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 |
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container_title | Journal of surgical oncology |
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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 |
format | Article |
fullrecord | <record><control><sourceid>istex_cross</sourceid><recordid>TN_cdi_crossref_primary_10_1002_jso_10212</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>ark_67375_WNG_5GC6JJGZ_0</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3892-53c257ff5aafbeca8a8875d52f62234041310a21caf038636f0b0e725ef78443</originalsourceid><addsrcrecordid>eNp1kD1PwzAQhi0EoqUw8AdQFgaGwNmOnWREFYRWFR2ohMRiOY4NLm1a2eEj_x63KXRiutPd897Hi9A5hmsMQG7mfhUSgskB6mPIeZxDnh2ifuiROElz6KET7-cAkOc8OUY9TDjOgeM-Go5q5bT0uooq-9ZWbrVunV3aytY6qvS28qrrAERSNfbTNm1k66jcaJpIyVppd4qOjFx4fbaLAzS7v5sNH-LJtBgNbyexollOYkYVYakxTEpTaiUzmWUpqxgxnBCaQIIpBkmwkgZoxik3UIJOCdMmzZKEDtBVN1a5lfdOG7EOl0rXCgxi44MIPoitD4G96Nj1R7nU1Z7cPR6Ayx0gvZIL48In1u-5hGPgZMPddNyXXej2_41i_DT9XR13Cusb_f2nkO5d8JSmTDw_FoIVQz4eFy8C6A8wr4Ms</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Increased dihydropyrimidine dehydrogenase activity in breast cancer</title><source>MEDLINE</source><source>Access via Wiley Online Library</source><creator>Anan, Keisei ; Mitsuyama, Shoshu ; Tamae, Keiyoshi ; Suehara, Nobuhiro ; Nishihara, Kazuyoshi ; Ogawa, Yoshiaki ; Abe, Yuji ; Iwashita, Toshimitsu ; Toyoshima, Satoshi</creator><creatorcontrib>Anan, Keisei ; Mitsuyama, Shoshu ; Tamae, Keiyoshi ; Suehara, Nobuhiro ; Nishihara, Kazuyoshi ; Ogawa, Yoshiaki ; Abe, Yuji ; Iwashita, Toshimitsu ; Toyoshima, Satoshi</creatorcontrib><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 < 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&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 < 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><subject>5-FU</subject><subject>Adult</subject><subject>Aged</subject><subject>Antimetabolites, Antineoplastic - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Breast Neoplasms - drug therapy</subject><subject>Breast Neoplasms - enzymology</subject><subject>Carcinoma, Ductal, Breast - drug therapy</subject><subject>Carcinoma, Ductal, Breast - enzymology</subject><subject>Carcinoma, Intraductal, Noninfiltrating - drug therapy</subject><subject>Carcinoma, Intraductal, Noninfiltrating - enzymology</subject><subject>Catalysis</subject><subject>Dihydrouracil Dehydrogenase (NADP)</subject><subject>Female</subject><subject>fluoropyrimidine</subject><subject>Fluorouracil - pharmacology</subject><subject>Gynecology. Andrology. 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 < 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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