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Overexpression of the Centrosomal Protein Aurora-A Kinase is Associated with Poor Prognosis in Epithelial Ovarian Cancer Patients
Purpose: To assess the clinical significance of Aurora-A kinase, a centrosome-regulating serine-threonine kinase, in ovarian carcinoma. Experimental Design: Aurora-A kinase expression was assessed by Western blot (cell lines) or immunohistochemistry (high-grade epithelial ovarian cancers), and clini...
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| Published in: | Clinical cancer research 2007-07, Vol.13 (14), p.4098-4104 |
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| container_title | Clinical cancer research |
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| creator | LANDEN, Charles N LIN, Yvonne G IMMANENI, Anand DEAVERS, Michael T MERRITT, William M SPANNUTH, Whitney A BODURKA, Diane C GERSHENSON, David M BRINKLEY, William R SOOD, Anil K |
| description | Purpose: To assess the clinical significance of Aurora-A kinase, a centrosome-regulating serine-threonine kinase, in ovarian carcinoma.
Experimental Design: Aurora-A kinase expression was assessed by Western blot (cell lines) or immunohistochemistry (high-grade epithelial ovarian
cancers), and clinical variables were collected by retrospective chart review. Centrosome amplification was assessed by immunofluorescence
in cell lines, and by immunohistochemistry in patient samples.
Results: All ovarian cancer cell lines exhibited significant Aurora-A kinase protein overexpression, and all except A2780-par had
centrosome amplification, a characteristic of mitotic dysregulation leading to genomic instability. Fifty-eight of 70 patient
samples (82.8%) exhibited Aurora-A kinase overexpression compared with normal ovarian surface epithelium. High Aurora-A kinase
expression was strongly associated with supernumerary centrosome count in tumor cells ( P < 0.001). Tumors with the greatest Aurora-A overexpression ( n = 24) had decreased patient survival (median survival, 1.44 versus 2.81 years; P = 0.01). High Aurora-A expression and suboptimal surgical cytoreduction remained predictors of poor survival ( P < 0.05) by multivariate analysis.
Conclusions: Aurora-A kinase is overexpressed by a substantial proportion of ovarian cancers and is associated with centrosome amplification
and poor survival. It may be a useful prognostic marker and target in ovarian cancer. |
| doi_str_mv | 10.1158/1078-0432.CCR-07-0431 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_70699463</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>70699463</sourcerecordid><originalsourceid>FETCH-LOGICAL-c423t-72c3819ea12754e3aefb849e4509a33ee49be391b8d2c2a85d6caabf78c00c413</originalsourceid><addsrcrecordid>eNpFkc1u1DAUhS1ERX_gEUDeUKmLFDu2Y3s5isqPqDQVgrV147lpjDLxYGdaWPLmdZhBXfnI_u490mdC3nJ2zbkyHzjTpmJS1Ndt-61iesn8BTnjSulK1I16WfJ_5pSc5_yTMS45k6_IKdeNkEqoM_J3_YAJf-8S5hziRGNP5wFpi9OcYo5bGOldijOGia72KSaoVvRrmCAjDZmuco4-wIwb-hjmgd7FmBb-foq5PJehm125xzGUPesHSAEm2sLksWAwh9KSX5OTHsaMb47nBfnx8eZ7-7m6XX_60q5uKy9rMVe69sJwi8BrrSQKwL4z0qJUzIIQiNJ2KCzvzKb2NRi1aTxA12vjGfOSiwtyedi7S_HXHvPstiF7HEeYMO6z06yxVjaigOoA-mIgJ-zdLoUtpD-OM7e4d4tXt3h1xb1jeslLwbtjwb7b4uZ56ii7AO-PAGQPY5-KiJCfOWO1YYIV7urADeF-eAwJnf-nrPwRQvKD48Jx6SSzRjwBWEGc0g</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>70699463</pqid></control><display><type>article</type><title>Overexpression of the Centrosomal Protein Aurora-A Kinase is Associated with Poor Prognosis in Epithelial Ovarian Cancer Patients</title><source>Freely Accessible Science Journals - check A-Z of ejournals</source><creator>LANDEN, Charles N ; LIN, Yvonne G ; IMMANENI, Anand ; DEAVERS, Michael T ; MERRITT, William M ; SPANNUTH, Whitney A ; BODURKA, Diane C ; GERSHENSON, David M ; BRINKLEY, William R ; SOOD, Anil K</creator><creatorcontrib>LANDEN, Charles N ; LIN, Yvonne G ; IMMANENI, Anand ; DEAVERS, Michael T ; MERRITT, William M ; SPANNUTH, Whitney A ; BODURKA, Diane C ; GERSHENSON, David M ; BRINKLEY, William R ; SOOD, Anil K</creatorcontrib><description>Purpose: To assess the clinical significance of Aurora-A kinase, a centrosome-regulating serine-threonine kinase, in ovarian carcinoma.
