LymphedemaV1, Main, Curation, bibRecord, 004958

9-Cis Retinoic Acid Promotes Lymphangiogenesis and Enhances Lymphatic Vessel Regeneration Therapeutic Implications of 9-Cis Retinoic Acid for Secondary Lymphedema

Identifieur interne : 004958 ( Main/Curation ); précédent : 004957; suivant : 004959

9-Cis Retinoic Acid Promotes Lymphangiogenesis and Enhances Lymphatic Vessel Regeneration Therapeutic Implications of 9-Cis Retinoic Acid for Secondary Lymphedema

Auteurs : Inho Choi [États-Unis] ; Sunju Lee [États-Unis] ; HEE KYOUNG CHUNG [États-Unis] ; YONG SUK LEE [États-Unis] ; KYU EUI KIM [États-Unis] ; Dongwon Choi [États-Unis] ; EUN KYUNG PARK [États-Unis] ; DONGYUN YANG [États-Unis] ; Tatiana Ecoiffier [États-Unis] ; John Monahan [États-Unis] ; WEN CHEN [États-Unis] ; Berenice Aguilar [États-Unis] ; HA NEUL LEE [États-Unis] ; Jaehyuk Yoo [États-Unis] ; Chester J. Koh [États-Unis] ; LU CHEN [États-Unis] ; Alex K. Wong [États-Unis] ; Young-Kwon Hong [États-Unis]

Source :

Circulation : (New York, N.Y.) [ 0009-7322 ] ; 2012.

RBID : Pascal:12-0114342

Descripteurs français

KwdFr :
- Animaux, Aurora kinases, Cellules endothéliales (), Cellules endothéliales (physiologie), Facteurs de croissance fibroblastique (physiologie), Inhibiteur p27 de kinase cycline-dépendante (génétique), Inhibiteur p57 de kinase cycline-dépendante (génétique), Lymphangiogenèse (), Lymphoedème (traitement médicamenteux), Mouvement cellulaire (), Prolifération cellulaire (), Protein-Serine-Threonine Kinases (génétique), Régions promotrices (génétique), Régénération (), Souris, Souris de lignée BALB C, Souris de lignée C57BL, Trétinoïne (pharmacologie), Trétinoïne (usage thérapeutique), Vaisseaux lymphatiques (), Vaisseaux lymphatiques (physiologie).
MESH :
- génétique : Inhibiteur p27 de kinase cycline-dépendante, Inhibiteur p57 de kinase cycline-dépendante, Protein-Serine-Threonine Kinases.
- pharmacologie : Trétinoïne.
- physiologie : Cellules endothéliales, Facteurs de croissance fibroblastique, Vaisseaux lymphatiques.
- traitement médicamenteux : Lymphoedème.
- usage thérapeutique : Trétinoïne.
Pascal (Inist)
- Animaux, Aurora kinases, Cellules endothéliales, Lymphangiogenèse, Lymphoedème, Mouvement cellulaire, Pathologie de l'appareil circulatoire, Alitrétinoïne, Prolifération cellulaire, Régions promotrices (génétique), Régénération, Souris, Souris de lignée BALB C, Souris de lignée C57BL, Système lymphatique, Régénération, Traitement, Acide rétinoïque, Anticancéreux, Vaisseaux lymphatiques.

English descriptors

KwdEn :
- Alitretinoin, Animals, Antineoplastic agent, Aurora Kinases, Cardiovascular disease, Cell Movement (drug effects), Cell Proliferation (drug effects), Cyclin-Dependent Kinase Inhibitor p27 (genetics), Cyclin-Dependent Kinase Inhibitor p57 (genetics), Endothelial Cells (drug effects), Endothelial Cells (physiology), Fibroblast Growth Factors (physiology), Lymphangiogenesis (drug effects), Lymphatic Vessels (drug effects), Lymphatic Vessels (physiology), Lymphatic system, Lymphedema, Lymphedema (drug therapy), Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Promoter Regions, Genetic, Protein-Serine-Threonine Kinases (genetics), Regeneration, Regeneration (drug effects), Retinoic acid, Treatment, Tretinoin (pharmacology), Tretinoin (therapeutic use).
MESH :
- chemical , genetics : Cyclin-Dependent Kinase Inhibitor p27, Cyclin-Dependent Kinase Inhibitor p57, Protein-Serine-Threonine Kinases.
- chemical , pharmacology : Tretinoin.
- chemical , physiology : Fibroblast Growth Factors.
- chemical , therapeutic use : Tretinoin.
- chemical : Aurora Kinases.
- drug effects : Cell Movement, Cell Proliferation, Endothelial Cells, Lymphangiogenesis, Lymphatic Vessels, Regeneration.
- drug therapy : Lymphedema.
- physiology : Endothelial Cells, Lymphatic Vessels.
- Animals, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Promoter Regions, Genetic.

Abstract

Background-The lymphatic system plays a key role in tissue fluid homeostasis and lymphatic dysfunction caused by genetic defects, or lymphatic vessel obstruction can cause lymphedema, disfiguring tissue swelling often associated with fibrosis and recurrent infections with no available cures to date. In this study, retinoic acids (RAs) were determined to be a potent therapeutic agent that is immediately applicable to reduce secondary lymphedema. Methods and Results-We report that RAs promote proliferation, migration, and tube formation of cultured lymphatic endothelial cells by activating fibroblast growth factor receptor signaling. Moreover, RAs control the expression of cell-cycle checkpoint regulators such as p27^Kipl, p57^Kip2 , and the aurora kinases through both an Akt-mediated nongenomic action and a transcription-dependent genomic action that is mediated by Prox1, a master regulator of lymphatic development. Moreover, 9-cisRA was found to activate in vivo lymphangiogenesis in animals in mouse trachea, Matrigel plug, and cornea pocket assays. Finally, we demonstrate that 9-cisRA can provide a strong therapeutic efficacy in ameliorating experimental mouse tail lymphedema by enhancing lymphatic vessel regeneration. Conclusion-These in vitro and animal studies demonstrate that 9-cisRA potently activates lymphangiogenesis and promotes lymphatic regeneration in an experimental lymphedema model, presenting it as a promising novel therapeutic agent to treat human lymphedema patients.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3327127

