Therapeutic potential of stem cells expressing suicide genes that selectively target human breast cancer cells: Evidence that they exert tumoricidal effects via tumor tropism
Identifieur interne : 000C46 ( Pmc/Curation ); précédent : 000C45; suivant : 000C47Therapeutic potential of stem cells expressing suicide genes that selectively target human breast cancer cells: Evidence that they exert tumoricidal effects via tumor tropism
Auteurs : Bo-Rim Yi [Corée du Sud] ; Kelvin J. Choi ; Seung U. Kim [Canada, Corée du Sud] ; Kyung-Chul Choi [Corée du Sud]Source :
- International Journal of Oncology [ 1019-6439 ] ; 2012.
Abstract
Breast cancer is the most prevalent cancer in women worldwide and is classified into ductal and lobular carcinoma. Breast cancer as well as lobular carcinoma is associated with various risk factors such as gender, age, female hormone exposure, ethnicity, family history and genetic risk factor-associated genes. Genes associated with a high risk of developing breast cancer include
Url:
DOI: 10.3892/ijo.2012.1523
PubMed: 22736197
PubMed Central: 3582792
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<author><name sortKey="Choi, Kyung Chul" sort="Choi, Kyung Chul" uniqKey="Choi K" first="Kyung-Chul" last="Choi">Kyung-Chul Choi</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Therapeutic potential of stem cells expressing suicide genes that selectively target human breast cancer cells: Evidence that they exert tumoricidal effects via tumor tropism</title>
<author><name sortKey="Yi, Bo Rim" sort="Yi, Bo Rim" uniqKey="Yi B" first="Bo-Rim" last="Yi">Bo-Rim Yi</name>
<affiliation wicri:level="1"><nlm:aff id="af1-ijo-41-03-0798">Laboratory of Veterinary Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk,<country>Republic of Korea</country>
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<country xml:lang="fr">Corée du Sud</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author><name sortKey="Choi, Kelvin J" sort="Choi, Kelvin J" uniqKey="Choi K" first="Kelvin J." last="Choi">Kelvin J. Choi</name>
<affiliation><nlm:aff wicri:cut=" and" id="af2-ijo-41-03-0798">Departments of Chemistry</nlm:aff>
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<author><name sortKey="Kim, Seung U" sort="Kim, Seung U" uniqKey="Kim S" first="Seung U." last="Kim">Seung U. Kim</name>
<affiliation wicri:level="1"><nlm:aff id="af3-ijo-41-03-0798">Medicine, University of British Columbia, Vancouver, British Columbia,<country>Canada</country>
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<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<affiliation wicri:level="1"><nlm:aff id="af4-ijo-41-03-0798">Medical Research Institute, Chung-Ang University College of Medicine, Seoul,<country>Republic of Korea</country>
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<country xml:lang="fr">Corée du Sud</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author><name sortKey="Choi, Kyung Chul" sort="Choi, Kyung Chul" uniqKey="Choi K" first="Kyung-Chul" last="Choi">Kyung-Chul Choi</name>
<affiliation wicri:level="1"><nlm:aff id="af1-ijo-41-03-0798">Laboratory of Veterinary Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk,<country>Republic of Korea</country>
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<country xml:lang="fr">Corée du Sud</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<series><title level="j">International Journal of Oncology</title>
<idno type="ISSN">1019-6439</idno>
<idno type="eISSN">1791-2423</idno>
<imprint><date when="2012">2012</date>
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<front><div type="abstract" xml:lang="en"><p>Breast cancer is the most prevalent cancer in women worldwide and is classified into ductal and lobular carcinoma. Breast cancer as well as lobular carcinoma is associated with various risk factors such as gender, age, female hormone exposure, ethnicity, family history and genetic risk factor-associated genes. Genes associated with a high risk of developing breast cancer include <italic>BRCA1</italic>