Experimental Design: Aurora-A kinase expression was assessed by Western blot (cell lines) or immunohistochemistry (high-grade epithelial ovarian
cancers), and clinical variables were collected by retrospective chart review. Centrosome amplification was assessed by immunofluorescence
in cell lines, and by immunohistochemistry in patient samples.
Results: All ovarian cancer cell lines exhibited significant Aurora-A kinase protein overexpression, and all except A2780-par had
centrosome amplification, a characteristic of mitotic dysregulation leading to genomic instability. Fifty-eight of 70 patient
samples (82.8%) exhibited Aurora-A kinase overexpression compared with normal ovarian surface epithelium. High Aurora-A kinase
expression was strongly associated with supernumerary centrosome count in tumor cells ( P < 0.001). Tumors with the greatest Aurora-A overexpression ( n = 24) had decreased patient survival (median survival, 1.44 versus 2.81 years; P = 0.01). High Aurora-A expression and suboptimal surgical cytoreduction remained predictors of poor survival ( P < 0.05) by multivariate analysis.
Conclusions: Aurora-A kinase is overexpressed by a substantial proportion of ovarian cancers and is associated with centrosome amplification
and poor survival. It may be a useful prognostic marker and target in ovarian cancer.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>DOI: 10.1158/1078-0432.CCR-07-0431</identifier><identifier>PMID: 17634535</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Antineoplastic agents ; Antineoplastic Agents - therapeutic use ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Aurora Kinases ; Aurora-A kinase ; Biological and medical sciences ; Cell Line, Tumor ; centrosome ; Centrosome - enzymology ; Centrosome - pathology ; clinical correlation ; Female ; Female genital diseases ; Gynecology. Andrology. Obstetrics ; Humans ; Immunohistochemistry ; Medical sciences ; Middle Aged ; Neoplasm Staging ; ovarian cancer ; Ovarian Neoplasms - drug therapy ; Ovarian Neoplasms - enzymology ; Ovarian Neoplasms - mortality ; Ovarian Neoplasms - pathology ; Pharmacology. Drug treatments ; Prognosis ; Protein-Serine-Threonine Kinases - genetics ; Survival Analysis ; Tumors</subject><ispartof>Clinical cancer research, 2007-07, Vol.13 (14), p.4098-4104</ispartof><rights>2007 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c423t-72c3819ea12754e3aefb849e4509a33ee49be391b8d2c2a85d6caabf78c00c413</citedby><cites>FETCH-LOGICAL-c423t-72c3819ea12754e3aefb849e4509a33ee49be391b8d2c2a85d6caabf78c00c413</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18978030$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17634535$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>LANDEN, Charles N</creatorcontrib><creatorcontrib>LIN, Yvonne G</creatorcontrib><creatorcontrib>IMMANENI, Anand</creatorcontrib><creatorcontrib>DEAVERS, Michael T</creatorcontrib><creatorcontrib>MERRITT, William M</creatorcontrib><creatorcontrib>SPANNUTH, Whitney A</creatorcontrib><creatorcontrib>BODURKA, Diane C</creatorcontrib><creatorcontrib>GERSHENSON, David M</creatorcontrib><creatorcontrib>BRINKLEY, William R</creatorcontrib><creatorcontrib>SOOD, Anil K</creatorcontrib><title>Overexpression of the Centrosomal Protein Aurora-A Kinase is Associated with Poor Prognosis in Epithelial Ovarian Cancer Patients</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>Purpose: To assess the clinical significance of Aurora-A kinase, a centrosome-regulating serine-threonine kinase, in ovarian carcinoma.
Experimental Design: Aurora-A kinase expression was assessed by Western blot (cell lines) or immunohistochemistry (high-grade epithelial ovarian
cancers), and clinical variables were collected by retrospective chart review. Centrosome amplification was assessed by immunofluorescence
in cell lines, and by immunohistochemistry in patient samples.