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Le document en format XML

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<author><name sortKey="Monahan, John" sort="Monahan, John" uniqKey="Monahan J" first="John" last="Monahan">John Monahan</name>
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<author><name sortKey="Wen Chen" sort="Wen Chen" uniqKey="Wen Chen" last="Wen Chen">WEN CHEN</name>
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<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Departments of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
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<author><name sortKey="Yoo, Jaehyuk" sort="Yoo, Jaehyuk" uniqKey="Yoo J" first="Jaehyuk" last="Yoo">Jaehyuk Yoo</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Departments of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
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<s2>Los Angeles</s2>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">9-Cis Retinoic Acid Promotes Lymphangiogenesis and Enhances Lymphatic Vessel Regeneration Therapeutic Implications of 9-Cis Retinoic Acid for Secondary Lymphedema</title>
<author><name sortKey="Choi, Inho" sort="Choi, Inho" uniqKey="Choi I" first="Inho" last="Choi">Inho Choi</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Departments of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
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<author><name sortKey="Lee, Sunju" sort="Lee, Sunju" uniqKey="Lee S" first="Sunju" last="Lee">Sunju Lee</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Departments of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
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<affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
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</author>
<author><name sortKey="Hee Kyoung Chung" sort="Hee Kyoung Chung" uniqKey="Hee Kyoung Chung" last="Hee Kyoung Chung">HEE KYOUNG CHUNG</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Departments of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
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<placeName><settlement type="city">Los Angeles</settlement>
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<s2>Los Angeles</s2>
<s3>USA</s3>
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</author>
<author><name sortKey="Yong Suk Lee" sort="Yong Suk Lee" uniqKey="Yong Suk Lee" last="Yong Suk Lee">YONG SUK LEE</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Departments of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
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<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
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<affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
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<placeName><settlement type="city">Los Angeles</settlement>
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</affiliation>
</author>
<author><name sortKey="Kyu Eui Kim" sort="Kyu Eui Kim" uniqKey="Kyu Eui Kim" last="Kyu Eui Kim">KYU EUI KIM</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Departments of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
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<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
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<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Choi, Dongwon" sort="Choi, Dongwon" uniqKey="Choi D" first="Dongwon" last="Choi">Dongwon Choi</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Departments of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
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<affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
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<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
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</affiliation>
</author>
<author><name sortKey="Eun Kyung Park" sort="Eun Kyung Park" uniqKey="Eun Kyung Park" last="Eun Kyung Park">EUN KYUNG PARK</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Departments of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
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<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
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</placeName>
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<affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
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<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Dongyun Yang" sort="Dongyun Yang" uniqKey="Dongyun Yang" last="Dongyun Yang">DONGYUN YANG</name>
<affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Preventive Medicine, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
<sZ>8 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Ecoiffier, Tatiana" sort="Ecoiffier, Tatiana" uniqKey="Ecoiffier T" first="Tatiana" last="Ecoiffier">Tatiana Ecoiffier</name>
<affiliation wicri:level="3"><inist:fA14 i1="05"><s1>Center of Eye Disease and Development, Program in Vision Science, and School of Optometry, University of California</s1>
<s2>Berkeley</s2>
<s3>USA</s3>
<sZ>9 aut.</sZ>
<sZ>16 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><settlement type="city">Berkeley (Californie)</settlement>
<region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Monahan, John" sort="Monahan, John" uniqKey="Monahan J" first="John" last="Monahan">John Monahan</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Departments of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
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<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
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</affiliation>
</author>
<author><name sortKey="Wen Chen" sort="Wen Chen" uniqKey="Wen Chen" last="Wen Chen">WEN CHEN</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Departments of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
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<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Aguilar, Berenice" sort="Aguilar, Berenice" uniqKey="Aguilar B" first="Berenice" last="Aguilar">Berenice Aguilar</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Departments of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
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<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
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<affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
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<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
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</author>
<author><name sortKey="Ha Neul Lee" sort="Ha Neul Lee" uniqKey="Ha Neul Lee" last="Ha Neul Lee">HA NEUL LEE</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Departments of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
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<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
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<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
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</author>
<author><name sortKey="Yoo, Jaehyuk" sort="Yoo, Jaehyuk" uniqKey="Yoo J" first="Jaehyuk" last="Yoo">Jaehyuk Yoo</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Departments of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
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<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
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<affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
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<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
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<author><name sortKey="Koh, Chester J" sort="Koh, Chester J" uniqKey="Koh C" first="Chester J." last="Koh">Chester J. Koh</name>
<affiliation wicri:level="3"><inist:fA14 i1="04"><s1>Division of Pediatric Urology, Children's Hospital Los Angeles and University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
<sZ>15 aut.</sZ>
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<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
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</affiliation>
</author>
<author><name sortKey="Lu Chen" sort="Lu Chen" uniqKey="Lu Chen" last="Lu Chen">LU CHEN</name>
