Exogenous cytosine deaminase gene expression in Bifidobacterium breve I-53-8w for tumor-targeting enzyme/prodrug therapy
Bifidobacteria are nonpathogenic, anaerobic domestic bacteria with health-promoting properties for the host. In our previous study, Bifidobacterium longum (B. longum) were found to be localized selectively and to proliferate within solid tumors after systemic application. Additionally, B. longum tra...
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Veröffentlicht in: | Bioscience, biotechnology, and biochemistry biotechnology, and biochemistry, 2007-12, Vol.71 (12), p.2921-2926 |
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creator | Hidaka, Ayumi Hamaji, Yoshinori Sasaki, Takayuki Taniguchi, Shun'ichiro Fujimori, Minoru |
description | Bifidobacteria are nonpathogenic, anaerobic domestic bacteria with health-promoting properties for the host. In our previous study, Bifidobacterium longum (B. longum) were found to be localized selectively and to proliferate within solid tumors after systemic application. Additionally, B. longum transformed by shuttle-plasmid including the cytosine deaminase (CD) gene expressed active CD, converted the prodrug 5-fluorocytosine (5-FC) to 5-fluorouracil (5-FU). We also demonstrated antitumor efficacy with a transformant of B. longum in rats. In this study, we found that Bifidobacterium breve (B. breve), the smallest species of human-derived bifidobacterium, expressed the exogenous transgene (CD), that CD enzymatic activity in the transformant of B. breve was much higher, and that the segregational stability of the plasmid was greater than that of B. longum. Thus, numerous transformants of B. breve were detected solely in the tumors after systemic administration. We consider the transformant of B. breve to be more beneficial in our enzyme/prodrug therapy. |
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In our previous study, Bifidobacterium longum (B. longum) were found to be localized selectively and to proliferate within solid tumors after systemic application. Additionally, B. longum transformed by shuttle-plasmid including the cytosine deaminase (CD) gene expressed active CD, converted the prodrug 5-fluorocytosine (5-FC) to 5-fluorouracil (5-FU). We also demonstrated antitumor efficacy with a transformant of B. longum in rats. In this study, we found that Bifidobacterium breve (B. breve), the smallest species of human-derived bifidobacterium, expressed the exogenous transgene (CD), that CD enzymatic activity in the transformant of B. breve was much higher, and that the segregational stability of the plasmid was greater than that of B. longum. Thus, numerous transformants of B. breve were detected solely in the tumors after systemic administration. We consider the transformant of B. breve to be more beneficial in our enzyme/prodrug therapy.</description><identifier>EISSN: 1347-6947</identifier><identifier>PMID: 18159091</identifier><language>eng</language><publisher>England</publisher><subject>Animals ; Antineoplastic Agents - metabolism ; Antineoplastic Agents - pharmacology ; Bifidobacterium - genetics ; Bifidobacterium - metabolism ; Cell Line, Tumor ; Cytosine Deaminase - genetics ; Cytosine Deaminase - metabolism ; Drug Delivery Systems ; Flucytosine - metabolism ; Flucytosine - therapeutic use ; Fluorouracil - metabolism ; Humans ; Lung Neoplasms - drug therapy ; Lung Neoplasms - microbiology ; Male ; Mice ; Mice, Inbred C57BL ; Neoplasm Transplantation ; Plasmids ; Prodrugs - metabolism ; Prodrugs - therapeutic use ; Transplantation, Heterologous</subject><ispartof>Bioscience, biotechnology, and biochemistry, 2007-12, Vol.71 (12), p.2921-2926</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18159091$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hidaka, Ayumi</creatorcontrib><creatorcontrib>Hamaji, Yoshinori</creatorcontrib><creatorcontrib>Sasaki, Takayuki</creatorcontrib><creatorcontrib>Taniguchi, Shun'ichiro</creatorcontrib><creatorcontrib>Fujimori, Minoru</creatorcontrib><title>Exogenous cytosine deaminase gene expression in Bifidobacterium breve I-53-8w for tumor-targeting enzyme/prodrug therapy</title><title>Bioscience, biotechnology, and biochemistry</title><addtitle>Biosci Biotechnol Biochem</addtitle><description>Bifidobacteria are nonpathogenic, anaerobic domestic bacteria with health-promoting properties for the host. In our previous study, Bifidobacterium longum (B. longum) were found to be localized selectively and to proliferate within solid tumors after systemic application. Additionally, B. longum transformed by shuttle-plasmid including the cytosine deaminase (CD) gene expressed active CD, converted the prodrug 5-fluorocytosine (5-FC) to 5-fluorouracil (5-FU). We also demonstrated antitumor efficacy with a transformant of B. longum in rats. In this study, we found that Bifidobacterium breve (B. breve), the smallest species of human-derived bifidobacterium, expressed the exogenous transgene (CD), that CD enzymatic activity in the transformant of B. breve was much higher, and that the segregational stability of the plasmid was greater than that of B. longum. Thus, numerous transformants of B. breve were detected solely in the tumors after systemic administration. We consider the transformant of B. breve to be more beneficial in our enzyme/prodrug therapy.