, <italic>BRCA2</italic>
, <italic>p53</italic>
, <italic>PTEN</italic>
, <italic>CHEK2</italic>
and <italic>ATM</italic>
. Surgery, chemotherapy, radiotherapy and hormone therapy are used to treat breast cancer but these therapies, except for surgery, have many side-effects such as alopecia, anesthesia, diarrhea and arthralgia. Gene-directed enzyme/prodrug therapy (GEPT) or suicide gene therapy, may improve the therapeutic efficacy of conventional cancer radiotherapy and chemotherapy without side-effects. GEPT most often involves the use of a viral vector to deliver a gene not found in mammalian cells and that produces enzymes which can convert a relatively non-toxic prodrug into a toxic agent. Examples of these systems include cytosine deaminase/5-fluorocytosine (CD/5-FC), carboxyl esterase/irinotecan (CE/CPT-11), and thymidine kinase/ganciclovir (TK/GCV). Recently, therapies based on genetically engineered stem cells (GESTECs) using a GEPT system have received a great deal of attention for their clinical and therapeutic potential to treat breast cancer. In this review, we discuss the potential of GESTECs via tumor tropism effects and therapeutic efficacy against several different types of cancer cells. GESTECs represent a useful tool for treating breast cancer without inducing injuries associated with conventional therapeutic modalities.</p>
</div>
</front>
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</TEI>
<pmc article-type="review-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Int J Oncol</journal-id>
<journal-id journal-id-type="iso-abbrev">Int. J. Oncol</journal-id>
<journal-id journal-id-type="publisher-id">IJO</journal-id>
<journal-title-group><journal-title>International Journal of Oncology</journal-title>
</journal-title-group>
<issn pub-type="ppub">1019-6439</issn>
<issn pub-type="epub">1791-2423</issn>
<publisher><publisher-name>D.A. Spandidos</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">22736197</article-id>
<article-id pub-id-type="pmc">3582792</article-id>
<article-id pub-id-type="doi">10.3892/ijo.2012.1523</article-id>
<article-id pub-id-type="publisher-id">ijo-41-03-0798</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Review</subject>
</subj-group>
</article-categories>
<title-group><article-title>Therapeutic potential of stem cells expressing suicide genes that selectively target human breast cancer cells: Evidence that they exert tumoricidal effects via tumor tropism</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>YI</surname>
<given-names>BO-RIM</given-names>
</name>
<xref ref-type="aff" rid="af1-ijo-41-03-0798"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>CHOI</surname>
<given-names>KELVIN J.</given-names>
</name>
<xref ref-type="aff" rid="af2-ijo-41-03-0798"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>KIM</surname>
<given-names>SEUNG U.</given-names>
</name>
<xref ref-type="aff" rid="af3-ijo-41-03-0798"><sup>3</sup>
</xref>
<xref ref-type="aff" rid="af4-ijo-41-03-0798"><sup>4</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>CHOI</surname>
<given-names>KYUNG-CHUL</given-names>
</name>
<xref ref-type="aff" rid="af1-ijo-41-03-0798"><sup>1</sup>
</xref>
<xref ref-type="corresp" rid="c1-ijo-41-03-0798"></xref>
</contrib>
</contrib-group>
<aff id="af1-ijo-41-03-0798"><label>1</label>
Laboratory of Veterinary Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk,<country>Republic of Korea</country>
;</aff>
<aff id="af2-ijo-41-03-0798"><label>2</label>
Departments of Chemistry and</aff>
<aff id="af3-ijo-41-03-0798"><label>3</label>
Medicine, University of British Columbia, Vancouver, British Columbia,<country>Canada</country>
;</aff>
<aff id="af4-ijo-41-03-0798"><label>4</label>
Medical Research Institute, Chung-Ang University College of Medicine, Seoul,<country>Republic of Korea</country>
</aff>
<author-notes><corresp id="c1-ijo-41-03-0798">Correspondence to: Professor Kyung-Chul Choi, Laboratory of Veterinary Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 361-763, Republic of Korea, E-mail: <email>kchoi@cbu.ac.kr</email>