<affiliation wicri:level="3"><inist:fA14 i1="05"><s1>Center of Eye Disease and Development, Program in Vision Science, and School of Optometry, University of California</s1>
<s2>Berkeley</s2>
<s3>USA</s3>
<sZ>9 aut.</sZ>
<sZ>16 aut.</sZ>
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<country>États-Unis</country>
<placeName><settlement type="city">Berkeley (Californie)</settlement>
<region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Wong, Alex K" sort="Wong, Alex K" uniqKey="Wong A" first="Alex K." last="Wong">Alex K. Wong</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Departments of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
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<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
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</affiliation>
</author>
<author><name sortKey="Hong, Young Kwon" sort="Hong, Young Kwon" uniqKey="Hong Y" first="Young-Kwon" last="Hong">Young-Kwon Hong</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Departments of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
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<sZ>14 aut.</sZ>
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<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
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<sZ>13 aut.</sZ>
<sZ>14 aut.</sZ>
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<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
</affiliation>
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</analytic>
<series><title level="j" type="main">Circulation : (New York, N.Y.)</title>
<title level="j" type="abbreviated">Circulation : (N. Y. N.Y.)</title>
<idno type="ISSN">0009-7322</idno>
<imprint><date when="2012">2012</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt><title level="j" type="main">Circulation : (New York, N.Y.)</title>
<title level="j" type="abbreviated">Circulation : (N. Y. N.Y.)</title>
<idno type="ISSN">0009-7322</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Alitretinoin</term>
<term>Animals</term>
<term>Antineoplastic agent</term>
<term>Aurora Kinases</term>
<term>Cardiovascular disease</term>
<term>Cell Movement (drug effects)</term>
<term>Cell Proliferation (drug effects)</term>
<term>Cyclin-Dependent Kinase Inhibitor p27 (genetics)</term>
<term>Cyclin-Dependent Kinase Inhibitor p57 (genetics)</term>
<term>Endothelial Cells (drug effects)</term>
<term>Endothelial Cells (physiology)</term>
<term>Fibroblast Growth Factors (physiology)</term>
<term>Lymphangiogenesis (drug effects)</term>
<term>Lymphatic Vessels (drug effects)</term>
<term>Lymphatic Vessels (physiology)</term>
<term>Lymphatic system</term>
<term>Lymphedema</term>
<term>Lymphedema (drug therapy)</term>
<term>Mice</term>
<term>Mice, Inbred BALB C</term>
<term>Mice, Inbred C57BL</term>
<term>Promoter Regions, Genetic</term>
<term>Protein-Serine-Threonine Kinases (genetics)</term>
<term>Regeneration</term>
<term>Regeneration (drug effects)</term>
<term>Retinoic acid</term>
<term>Treatment</term>
<term>Tretinoin (pharmacology)</term>
<term>Tretinoin (therapeutic use)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term>
<term>Aurora kinases</term>
<term>Cellules endothéliales ()</term>
<term>Cellules endothéliales (physiologie)</term>
<term>Facteurs de croissance fibroblastique (physiologie)</term>
<term>Inhibiteur p27 de kinase cycline-dépendante (génétique)</term>
<term>Inhibiteur p57 de kinase cycline-dépendante (génétique)</term>
<term>Lymphangiogenèse ()</term>
<term>Lymphoedème (traitement médicamenteux)</term>
<term>Mouvement cellulaire ()</term>
<term>Prolifération cellulaire ()</term>
<term>Protein-Serine-Threonine Kinases (génétique)</term>
<term>Régions promotrices (génétique)</term>
<term>Régénération ()</term>
<term>Souris</term>
<term>Souris de lignée BALB C</term>
<term>Souris de lignée C57BL</term>
<term>Trétinoïne (pharmacologie)</term>
<term>Trétinoïne (usage thérapeutique)</term>
<term>Vaisseaux lymphatiques ()</term>
<term>Vaisseaux lymphatiques (physiologie)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Cyclin-Dependent Kinase Inhibitor p27</term>
<term>Cyclin-Dependent Kinase Inhibitor p57</term>
<term>Protein-Serine-Threonine Kinases</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Tretinoin</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="physiology" xml:lang="en"><term>Fibroblast Growth Factors</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Tretinoin</term>
</keywords>
<keywords scheme="MESH" type="chemical" xml:lang="en"><term>Aurora Kinases</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Cell Movement</term>
<term>Cell Proliferation</term>
<term>Endothelial Cells</term>
<term>Lymphangiogenesis</term>
<term>Lymphatic Vessels</term>
<term>Regeneration</term>
</keywords>
<keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Lymphedema</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Inhibiteur p27 de kinase cycline-dépendante</term>
<term>Inhibiteur p57 de kinase cycline-dépendante</term>
<term>Protein-Serine-Threonine Kinases</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Trétinoïne</term>
</keywords>
<keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Cellules endothéliales</term>
<term>Facteurs de croissance fibroblastique</term>
<term>Vaisseaux lymphatiques</term>
</keywords>
<keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Endothelial Cells</term>
<term>Lymphatic Vessels</term>
</keywords>
<keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Lymphoedème</term>
</keywords>
<keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Trétinoïne</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Mice</term>
<term>Mice, Inbred BALB C</term>
<term>Mice, Inbred C57BL</term>
<term>Promoter Regions, Genetic</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Animaux</term>
<term>Aurora kinases</term>
<term>Cellules endothéliales</term>
<term>Lymphangiogenèse</term>
<term>Lymphoedème</term>
<term>Mouvement cellulaire</term>
<term>Pathologie de l'appareil circulatoire</term>
<term>Alitrétinoïne</term>
<term>Prolifération cellulaire</term>
<term>Régions promotrices (génétique)</term>
<term>Régénération</term>
<term>Souris</term>
<term>Souris de lignée BALB C</term>
<term>Souris de lignée C57BL</term>
<term>Système lymphatique</term>
<term>Régénération</term>
<term>Traitement</term>
<term>Acide rétinoïque</term>
<term>Anticancéreux</term>
<term>Vaisseaux lymphatiques</term>
</keywords>
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</teiHeader>
<front><div type="abstract" xml:lang="en">Background-The lymphatic system plays a key role in tissue fluid homeostasis and lymphatic dysfunction caused by genetic defects, or lymphatic vessel obstruction can cause lymphedema, disfiguring tissue swelling often associated with fibrosis and recurrent infections with no available cures to date. In this study, retinoic acids (RAs) were determined to be a potent therapeutic agent that is immediately applicable to reduce secondary lymphedema. Methods and Results-We report that RAs promote proliferation, migration, and tube formation of cultured lymphatic endothelial cells by activating fibroblast growth factor receptor signaling. Moreover, RAs control the expression of cell-cycle checkpoint regulators such as p27<sup> Kip</sup>
l, p57<sup> Kip</sup>
2 , and the aurora kinases through both an Akt-mediated nongenomic action and a transcription-dependent genomic action that is mediated by Prox1, a master regulator of lymphatic development. Moreover, 9-cisRA was found to activate in vivo lymphangiogenesis in animals in mouse trachea, Matrigel plug, and cornea pocket assays. Finally, we demonstrate that 9-cisRA can provide a strong therapeutic efficacy in ameliorating experimental mouse tail lymphedema by enhancing lymphatic vessel regeneration. Conclusion-These in vitro and animal studies demonstrate that 9-cisRA potently activates lymphangiogenesis and promotes lymphatic regeneration in an experimental lymphedema model, presenting it as a promising novel therapeutic agent to treat human lymphedema patients.</div>
</front>
</TEI>
<double idat="0009-7322:2012:Choi I:cis:retinoic:acid"><INIST><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en" level="a">9-Cis Retinoic Acid Promotes Lymphangiogenesis and Enhances Lymphatic Vessel Regeneration Therapeutic Implications of 9-Cis Retinoic Acid for Secondary Lymphedema</title>
