Topical tacrolimus for the treatment of secondary lymphedema.
Identifieur interne : 000046 ( PubMed/Checkpoint ); précédent : 000045; suivant : 000047Topical 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.
DOI: 10.1038/ncomms14345
PubMed: 28186091
Affiliations:
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Nitti</name><affiliation wicri:level="1"><nlm:affiliation>Division of Plastic and Reconstructive Surgery, Department of Surgery, Memorial Sloan Kettering Cancer Center New York, New York, New York 10065, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Plastic and Reconstructive Surgery, Department of Surgery, Memorial Sloan Kettering Cancer Center New York, New York, New York 10065</wicri:regionArea><wicri:noRegion>New York 10065</wicri:noRegion></affiliation></author><author><name sortKey="Schofield, Ryan C" sort="Schofield, Ryan C" uniqKey="Schofield R" first="Ryan C" last="Schofield">Ryan C. Schofield</name><affiliation wicri:level="1"><nlm:affiliation>Department of Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065</wicri:regionArea><wicri:noRegion>New York 10065</wicri:noRegion></affiliation></author><author><name sortKey="Carlow, Dean C" sort="Carlow, Dean C" uniqKey="Carlow D" first="Dean C" last="Carlow">Dean C. Carlow</name><affiliation wicri:level="1"><nlm:affiliation>Department of Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065</wicri:regionArea><wicri:noRegion>New York 10065</wicri:noRegion></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:affiliation>Division of Plastic and Reconstructive Surgery, Department of Surgery, Memorial Sloan Kettering Cancer Center New York, New York, New York 10065, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Plastic and Reconstructive Surgery, Department of Surgery, Memorial Sloan Kettering Cancer Center New York, New York, New York 10065</wicri:regionArea><wicri:noRegion>New York 10065</wicri:noRegion></affiliation></author></analytic><series><title level="j">Nature communications</title><idno type="eISSN">2041-1723</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><pubmed><MedlineCitation Status="In-Data-Review" Owner="NLM"><PMID Version="1">28186091</PMID><DateCreated><Year>2017</Year><Month>02</Month><Day>10</Day></DateCreated><DateRevised><Year>2017</Year><Month>04</Month><Day>29</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">2041-1723</ISSN><JournalIssue CitedMedium="Internet"><Volume>8</Volume><PubDate><Year>2017</Year><Month>Feb</Month><Day>10</Day></PubDate></JournalIssue><Title>Nature communications</Title><ISOAbbreviation>Nat Commun</ISOAbbreviation></Journal><ArticleTitle>Topical tacrolimus for the treatment of secondary lymphedema.</ArticleTitle><Pagination><MedlinePgn>14345</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1038/ncomms14345</ELocationID><Abstract><AbstractText>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.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Gardenier</LastName><ForeName>Jason C</ForeName><Initials>JC</Initials><AffiliationInfo><Affiliation>Division of Plastic and Reconstructive Surgery, Department of Surgery, Memorial Sloan Kettering Cancer Center New York, New York, New York 10065, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kataru</LastName><ForeName>Raghu P</ForeName><Initials>RP</Initials><AffiliationInfo><Affiliation>Division of Plastic and Reconstructive Surgery, Department of Surgery, Memorial Sloan Kettering Cancer Center New York, New York, New York 10065, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hespe</LastName><ForeName>Geoffrey E</ForeName><Initials>GE</Initials><Identifier Source="ORCID">http://orcid.org/0000-0003-1961-7484</Identifier><AffiliationInfo><Affiliation>Division of Plastic and Reconstructive Surgery, Department of Surgery, Memorial Sloan Kettering Cancer Center New York, New York, New York 10065, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Savetsky</LastName><ForeName>Ira L</ForeName><Initials>IL</Initials><AffiliationInfo><Affiliation>Division of Plastic and Reconstructive Surgery, Department of Surgery, Memorial Sloan Kettering Cancer Center New York, New York, New York 10065, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Torrisi</LastName><ForeName>Jeremy S</ForeName><Initials>JS</Initials><AffiliationInfo><Affiliation>Division of Plastic and Reconstructive Surgery, Department of Surgery, Memorial Sloan Kettering Cancer Center New York, New York, New York 10065, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nores</LastName><ForeName>Gabriela D García</ForeName><Initials>GD</Initials><AffiliationInfo><Affiliation>Division of Plastic and Reconstructive Surgery, Department of Surgery, Memorial Sloan Kettering Cancer Center New York, New York, New York 10065, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jowhar</LastName><ForeName>Dawit K</ForeName><Initials>DK</Initials><AffiliationInfo><Affiliation>Weill Cornell Medical College New York, New York, New York 10065, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nitti</LastName><ForeName>Matthew D</ForeName><Initials>MD</Initials><AffiliationInfo><Affiliation>Division of Plastic and Reconstructive Surgery, Department of Surgery, Memorial Sloan Kettering Cancer Center New York, New York, New York 10065, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Schofield</LastName><ForeName>Ryan C</ForeName><Initials>RC</Initials><AffiliationInfo><Affiliation>Department of Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Carlow</LastName><ForeName>Dean C</ForeName><Initials>DC</Initials><AffiliationInfo><Affiliation>Department of Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mehrara</LastName><ForeName>Babak J</ForeName><Initials>BJ</Initials><AffiliationInfo><Affiliation>Division of Plastic and Reconstructive Surgery, Department of Surgery, Memorial Sloan Kettering Cancer Center New York, New York, New York 10065, USA.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>R25 CA020449</GrantID><Acronym>CA</Acronym><Agency>NCI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>T32 CA009501</GrantID><Acronym>CA</Acronym><Agency>NCI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>P30 CA008748</GrantID><Acronym>CA</Acronym><Agency>NCI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>T32 CA009685</GrantID><Acronym>CA</Acronym><Agency>NCI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 HL111130</GrantID><Acronym>HL</Acronym><Agency>NHLBI NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2017</Year><Month>02</Month><Day>10</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Nat Commun</MedlineTA><NlmUniqueID>101528555</NlmUniqueID><ISSNLinking>2041-1723</ISSNLinking></MedlineJournalInfo><CommentsCorrectionsList><CommentsCorrections RefType="Cites"><RefSource>Am J Physiol Cell Physiol. 2012 Jan 15;302(2):C392-404</RefSource><PMID 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PubStatus="received"><Year>2016</Year><Month>01</Month><Day>11</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2016</Year><Month>12</Month><Day>20</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2017</Year><Month>2</Month><Day>11</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2017</Year><Month>2</Month><Day>12</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2017</Year><Month>2</Month><Day>12</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">28186091</ArticleId><ArticleId IdType="pii">ncomms14345</ArticleId><ArticleId IdType="doi">10.1038/ncomms14345</ArticleId><ArticleId IdType="pmc">PMC5309859</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>États-Unis</li></country></list><tree><country name="États-Unis"><noRegion><name sortKey="Gardenier, Jason C" sort="Gardenier, Jason C" uniqKey="Gardenier J" first="Jason C" last="Gardenier">Jason C. Gardenier</name></noRegion><name sortKey="Carlow, Dean C" sort="Carlow, Dean C" uniqKey="Carlow D" first="Dean C" last="Carlow">Dean C. 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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