Increased dihydropyrimidine dehydrogenase activity in breast cancer

Background and Objectives Although studies have focused on modulating the bioavailability of 5‐FU through inhibition of dihydropyrimidine dehydrogenase (DPD) to improve efficacy of the drug, activity of this enzyme in breast cancer has not been thoroughly examined. We measured DPD activity in primar...

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Veröffentlicht in:Journal of surgical oncology 2003-03, Vol.82 (3), p.174-179
Hauptverfasser: Anan, Keisei, Mitsuyama, Shoshu, Tamae, Keiyoshi, Suehara, Nobuhiro, Nishihara, Kazuyoshi, Ogawa, Yoshiaki, Abe, Yuji, Iwashita, Toshimitsu, Toyoshima, Satoshi
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container_issue 3
container_start_page 174
container_title Journal of surgical oncology
container_volume 82
creator Anan, Keisei
Mitsuyama, Shoshu
Tamae, Keiyoshi
Suehara, Nobuhiro
Nishihara, Kazuyoshi
Ogawa, Yoshiaki
Abe, Yuji
Iwashita, Toshimitsu
Toyoshima, Satoshi
description Background and Objectives Although studies have focused on modulating the bioavailability of 5‐FU through inhibition of dihydropyrimidine dehydrogenase (DPD) to improve efficacy of the drug, activity of this enzyme in breast cancer has not been thoroughly examined. We measured DPD activity in primary and metastatic lesions and benign breast tumors to evaluate the clinical significance of this enzyme in the treatment of breast cancer. Methods DPD activity was measured by catalytic assay and compared in 100 primary tumors (95 invasive carcinomas, 5 intraductal carcinomas), 26 uninvolved adjacent breast tissue specimens, 6 metastatic sites, and 7 intraductal papillomas. Results The enzyme level in the carcinomas was 4‐fold that of adjacent uninvolved breast tissues (101 vs 23 pmol/min/mg protein, P 
doi_str_mv 10.1002/jso.10212
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We measured DPD activity in primary and metastatic lesions and benign breast tumors to evaluate the clinical significance of this enzyme in the treatment of breast cancer. Methods DPD activity was measured by catalytic assay and compared in 100 primary tumors (95 invasive carcinomas, 5 intraductal carcinomas), 26 uninvolved adjacent breast tissue specimens, 6 metastatic sites, and 7 intraductal papillomas. Results The enzyme level in the carcinomas was 4‐fold that of adjacent uninvolved breast tissues (101 vs 23 pmol/min/mg protein, P &lt; 0.001). Enzyme activity in intraductal papilloma (120 pmol/min/mg protein) was comparable to that in invasive carcinoma. There were no significant differences in DPD activity related to clinicopathologic features, but a tendency toward increased DPD activity was observed in progesterone receptor‐negative breast cancer (P = 0.09). There was marginal correlation in enzyme activity between primary and metastatic lesions (P = 0.07). Conclusions DPD activity is substantially upregulated in breast cancer tissue and is higher than that reported previously. The clinical implications of DPD inhibitors in patients being treated for breast cancer with oral fluoropyrimidine chemotherapy should be further investigated. J. Surg. Oncol. 2003;82:174–179. © 2003 Wiley‐Liss, Inc.</description><identifier>ISSN: 0022-4790</identifier><identifier>EISSN: 1096-9098</identifier><identifier>DOI: 10.1002/jso.10212</identifier><identifier>PMID: 12619061</identifier><identifier>CODEN: JSONAU</identifier><language>eng</language><publisher>New York: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>5-FU ; Adult ; Aged ; Antimetabolites, Antineoplastic - pharmacology ; Biological and medical sciences ; Breast Neoplasms - drug therapy ; Breast Neoplasms - enzymology ; Carcinoma, Ductal, Breast - drug therapy ; Carcinoma, Ductal, Breast - enzymology ; Carcinoma, Intraductal, Noninfiltrating - drug therapy ; Carcinoma, Intraductal, Noninfiltrating - enzymology ; Catalysis ; Dihydrouracil Dehydrogenase (NADP) ; Female ; fluoropyrimidine ; Fluorouracil - pharmacology ; Gynecology. Andrology. Obstetrics ; Humans ; Mammary gland diseases ; Medical sciences ; Middle Aged ; oral agent ; Oxidoreductases - pharmacology ; Prospective Studies ; third-line chemotherapy ; Tumors ; Up-Regulation</subject><ispartof>Journal of surgical oncology, 2003-03, Vol.82 (3), p.174-179</ispartof><rights>Copyright © 2003 Wiley‐Liss, Inc.