<author><name sortKey="Choi, Inho" sort="Choi, Inho" uniqKey="Choi I" first="Inho" last="Choi">Inho Choi</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Departments of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>10 aut.</sZ>
<sZ>11 aut.</sZ>
<sZ>12 aut.</sZ>
<sZ>13 aut.</sZ>
<sZ>14 aut.</sZ>
<sZ>17 aut.</sZ>
<sZ>18 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
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<sZ>12 aut.</sZ>
<sZ>13 aut.</sZ>
<sZ>14 aut.</sZ>
<sZ>18 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Lee, Sunju" sort="Lee, Sunju" uniqKey="Lee S" first="Sunju" last="Lee">Sunju Lee</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Departments of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
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<country>États-Unis</country>
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<affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
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</inist:fA14>
<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Hee Kyoung Chung" sort="Hee Kyoung Chung" uniqKey="Hee Kyoung Chung" last="Hee Kyoung Chung">HEE KYOUNG CHUNG</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Departments of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
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</inist:fA14>
<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
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<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Yong Suk Lee" sort="Yong Suk Lee" uniqKey="Yong Suk Lee" last="Yong Suk Lee">YONG SUK LEE</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Departments of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
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</inist:fA14>
<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
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</inist:fA14>
<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Kyu Eui Kim" sort="Kyu Eui Kim" uniqKey="Kyu Eui Kim" last="Kyu Eui Kim">KYU EUI KIM</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Departments of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
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</inist:fA14>
<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
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</inist:fA14>
<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Choi, Dongwon" sort="Choi, Dongwon" uniqKey="Choi D" first="Dongwon" last="Choi">Dongwon Choi</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Departments of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
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<sZ>14 aut.</sZ>
<sZ>17 aut.</sZ>
<sZ>18 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
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</inist:fA14>
<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Eun Kyung Park" sort="Eun Kyung Park" uniqKey="Eun Kyung Park" last="Eun Kyung Park">EUN KYUNG PARK</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Departments of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
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<sZ>18 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
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<sZ>13 aut.</sZ>
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</inist:fA14>
<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Dongyun Yang" sort="Dongyun Yang" uniqKey="Dongyun Yang" last="Dongyun Yang">DONGYUN YANG</name>
<affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Preventive Medicine, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
<sZ>8 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Ecoiffier, Tatiana" sort="Ecoiffier, Tatiana" uniqKey="Ecoiffier T" first="Tatiana" last="Ecoiffier">Tatiana Ecoiffier</name>
<affiliation wicri:level="3"><inist:fA14 i1="05"><s1>Center of Eye Disease and Development, Program in Vision Science, and School of Optometry, University of California</s1>
<s2>Berkeley</s2>
<s3>USA</s3>
<sZ>9 aut.</sZ>
<sZ>16 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><settlement type="city">Berkeley (Californie)</settlement>
<region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Monahan, John" sort="Monahan, John" uniqKey="Monahan J" first="John" last="Monahan">John Monahan</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Departments of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
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<sZ>13 aut.</sZ>
<sZ>14 aut.</sZ>
<sZ>17 aut.</sZ>
<sZ>18 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Wen Chen" sort="Wen Chen" uniqKey="Wen Chen" last="Wen Chen">WEN CHEN</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Departments of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
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<sZ>6 aut.</sZ>
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<sZ>10 aut.</sZ>
<sZ>11 aut.</sZ>
<sZ>12 aut.</sZ>
<sZ>13 aut.</sZ>
<sZ>14 aut.</sZ>
<sZ>17 aut.</sZ>
<sZ>18 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Aguilar, Berenice" sort="Aguilar, Berenice" uniqKey="Aguilar B" first="Berenice" last="Aguilar">Berenice Aguilar</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Departments of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
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<sZ>13 aut.</sZ>
<sZ>14 aut.</sZ>
<sZ>17 aut.</sZ>
<sZ>18 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
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<sZ>13 aut.</sZ>
<sZ>14 aut.</sZ>
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</inist:fA14>
<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Ha Neul Lee" sort="Ha Neul Lee" uniqKey="Ha Neul Lee" last="Ha Neul Lee">HA NEUL LEE</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Departments of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
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<sZ>11 aut.</sZ>
<sZ>12 aut.</sZ>
<sZ>13 aut.</sZ>
<sZ>14 aut.</sZ>
<sZ>17 aut.</sZ>
<sZ>18 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
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<sZ>12 aut.</sZ>
<sZ>13 aut.</sZ>
<sZ>14 aut.</sZ>
<sZ>18 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Yoo, Jaehyuk" sort="Yoo, Jaehyuk" uniqKey="Yoo J" first="Jaehyuk" last="Yoo">Jaehyuk Yoo</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Departments of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>10 aut.</sZ>
<sZ>11 aut.</sZ>
<sZ>12 aut.</sZ>
<sZ>13 aut.</sZ>
<sZ>14 aut.</sZ>
<sZ>17 aut.</sZ>
<sZ>18 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
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<sZ>12 aut.</sZ>
<sZ>13 aut.</sZ>
<sZ>14 aut.</sZ>
<sZ>18 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Koh, Chester J" sort="Koh, Chester J" uniqKey="Koh C" first="Chester J." last="Koh">Chester J. Koh</name>
<affiliation wicri:level="3"><inist:fA14 i1="04"><s1>Division of Pediatric Urology, Children's Hospital Los Angeles and University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
<sZ>15 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Lu Chen" sort="Lu Chen" uniqKey="Lu Chen" last="Lu Chen">LU CHEN</name>
<affiliation wicri:level="3"><inist:fA14 i1="05"><s1>Center of Eye Disease and Development, Program in Vision Science, and School of Optometry, University of California</s1>
<s2>Berkeley</s2>
<s3>USA</s3>
<sZ>9 aut.</sZ>
<sZ>16 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><settlement type="city">Berkeley (Californie)</settlement>
<region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Wong, Alex K" sort="Wong, Alex K" uniqKey="Wong A" first="Alex K." last="Wong">Alex K. Wong</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Departments of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
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<sZ>10 aut.</sZ>
<sZ>11 aut.</sZ>
<sZ>12 aut.</sZ>
<sZ>13 aut.</sZ>
<sZ>14 aut.</sZ>
<sZ>17 aut.</sZ>
<sZ>18 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Hong, Young Kwon" sort="Hong, Young Kwon" uniqKey="Hong Y" first="Young-Kwon" last="Hong">Young-Kwon Hong</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Departments of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
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<sZ>10 aut.</sZ>
<sZ>11 aut.</sZ>
<sZ>12 aut.</sZ>
<sZ>13 aut.</sZ>
<sZ>14 aut.</sZ>
<sZ>17 aut.</sZ>
<sZ>18 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
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<sZ>12 aut.</sZ>
<sZ>13 aut.</sZ>
<sZ>14 aut.</sZ>
