Crizotinib induces autophagy through inhibition of the STAT3 pathway in multiple lung cancer cell lines.
Identifieur interne : 000E92 ( Main/Exploration ); précédent : 000E91; suivant : 000E93Crizotinib induces autophagy through inhibition of the STAT3 pathway in multiple lung cancer cell lines.
Auteurs : Liangkun You [République populaire de Chine] ; Jiawei Shou [République populaire de Chine] ; Danchen Deng [République populaire de Chine] ; Liming Jiang [République populaire de Chine] ; Zhao Jing [République populaire de Chine] ; Junlin Yao [République populaire de Chine] ; Hongsen Li [République populaire de Chine] ; Jiansheng Xie [République populaire de Chine] ; Zhanggui Wang [République populaire de Chine] ; Qin Pan [République populaire de Chine] ; Hongming Pan [République populaire de Chine] ; Wendong Huang [États-Unis] ; Weidong Han [République populaire de Chine]Source :
- Oncotarget [ 1949-2553 ] ; 2015.
Descripteurs français
- KwdFr :
- Animaux, Autophagie (), Facteur de transcription STAT-3 (métabolisme), Facteur-2 d'initiation eucaryote (métabolisme), Femelle, Humains, Hydroxychloroquine (pharmacologie), Immunotransfert, Lignée cellulaire tumorale, Microscopie de fluorescence, Microscopie électronique à transmission, Phagosomes (), Phagosomes (métabolisme), Phagosomes (ultrastructure), Phosphorylation (), Protéines associées aux microtubules (métabolisme), Protéines proto-oncogènes c-bcl-2 (métabolisme), Pyrazoles (pharmacologie), Pyridines (pharmacologie), Souris de lignée BALB C, Souris nude, Survie cellulaire (), Synergie des médicaments, Tests d'activité antitumorale sur modèle de xénogreffe, Transduction du signal (), Tumeurs du poumon (métabolisme), Tumeurs du poumon (traitement médicamenteux).
- MESH :
- métabolisme : Facteur de transcription STAT-3, Facteur-2 d'initiation eucaryote, Phagosomes, Protéines associées aux microtubules, Protéines proto-oncogènes c-bcl-2, Tumeurs du poumon.
- pharmacologie : Hydroxychloroquine, Pyrazoles, Pyridines.
- traitement médicamenteux : Tumeurs du poumon.
- Animaux, Autophagie, Femelle, Humains, Immunotransfert, Lignée cellulaire tumorale, Microscopie de fluorescence, Microscopie électronique à transmission, Phagosomes, Phosphorylation, Souris de lignée BALB C, Souris nude, Survie cellulaire, Synergie des médicaments, Tests d'activité antitumorale sur modèle de xénogreffe, Transduction du signal.
English descriptors
- KwdEn :
- Animals, Autophagy (drug effects), Cell Line, Tumor, Cell Survival (drug effects), Crizotinib, Drug Synergism, Eukaryotic Initiation Factor-2 (metabolism), Female, Humans, Hydroxychloroquine (pharmacology), Immunoblotting, Lung Neoplasms (drug therapy), Lung Neoplasms (metabolism), Mice, Inbred BALB C, Mice, Nude, Microscopy, Electron, Transmission, Microscopy, Fluorescence, Microtubule-Associated Proteins (metabolism), Phagosomes (drug effects), Phagosomes (metabolism), Phagosomes (ultrastructure), Phosphorylation (drug effects), Proto-Oncogene Proteins c-bcl-2 (metabolism), Pyrazoles (pharmacology), Pyridines (pharmacology), STAT3 Transcription Factor (metabolism), Signal Transduction (drug effects), Xenograft Model Antitumor Assays.
- MESH :
- chemical , metabolism : Eukaryotic Initiation Factor-2, Microtubule-Associated Proteins, Proto-Oncogene Proteins c-bcl-2, STAT3 Transcription Factor.