</rights><rights>2003 INIST-CNRS</rights><rights>Copyright 2003 Wiley-Liss, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3892-53c257ff5aafbeca8a8875d52f62234041310a21caf038636f0b0e725ef78443</citedby><cites>FETCH-LOGICAL-c3892-53c257ff5aafbeca8a8875d52f62234041310a21caf038636f0b0e725ef78443</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjso.10212$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjso.10212$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=14610621$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12619061$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Anan, Keisei</creatorcontrib><creatorcontrib>Mitsuyama, Shoshu</creatorcontrib><creatorcontrib>Tamae, Keiyoshi</creatorcontrib><creatorcontrib>Suehara, Nobuhiro</creatorcontrib><creatorcontrib>Nishihara, Kazuyoshi</creatorcontrib><creatorcontrib>Ogawa, Yoshiaki</creatorcontrib><creatorcontrib>Abe, Yuji</creatorcontrib><creatorcontrib>Iwashita, Toshimitsu</creatorcontrib><creatorcontrib>Toyoshima, Satoshi</creatorcontrib><title>Increased dihydropyrimidine dehydrogenase activity in breast cancer</title><title>Journal of surgical oncology</title><addtitle>J. Surg. Oncol</addtitle><description>Background and Objectives Although studies have focused on modulating the bioavailability of 5‐FU through inhibition of dihydropyrimidine dehydrogenase (DPD) to improve efficacy of the drug, activity of this enzyme in breast cancer has not been thoroughly examined. We measured DPD activity in primary and metastatic lesions and benign breast tumors to evaluate the clinical significance of this enzyme in the treatment of breast cancer. Methods DPD activity was measured by catalytic assay and compared in 100 primary tumors (95 invasive carcinomas, 5 intraductal carcinomas), 26 uninvolved adjacent breast tissue specimens, 6 metastatic sites, and 7 intraductal papillomas. Results The enzyme level in the carcinomas was 4‐fold that of adjacent uninvolved breast tissues (101 vs 23 pmol/min/mg protein, P &lt; 0.001). Enzyme activity in intraductal papilloma (120 pmol/min/mg protein) was comparable to that in invasive carcinoma. There were no significant differences in DPD activity related to clinicopathologic features, but a tendency toward increased DPD activity was observed in progesterone receptor‐negative breast cancer (P = 0.09). There was marginal correlation in enzyme activity between primary and metastatic lesions (P = 0.07). Conclusions DPD activity is substantially upregulated in breast cancer tissue and is higher than that reported previously. The clinical implications of DPD inhibitors in patients being treated for breast cancer with oral fluoropyrimidine chemotherapy should be further investigated. J. Surg. 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Obstetrics</subject><subject>Humans</subject><subject>Mammary gland diseases</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>oral agent</subject><subject>Oxidoreductases - pharmacology</subject><subject>Prospective Studies</subject><subject>third-line chemotherapy</subject><subject>Tumors</subject><subject>Up-Regulation</subject><issn>0022-4790</issn><issn>1096-9098</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kD1PwzAQhi0EoqUw8AdQFgaGwNmOnWREFYRWFR2ohMRiOY4NLm1a2eEj_x63KXRiutPd897Hi9A5hmsMQG7mfhUSgskB6mPIeZxDnh2ifuiROElz6KET7-cAkOc8OUY9TDjOgeM-Go5q5bT0uooq-9ZWbrVunV3aytY6qvS28qrrAERSNfbTNm1k66jcaJpIyVppd4qOjFx4fbaLAzS7v5sNH-LJtBgNbyexollOYkYVYakxTEpTaiUzmWUpqxgxnBCaQIIpBkmwkgZoxik3UIJOCdMmzZKEDtBVN1a5lfdOG7EOl0rXCgxi44MIPoitD4G96Nj1R7nU1Z7cPR6Ayx0gvZIL48In1u-5hGPgZMPddNyXXej2_41i_DT9XR13Cusb_f2nkO5d8JSmTDw_FoIVQz4eFy8C6A8wr4Ms</recordid><startdate>200303</startdate><enddate>200303</enddate><creator>Anan, Keisei</creator><creator>Mitsuyama, Shoshu</creator><creator>Tamae, Keiyoshi</creator><creator>Suehara, Nobuhiro</creator><creator>Nishihara, Kazuyoshi</creator><creator>Ogawa, Yoshiaki</creator><creator>Abe, Yuji</creator><creator>Iwashita, Toshimitsu</creator><creator>Toyoshima, Satoshi</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley-Liss</general><scope>BSCLL</scope><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></search><sort><creationdate>200303</creationdate><title>Increased dihydropyrimidine dehydrogenase activity in breast cancer</title><author>Anan, Keisei ; Mitsuyama, Shoshu ; Tamae, Keiyoshi ; Suehara, Nobuhiro ; Nishihara, Kazuyoshi ; Ogawa, Yoshiaki ; Abe, Yuji ; Iwashita, Toshimitsu ; Toyoshima, Satoshi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3892-53c257ff5aafbeca8a8875d52f62234041310a21caf038636f0b0e725ef78443</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>5-FU</topic><topic>Adult</topic><topic>Aged</topic><topic>Antimetabolites, Antineoplastic - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Breast Neoplasms - drug therapy</topic><topic>Breast Neoplasms - enzymology</topic><topic>Carcinoma, Ductal, Breast - drug therapy</topic><topic>Carcinoma, Ductal, Breast - enzymology</topic><topic>Carcinoma, Intraductal, Noninfiltrating - drug therapy</topic><topic>Carcinoma, Intraductal, Noninfiltrating - enzymology</topic><topic>Catalysis</topic><topic>Dihydrouracil Dehydrogenase (NADP)</topic><topic>Female</topic><topic>fluoropyrimidine</topic><topic>Fluorouracil - pharmacology</topic><topic>Gynecology. Andrology. Obstetrics</topic><topic>Humans</topic><topic>Mammary gland diseases</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>oral agent</topic><topic>Oxidoreductases - pharmacology</topic><topic>Prospective Studies</topic><topic>third-line chemotherapy</topic><topic>Tumors</topic><topic>Up-Regulation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Anan, Keisei</creatorcontrib><creatorcontrib>Mitsuyama, Shoshu</creatorcontrib><creatorcontrib>Tamae, Keiyoshi</creatorcontrib><creatorcontrib>Suehara, Nobuhiro</creatorcontrib><creatorcontrib>Nishihara, Kazuyoshi</creatorcontrib><creatorcontrib>Ogawa, Yoshiaki</creatorcontrib><creatorcontrib>Abe, Yuji</creatorcontrib><creatorcontrib>Iwashita, Toshimitsu</creatorcontrib><creatorcontrib>Toyoshima, Satoshi</creatorcontrib><collection>Istex</collection><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><jtitle>Journal of surgical oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Anan, Keisei</au><au>Mitsuyama, Shoshu</au><au>Tamae, Keiyoshi</au><au>Suehara, Nobuhiro</au><au>Nishihara, Kazuyoshi</au><au>Ogawa, Yoshiaki</au><au>Abe, Yuji</au><au>Iwashita, Toshimitsu</au><au>Toyoshima, Satoshi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Increased dihydropyrimidine dehydrogenase activity in breast cancer</atitle><jtitle>Journal of surgical oncology</jtitle><addtitle>J. Surg. Oncol</addtitle><date>2003-03</date><risdate>2003</risdate><volume>82</volume><issue>3</issue><spage>174</spage><epage>179</epage><pages>174-179</pages><issn>0022-4790</issn><eissn>1096-9098</eissn><coden>JSONAU</coden><abstract>Background and Objectives Although studies have focused on modulating the bioavailability of 5‐FU through inhibition of dihydropyrimidine dehydrogenase (DPD) to improve efficacy of the drug, activity of this enzyme in breast cancer has not been thoroughly examined. We measured DPD activity in primary and metastatic lesions and benign breast tumors to evaluate the clinical significance of this enzyme in the treatment of breast cancer. Methods DPD activity was measured by catalytic assay and compared in 100 primary tumors (95 invasive carcinomas, 5 intraductal carcinomas), 26 uninvolved adjacent breast tissue specimens, 6 metastatic sites, and 7 intraductal papillomas. Results The enzyme level in the carcinomas was 4‐fold that of adjacent uninvolved breast tissues (101 vs 23 pmol/min/mg protein, P &lt; 0.001). Enzyme activity in intraductal papilloma (120 pmol/min/mg protein) was comparable to that in invasive carcinoma. There were no significant differences in DPD activity related to clinicopathologic features, but a tendency toward increased DPD activity was observed in progesterone receptor‐negative breast cancer (P = 0.09). There was marginal correlation in enzyme activity between primary and metastatic lesions (P = 0.07). Conclusions DPD activity is substantially upregulated in breast cancer tissue and is higher than that reported previously. The clinical implications of DPD inhibitors in patients being treated for breast cancer with oral fluoropyrimidine chemotherapy should be further investigated. J. Surg. Oncol. 2003;82:174–179. © 2003 Wiley‐Liss, Inc.</abstract><cop>New York</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>12619061</pmid><doi>10.1002/jso.10212</doi><tpages>6</tpages></addata></record>
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subjects 5-FU
Adult
Aged
Antimetabolites, Antineoplastic - pharmacology
Biological and medical sciences
Breast Neoplasms - drug therapy
Breast Neoplasms - enzymology
Carcinoma, Ductal, Breast - drug therapy
Carcinoma, Ductal, Breast - enzymology
Carcinoma, Intraductal, Noninfiltrating - drug therapy
Carcinoma, Intraductal, Noninfiltrating - enzymology
Catalysis
Dihydrouracil Dehydrogenase (NADP)
Female
fluoropyrimidine
Fluorouracil - pharmacology
Gynecology. Andrology. Obstetrics
Humans
Mammary gland diseases
Medical sciences
Middle Aged
oral agent
Oxidoreductases - pharmacology
Prospective Studies
third-line chemotherapy
Tumors
Up-Regulation
title Increased dihydropyrimidine dehydrogenase activity in breast cancer
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