<sZ>18 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
</affiliation>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">9-Cis Retinoic Acid Promotes Lymphangiogenesis and Enhances Lymphatic Vessel Regeneration Therapeutic Implications of 9-Cis Retinoic Acid for Secondary Lymphedema</title>
<author><name sortKey="Choi, Inho" sort="Choi, Inho" uniqKey="Choi I" first="Inho" last="Choi">Inho Choi</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Departments of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
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<affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
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<author><name sortKey="Lee, Sunju" sort="Lee, Sunju" uniqKey="Lee S" first="Sunju" last="Lee">Sunju Lee</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Departments of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
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<affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
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</affiliation>
</author>
<author><name sortKey="Hee Kyoung Chung" sort="Hee Kyoung Chung" uniqKey="Hee Kyoung Chung" last="Hee Kyoung Chung">HEE KYOUNG CHUNG</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Departments of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
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<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
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<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Yong Suk Lee" sort="Yong Suk Lee" uniqKey="Yong Suk Lee" last="Yong Suk Lee">YONG SUK LEE</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Departments of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
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<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
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<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Kyu Eui Kim" sort="Kyu Eui Kim" uniqKey="Kyu Eui Kim" last="Kyu Eui Kim">KYU EUI KIM</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Departments of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
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<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
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<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Choi, Dongwon" sort="Choi, Dongwon" uniqKey="Choi D" first="Dongwon" last="Choi">Dongwon Choi</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Departments of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
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<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
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<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
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</affiliation>
</author>
<author><name sortKey="Eun Kyung Park" sort="Eun Kyung Park" uniqKey="Eun Kyung Park" last="Eun Kyung Park">EUN KYUNG PARK</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Departments of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
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<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
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<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
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</affiliation>
</author>
<author><name sortKey="Dongyun Yang" sort="Dongyun Yang" uniqKey="Dongyun Yang" last="Dongyun Yang">DONGYUN YANG</name>
<affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Preventive Medicine, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
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<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Ecoiffier, Tatiana" sort="Ecoiffier, Tatiana" uniqKey="Ecoiffier T" first="Tatiana" last="Ecoiffier">Tatiana Ecoiffier</name>
<affiliation wicri:level="3"><inist:fA14 i1="05"><s1>Center of Eye Disease and Development, Program in Vision Science, and School of Optometry, University of California</s1>
<s2>Berkeley</s2>
<s3>USA</s3>
<sZ>9 aut.</sZ>
<sZ>16 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><settlement type="city">Berkeley (Californie)</settlement>
<region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Monahan, John" sort="Monahan, John" uniqKey="Monahan J" first="John" last="Monahan">John Monahan</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Departments of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
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<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Wen Chen" sort="Wen Chen" uniqKey="Wen Chen" last="Wen Chen">WEN CHEN</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Departments of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
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<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Aguilar, Berenice" sort="Aguilar, Berenice" uniqKey="Aguilar B" first="Berenice" last="Aguilar">Berenice Aguilar</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Departments of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
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<sZ>14 aut.</sZ>
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<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
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<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Ha Neul Lee" sort="Ha Neul Lee" uniqKey="Ha Neul Lee" last="Ha Neul Lee">HA NEUL LEE</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Departments of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
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<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
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<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
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</author>
<author><name sortKey="Yoo, Jaehyuk" sort="Yoo, Jaehyuk" uniqKey="Yoo J" first="Jaehyuk" last="Yoo">Jaehyuk Yoo</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Departments of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
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<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
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<affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
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<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
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</author>
<author><name sortKey="Koh, Chester J" sort="Koh, Chester J" uniqKey="Koh C" first="Chester J." last="Koh">Chester J. Koh</name>
<affiliation wicri:level="3"><inist:fA14 i1="04"><s1>Division of Pediatric Urology, Children's Hospital Los Angeles and University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
<s3>USA</s3>
<sZ>15 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
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</author>
<author><name sortKey="Lu Chen" sort="Lu Chen" uniqKey="Lu Chen" last="Lu Chen">LU CHEN</name>
<affiliation wicri:level="3"><inist:fA14 i1="05"><s1>Center of Eye Disease and Development, Program in Vision Science, and School of Optometry, University of California</s1>
<s2>Berkeley</s2>
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</author>
<author><name sortKey="Wong, Alex K" sort="Wong, Alex K" uniqKey="Wong A" first="Alex K." last="Wong">Alex K. Wong</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Departments of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
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</affiliation>
</author>
<author><name sortKey="Hong, Young Kwon" sort="Hong, Young Kwon" uniqKey="Hong Y" first="Young-Kwon" last="Hong">Young-Kwon Hong</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Departments of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
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<region type="state">Californie</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine</s1>
<s2>Los Angeles</s2>
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<region type="state">Californie</region>
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</analytic>
<series><title level="j" type="main">Circulation : (New York, N.Y.)</title>
<title level="j" type="abbreviated">Circulation : (N. Y. N.Y.)</title>
<idno type="ISSN">0009-7322</idno>
<imprint><date when="2012">2012</date>
</imprint>
</series>
