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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Radiation therapy causes loss of dermal lymphatic vessels and interferes with lymphatic function by TGF-β1-mediated tissue fibrosis</title><author><name sortKey="Avraham, Tomer" sort="Avraham, Tomer" uniqKey="Avraham T" first="Tomer" last="Avraham">Tomer Avraham</name><affiliation><nlm:aff wicri:cut=", and" id="aff1">Division of Plastic and Reconstructive Surgery, Department of Surgery</nlm:aff></affiliation></author><author><name sortKey="Yan, Alan" sort="Yan, Alan" uniqKey="Yan A" first="Alan" last="Yan">Alan Yan</name><affiliation><nlm:aff wicri:cut=", and" id="aff1">Division of Plastic and Reconstructive Surgery, Department of Surgery</nlm:aff></affiliation></author><author><name sortKey="Zampell, Jamie C" sort="Zampell, Jamie C" uniqKey="Zampell J" first="Jamie C." last="Zampell">Jamie C. Zampell</name><affiliation><nlm:aff wicri:cut=", and" id="aff1">Division of Plastic and Reconstructive Surgery, Department of Surgery</nlm:aff></affiliation></author><author><name sortKey="Daluvoy, Sanjay V" sort="Daluvoy, Sanjay V" uniqKey="Daluvoy S" first="Sanjay V." last="Daluvoy">Sanjay V. Daluvoy</name><affiliation><nlm:aff wicri:cut=", and" id="aff1">Division of Plastic and Reconstructive Surgery, Department of Surgery</nlm:aff></affiliation></author><author><name sortKey="Haimovitz Friedman, Adriana" sort="Haimovitz Friedman, Adriana" uniqKey="Haimovitz Friedman A" first="Adriana" last="Haimovitz-Friedman">Adriana Haimovitz-Friedman</name><affiliation><nlm:aff id="aff2">Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York</nlm:aff></affiliation></author><author><name sortKey="Cordeiro, Andrew P" sort="Cordeiro, Andrew P" uniqKey="Cordeiro A" first="Andrew P." last="Cordeiro">Andrew P. Cordeiro</name><affiliation><nlm:aff wicri:cut=", and" id="aff1">Division of Plastic and Reconstructive Surgery, Department of Surgery</nlm:aff></affiliation></author><author><name sortKey="Mehrara, Babak J" sort="Mehrara, Babak J" uniqKey="Mehrara B" first="Babak J." last="Mehrara">Babak J. Mehrara</name><affiliation><nlm:aff wicri:cut=", and" id="aff1">Division of Plastic and Reconstructive Surgery, Department of Surgery</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">20519446</idno><idno type="pmc">2944320</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2944320</idno><idno type="RBID">PMC:2944320</idno><idno type="doi">10.1152/ajpcell.00535.2009</idno><date when="2010">2010</date><idno type="wicri:Area/Pmc/Corpus">002B73</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002B73</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Radiation therapy causes loss of dermal lymphatic vessels and interferes with lymphatic function by TGF-β1-mediated tissue fibrosis</title><author><name sortKey="Avraham, Tomer" sort="Avraham, Tomer" uniqKey="Avraham T" first="Tomer" last="Avraham">Tomer Avraham</name><affiliation><nlm:aff wicri:cut=", and" id="aff1">Division of Plastic and Reconstructive Surgery, Department of Surgery</nlm:aff></affiliation></author><author><name sortKey="Yan, Alan" sort="Yan, Alan" uniqKey="Yan A" first="Alan" last="Yan">Alan Yan</name><affiliation><nlm:aff wicri:cut=", and" id="aff1">Division of Plastic and Reconstructive Surgery, Department of Surgery</nlm:aff></affiliation></author><author><name sortKey="Zampell, Jamie C" sort="Zampell, Jamie C" uniqKey="Zampell J" first="Jamie C." last="Zampell">Jamie C. Zampell</name><affiliation><nlm:aff wicri:cut=", and" id="aff1">Division of Plastic and Reconstructive Surgery, Department of Surgery</nlm:aff></affiliation></author><author><name sortKey="Daluvoy, Sanjay V" sort="Daluvoy, Sanjay V" uniqKey="Daluvoy S" first="Sanjay V." last="Daluvoy">Sanjay V. Daluvoy</name><affiliation><nlm:aff wicri:cut=", and" id="aff1">Division of Plastic and Reconstructive Surgery, Department of Surgery</nlm:aff></affiliation></author><author><name sortKey="Haimovitz Friedman, Adriana" sort="Haimovitz Friedman, Adriana" uniqKey="Haimovitz