Therapeutic effects of hyaluronidase on acquired lymphedema using a newly developed mouse limb model.
Identifieur interne : 000067 ( Main/Exploration ); précédent : 000066; suivant : 000068Therapeutic effects of hyaluronidase on acquired lymphedema using a newly developed mouse limb model.
Auteurs : Kangsan Roh [Corée du Sud] ; Sungrae Cho [Corée du Sud] ; Jae-Hyun Park [Corée du Sud] ; Byong Chul Yoo [Corée du Sud] ; Won-Ki Kim [Corée du Sud] ; Seok-Ki Kim [Corée du Sud] ; Kyewon Park [Corée du Sud] ; Hee Kang [Corée du Sud] ; Jin-Mo Ku [Corée du Sud] ; Chang-Hwan Yeom [Corée du Sud] ; Kyunghoon Lee [Corée du Sud] ; Sukchan Lee [Corée du Sud]Source :
- Experimental biology and medicine (Maywood, N.J.) [ 1535-3699 ] ; 2017.
Descripteurs français
- KwdFr :
- MESH :
- traitement médicamenteux : Lymphoedème.
- usage thérapeutique : Hyaluronoglucosaminidase.
- étiologie : Lymphoedème.
- Animaux, Lymphadénectomie, Membre pelvien, Modèles animaux de maladie humaine, Mâle, Souris, Souris de lignée ICR, Tumeurs.
English descriptors
- KwdEn :
- MESH :
- chemical , therapeutic use : Hyaluronoglucosaminidase.
- complications : Neoplasms.
- drug therapy : Lymphedema.
- etiology : Lymphedema.
- Animals, Disease Models, Animal, Hindlimb, Lymph Node Excision, Male, Mice, Mice, Inbred ICR.
Abstract
Acquired lymphedema is one of the most dreaded side effects of cancer treatment, such as surgical treatment or irradiation. However, due to the lack of appropriate animal models, there is no effective therapeutic method to cure acquired lymphedema. To develop a reproducible acquired lymphedema animal model, we devised a mouse hind limb model by removing a superficial inguinal lymph node, a popliteal lymph node, a deep inguinal lymph node, and the femoral lymphatic vessel. We measured the volume of lymphedematous leg and observed the change in level of hyaluronic acid (HA) and lymphangiogenic factors after injecting hyaluronidase. Our model showed the distinguishable swelling and the reliable symptoms compared to previously reported models. In the lymphedematous regions of our model, we confirmed that HA, a major component of extracellular matrix, accumulated to higher levels than in a normal mouse. This lymphedema volume was rapidly reduced by treating hyaluronidase. Following hyaluronidase injection, the lymphedematous region of our model resembled a normal hind limb. Our findings indicated that hyaluronidase promoted lymphangiogenesis on the lymphedematous limb. Based on hyaluronidase treatment in the lymphedematous region, this could potentially be a new therapeutic approach for acquired lymphedema mediated through the modification of the size of HA fragments. Impact statement In this manuscript, the essence of the work described in this manuscript involves the development of (1) a mouse limb model showing acquired lymphedema and (2) a potent therapeutic treatment using hyaluronidase to remedy acquired lymphedema in our model. In order to develop a reproducible acquired lymphedema animal model that reflects the most common symptoms experienced by lymphedema patients, we devised a mouse hind limb model by removing lymph nodes and lymphatics. Our model showed the distinguishable swelling and the reliable symptoms compared to previously reported models. In the lymphedematous regions of our model, we confirmed that hyaluronic acid (HA) accumulated to higher levels than in a normal mouse. This lymphedema volume was rapidly reduced by treating the lymphedematous leg with hyaluronidase, which also degraded high molecular weight HA to low molecular weight HA. Immunohistochemical analysis, quantitative real-time PCR analysis and lymphangioscintigraphy showed that hyaluronidase enhanced lymphangiogenesis in the lymphedematous limb.
