Topical tacrolimus for the treatment of secondary lymphedema
Identifieur interne : 000061 ( Main/Exploration ); précédent : 000060; suivant : 000062Topical tacrolimus for the treatment of secondary lymphedema
Auteurs : Jason C. Gardenier [États-Unis] ; Raghu P. Kataru [États-Unis] ; Geoffrey E. Hespe [États-Unis] ; Ira L. Savetsky [États-Unis] ; Jeremy S. Torrisi [États-Unis] ; Gabriela D. García Nores [États-Unis] ; Dawit K. Jowhar [États-Unis] ; Matthew D. Nitti [États-Unis] ; Ryan C. Schofield [États-Unis] ; Dean C. Carlow [États-Unis] ; Babak J. Mehrara [États-Unis]Source :
- Nature Communications [ 2041-1723 ] ; 2017.
Abstract
Secondary lymphedema, a life-long complication of cancer treatment, currently has no cure. Lymphedema patients have decreased quality of life and recurrent infections with treatments limited to palliative measures. Accumulating evidence indicates that T cells play a key role in the pathology of lymphedema by promoting tissue fibrosis and inhibiting lymphangiogenesis. Here using mouse models, we show that topical therapy with tacrolimus, an anti-T-cell immunosuppressive drug, is highly effective in preventing lymphedema development and treating established lymphedema. This intervention markedly decreases swelling, T-cell infiltration and tissue fibrosis while significantly increasing formation of lymphatic collaterals with minimal systemic absorption. Animals treated with tacrolimus have markedly improved lymphatic function with increased collecting vessel contraction frequency and decreased dermal backflow. These results have profound implications for lymphedema treatment as topical tacrolimus is FDA-approved for other chronic skin conditions and has an established record of safety and tolerability.
Url:
DOI: 10.1038/ncomms14345
PubMed: 28186091
PubMed Central: 5309859
Affiliations:
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Torrisi</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Division of Plastic and Reconstructive Surgery, Department of Surgery, Memorial Sloan Kettering Cancer Center New York</institution>, New York, New York 10065,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Nores, Gabriela D Garcia" sort="Nores, Gabriela D Garcia" uniqKey="Nores G" first="Gabriela D. García" last="Nores">Gabriela D. García Nores</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Division of Plastic and Reconstructive Surgery, Department of Surgery, Memorial Sloan Kettering Cancer Center New York</institution>, New York, New York 10065,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Jowhar, Dawit K" sort="Jowhar, Dawit K" uniqKey="Jowhar D" first="Dawit K." last="Jowhar">Dawit K. Jowhar</name><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Weill Cornell Medical College New York</institution>, New York, New York 10065,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Nitti, Matthew D" sort="Nitti, Matthew D" uniqKey="Nitti M" first="Matthew D." last="Nitti">Matthew D. 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Carlow</name><affiliation wicri:level="1"><nlm:aff id="a3"><institution>Department of Laboratory Medicine, Memorial Sloan Kettering Cancer Center</institution>, New York, New York 10065,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></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 wicri:level="1"><nlm:aff id="a1"><institution>Division of Plastic and Reconstructive Surgery, Department of Surgery, Memorial Sloan Kettering Cancer Center New York</institution>, New York, New York 10065,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Nature Communications</title><idno type="eISSN">2041-1723</idno><imprint><date when="2017">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Secondary lymphedema, a life-long complication of cancer treatment, currently has no cure. Lymphedema patients have decreased quality of life and recurrent infections with treatments limited to palliative measures. Accumulating evidence indicates that T cells play a key role in the pathology of lymphedema by promoting tissue fibrosis and inhibiting lymphangiogenesis. Here using mouse models, we show that topical therapy with tacrolimus, an anti-T-cell immunosuppressive drug, is highly effective in preventing lymphedema development and treating established lymphedema. This intervention markedly decreases swelling, T-cell infiltration and tissue fibrosis while significantly increasing formation of lymphatic collaterals with minimal systemic absorption. Animals treated with tacrolimus have markedly improved lymphatic function with increased collecting vessel contraction frequency and decreased dermal backflow. These results have profound implications for lymphedema treatment as topical tacrolimus is FDA-approved for other chronic skin conditions and has an established record of safety and tolerability.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Disipio, T" uniqKey="Disipio T">T. DiSipio</name></author><author><name sortKey="Rye, S" uniqKey="Rye S">S. Rye</name></author><author><name sortKey="Newman, B" uniqKey="Newman B">B. Newman</name></author><author><name sortKey="Hayes, S" uniqKey="Hayes S">S. Hayes</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Petrek, J A" uniqKey="Petrek J">J. A. Petrek</name></author><author><name sortKey="Heelan, M C" uniqKey="Heelan M">M. C. Heelan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rockson, S G" uniqKey="Rockson S">S. G. Rockson</name></author><author><name sortKey="Rivera, K K" uniqKey="Rivera K">K. K. 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Carlow</name><name sortKey="Hespe, Geoffrey E" sort="Hespe, Geoffrey E" uniqKey="Hespe G" first="Geoffrey E." last="Hespe">Geoffrey E. Hespe</name><name sortKey="Jowhar, Dawit K" sort="Jowhar, Dawit K" uniqKey="Jowhar D" first="Dawit K." last="Jowhar">Dawit K. Jowhar</name><name sortKey="Kataru, Raghu P" sort="Kataru, Raghu P" uniqKey="Kataru R" first="Raghu P." last="Kataru">Raghu P. Kataru</name><name sortKey="Mehrara, Babak J" sort="Mehrara, Babak J" uniqKey="Mehrara B" first="Babak J." last="Mehrara">Babak J. Mehrara</name><name sortKey="Nitti, Matthew D" sort="Nitti, Matthew D" uniqKey="Nitti M" first="Matthew D." last="Nitti">Matthew D. Nitti</name><name sortKey="Nores, Gabriela D Garcia" sort="Nores, Gabriela D Garcia" uniqKey="Nores G" first="Gabriela D. García" last="Nores">Gabriela D. García Nores</name><name sortKey="Savetsky, Ira L" sort="Savetsky, Ira L" uniqKey="Savetsky I" first="Ira L." last="Savetsky">Ira L. Savetsky</name><name sortKey="Schofield, Ryan C" sort="Schofield, Ryan C" uniqKey="Schofield R" first="Ryan C." last="Schofield">Ryan C. Schofield</name><name sortKey="Torrisi, Jeremy S" sort="Torrisi, Jeremy S" uniqKey="Torrisi J" first="Jeremy S." last="Torrisi">Jeremy S. Torrisi</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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