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</sourceDesc>
<seriesStmt><title level="j" type="main">Circulation : (New York, N.Y.)</title>
<title level="j" type="abbreviated">Circulation : (N. Y. N.Y.)</title>
<idno type="ISSN">0009-7322</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Alitretinoin</term>
<term>Antineoplastic agent</term>
<term>Cardiovascular disease</term>
<term>Lymphatic system</term>
<term>Lymphedema</term>
<term>Regeneration</term>
<term>Retinoic acid</term>
<term>Treatment</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Lymphoedème</term>
<term>Pathologie de l'appareil circulatoire</term>
<term>Alitrétinoïne</term>
<term>Système lymphatique</term>
<term>Régénération</term>
<term>Traitement</term>
<term>Acide rétinoïque</term>
<term>Anticancéreux</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Background-The lymphatic system plays a key role in tissue fluid homeostasis and lymphatic dysfunction caused by genetic defects, or lymphatic vessel obstruction can cause lymphedema, disfiguring tissue swelling often associated with fibrosis and recurrent infections with no available cures to date. In this study, retinoic acids (RAs) were determined to be a potent therapeutic agent that is immediately applicable to reduce secondary lymphedema. Methods and Results-We report that RAs promote proliferation, migration, and tube formation of cultured lymphatic endothelial cells by activating fibroblast growth factor receptor signaling. Moreover, RAs control the expression of cell-cycle checkpoint regulators such as p27<sup> Kip</sup>
l, p57<sup> Kip</sup>
2 , and the aurora kinases through both an Akt-mediated nongenomic action and a transcription-dependent genomic action that is mediated by Prox1, a master regulator of lymphatic development. Moreover, 9-cisRA was found to activate in vivo lymphangiogenesis in animals in mouse trachea, Matrigel plug, and cornea pocket assays. Finally, we demonstrate that 9-cisRA can provide a strong therapeutic efficacy in ameliorating experimental mouse tail lymphedema by enhancing lymphatic vessel regeneration. Conclusion-These in vitro and animal studies demonstrate that 9-cisRA potently activates lymphangiogenesis and promotes lymphatic regeneration in an experimental lymphedema model, presenting it as a promising novel therapeutic agent to treat human lymphedema patients.</div>
</front>
</TEI>
</INIST>
<PMC><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">9-Cis Retinoic Acid Promotes Lymphangiogenesis and Enhances Lymphatic Vessel Regeneration: Therapeutic Implications of 9-Cis Retinoic Acid for Secondary Lymphedema</title>
<author><name sortKey="Choi, Inho" sort="Choi, Inho" uniqKey="Choi I" first="Inho" last="Choi">Inho Choi</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Dept of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, CA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Dept of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="A2">Dept of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, CA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Dept of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Lee, Sunju" sort="Lee, Sunju" uniqKey="Lee S" first="Sunju" last="Lee">Sunju Lee</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Dept of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, CA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Dept of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="A2">Dept of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, CA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Dept of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Chung, Hee Kyoung" sort="Chung, Hee Kyoung" uniqKey="Chung H" first="Hee Kyoung" last="Chung">Hee Kyoung Chung</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Dept of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, CA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Dept of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="A2">Dept of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, CA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
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</affiliation>
</author>
<author><name sortKey="Lee, Yong Suk" sort="Lee, Yong Suk" uniqKey="Lee Y" first="Yong Suk" last="Lee">Yong Suk Lee</name>
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<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
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</affiliation>
<affiliation wicri:level="2"><nlm:aff id="A2">Dept of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, CA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Dept of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Kim, Kyu Eui" sort="Kim, Kyu Eui" uniqKey="Kim K" first="Kyu Eui" last="Kim">Kyu Eui Kim</name>
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<placeName><region type="state">Californie</region>
</placeName>
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</affiliation>
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<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
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</affiliation>
</author>
<author><name sortKey="Choi, Dongwon" sort="Choi, Dongwon" uniqKey="Choi D" first="Dongwon" last="Choi">Dongwon Choi</name>
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<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
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</affiliation>
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<placeName><region type="state">Californie</region>
</placeName>
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</affiliation>
</author>
<author><name sortKey="Park, Eun Kyung" sort="Park, Eun Kyung" uniqKey="Park E" first="Eun Kyung" last="Park">Eun Kyung Park</name>
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<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
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</affiliation>
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<placeName><region type="state">Californie</region>
</placeName>
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</affiliation>
</author>
<author><name sortKey="Yang, Dongyun" sort="Yang, Dongyun" uniqKey="Yang D" first="Dongyun" last="Yang">Dongyun Yang</name>
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<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Dept of Preventive Medicine, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Ecoiffier, Tatiana" sort="Ecoiffier, Tatiana" uniqKey="Ecoiffier T" first="Tatiana" last="Ecoiffier">Tatiana Ecoiffier</name>
<affiliation wicri:level="2"><nlm:aff id="A5">Center of Eye Disease and Development, Program in Vision Science, and School of Optometry, University of California, Berkeley, CA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Center of Eye Disease and Development, Program in Vision Science, and School of Optometry, University of California, Berkeley</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Monahan, John" sort="Monahan, John" uniqKey="Monahan J" first="John" last="Monahan">John Monahan</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Dept of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, CA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Dept of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Chen, Wen" sort="Chen, Wen" uniqKey="Chen W" first="Wen" last="Chen">Wen Chen</name>
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<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Dept of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Aguilar, Berenice" sort="Aguilar, Berenice" uniqKey="Aguilar B" first="Berenice" last="Aguilar">Berenice Aguilar</name>
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<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Dept of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="A2">Dept of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, CA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Dept of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Lee, Ha Neul" sort="Lee, Ha Neul" uniqKey="Lee H" first="Ha Neul" last="Lee">Ha Neul Lee</name>
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<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Dept of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="A2">Dept of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, CA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Dept of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Yoo, Jaehyuk" sort="Yoo, Jaehyuk" uniqKey="Yoo J" first="Jaehyuk" last="Yoo">Jaehyuk Yoo</name>