Results: All ovarian cancer cell lines exhibited significant Aurora-A kinase protein overexpression, and all except A2780-par had
centrosome amplification, a characteristic of mitotic dysregulation leading to genomic instability. Fifty-eight of 70 patient
samples (82.8%) exhibited Aurora-A kinase overexpression compared with normal ovarian surface epithelium. High Aurora-A kinase
expression was strongly associated with supernumerary centrosome count in tumor cells ( P < 0.001). Tumors with the greatest Aurora-A overexpression ( n = 24) had decreased patient survival (median survival, 1.44 versus 2.81 years; P = 0.01). High Aurora-A expression and suboptimal surgical cytoreduction remained predictors of poor survival ( P < 0.05) by multivariate analysis.
Conclusions: Aurora-A kinase is overexpressed by a substantial proportion of ovarian cancers and is associated with centrosome amplification
and poor survival. It may be a useful prognostic marker and target in ovarian cancer.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Antineoplastic agents</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Aurora Kinases</subject><subject>Aurora-A kinase</subject><subject>Biological and medical sciences</subject><subject>Cell Line, Tumor</subject><subject>centrosome</subject><subject>Centrosome - enzymology</subject><subject>Centrosome - pathology</subject><subject>clinical correlation</subject><subject>Female</subject><subject>Female genital diseases</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Neoplasm Staging</subject><subject>ovarian cancer</subject><subject>Ovarian Neoplasms - drug therapy</subject><subject>Ovarian Neoplasms - enzymology</subject><subject>Ovarian Neoplasms - mortality</subject><subject>Ovarian Neoplasms - pathology</subject><subject>Pharmacology. Drug treatments</subject><subject>Prognosis</subject><subject>Protein-Serine-Threonine Kinases - genetics</subject><subject>Survival Analysis</subject><subject>Tumors</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><recordid>eNpFkc1u1DAUhS1ERX_gEUDeUKmLFDu2Y3s5isqPqDQVgrV147lpjDLxYGdaWPLmdZhBXfnI_u490mdC3nJ2zbkyHzjTpmJS1Ndt-61iesn8BTnjSulK1I16WfJ_5pSc5_yTMS45k6_IKdeNkEqoM_J3_YAJf-8S5hziRGNP5wFpi9OcYo5bGOldijOGia72KSaoVvRrmCAjDZmuco4-wIwb-hjmgd7FmBb-foq5PJehm125xzGUPesHSAEm2sLksWAwh9KSX5OTHsaMb47nBfnx8eZ7-7m6XX_60q5uKy9rMVe69sJwi8BrrSQKwL4z0qJUzIIQiNJ2KCzvzKb2NRi1aTxA12vjGfOSiwtyedi7S_HXHvPstiF7HEeYMO6z06yxVjaigOoA-mIgJ-zdLoUtpD-OM7e4d4tXt3h1xb1jeslLwbtjwb7b4uZ56ii7AO-PAGQPY5-KiJCfOWO1YYIV7urADeF-eAwJnf-nrPwRQvKD48Jx6SSzRjwBWEGc0g</recordid><startdate>20070715</startdate><enddate>20070715</enddate><creator>LANDEN, Charles N</creator><creator>LIN, Yvonne G</creator><creator>IMMANENI, Anand</creator><creator>DEAVERS, Michael T</creator><creator>MERRITT, William M</creator><creator>SPANNUTH, Whitney A</creator><creator>BODURKA, Diane C</creator><creator>GERSHENSON, David M</creator><creator>BRINKLEY, William R</creator><creator>SOOD, Anil K</creator><general>American Association for Cancer Research</general><scope>IQODW</scope><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>20070715</creationdate><title>Overexpression of the Centrosomal Protein Aurora-A Kinase is Associated with Poor Prognosis in Epithelial Ovarian Cancer Patients</title><author>LANDEN, Charles N ; LIN, Yvonne G ; IMMANENI, Anand ; DEAVERS, Michael T ; MERRITT, William M ; SPANNUTH, Whitney A ; BODURKA, Diane C ; GERSHENSON, David M ; BRINKLEY, William R ; SOOD, Anil K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c423t-72c3819ea12754e3aefb849e4509a33ee49be391b8d2c2a85d6caabf78c00c413</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Antineoplastic agents</topic><topic>Antineoplastic Agents - therapeutic use</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Aurora Kinases</topic><topic>Aurora-A kinase</topic><topic>Biological and medical sciences</topic><topic>Cell Line, Tumor</topic><topic>centrosome</topic><topic>Centrosome - enzymology</topic><topic>Centrosome - pathology</topic><topic>clinical correlation</topic><topic>Female</topic><topic>Female genital diseases</topic><topic>Gynecology. Andrology. Obstetrics</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Neoplasm Staging</topic><topic>ovarian cancer</topic><topic>Ovarian Neoplasms - drug therapy</topic><topic>Ovarian