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A Change in Promoter Methylation of hMLH1 is a Cause of Acquired Resistance to Platinum-based Chemotherapy in Epithelial Ovarian Cancer
Background: Acquired resistance to platinum-based chemotherapy (Pt-chemo) is a major problem for improving the prognosis for patients with advanced epithelial ovarian cancer (EOC). However, the molecular mechanism of acquired resistance to Pt-chemo is not well understood. Materials and Methods: hMLH...
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| Published in: | Anticancer research 2007-05, Vol.27 (3B), p.1449-1452 |
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| container_end_page | 1452 |
| container_issue | 3B |
| container_start_page | 1449 |
| container_title | Anticancer research |
| container_volume | 27 |
| creator | WATANABE, Yoh UEDA, Haruhiko ETOH, Tomomaro KOIKE, Eiji FUJINAMI, Nahoko MITSUHASHI, Akiyo HOSHIAI, Hiroshi |
| description | Background: Acquired resistance to platinum-based chemotherapy (Pt-chemo) is a major problem for improving the prognosis for
patients with advanced epithelial ovarian cancer (EOC). However, the molecular mechanism of acquired resistance to Pt-chemo
is not well understood. Materials and Methods: hMLH1 promoter methylation (hMLH1 MET) and hMLH1 protein expression was examined
in 36 paired samples of primary and secondary resected tumors by methylation-specific polymerase chain reaction (PCR). Results:
No primary tumors exhibited hMLH1 MET, while 56.3% of secondary tumors showed hMLH1 MET. Moreover, no significant correlation
was observed between hMLH1 MET and histological subtype, while hMLH1 MET was significantly greater (p |
| format | article |
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patients with advanced epithelial ovarian cancer (EOC). However, the molecular mechanism of acquired resistance to Pt-chemo
is not well understood. Materials and Methods: hMLH1 promoter methylation (hMLH1 MET) and hMLH1 protein expression was examined
in 36 paired samples of primary and secondary resected tumors by methylation-specific polymerase chain reaction (PCR). Results:
No primary tumors exhibited hMLH1 MET, while 56.3% of secondary tumors showed hMLH1 MET. Moreover, no significant correlation
was observed between hMLH1 MET and histological subtype, while hMLH1 MET was significantly greater (p<0.001) in partially
responsive secondary tumors compared with no change or progressive disease, and hMLH1 MET also occurred more frequently (p=0.059)
in tumors treated with four or more courses of Pt-chemo. Conclusion: A change in hMLH1 MET is a major molecular cause of acquired
resistance to Pt-chemo in EOC.</description><identifier>ISSN: 0250-7005</identifier><identifier>EISSN: 1791-7530</identifier><identifier>PMID: 17595760</identifier><language>eng</language><publisher>Attiki: International Institute of Anticancer Research</publisher><subject>Adaptor Proteins, Signal Transducing - genetics ; Adult ; Aged ; Antineoplastic Agents - therapeutic use ; Biological and medical sciences ; Carcinoma - drug therapy ; DNA - analysis ; DNA - metabolism ; DNA Methylation - drug effects ; Drug Resistance, Neoplasm - genetics ; Female ; Female genital diseases ; Gynecology. Andrology. Obstetrics ; Humans ; Male ; Medical sciences ; Microsatellite Repeats ; Middle Aged ; MutL Protein Homolog 1 ; Nuclear Proteins - genetics ; Ovarian Neoplasms - drug therapy ; Platinum Compounds - therapeutic use ; Promoter Regions, Genetic ; Sequence Analysis, DNA ; Tumors</subject><ispartof>Anticancer research, 2007-05, Vol.27 (3B), p.1449-1452</ispartof><rights>2007 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18853773$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17595760$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>WATANABE, Yoh</creatorcontrib><creatorcontrib>UEDA, Haruhiko</creatorcontrib><creatorcontrib>ETOH, Tomomaro</creatorcontrib><creatorcontrib>KOIKE, Eiji</creatorcontrib><creatorcontrib>FUJINAMI, Nahoko</creatorcontrib><creatorcontrib>MITSUHASHI, Akiyo</creatorcontrib><creatorcontrib>HOSHIAI, Hiroshi</creatorcontrib><title>A Change in Promoter Methylation of hMLH1 is a Cause of Acquired Resistance to Platinum-based Chemotherapy in Epithelial Ovarian Cancer</title><title>Anticancer research</title><addtitle>Anticancer Res</addtitle><description>Background: Acquired resistance to platinum-based chemotherapy (Pt-chemo) is a major problem for improving the prognosis for
