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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Biological Ablation of Sentinel Lymph Node Metastasis in Submucosally Invaded Early Gastrointestinal Cancer</title>
<author><name sortKey="Kikuchi, Satoru" sort="Kikuchi, Satoru" uniqKey="Kikuchi S" first="Satoru" last="Kikuchi">Satoru Kikuchi</name>
<affiliation><nlm:aff id="aff1"><institution>Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences</institution>
, Okayama,<country>Japan</country>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kishimoto, Hiroyuki" sort="Kishimoto, Hiroyuki" uniqKey="Kishimoto H" first="Hiroyuki" last="Kishimoto">Hiroyuki Kishimoto</name>
<affiliation><nlm:aff id="aff1"><institution>Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences</institution>
, Okayama,<country>Japan</country>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Tazawa, Hiroshi" sort="Tazawa, Hiroshi" uniqKey="Tazawa H" first="Hiroshi" last="Tazawa">Hiroshi Tazawa</name>
<affiliation><nlm:aff id="aff1"><institution>Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences</institution>
, Okayama,<country>Japan</country>
</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff2"><institution>Center for Innovative Clinical Medicine, Okayama University Hospital</institution>
, Okayama,<country>Japan</country>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Hashimoto, Yuuri" sort="Hashimoto, Yuuri" uniqKey="Hashimoto Y" first="Yuuri" last="Hashimoto">Yuuri Hashimoto</name>
<affiliation><nlm:aff id="aff1"><institution>Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences</institution>
, Okayama,<country>Japan</country>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kuroda, Shinji" sort="Kuroda, Shinji" uniqKey="Kuroda S" first="Shinji" last="Kuroda">Shinji Kuroda</name>
<affiliation><nlm:aff id="aff1"><institution>Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences</institution>
, Okayama,<country>Japan</country>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Nishizaki, Masahiko" sort="Nishizaki, Masahiko" uniqKey="Nishizaki M" first="Masahiko" last="Nishizaki">Masahiko Nishizaki</name>
<affiliation><nlm:aff id="aff1"><institution>Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences</institution>
, Okayama,<country>Japan</country>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Nagasaka, Takeshi" sort="Nagasaka, Takeshi" uniqKey="Nagasaka T" first="Takeshi" last="Nagasaka">Takeshi Nagasaka</name>
<affiliation><nlm:aff id="aff1"><institution>Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences</institution>
, Okayama,<country>Japan</country>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Shirakawa, Yasuhiro" sort="Shirakawa, Yasuhiro" uniqKey="Shirakawa Y" first="Yasuhiro" last="Shirakawa">Yasuhiro Shirakawa</name>
<affiliation><nlm:aff id="aff1"><institution>Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences</institution>
, Okayama,<country>Japan</country>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kagawa, Shunsuke" sort="Kagawa, Shunsuke" uniqKey="Kagawa S" first="Shunsuke" last="Kagawa">Shunsuke Kagawa</name>
<affiliation><nlm:aff id="aff1"><institution>Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences</institution>
, Okayama,<country>Japan</country>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Urata, Yasuo" sort="Urata, Yasuo" uniqKey="Urata Y" first="Yasuo" last="Urata">Yasuo Urata</name>
<affiliation><nlm:aff id="aff3"><institution>Oncolys BioPharma, Inc.</institution>
, Tokyo,<country>Japan</country>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Hoffman, Robert M" sort="Hoffman, Robert M" uniqKey="Hoffman R" first="Robert M" last="Hoffman">Robert M. Hoffman</name>
<affiliation><nlm:aff id="aff4"><institution>Department of Surgery, University of California</institution>
, San Diego, California,<country>USA</country>
</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff5"><institution>AntiCancer, Inc.</institution>
, San Diego, California,<country>USA</country>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Fujiwara, Toshiyoshi" sort="Fujiwara, Toshiyoshi" uniqKey="Fujiwara T" first="Toshiyoshi" last="Fujiwara">Toshiyoshi Fujiwara</name>
<affiliation><nlm:aff id="aff1"><institution>Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences</institution>
, Okayama,<country>Japan</country>
</nlm:aff>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">25523761</idno>
<idno type="pmc">4351467</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4351467</idno>
<idno type="RBID">PMC:4351467</idno>
<idno type="doi">10.1038/mt.2014.244</idno>
<date when="2015">2015</date>
<idno type="wicri:Area/Pmc/Corpus">000062</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000062</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Biological Ablation of Sentinel Lymph Node Metastasis in Submucosally Invaded Early Gastrointestinal Cancer</title>
<author><name sortKey="Kikuchi, Satoru" sort="Kikuchi, Satoru" uniqKey="Kikuchi S" first="Satoru" last="Kikuchi">Satoru Kikuchi</name>
<affiliation><nlm:aff id="aff1"><institution>Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences</institution>
, Okayama,<country>Japan</country>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kishimoto, Hiroyuki" sort="Kishimoto, Hiroyuki" uniqKey="Kishimoto H" first="Hiroyuki" last="Kishimoto">Hiroyuki Kishimoto</name>
