897f63a7761de27eb655d62ab1ff05fa24d923021e2695ee65c3202cbbecc3c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Adenocarcinoma, Clear Cell - pathology</topic><topic>Adenocarcinoma, Clear Cell - therapy</topic><topic>Angiogenesis Inhibitors - pharmacology</topic><topic>Animals</topic><topic>Antibodies, Monoclonal - pharmacology</topic><topic>Antibodies, Monoclonal, Humanized</topic><topic>Bevacizumab</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation - drug effects</topic><topic>Cisplatin - pharmacology</topic><topic>Cystadenocarcinoma, Serous - pathology</topic><topic>Cystadenocarcinoma, Serous - therapy</topic><topic>Drug Resistance, Neoplasm - drug effects</topic><topic>Female</topic><topic>Humans</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Ovarian Neoplasms - pathology</topic><topic>Ovarian Neoplasms - therapy</topic><topic>Vascular Endothelial Growth Factors - biosynthesis</topic><topic>Vascular Endothelial Growth Factors - metabolism</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mabuchi, Seiji</creatorcontrib><creatorcontrib>Kawase, Chiaki</creatorcontrib><creatorcontrib>Altomare, Deborah A</creatorcontrib><creatorcontrib>Morishige, Kenichirou</creatorcontrib><creatorcontrib>Hayashi, Masami</creatorcontrib><creatorcontrib>Sawada, Kenjiro</creatorcontrib><creatorcontrib>Ito, Kimihiko</creatorcontrib><creatorcontrib>Terai, Yoshito</creatorcontrib><creatorcontrib>Nishio, Yukihiro</creatorcontrib><creatorcontrib>Klein-Szanto, Andres J</creatorcontrib><creatorcontrib>Burger, Robert A</creatorcontrib><creatorcontrib>Ohmichi, Masahide</creatorcontrib><creatorcontrib>Testa, Joseph R</creatorcontrib><creatorcontrib>Kimura, Tadashi</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular cancer therapeutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mabuchi, Seiji</au><au>Kawase, Chiaki</au><au>Altomare, Deborah A</au><au>Morishige, Kenichirou</au><au>Hayashi, Masami</au><au>Sawada, Kenjiro</au><au>Ito, Kimihiko</au><au>Terai, Yoshito</au><au>Nishio, Yukihiro</au><au>Klein-Szanto, Andres J</au><au>Burger, Robert A</au><au>Ohmichi, Masahide</au><au>Testa, Joseph R</au><au>Kimura, Tadashi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Vascular endothelial growth factor is a promising therapeutic target for the treatment of clear cell carcinoma of the ovary</atitle><jtitle>Molecular cancer therapeutics</jtitle><addtitle>Mol Cancer Ther</addtitle><date>2010-08</date><risdate>2010</risdate><volume>9</volume><issue>8</issue><spage>2411</spage><epage>2422</epage><pages>2411-2422</pages><issn>1535-7163</issn><eissn>1538-8514</eissn><abstract>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.</abstract><cop>United States</cop><pmid>20663925</pmid><doi>10.1158/1535-7163.MCT-10-0169</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record>
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subjects Adenocarcinoma, Clear Cell - pathology
Adenocarcinoma, Clear Cell - therapy
Angiogenesis Inhibitors - pharmacology
Animals
Antibodies, Monoclonal - pharmacology
Antibodies, Monoclonal, Humanized
Bevacizumab
Cell Line, Tumor
Cell Proliferation - drug effects
Cisplatin - pharmacology
Cystadenocarcinoma, Serous - pathology
Cystadenocarcinoma, Serous - therapy
Drug Resistance, Neoplasm - drug effects
Female
Humans
Mice
Mice, Nude
Ovarian Neoplasms - pathology
Ovarian Neoplasms - therapy
Vascular Endothelial Growth Factors - biosynthesis
Vascular Endothelial Growth Factors - metabolism
Xenograft Model Antitumor Assays
title Vascular endothelial growth factor is a promising therapeutic target for the treatment of clear cell carcinoma of the ovary
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