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<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Dept of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="A2">Dept of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, CA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
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</placeName>
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</affiliation>
</author>
<author><name sortKey="Koh, Chester J" sort="Koh, Chester J" uniqKey="Koh C" first="Chester J." last="Koh">Chester J. Koh</name>
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<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Division of Pediatric Urology, Children’s Hospital Los Angeles and University of Southern California Keck School of Medicine, Los Angeles</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Chen, Lu" sort="Chen, Lu" uniqKey="Chen L" first="Lu" last="Chen">Lu Chen</name>
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<placeName><region type="state">Californie</region>
</placeName>
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</affiliation>
</author>
<author><name sortKey="Wong, Alex K" sort="Wong, Alex K" uniqKey="Wong A" first="Alex K." last="Wong">Alex K. Wong</name>
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</placeName>
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</affiliation>
</author>
<author><name sortKey="Hong, Young Kwon" sort="Hong, Young Kwon" uniqKey="Hong Y" first="Young-Kwon" last="Hong">Young-Kwon Hong</name>
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<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
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<affiliation wicri:level="2"><nlm:aff id="A2">Dept of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, CA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">9-Cis Retinoic Acid Promotes Lymphangiogenesis and Enhances Lymphatic Vessel Regeneration: Therapeutic Implications of 9-Cis Retinoic Acid for Secondary Lymphedema</title>
<author><name sortKey="Choi, Inho" sort="Choi, Inho" uniqKey="Choi I" first="Inho" last="Choi">Inho Choi</name>
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<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Dept of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="A2">Dept of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, CA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Dept of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Lee, Sunju" sort="Lee, Sunju" uniqKey="Lee S" first="Sunju" last="Lee">Sunju Lee</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Dept of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, CA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Dept of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="A2">Dept of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, CA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Dept of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Chung, Hee Kyoung" sort="Chung, Hee Kyoung" uniqKey="Chung H" first="Hee Kyoung" last="Chung">Hee Kyoung Chung</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Dept of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, CA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Dept of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="A2">Dept of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, CA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Dept of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Lee, Yong Suk" sort="Lee, Yong Suk" uniqKey="Lee Y" first="Yong Suk" last="Lee">Yong Suk Lee</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Dept of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, CA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Dept of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="A2">Dept of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, CA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Dept of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Kim, Kyu Eui" sort="Kim, Kyu Eui" uniqKey="Kim K" first="Kyu Eui" last="Kim">Kyu Eui Kim</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Dept of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, CA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Dept of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="A2">Dept of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, CA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Dept of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Choi, Dongwon" sort="Choi, Dongwon" uniqKey="Choi D" first="Dongwon" last="Choi">Dongwon Choi</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Dept of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, CA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Dept of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="A2">Dept of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, CA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Dept of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Park, Eun Kyung" sort="Park, Eun Kyung" uniqKey="Park E" first="Eun Kyung" last="Park">Eun Kyung Park</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Dept of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, CA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Dept of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="A2">Dept of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, CA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Dept of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Yang, Dongyun" sort="Yang, Dongyun" uniqKey="Yang D" first="Dongyun" last="Yang">Dongyun Yang</name>
<affiliation wicri:level="2"><nlm:aff id="A3">Dept of Preventive Medicine, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, CA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Dept of Preventive Medicine, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Ecoiffier, Tatiana" sort="Ecoiffier, Tatiana" uniqKey="Ecoiffier T" first="Tatiana" last="Ecoiffier">Tatiana Ecoiffier</name>
<affiliation wicri:level="2"><nlm:aff id="A5">Center of Eye Disease and Development, Program in Vision Science, and School of Optometry, University of California, Berkeley, CA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Center of Eye Disease and Development, Program in Vision Science, and School of Optometry, University of California, Berkeley</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Monahan, John" sort="Monahan, John" uniqKey="Monahan J" first="John" last="Monahan">John Monahan</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Dept of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, CA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Dept of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Chen, Wen" sort="Chen, Wen" uniqKey="Chen W" first="Wen" last="Chen">Wen Chen</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Dept of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, CA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Dept of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Aguilar, Berenice" sort="Aguilar, Berenice" uniqKey="Aguilar B" first="Berenice" last="Aguilar">Berenice Aguilar</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Dept of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, CA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Dept of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="A2">Dept of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, CA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Dept of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Lee, Ha Neul" sort="Lee, Ha Neul" uniqKey="Lee H" first="Ha Neul" last="Lee">Ha Neul Lee</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Dept of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, CA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Dept of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="A2">Dept of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, CA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Dept of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Yoo, Jaehyuk" sort="Yoo, Jaehyuk" uniqKey="Yoo J" first="Jaehyuk" last="Yoo">Jaehyuk Yoo</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Dept of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, CA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Dept of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="A2">Dept of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, CA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Dept of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Koh, Chester J" sort="Koh, Chester J" uniqKey="Koh C" first="Chester J." last="Koh">Chester J. Koh</name>