<affiliation><nlm:aff id="aff1"><institution>Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences</institution>
, Okayama,<country>Japan</country>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Tazawa, Hiroshi" sort="Tazawa, Hiroshi" uniqKey="Tazawa H" first="Hiroshi" last="Tazawa">Hiroshi Tazawa</name>
<affiliation><nlm:aff id="aff1"><institution>Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences</institution>
, Okayama,<country>Japan</country>
</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff2"><institution>Center for Innovative Clinical Medicine, Okayama University Hospital</institution>
, Okayama,<country>Japan</country>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Hashimoto, Yuuri" sort="Hashimoto, Yuuri" uniqKey="Hashimoto Y" first="Yuuri" last="Hashimoto">Yuuri Hashimoto</name>
<affiliation><nlm:aff id="aff1"><institution>Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences</institution>
, Okayama,<country>Japan</country>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kuroda, Shinji" sort="Kuroda, Shinji" uniqKey="Kuroda S" first="Shinji" last="Kuroda">Shinji Kuroda</name>
<affiliation><nlm:aff id="aff1"><institution>Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences</institution>
, Okayama,<country>Japan</country>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Nishizaki, Masahiko" sort="Nishizaki, Masahiko" uniqKey="Nishizaki M" first="Masahiko" last="Nishizaki">Masahiko Nishizaki</name>
<affiliation><nlm:aff id="aff1"><institution>Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences</institution>
, Okayama,<country>Japan</country>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Nagasaka, Takeshi" sort="Nagasaka, Takeshi" uniqKey="Nagasaka T" first="Takeshi" last="Nagasaka">Takeshi Nagasaka</name>
<affiliation><nlm:aff id="aff1"><institution>Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences</institution>
, Okayama,<country>Japan</country>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Shirakawa, Yasuhiro" sort="Shirakawa, Yasuhiro" uniqKey="Shirakawa Y" first="Yasuhiro" last="Shirakawa">Yasuhiro Shirakawa</name>
<affiliation><nlm:aff id="aff1"><institution>Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences</institution>
, Okayama,<country>Japan</country>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kagawa, Shunsuke" sort="Kagawa, Shunsuke" uniqKey="Kagawa S" first="Shunsuke" last="Kagawa">Shunsuke Kagawa</name>
<affiliation><nlm:aff id="aff1"><institution>Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences</institution>
, Okayama,<country>Japan</country>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Urata, Yasuo" sort="Urata, Yasuo" uniqKey="Urata Y" first="Yasuo" last="Urata">Yasuo Urata</name>
<affiliation><nlm:aff id="aff3"><institution>Oncolys BioPharma, Inc.</institution>
, Tokyo,<country>Japan</country>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Hoffman, Robert M" sort="Hoffman, Robert M" uniqKey="Hoffman R" first="Robert M" last="Hoffman">Robert M. Hoffman</name>
<affiliation><nlm:aff id="aff4"><institution>Department of Surgery, University of California</institution>
, San Diego, California,<country>USA</country>
</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff5"><institution>AntiCancer, Inc.</institution>
, San Diego, California,<country>USA</country>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Fujiwara, Toshiyoshi" sort="Fujiwara, Toshiyoshi" uniqKey="Fujiwara T" first="Toshiyoshi" last="Fujiwara">Toshiyoshi Fujiwara</name>
<affiliation><nlm:aff id="aff1"><institution>Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences</institution>
, Okayama,<country>Japan</country>
</nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">Molecular Therapy</title>
<idno type="ISSN">1525-0016</idno>
<idno type="eISSN">1525-0024</idno>
<imprint><date when="2015">2015</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>Currently, early gastrointestinal cancers are treated endoscopically, as long as there are no lymph node metastases. However, once a gastrointestinal cancer invades the submucosal layer, the lymph node metastatic rate rises to higher than 10%. Therefore, surgery is still the gold standard to remove regional lymph nodes containing possible metastases. Here, to avoid prophylactic surgery, we propose a less-invasive biological ablation of lymph node metastasis in submucosally invaded gastrointestinal cancer patients. We have established an orthotopic early rectal cancer xenograft model with spontaneous lymph node metastasis by implantation of green fluorescent protein (GFP)-labeled human colon cancer cells into the submucosal layer of the murine rectum. A solution containing telomerase-specific oncolytic adenovirus was injected into the peritumoral submucosal space, followed by excision of the primary rectal tumors mimicking the endoscopic submucosal dissection (ESD) technique. Seven days after treatment, GFP signals had completely disappeared indicating that sentinel lymph node metastasis was selectively eradicated. Moreover, biologically treated mice were confirmed to be relapse-free even 4 weeks after treatment. These results indicate that virus-mediated biological ablation selectively targets lymph node metastasis and provides a potential alternative to surgery for submucosal invasive gastrointestinal cancer patients.</p>
</div>
</front>
</TEI>
<pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Mol Ther</journal-id>