Neoplasms - enzymology</topic><topic>Ovarian Neoplasms - mortality</topic><topic>Ovarian Neoplasms - pathology</topic><topic>Pharmacology. Drug treatments</topic><topic>Prognosis</topic><topic>Protein-Serine-Threonine Kinases - genetics</topic><topic>Survival Analysis</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>LANDEN, Charles N</creatorcontrib><creatorcontrib>LIN, Yvonne G</creatorcontrib><creatorcontrib>IMMANENI, Anand</creatorcontrib><creatorcontrib>DEAVERS, Michael T</creatorcontrib><creatorcontrib>MERRITT, William M</creatorcontrib><creatorcontrib>SPANNUTH, Whitney A</creatorcontrib><creatorcontrib>BODURKA, Diane C</creatorcontrib><creatorcontrib>GERSHENSON, David M</creatorcontrib><creatorcontrib>BRINKLEY, William R</creatorcontrib><creatorcontrib>SOOD, Anil K</creatorcontrib><collection>Pascal-Francis</collection><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>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>LANDEN, Charles N</au><au>LIN, Yvonne G</au><au>IMMANENI, Anand</au><au>DEAVERS, Michael T</au><au>MERRITT, William M</au><au>SPANNUTH, Whitney A</au><au>BODURKA, Diane C</au><au>GERSHENSON, David M</au><au>BRINKLEY, William R</au><au>SOOD, Anil K</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Overexpression of the Centrosomal Protein Aurora-A Kinase is Associated with Poor Prognosis in Epithelial Ovarian Cancer Patients</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2007-07-15</date><risdate>2007</risdate><volume>13</volume><issue>14</issue><spage>4098</spage><epage>4104</epage><pages>4098-4104</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><abstract>Purpose: To assess the clinical significance of Aurora-A kinase, a centrosome-regulating serine-threonine kinase, in ovarian carcinoma.
Experimental Design: Aurora-A kinase expression was assessed by Western blot (cell lines) or immunohistochemistry (high-grade epithelial ovarian
cancers), and clinical variables were collected by retrospective chart review. Centrosome amplification was assessed by immunofluorescence
in cell lines, and by immunohistochemistry in patient samples.
Results: All ovarian cancer cell lines exhibited significant Aurora-A kinase protein overexpression, and all except A2780-par had
centrosome amplification, a characteristic of mitotic dysregulation leading to genomic instability. Fifty-eight of 70 patient
samples (82.8%) exhibited Aurora-A kinase overexpression compared with normal ovarian surface epithelium. High Aurora-A kinase
expression was strongly associated with supernumerary centrosome count in tumor cells ( P < 0.001). Tumors with the greatest Aurora-A overexpression ( n = 24) had decreased patient survival (median survival, 1.44 versus 2.81 years; P = 0.01). High Aurora-A expression and suboptimal surgical cytoreduction remained predictors of poor survival ( P < 0.05) by multivariate analysis.
Conclusions: Aurora-A kinase is overexpressed by a substantial proportion of ovarian cancers and is associated with centrosome amplification
and poor survival. It may be a useful prognostic marker and target in ovarian cancer.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>17634535</pmid><doi>10.1158/1078-0432.CCR-07-0431</doi><tpages>7</tpages></addata></record> |
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| source | Freely Accessible Science Journals - check A-Z of ejournals |
| subjects | Adult Aged Aged, 80 and over Antineoplastic agents Antineoplastic Agents - therapeutic use Antineoplastic Combined Chemotherapy Protocols - therapeutic use Aurora Kinases Aurora-A kinase Biological and medical sciences Cell Line, Tumor centrosome Centrosome - enzymology Centrosome - pathology clinical correlation Female Female genital diseases Gynecology. Andrology. Obstetrics Humans Immunohistochemistry Medical sciences Middle Aged Neoplasm Staging ovarian cancer Ovarian Neoplasms - drug therapy Ovarian Neoplasms - enzymology Ovarian Neoplasms - mortality Ovarian Neoplasms - pathology Pharmacology. Drug treatments Prognosis Protein-Serine-Threonine Kinases - genetics Survival Analysis Tumors |
| title | Overexpression of the Centrosomal Protein Aurora-A Kinase is Associated with Poor Prognosis in Epithelial Ovarian Cancer Patients |
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