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 |
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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. 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.</description><identifier>ISSN: 1535-7163</identifier><identifier>EISSN: 1538-8514</identifier><identifier>DOI: 10.1158/1535-7163.MCT-10-0169</identifier><identifier>PMID: 20663925</identifier><language>eng</language><publisher>United States</publisher><subject>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</subject><ispartof>Molecular cancer therapeutics, 2010-08, Vol.9 (8), p.2411-2422</ispartof><rights>(c) 2010 AACR.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c421t-5897f63a7761de27eb655d62ab1ff05fa24d923021e2695ee65c3202cbbecc3c3</citedby><cites>FETCH-LOGICAL-c421t-5897f63a7761de27eb655d62ab1ff05fa24d923021e2695ee65c3202cbbecc3c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,3343,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20663925$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><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><title>Vascular endothelial growth factor is a promising therapeutic target for the treatment of clear cell carcinoma of the ovary</title><title>Molecular cancer therapeutics</title><addtitle>Mol Cancer Ther</addtitle><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.</description><subject>Adenocarcinoma, Clear Cell - pathology</subject><subject>Adenocarcinoma, Clear Cell - therapy</subject><subject>Angiogenesis Inhibitors - pharmacology</subject><subject>Animals</subject><subject>Antibodies, Monoclonal - pharmacology</subject><subject>Antibodies, Monoclonal, Humanized</subject><subject>Bevacizumab</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - drug effects</subject><subject>Cisplatin - pharmacology</subject><subject>Cystadenocarcinoma, Serous - pathology</subject><subject>Cystadenocarcinoma, Serous - therapy</subject><subject>Drug Resistance, Neoplasm - drug effects</subject><subject>Female</subject><subject>Humans</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Ovarian Neoplasms - pathology</subject><subject>Ovarian Neoplasms - therapy</subject><subject>Vascular Endothelial Growth Factors - biosynthesis</subject><subject>Vascular Endothelial Growth Factors - metabolism</subject><subject>Xenograft Model Antitumor Assays</subject><issn>1535-7163</issn><issn>1538-8514</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kMtOwzAQRS0EglL4BJB3rAJ-xE6yRBUvCcSmsI0cZ9wGJXGxHRDi57FpYeXR1ZnxzEHojJJLSkV5RQUXWUElv3xaLDNKMkJltYdmMS-zUtB8_7feMkfo2Ps3QmhZMXqIjhiRkldMzND3q_J66pXDMLY2rKHvVI9Xzn6GNTZKB-tw57HCG2eHznfjCkfIqQ1ModM4KLeCgE2kYoyDAxUGGAO2Buse4lgNfY-1crob7aBSnkD7odzXCTowqvdwunvn6OX2Zrm4zx6f7x4W14-ZzhkNmSirwkiuikLSFlgBjRSilUw11BgijGJ5WzFOGAUmKwEgheaMMN00oDXXfI4utnPjDe8T-FDHS9JeagQ7-brIy4rLnMhIii2pnfXegak3rhviqjUlddJeJ6V1UlpH7SlN2mPf-e6HqRmg_e_688x_AP7VgHc</recordid><startdate>201008</startdate><enddate>201008</enddate><creator>Mabuchi, Seiji</creator><creator>Kawase, Chiaki</creator><creator>Altomare, Deborah A</creator><creator>Morishige, Kenichirou</creator><creator>Hayashi, Masami</creator><creator>Sawada, Kenjiro</creator><creator>Ito, Kimihiko</creator><creator>Terai, Yoshito</creator><creator>Nishio, Yukihiro</creator><creator>Klein-Szanto, Andres J</creator><creator>Burger, Robert A</creator><creator>Ohmichi, Masahide</creator><creator>Testa, Joseph R</creator><creator>Kimura, Tadashi</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>201008</creationdate><title>Vascular endothelial growth factor is a promising therapeutic target for the treatment of clear cell carcinoma of the ovary</title><author>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</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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