DOI: 10.1177/1535370216688570
PubMed: 28092183
Affiliations:
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first="Kangsan" last="Roh">Kangsan Roh</name><affiliation wicri:level="1"><nlm:affiliation>1 Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>1 Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746</wicri:regionArea><wicri:noRegion>Suwon 440-746</wicri:noRegion></affiliation></author><author><name sortKey="Cho, Sungrae" sort="Cho, Sungrae" uniqKey="Cho S" first="Sungrae" last="Cho">Sungrae Cho</name><affiliation wicri:level="1"><nlm:affiliation>1 Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>1 Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746</wicri:regionArea><wicri:noRegion>Suwon 440-746</wicri:noRegion></affiliation></author><author><name sortKey="Park, Jae Hyun" sort="Park, Jae Hyun" uniqKey="Park J" first="Jae-Hyun" last="Park">Jae-Hyun Park</name><affiliation wicri:level="1"><nlm:affiliation>1 Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>1 Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746</wicri:regionArea><wicri:noRegion>Suwon 440-746</wicri:noRegion></affiliation></author><author><name sortKey="Yoo, Byong Chul" sort="Yoo, Byong Chul" uniqKey="Yoo B" first="Byong Chul" last="Yoo">Byong Chul Yoo</name><affiliation wicri:level="1"><nlm:affiliation>2 Colorectal Cancer Branch, Division of Translational and Clinical Research I, Research Institute, National Cancer Center, Goyang 410-769, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>2 Colorectal Cancer Branch, Division of Translational and Clinical Research I, Research Institute, National Cancer Center, Goyang 410-769</wicri:regionArea><wicri:noRegion>Goyang 410-769</wicri:noRegion></affiliation></author><author><name sortKey="Kim, Won Ki" sort="Kim, Won Ki" uniqKey="Kim W" first="Won-Ki" last="Kim">Won-Ki Kim</name><affiliation wicri:level="1"><nlm:affiliation>2 Colorectal Cancer Branch, Division of Translational and Clinical Research I, Research Institute, National Cancer Center, Goyang 410-769, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>2 Colorectal Cancer Branch, Division of Translational and Clinical Research I, Research Institute, National Cancer Center, Goyang 410-769</wicri:regionArea><wicri:noRegion>Goyang 410-769</wicri:noRegion></affiliation></author><author><name sortKey="Kim, Seok Ki" sort="Kim, Seok Ki" uniqKey="Kim S" first="Seok-Ki" last="Kim">Seok-Ki Kim</name><affiliation wicri:level="1"><nlm:affiliation>3 Molecular Imaging & Therapy Branch, National Cancer Center, Goyang 410-769, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>3 Molecular Imaging & Therapy Branch, National Cancer Center, Goyang 410-769</wicri:regionArea><wicri:noRegion>Goyang 410-769</wicri:noRegion></affiliation></author><author><name sortKey="Park, Kyewon" sort="Park, Kyewon" uniqKey="Park K" first="Kyewon" last="Park">Kyewon Park</name><affiliation wicri:level="1"><nlm:affiliation>4 Department of Food Science and Biotechnology, Sungkyunkwan University, Suwon 440-746, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>4 Department of Food Science and Biotechnology, Sungkyunkwan University, Suwon 440-746</wicri:regionArea><wicri:noRegion>Suwon 440-746</wicri:noRegion></affiliation></author><author><name sortKey="Kang, Hee" sort="Kang, Hee" uniqKey="Kang H" first="Hee" last="Kang">Hee Kang</name><affiliation wicri:level="1"><nlm:affiliation>5 Department of Oriental Medical Science, Graduate School of East-West Medicine, Kyunghee University, Secheondong, Yongin 446-701, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>5 Department of Oriental Medical Science, Graduate School of East-West Medicine, Kyunghee University, Secheondong, Yongin 446-701</wicri:regionArea><wicri:noRegion>Yongin 446-701</wicri:noRegion></affiliation></author><author><name