patients with advanced epithelial ovarian cancer (EOC). However, the molecular mechanism of acquired resistance to Pt-chemo
is not well understood. Materials and Methods: hMLH1 promoter methylation (hMLH1 MET) and hMLH1 protein expression was examined
in 36 paired samples of primary and secondary resected tumors by methylation-specific polymerase chain reaction (PCR). Results:
No primary tumors exhibited hMLH1 MET, while 56.3% of secondary tumors showed hMLH1 MET. Moreover, no significant correlation
was observed between hMLH1 MET and histological subtype, while hMLH1 MET was significantly greater (p<0.001) in partially
responsive secondary tumors compared with no change or progressive disease, and hMLH1 MET also occurred more frequently (p=0.059)
in tumors treated with four or more courses of Pt-chemo. Conclusion: A change in hMLH1 MET is a major molecular cause of acquired
resistance to Pt-chemo in EOC.</description><subject>Adaptor Proteins, Signal Transducing - genetics</subject><subject>Adult</subject><subject>Aged</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Carcinoma - drug therapy</subject><subject>DNA - analysis</subject><subject>DNA - metabolism</subject><subject>DNA Methylation - drug effects</subject><subject>Drug Resistance, Neoplasm - genetics</subject><subject>Female</subject><subject>Female genital diseases</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Humans</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Microsatellite Repeats</subject><subject>Middle Aged</subject><subject>MutL Protein Homolog 1</subject><subject>Nuclear Proteins - genetics</subject><subject>Ovarian Neoplasms - drug therapy</subject><subject>Platinum Compounds - therapeutic use</subject><subject>Promoter Regions, Genetic</subject><subject>Sequence Analysis, DNA</subject><subject>Tumors</subject><issn>0250-7005</issn><issn>1791-7530</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><recordid>eNqFkMtO3EAQRS2UiBkev4B6k-wsdbvdr-XEIoA0I1AEa6tsl3Gj9oNuO2i-gN-mR0zEMqtSVZ26V3VPkjVThqVKcPotWdNM0FRRKlbJWQgvlEppND9NVkwJI5Sk6-R9Q4oOhmckdiAPfuzHGT3Z4dztHcx2HMjYkm63vWXEBgKkgCXgYbapXxfrsSF_MNgww1AjmUfycLgalj6tIMRl0WFU7NDDtD84XE82ds6CI_d_wVsYomI89RfJ9xZcwMtjPU-efl8_Frfp9v7mrths045TNqetBpmxnKNuBOccqdBKZVWlK2ZkKzPkjQQjKk2lYrypVY25xtrklZFAm5afJz8_dSc_vi4Y5rK3oUbnYMBxCaWiUigh5X9BZlRuODcRvDqCS9VjU07e9uD35b-MI_DjCECowbU-PmzDF6e14ErxL8fOPndvMdsy9OBclOUl-EyV_FfJ8mj6AcNIkvM</recordid><startdate>20070501</startdate><enddate>20070501</enddate><creator>WATANABE, Yoh</creator><creator>UEDA, Haruhiko</creator><creator>ETOH, Tomomaro</creator><creator>KOIKE, Eiji</creator><creator>FUJINAMI, Nahoko</creator><creator>MITSUHASHI, Akiyo</creator><creator>HOSHIAI, Hiroshi</creator><general>International Institute of Anticancer Research</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7TM</scope><scope>7X8</scope></search><sort><creationdate>20070501</creationdate><title>A Change in Promoter Methylation of hMLH1 is a Cause of Acquired Resistance to Platinum-based Chemotherapy in Epithelial Ovarian Cancer</title><author>WATANABE, Yoh ; UEDA, Haruhiko ; ETOH, Tomomaro ; KOIKE, Eiji ; FUJINAMI, Nahoko ; MITSUHASHI, Akiyo ; HOSHIAI, Hiroshi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h301t-f8a62143e8d5333e058772bb8b196f62e3d6a95b806713dc7ce48ec94b96a0df3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Adaptor Proteins, Signal Transducing - genetics</topic><topic>Adult</topic><topic>Aged</topic><topic>Antineoplastic Agents - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Carcinoma - drug therapy</topic><topic>DNA - analysis</topic><topic>DNA - metabolism</topic><topic>DNA Methylation - drug effects</topic><topic>Drug Resistance, Neoplasm - genetics</topic><topic>Female</topic><topic>Female genital diseases</topic><topic>Gynecology. Andrology. Obstetrics</topic><topic>Humans</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Microsatellite Repeats</topic><topic>Middle Aged</topic><topic>MutL Protein Homolog 1</topic><topic>Nuclear Proteins - genetics</topic><topic>Ovarian Neoplasms - drug therapy</topic><topic>Platinum Compounds - therapeutic use</topic><topic>Promoter Regions, Genetic</topic><topic>Sequence Analysis, DNA</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>WATANABE, Yoh</creatorcontrib><creatorcontrib>UEDA, Haruhiko</creatorcontrib><creatorcontrib>ETOH, Tomomaro</creatorcontrib><creatorcontrib>KOIKE, Eiji</creatorcontrib><creatorcontrib>FUJINAMI, Nahoko</creatorcontrib><creatorcontrib>MITSUHASHI, Akiyo</creatorcontrib><creatorcontrib>HOSHIAI, Hiroshi</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>Nucleic Acids Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Anticancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>WATANABE, Yoh</au><au>UEDA, Haruhiko</au><au>ETOH, Tomomaro</au><au>KOIKE, Eiji</au><au>FUJINAMI, Nahoko</au><au>MITSUHASHI, Akiyo</au><au>HOSHIAI, Hiroshi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Change in Promoter Methylation of hMLH1 is a Cause of Acquired Resistance to Platinum-based Chemotherapy in Epithelial Ovarian Cancer</atitle><jtitle>Anticancer research</jtitle><addtitle>Anticancer Res</addtitle><date>2007-05-01</date><risdate>2007</risdate><volume>27</volume><issue>3B</issue><spage>1449</spage><epage>1452</epage><pages>1449-1452</pages><issn>0250-7005</issn><eissn>1791-7530</eissn><abstract>Background: Acquired resistance to platinum-based chemotherapy (Pt-chemo) is a major problem for improving the prognosis for
patients with advanced epithelial ovarian cancer (EOC). However, the molecular mechanism of acquired resistance to Pt-chemo
is not well understood. Materials and Methods: hMLH1 promoter methylation (hMLH1 MET) and hMLH1 protein expression was examined
in 36 paired samples of primary and secondary resected tumors by methylation-specific polymerase chain reaction (PCR). Results:
No primary tumors exhibited hMLH1 MET, while 56.3% of secondary tumors showed hMLH1 MET. Moreover, no significant correlation
was observed between hMLH1 MET and histological subtype, while hMLH1 MET was significantly greater (p<0.001) in partially
responsive secondary tumors compared with no change or progressive disease, and hMLH1 MET also occurred more frequently (p=0.059)
in tumors treated with four or more courses of Pt-chemo. Conclusion: A change in hMLH1 MET is a major molecular cause of acquired
resistance to Pt-chemo in EOC.</abstract><cop>Attiki</cop><pub>International Institute of Anticancer Research</pub><pmid>17595760</pmid><tpages>4</tpages></addata></record> |
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| subjects | Adaptor Proteins, Signal Transducing - genetics Adult Aged Antineoplastic Agents - therapeutic use Biological and medical sciences Carcinoma - drug therapy DNA - analysis DNA - metabolism DNA Methylation - drug effects Drug Resistance, Neoplasm - genetics Female Female genital diseases Gynecology. Andrology. Obstetrics Humans Male Medical sciences Microsatellite Repeats Middle Aged MutL Protein Homolog 1 Nuclear Proteins - genetics Ovarian Neoplasms - drug therapy Platinum Compounds - therapeutic use Promoter Regions, Genetic Sequence Analysis, DNA Tumors |
| title | A Change in Promoter Methylation of hMLH1 is a Cause of Acquired Resistance to Platinum-based Chemotherapy in Epithelial Ovarian Cancer |
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