Friedman A" first="Adriana" last="Haimovitz-Friedman">Adriana Haimovitz-Friedman</name><affiliation><nlm:aff id="aff2">Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York</nlm:aff></affiliation></author><author><name sortKey="Cordeiro, Andrew P" sort="Cordeiro, Andrew P" uniqKey="Cordeiro A" first="Andrew P." last="Cordeiro">Andrew P. Cordeiro</name><affiliation><nlm:aff wicri:cut=", and" id="aff1">Division of Plastic and Reconstructive Surgery, Department of Surgery</nlm:aff></affiliation></author><author><name sortKey="Mehrara, Babak J" sort="Mehrara, Babak J" uniqKey="Mehrara B" first="Babak J." last="Mehrara">Babak J. Mehrara</name><affiliation><nlm:aff wicri:cut=", and" id="aff1">Division of Plastic and Reconstructive Surgery, Department of Surgery</nlm:aff></affiliation></author></analytic><series><title level="j">American Journal of Physiology - Cell Physiology</title><idno type="ISSN">0363-6143</idno><idno type="eISSN">1522-1563</idno><imprint><date when="2010">2010</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Although radiation therapy is a major risk factor for the development of lymphedema following lymphadenectomy, the mechanisms responsible for this effect remain unknown. The purpose of this study was therefore to determine the effects of radiation on lymphatic endothelial cells (LECs) and lymphatic function. The tails of wild-type or acid sphingomyelinase (ASM)-deficient mice were treated with 0, 15, or 30 Gy of radiation and then analyzed for LEC apoptosis and lymphatic function at various time points. To analyze the effects of radiation fibrosis on lymphatic function, we determined the effects of transforming growth factor (TGF)-β1 blockade after radiation in vivo. Finally, we determined the effects of radiation and exogenous TGF-β1 on LECs in vitro. Radiation caused mild edema that resolved after 12–24 wk. Interestingly, despite resolution of tail edema, irradiated animals displayed persistent lymphatic dysfunction. Radiation caused loss of capillary lymphatics and was associated with a dose-dependent increase in LEC apoptosis. ASM−/− mice had significantly less LEC apoptosis; however, this finding did not translate to improved lymphatic function at later time points. Short-term blockade of TGF-β1 function after radiation markedly decreased tissue fibrosis and significantly improved lymphatic function but did not alter LEC apoptosis. Radiation therapy decreases lymphatic reserve by causing depletion of lymphatic vessels and LECs as well as promoting soft tissue fibrosis. Short-term inhibition of TGF-β1 activity following radiation improves lymphatic function and is associated with decreased soft tissue fibrosis. ASM deficiency confers LEC protection from radiation-induced apoptosis but does not prevent lymphatic dysfunction.</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">Am J Physiol Cell Physiol</journal-id><journal-id journal-id-type="hwp">ajpcell</journal-id><journal-id journal-id-type="pmc">ajpcell</journal-id><journal-id journal-id-type="publisher-id">AJPCELL</journal-id><journal-title-group><journal-title>American Journal of Physiology - Cell Physiology</journal-title></journal-title-group><issn pub-type="ppub">0363-6143</issn><issn pub-type="epub">1522-1563</issn><publisher><publisher-name>American Physiological Society</publisher-name><publisher-loc>Bethesda, MD</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">20519446</article-id><article-id pub-id-type="pmc">2944320</article-id><article-id pub-id-type="publisher-id">C-00535-2009</article-id><article-id pub-id-type="doi">10.1152/ajpcell.00535.2009</article-id><article-categories><subj-group subj-group-type="heading"><subject>Vascular Biology</subject></subj-group></article-categories><title-group><article-title>Radiation therapy causes loss of dermal lymphatic vessels and interferes with lymphatic function by TGF-β1-mediated tissue fibrosis</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Avraham</surname><given-names>Tomer</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Yan</surname><given-names>Alan</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Zampell</surname><given-names>Jamie C.