</description><subject>Animals</subject><subject>Antineoplastic Agents - metabolism</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Bifidobacterium - genetics</subject><subject>Bifidobacterium - metabolism</subject><subject>Cell Line, Tumor</subject><subject>Cytosine Deaminase - genetics</subject><subject>Cytosine Deaminase - metabolism</subject><subject>Drug Delivery Systems</subject><subject>Flucytosine - metabolism</subject><subject>Flucytosine - therapeutic use</subject><subject>Fluorouracil - metabolism</subject><subject>Humans</subject><subject>Lung Neoplasms - drug therapy</subject><subject>Lung Neoplasms - microbiology</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Neoplasm Transplantation</subject><subject>Plasmids</subject><subject>Prodrugs - metabolism</subject><subject>Prodrugs - therapeutic use</subject><subject>Transplantation, Heterologous</subject><issn>1347-6947</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo1kFFLwzAUhYMgbk7_guTJt2CyNGnzqGPqYODL3kva3tTImtQk1dVfb8DJfbgczsc9nHuBlowXJZGqKBfoOsYPSqligl2hBauYUFks0Wl78j04P0XczslH6wB3oAfrdAScHcBwGgPEaL3D1uEna2znG90mCHYacBPgC_COCE6qb2x8wGkafCBJhx6SdT0G9zMP8DAG34Wpx-kdgh7nG3Rp9DHC7Xmv0OF5e9i8kv3by27zuCejKBjpqBSGCdM2XLRUKMFArNelLspKC91IbhSALgqQtGGtEdLkXgxYyajiLM8K3f-dzfGfE8RUDza2cDxqB7l0LRWtZMV5Bu_O4NQM0NVjsIMOc_3_Kv4L7Mll1A</recordid><startdate>200712</startdate><enddate>200712</enddate><creator>Hidaka, Ayumi</creator><creator>Hamaji, Yoshinori</creator><creator>Sasaki, Takayuki</creator><creator>Taniguchi, Shun'ichiro</creator><creator>Fujimori, Minoru</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>200712</creationdate><title>Exogenous cytosine deaminase gene expression in Bifidobacterium breve I-53-8w for tumor-targeting enzyme/prodrug therapy</title><author>Hidaka, Ayumi ; Hamaji, Yoshinori ; Sasaki, Takayuki ; Taniguchi, Shun'ichiro ; Fujimori, Minoru</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p541-d065f15fcb35c05951e5227a478a5ab63f9eea44e60b1cf56f5901e1710931313</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Animals</topic><topic>Antineoplastic Agents - metabolism</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Bifidobacterium - genetics</topic><topic>Bifidobacterium - metabolism</topic><topic>Cell Line, Tumor</topic><topic>Cytosine Deaminase - genetics</topic><topic>Cytosine Deaminase - metabolism</topic><topic>Drug Delivery Systems</topic><topic>Flucytosine - metabolism</topic><topic>Flucytosine - therapeutic use</topic><topic>Fluorouracil - metabolism</topic><topic>Humans</topic><topic>Lung Neoplasms - drug therapy</topic><topic>Lung Neoplasms - microbiology</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Neoplasm Transplantation</topic><topic>Plasmids</topic><topic>Prodrugs - metabolism</topic><topic>Prodrugs - therapeutic use</topic><topic>Transplantation, Heterologous</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hidaka, Ayumi</creatorcontrib><creatorcontrib>Hamaji, Yoshinori</creatorcontrib><creatorcontrib>Sasaki, Takayuki</creatorcontrib><creatorcontrib>Taniguchi, Shun'ichiro</creatorcontrib><creatorcontrib>Fujimori, Minoru</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Bioscience, biotechnology, and biochemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hidaka, Ayumi</au><au>Hamaji, Yoshinori</au><au>Sasaki, Takayuki</au><au>Taniguchi, Shun'ichiro</au><au>Fujimori, Minoru</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Exogenous cytosine deaminase gene expression in Bifidobacterium breve I-53-8w for tumor-targeting enzyme/prodrug therapy</atitle><jtitle>Bioscience, biotechnology, and biochemistry</jtitle><addtitle>Biosci Biotechnol Biochem</addtitle><date>2007-12</date><risdate>2007</risdate><volume>71</volume><issue>12</issue><spage>2921</spage><epage>2926</epage><pages>2921-2926</pages><eissn>1347-6947</eissn><abstract>Bifidobacteria are nonpathogenic, anaerobic domestic bacteria with health-promoting properties for the host. In our previous study, Bifidobacterium longum (B. longum) were found to be localized selectively and to proliferate within solid tumors after systemic application. Additionally, B. longum transformed by shuttle-plasmid including the cytosine deaminase (CD) gene expressed active CD, converted the prodrug 5-fluorocytosine (5-FC) to 5-fluorouracil (5-FU). We also demonstrated antitumor efficacy with a transformant of B. longum in rats. In this study, we found that Bifidobacterium breve (B. breve), the smallest species of human-derived bifidobacterium, expressed the exogenous transgene (CD), that CD enzymatic activity in the transformant of B. breve was much higher, and that the segregational stability of the plasmid was greater than that of B. longum. Thus, numerous transformants of B. breve were detected solely in the tumors after systemic administration. We consider the transformant of B. breve to be more beneficial in our enzyme/prodrug therapy.</abstract><cop>England</cop><pmid>18159091</pmid><tpages>6</tpages></addata></record> |
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subjects | Animals Antineoplastic Agents - metabolism Antineoplastic Agents - pharmacology Bifidobacterium - genetics Bifidobacterium - metabolism Cell Line, Tumor Cytosine Deaminase - genetics Cytosine Deaminase - metabolism Drug Delivery Systems Flucytosine - metabolism Flucytosine - therapeutic use Fluorouracil - metabolism Humans Lung Neoplasms - drug therapy Lung Neoplasms - microbiology Male Mice Mice, Inbred C57BL Neoplasm Transplantation Plasmids Prodrugs - metabolism Prodrugs - therapeutic use Transplantation, Heterologous |
title | Exogenous cytosine deaminase gene expression in Bifidobacterium breve I-53-8w for tumor-targeting enzyme/prodrug therapy |
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