sortKey="Ku, Jin Mo" sort="Ku, Jin Mo" uniqKey="Ku J" first="Jin-Mo" last="Ku">Jin-Mo Ku</name><affiliation wicri:level="1"><nlm:affiliation>6 Natural Products Research Department, Gyeonggi Institute of Science & Technology, Suwon 443-270, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>6 Natural Products Research Department, Gyeonggi Institute of Science & Technology, Suwon 443-270</wicri:regionArea><wicri:noRegion>Suwon 443-270</wicri:noRegion></affiliation></author><author><name sortKey="Yeom, Chang Hwan" sort="Yeom, Chang Hwan" uniqKey="Yeom C" first="Chang-Hwan" last="Yeom">Chang-Hwan Yeom</name><affiliation wicri:level="1"><nlm:affiliation>7 U-Cell Clinic, Seoul 137-071, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>7 U-Cell Clinic, Seoul 137-071</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Lee, Kyunghoon" sort="Lee, Kyunghoon" uniqKey="Lee K" first="Kyunghoon" last="Lee">Kyunghoon Lee</name><affiliation wicri:level="1"><nlm:affiliation>8 Department of Anatomy, School of Medicine, Sungkyunkwan University, Suwon 440-746, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>8 Department of Anatomy, School of Medicine, Sungkyunkwan University, Suwon 440-746</wicri:regionArea><wicri:noRegion>Suwon 440-746</wicri:noRegion></affiliation></author><author><name sortKey="Lee, Sukchan" sort="Lee, Sukchan" uniqKey="Lee S" first="Sukchan" last="Lee">Sukchan Lee</name><affiliation wicri:level="1"><nlm:affiliation>1 Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>1 Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746</wicri:regionArea><wicri:noRegion>Suwon 440-746</wicri:noRegion></affiliation></author></analytic><series><title level="j">Experimental biology and medicine (Maywood, N.J.)</title><idno type="eISSN">1535-3699</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Disease Models, Animal</term><term>Hindlimb</term><term>Hyaluronoglucosaminidase (therapeutic use)</term><term>Lymph Node Excision</term><term>Lymphedema (drug therapy)</term><term>Lymphedema (etiology)</term><term>Male</term><term>Mice</term><term>Mice, Inbred ICR</term><term>Neoplasms (complications)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Hyaluronoglucosaminidase (usage thérapeutique)</term><term>Lymphadénectomie</term><term>Lymphoedème (traitement médicamenteux)</term><term>Lymphoedème (étiologie)</term><term>Membre pelvien</term><term>Modèles animaux de maladie humaine</term><term>Mâle</term><term>Souris</term><term>Souris de lignée ICR</term><term>Tumeurs ()</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Hyaluronoglucosaminidase</term></keywords><keywords scheme="MESH" qualifier="complications" xml:lang="en"><term>Neoplasms</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Lymphedema</term></keywords><keywords scheme="MESH" qualifier="etiology" xml:lang="en"><term>Lymphedema</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>Hyaluronoglucosaminidase</term></keywords><keywords scheme="MESH" qualifier="étiologie" xml:lang="fr"><term>Lymphoedème</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Disease Models, Animal</term><term>Hindlimb</term><term>Lymph Node Excision</term><term>Male</term><term>Mice</term><term>Mice, Inbred ICR</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Lymphadénectomie</term><term>Membre pelvien</term><term>Modèles animaux de maladie humaine</term><term>Mâle</term><term>Souris</term><term>Souris de lignée ICR</term><term>Tumeurs</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Acquired lymphedema is one of the most dreaded side effects of cancer treatment, such as surgical treatment or irradiation. However, due to the lack of appropriate animal models, there is no effective therapeutic method to cure acquired lymphedema. To develop a reproducible acquired lymphedema animal model, we devised