<journal-id journal-id-type="iso-abbrev">Mol. Ther</journal-id>
<journal-title-group><journal-title>Molecular Therapy</journal-title>
</journal-title-group>
<issn pub-type="ppub">1525-0016</issn>
<issn pub-type="epub">1525-0024</issn>
<publisher><publisher-name>Nature Publishing Group</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">25523761</article-id>
<article-id pub-id-type="pmc">4351467</article-id>
<article-id pub-id-type="pii">mt2014244</article-id>
<article-id pub-id-type="doi">10.1038/mt.2014.244</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Original Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Biological Ablation of Sentinel Lymph Node Metastasis in Submucosally Invaded Early Gastrointestinal Cancer</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Kikuchi</surname>
<given-names>Satoru</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kishimoto</surname>
<given-names>Hiroyuki</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Tazawa</surname>
<given-names>Hiroshi</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
<xref ref-type="aff" rid="aff2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hashimoto</surname>
<given-names>Yuuri</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kuroda</surname>
<given-names>Shinji</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Nishizaki</surname>
<given-names>Masahiko</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Nagasaka</surname>
<given-names>Takeshi</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Shirakawa</surname>
<given-names>Yasuhiro</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kagawa</surname>
<given-names>Shunsuke</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Urata</surname>
<given-names>Yasuo</given-names>
</name>
<xref ref-type="aff" rid="aff3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hoffman</surname>
<given-names>Robert M</given-names>
</name>
<xref ref-type="aff" rid="aff4">4</xref>
<xref ref-type="aff" rid="aff5">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Fujiwara</surname>
<given-names>Toshiyoshi</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
<xref ref-type="corresp" rid="caf1">*</xref>
</contrib>
<aff id="aff1"><label>1</label>
<institution>Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences</institution>
, Okayama,<country>Japan</country>
</aff>
<aff id="aff2"><label>2</label>
<institution>Center for Innovative Clinical Medicine, Okayama University Hospital</institution>
, Okayama,<country>Japan</country>
</aff>
<aff id="aff3"><label>3</label>
<institution>Oncolys BioPharma, Inc.</institution>
, Tokyo,<country>Japan</country>
</aff>
<aff id="aff4"><label>4</label>
<institution>Department of Surgery, University of California</institution>
, San Diego, California,<country>USA</country>
</aff>
<aff id="aff5"><label>5</label>
<institution>AntiCancer, Inc.</institution>
, San Diego, California,<country>USA</country>
</aff>
</contrib-group>
<author-notes><corresp id="caf1"><label>*</label>
Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700–8558, Japan. E-mail: <email>toshi_f@md.okayama-u.ac.jp</email>
</corresp>
</author-notes>
<pub-date pub-type="ppub"><month>03</month>
<year>2015</year>
</pub-date>
<pub-date pub-type="epreprint"><day>19</day>
<month>12</month>
<year>2014</year>
</pub-date>
<pub-date pub-type="epub"><day>20</day>
<month>01</month>
<year>2015</year>
</pub-date>
<volume>23</volume>
<issue>3</issue>
<fpage>501</fpage>
<lpage>509</lpage>
<history><date date-type="received"><day>21</day>
<month>10</month>
<year>2014</year>
</date>
<date date-type="accepted"><day>14</day>
<month>12</month>
<year>2014</year>
</date>
</history>
<permissions><copyright-statement>Copyright © 2015 American Society of Gene & Cell Therapy</copyright-statement>
<copyright-year>2015</copyright-year>
<copyright-holder>American Society of Gene & Cell Therapy</copyright-holder>
</permissions>
<abstract><p>Currently, early gastrointestinal cancers are treated endoscopically, as long as there are no lymph node metastases. However, once a gastrointestinal cancer invades the submucosal layer, the lymph node metastatic rate rises to higher than 10%. Therefore, surgery is still the gold standard to remove regional lymph nodes containing possible metastases. Here, to avoid prophylactic surgery, we propose a less-invasive biological ablation of lymph node metastasis in submucosally invaded gastrointestinal cancer patients. We have established an orthotopic early rectal cancer xenograft model with spontaneous lymph node metastasis by implantation of green fluorescent protein (GFP)-labeled human colon cancer cells into the submucosal layer of the murine rectum. A solution containing telomerase-specific oncolytic adenovirus was injected into the peritumoral submucosal space, followed by excision of the primary rectal tumors mimicking the endoscopic submucosal dissection (ESD) technique. Seven days after treatment, GFP signals had completely disappeared indicating that sentinel lymph node metastasis was selectively eradicated. Moreover, biologically treated mice were confirmed to be relapse-free even 4 weeks after treatment. These results indicate that virus-mediated biological ablation selectively targets lymph node metastasis and provides a potential alternative to surgery for submucosal invasive gastrointestinal cancer patients.</p>
</abstract>
</article-meta>
</front>
</pmc>
</record>
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