<affiliation wicri:level="2"><nlm:aff id="A4">Division of Pediatric Urology, Children’s Hospital Los Angeles and University of Southern California Keck School of Medicine, Los Angeles, CA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Division of Pediatric Urology, Children’s Hospital Los Angeles and University of Southern California Keck School of Medicine, Los Angeles</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Chen, Lu" sort="Chen, Lu" uniqKey="Chen L" first="Lu" last="Chen">Lu Chen</name>
<affiliation wicri:level="2"><nlm:aff id="A5">Center of Eye Disease and Development, Program in Vision Science, and School of Optometry, University of California, Berkeley, CA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Center of Eye Disease and Development, Program in Vision Science, and School of Optometry, University of California, Berkeley</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Wong, Alex K" sort="Wong, Alex K" uniqKey="Wong A" first="Alex K." last="Wong">Alex K. Wong</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Dept of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, CA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Dept of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Hong, Young Kwon" sort="Hong, Young Kwon" uniqKey="Hong Y" first="Young-Kwon" last="Hong">Young-Kwon Hong</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Dept of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, CA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Dept of Surgery, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="A2">Dept of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, CA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Dept of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles</wicri:cityArea>
</affiliation>
</author>
</analytic>
<series><title level="j">Circulation</title>
<idno type="ISSN">0009-7322</idno>
<idno type="eISSN">1524-4539</idno>
<imprint><date when="2012">2012</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term>
<term>Aurora Kinases</term>
<term>Cell Movement (drug effects)</term>
<term>Cell Proliferation (drug effects)</term>
<term>Cyclin-Dependent Kinase Inhibitor p27 (genetics)</term>
<term>Cyclin-Dependent Kinase Inhibitor p57 (genetics)</term>
<term>Endothelial Cells (drug effects)</term>
<term>Endothelial Cells (physiology)</term>
<term>Fibroblast Growth Factors (physiology)</term>
<term>Lymphangiogenesis (drug effects)</term>
<term>Lymphatic Vessels (drug effects)</term>
<term>Lymphatic Vessels (physiology)</term>
<term>Lymphedema (drug therapy)</term>
<term>Mice</term>
<term>Mice, Inbred BALB C</term>
<term>Mice, Inbred C57BL</term>
<term>Promoter Regions, Genetic</term>
<term>Protein-Serine-Threonine Kinases (genetics)</term>
<term>Regeneration (drug effects)</term>
<term>Tretinoin (pharmacology)</term>
<term>Tretinoin (therapeutic use)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term>
<term>Aurora kinases</term>
<term>Cellules endothéliales ()</term>
<term>Cellules endothéliales (physiologie)</term>
<term>Facteurs de croissance fibroblastique (physiologie)</term>
<term>Inhibiteur p27 de kinase cycline-dépendante (génétique)</term>
<term>Inhibiteur p57 de kinase cycline-dépendante (génétique)</term>
<term>Lymphangiogenèse ()</term>
<term>Lymphoedème (traitement médicamenteux)</term>
<term>Mouvement cellulaire ()</term>
<term>Prolifération cellulaire ()</term>
<term>Protein-Serine-Threonine Kinases (génétique)</term>
<term>Régions promotrices (génétique)</term>
<term>Régénération ()</term>
<term>Souris</term>
<term>Souris de lignée BALB C</term>
<term>Souris de lignée C57BL</term>
<term>Trétinoïne (pharmacologie)</term>
<term>Trétinoïne (usage thérapeutique)</term>
<term>Vaisseaux lymphatiques ()</term>
<term>Vaisseaux lymphatiques (physiologie)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Cyclin-Dependent Kinase Inhibitor p27</term>
<term>Cyclin-Dependent Kinase Inhibitor p57</term>
<term>Protein-Serine-Threonine Kinases</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Tretinoin</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="physiology" xml:lang="en"><term>Fibroblast Growth Factors</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Tretinoin</term>
</keywords>
<keywords scheme="MESH" type="chemical" xml:lang="en"><term>Aurora Kinases</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Cell Movement</term>
<term>Cell Proliferation</term>
<term>Endothelial Cells</term>
<term>Lymphangiogenesis</term>
<term>Lymphatic Vessels</term>
<term>Regeneration</term>
</keywords>
<keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Lymphedema</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Inhibiteur p27 de kinase cycline-dépendante</term>
<term>Inhibiteur p57 de kinase cycline-dépendante</term>
<term>Protein-Serine-Threonine Kinases</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Trétinoïne</term>
</keywords>
<keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Cellules endothéliales</term>
<term>Facteurs de croissance fibroblastique</term>
<term>Vaisseaux lymphatiques</term>
</keywords>
<keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Endothelial Cells</term>
<term>Lymphatic Vessels</term>
</keywords>
<keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Lymphoedème</term>
</keywords>
<keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Trétinoïne</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Mice</term>
<term>Mice, Inbred BALB C</term>
<term>Mice, Inbred C57BL</term>
<term>Promoter Regions, Genetic</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Animaux</term>
<term>Aurora kinases</term>
<term>Cellules endothéliales</term>
<term>Lymphangiogenèse</term>
<term>Mouvement cellulaire</term>
<term>Prolifération cellulaire</term>
<term>Régions promotrices (génétique)</term>
<term>Régénération</term>
<term>Souris</term>
<term>Souris de lignée BALB C</term>
<term>Souris de lignée C57BL</term>
<term>Vaisseaux lymphatiques</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><sec id="S1"><title>Background</title>
<p id="P2">The lymphatic system plays a key role in tissue fluid homeostasis and lymphatic dysfunction due to genetic defects or lymphatic vessel obstruction can cause lymphedema, disfiguring tissue swellings often associated with fibrosis and recurrent infections without available cures to date. In this study, retinoic acids (RAs) were determined to be a potent therapeutic agent that is immediately applicable to reduce secondary lymphedema.</p>
</sec>
<sec sec-type="methods" id="S2"><title>Methods and Results</title>
<p id="P3">We report that RAs promote proliferation, migration and tube formation of cultured lymphatic endothelial cells (LECs) by activating FGF-receptor signaling. Moreover, RAs control the expression of cell-cycle checkpoint regulators such as p27<sup>Kip1</sup>
, p57<sup>Kip2</sup>
 and the aurora kinases through both an Akt-mediated non-genomic action and a transcription-dependent genomic action that is mediated by Prox1, a master regulator of lymphatic development. Moreover, 9-cisRA was found to activate <italic>in vivo</italic>
 lymphangiogenesis in animals based on mouse trachea, matrigel plug and cornea pocket assays. Finally, we demonstrate that 9-cisRA can provide a strong therapeutic efficacy in ameliorating the experimental mouse tail lymphedema by enhancing lymphatic vessel regeneration.</p>
</sec>
<sec id="S3"><title>Conclusions</title>
<p id="P4">These <italic>in vitro</italic>
 and animal studies demonstrate that 9-cisRA potently activates lymphangiogenesis and promotes lymphatic regeneration in an experimental lymphedema model, presenting it as a promising novel therapeutic agent to treat human lymphedema patients.</p>
</sec>
</div>
</front>
</TEI>
</PMC>
</double>
</record>

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9-Cis Retinoic Acid Promotes Lymphangiogenesis and Enhances Lymphatic Vessel Regeneration Therapeutic Implications of 9-Cis Retinoic Acid for Secondary Lymphedema

9-Cis Retinoic Acid Promotes Lymphangiogenesis and Enhances Lymphatic Vessel Regeneration Therapeutic Implications of 9-Cis Retinoic Acid for Secondary Lymphedema

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