a mouse hind limb model by removing a superficial inguinal lymph node, a popliteal lymph node, a deep inguinal lymph node, and the femoral lymphatic vessel. We measured the volume of lymphedematous leg and observed the change in level of hyaluronic acid (HA) and lymphangiogenic factors after injecting hyaluronidase. Our model showed the distinguishable swelling and the reliable symptoms compared to previously reported models. In the lymphedematous regions of our model, we confirmed that HA, a major component of extracellular matrix, accumulated to higher levels than in a normal mouse. This lymphedema volume was rapidly reduced by treating hyaluronidase. Following hyaluronidase injection, the lymphedematous region of our model resembled a normal hind limb. Our findings indicated that hyaluronidase promoted lymphangiogenesis on the lymphedematous limb. Based on hyaluronidase treatment in the lymphedematous region, this could potentially be a new therapeutic approach for acquired lymphedema mediated through the modification of the size of HA fragments. Impact statement In this manuscript, the essence of the work described in this manuscript involves the development of (1) a mouse limb model showing acquired lymphedema and (2) a potent therapeutic treatment using hyaluronidase to remedy acquired lymphedema in our model. In order to develop a reproducible acquired lymphedema animal model that reflects the most common symptoms experienced by lymphedema patients, we devised a mouse hind limb model by removing lymph nodes and lymphatics. Our model showed the distinguishable swelling and the reliable symptoms compared to previously reported models. In the lymphedematous regions of our model, we confirmed that hyaluronic acid (HA) accumulated to higher levels than in a normal mouse. This lymphedema volume was rapidly reduced by treating the lymphedematous leg with hyaluronidase, which also degraded high molecular weight HA to low molecular weight HA. Immunohistochemical analysis, quantitative real-time PCR analysis and lymphangioscintigraphy showed that hyaluronidase enhanced lymphangiogenesis in the lymphedematous limb.</div></front></TEI><affiliations><list><country><li>Corée du Sud</li></country><region><li>Région capitale de Séoul</li></region><settlement><li>Séoul</li></settlement></list><tree><country name="Corée du Sud"><noRegion><name sortKey="Roh, Kangsan" sort="Roh, Kangsan" uniqKey="Roh K" first="Kangsan" last="Roh">Kangsan Roh</name></noRegion><name sortKey="Cho, Sungrae" sort="Cho, Sungrae" uniqKey="Cho S" first="Sungrae" last="Cho">Sungrae Cho</name><name sortKey="Kang, Hee" sort="Kang, Hee" uniqKey="Kang H" first="Hee" last="Kang">Hee Kang</name><name sortKey="Kim, Seok Ki" sort="Kim, Seok Ki" uniqKey="Kim S" first="Seok-Ki" last="Kim">Seok-Ki Kim</name><name sortKey="Kim, Won Ki" sort="Kim, Won Ki" uniqKey="Kim W" first="Won-Ki" last="Kim">Won-Ki Kim</name><name sortKey="Ku, Jin Mo" sort="Ku, Jin Mo" uniqKey="Ku J" first="Jin-Mo" last="Ku">Jin-Mo Ku</name><name sortKey="Lee, Kyunghoon" sort="Lee, Kyunghoon" uniqKey="Lee K" first="Kyunghoon" last="Lee">Kyunghoon Lee</name><name sortKey="Lee, Sukchan" sort="Lee, Sukchan" uniqKey="Lee S" first="Sukchan" last="Lee">Sukchan Lee</name><name sortKey="Park, Jae Hyun" sort="Park, Jae Hyun" uniqKey="Park J" first="Jae-Hyun" last="Park">Jae-Hyun Park</name><name sortKey="Park, Kyewon" sort="Park, Kyewon" uniqKey="Park K" first="Kyewon" last="Park">Kyewon Park</name><name sortKey="Yeom, Chang Hwan" sort="Yeom, Chang Hwan" uniqKey="Yeom C" first="Chang-Hwan" last="Yeom">Chang-Hwan Yeom</name><name sortKey="Yoo, Byong Chul" sort="Yoo, Byong Chul" uniqKey="Yoo B" first="Byong Chul" last="Yoo">Byong Chul Yoo</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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