</corresp>
</author-notes>
<pub-date pub-type="collection"><month>9</month>
<year>2012</year>
</pub-date>
<pub-date pub-type="epub"><day>20</day>
<month>6</month>
<year>2012</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>20</day>
<month>6</month>
<year>2012</year>
</pub-date>
<pmc-comment> PMC Release delay is 0 months and 0 days and was based on the
. </pmc-comment>
<volume>41</volume>
<issue>3</issue>
<fpage>798</fpage>
<lpage>804</lpage>
<history><date date-type="received"><day>21</day>
<month>3</month>
<year>2012</year>
</date>
<date date-type="accepted"><day>30</day>
<month>5</month>
<year>2012</year>
</date>
</history>
<permissions><copyright-statement>Copyright © 2012, Spandidos Publications</copyright-statement>
<copyright-year>2012</copyright-year>
<license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/3.0"><license-p>This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.</license-p>
</license>
</permissions>
<abstract><p>Breast cancer is the most prevalent cancer in women worldwide and is classified into ductal and lobular carcinoma. Breast cancer as well as lobular carcinoma is associated with various risk factors such as gender, age, female hormone exposure, ethnicity, family history and genetic risk factor-associated genes. Genes associated with a high risk of developing breast cancer include <italic>BRCA1</italic>
, <italic>BRCA2</italic>
, <italic>p53</italic>
, <italic>PTEN</italic>
, <italic>CHEK2</italic>
and <italic>ATM</italic>
. Surgery, chemotherapy, radiotherapy and hormone therapy are used to treat breast cancer but these therapies, except for surgery, have many side-effects such as alopecia, anesthesia, diarrhea and arthralgia. Gene-directed enzyme/prodrug therapy (GEPT) or suicide gene therapy, may improve the therapeutic efficacy of conventional cancer radiotherapy and chemotherapy without side-effects. GEPT most often involves the use of a viral vector to deliver a gene not found in mammalian cells and that produces enzymes which can convert a relatively non-toxic prodrug into a toxic agent. Examples of these systems include cytosine deaminase/5-fluorocytosine (CD/5-FC), carboxyl esterase/irinotecan (CE/CPT-11), and thymidine kinase/ganciclovir (TK/GCV). Recently, therapies based on genetically engineered stem cells (GESTECs) using a GEPT system have received a great deal of attention for their clinical and therapeutic potential to treat breast cancer. In this review, we discuss the potential of GESTECs via tumor tropism effects and therapeutic efficacy against several different types of cancer cells. GESTECs represent a useful tool for treating breast cancer without inducing injuries associated with conventional therapeutic modalities.</p>
</abstract>
<kwd-group><kwd>gene-direct enzyme/prodrug therapy</kwd>
<kwd>stem cell therapy</kwd>
<kwd>cytosine deaminase</kwd>
<kwd>carboxyl esterase</kwd>
<kwd>thymidine kinase</kwd>
<kwd>breast cancer</kwd>
</kwd-group>
</article-meta>
</front>
<floats-group><fig id="f1-ijo-41-03-0798" orientation="portrait" position="float"><label>Figure 1</label>
<caption><p>Schematic of genetically engineered stem cell (GESTEC)-based therapy. GESTECs are immortalized by retroviral vectors and contain suicide genes such as ones encoding cytosine deaminase (CD), carboxyl esterase (CE), and thymidine kinase (TK). CD converts the prodrug 5-fluorocytosine (5-FC) into a toxic agent, 5-fluorouracil (5-FU), which inhibits RNA and DNA synthesis. CPT-11 is a prodrug converted by CE into its active form, SN-38, which is a potent mammalian topoisomerase I inhibitor. Finally, the TK gene is found in herpes simplex virus (HSV). The product of this gene converts non-toxic ganciclovir into its toxic active form. These GESTECs exert tumor-tropism effects and may be used to treat several types of tumors.</p>
</caption>
<graphic xlink:href="IJO-41-03-0798-g00"></graphic>
</fig>
</floats-group>
</pmc>
</record>
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