</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Daluvoy</surname><given-names>Sanjay V.</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Haimovitz-Friedman</surname><given-names>Adriana</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Cordeiro</surname><given-names>Andrew P.</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Mehrara</surname><given-names>Babak J.</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><aff id="aff1"><sup>1</sup>Division of Plastic and Reconstructive Surgery, Department of Surgery, and</aff><aff id="aff2"><sup>2</sup>Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York</aff></contrib-group><author-notes><corresp>Address for reprint requests and other correspondence: B. J. Mehrara,
<addr-line>1275 York Ave., Rm. MRI 1005, New York, NY 10065</addr-line> (e-mail: <email>mehrarab@mskcc.org</email>).</corresp></author-notes><pub-date pub-type="ppub"><month>9</month><year>2010</year></pub-date><pub-date pub-type="epub"><day>2</day><month>6</month><year>2010</year></pub-date><pub-date pub-type="pmc-release"><day>1</day><month>9</month><year>2011</year></pub-date><pmc-comment> PMC Release delay is 12 months and 0 days and was based on the
<volume>299</volume><issue>3</issue><fpage>C589</fpage><lpage>C605</lpage><history><date date-type="received"><day>8</day><month>12</month><year>2009</year></date><date date-type="accepted"><day>1</day><month>6</month><year>2010</year></date></history><permissions><copyright-statement>Copyright © 2010 the American Physiological Society</copyright-statement></permissions><self-uri xlink:title="pdf" xlink:type="simple" xlink:href="zh000910000589.pdf"></self-uri><abstract><p>Although radiation therapy is a major risk factor for the development of lymphedema following lymphadenectomy, the mechanisms responsible for this effect remain unknown. The purpose of this study was therefore to determine the effects of radiation on lymphatic endothelial cells (LECs) and lymphatic function. The tails of wild-type or acid sphingomyelinase (ASM)-deficient mice were treated with 0, 15, or 30 Gy of radiation and then analyzed for LEC apoptosis and lymphatic function at various time points. To analyze the effects of radiation fibrosis on lymphatic function, we determined the effects of transforming growth factor (TGF)-β1 blockade after radiation in vivo. Finally, we determined the effects of radiation and exogenous TGF-β1 on LECs in vitro. Radiation caused mild edema that resolved after 12–24 wk. Interestingly, despite resolution of tail edema, irradiated animals displayed persistent lymphatic dysfunction. Radiation caused loss of capillary lymphatics and was associated with a dose-dependent increase in LEC apoptosis. ASM−/− mice had significantly less LEC apoptosis; however, this finding did not translate to improved lymphatic function at later time points. Short-term blockade of TGF-β1 function after radiation markedly decreased tissue fibrosis and significantly improved lymphatic function but did not alter LEC apoptosis. Radiation therapy decreases lymphatic reserve by causing depletion of lymphatic vessels and LECs as well as promoting soft tissue fibrosis. Short-term inhibition of TGF-β1 activity following radiation improves lymphatic function and is associated with decreased soft tissue fibrosis. ASM deficiency confers LEC protection from radiation-induced apoptosis but does not prevent lymphatic dysfunction.</p></abstract><kwd-group><kwd>lymphedema</kwd><kwd>endothelium</kwd><kwd>transforming growth factor-β1</kwd></kwd-group><funding-group><award-group><funding-source id="CS100">National Institutes of Health</funding-source><award-id rid="CS100">R24-CA-83084</award-id><award-id rid="CS100">P30-CA-08748</award-id></award-group></funding-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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