- chemical , pharmacology : Hydroxychloroquine, Pyrazoles, Pyridines.
- chemical : Crizotinib.
- drug effects : Autophagy, Cell Survival, Phagosomes, Phosphorylation, Signal Transduction.
- drug therapy : Lung Neoplasms.
- metabolism : Lung Neoplasms, Phagosomes.
- ultrastructure : Phagosomes.
- Animals, Cell Line, Tumor, Drug Synergism, Female, Humans, Immunoblotting, Mice, Inbred BALB C, Mice, Nude, Microscopy, Electron, Transmission, Microscopy, Fluorescence, Xenograft Model Antitumor Assays.
Abstract
Autophagy is an evolutionarily conserved survival pathway in eukaryote and is frequently upregulated in cancer cells after chemotherapy or targeted therapy. Thus induction of autophagy has emerged as a drug resistance mechanism. In this study, we found that crizotinib induced a high level of autophagy in lung cancer cells through inhibition of STAT3. Ectopic expression of wild-type or constitutive activated STAT3 significantly suppressed the effect of crizotinib on autophagy. Interestingly, crizotinib-mediated inhibition of STAT3 is in a step-wise manner. Firstly it inhibited cytoplasmic STAT3, which leads to the phosphorylation of EIF2A, then inhibited nuclear STAT3, which leads to the downregulation of BCL-2. Cell death induced by crizotinib was greatly enhanced after the inhibition of autophagy by the pharmacological inhibitors or shRNAs against Beclin-1. Moreover, the autophagy inhibitor HCQ significantly augmented the anti-tumor effect of crizotinib in a mouse xenograft model. In conclusion, crizotinib can induce cytoprotective autophagy by suppression of STAT3 in lung cancer cells. Thus, autophagy inhibition represents a promising approach to improve the efficacy of crizotinib in the treatment of targeted lung cancer patients.
DOI: 10.18632/oncotarget.5592
PubMed: 26384345
Affiliations:
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sort="Wang, Zhanggui" uniqKey="Wang Z" first="Zhanggui" last="Wang">Zhanggui Wang</name><affiliation wicri:level="4"><nlm:affiliation>Department of Medical Oncology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Medical Oncology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang</wicri:regionArea><orgName type="university">Université de Zhejiang</orgName><placeName><settlement type="city">Hangzhou</settlement><region type="province">Zhejiang</region></placeName></affiliation></author><author><name sortKey="Pan, Qin" sort="Pan, Qin" uniqKey="Pan Q" first="Qin" last="Pan">Qin Pan</name><affiliation wicri:level="4"><nlm:affiliation>Department of Medical Oncology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.</nlm:affiliation><country 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of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Medical Oncology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang</wicri:regionArea><orgName type="university">Université de Zhejiang</orgName><placeName><settlement type="city">Hangzhou</settlement><region type="province">Zhejiang</region></placeName></affiliation></author><author><name sortKey="Shou, Jiawei" sort="Shou, Jiawei" uniqKey="Shou J" first="Jiawei" last="Shou">Jiawei Shou</name><affiliation wicri:level="4"><nlm:affiliation>Department of Medical Oncology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Medical Oncology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang</wicri:regionArea><orgName type="university">Université de Zhejiang</orgName><placeName><settlement type="city">Hangzhou</settlement><region type="province">Zhejiang</region></placeName></affiliation></author><author><name sortKey="Deng, Danchen" sort="Deng, Danchen" uniqKey="Deng D" first="Danchen" last="Deng">Danchen Deng</name><affiliation wicri:level="4"><nlm:affiliation>Department of Gynaecology and Obstetrics, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Gynaecology and Obstetrics, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang</wicri:regionArea><orgName type="university">Université de Zhejiang</orgName><placeName><settlement type="city">Hangzhou</settlement><region type="province">Zhejiang</region></placeName></affiliation></author><author><name sortKey="Jiang, Liming" sort="Jiang, Liming" uniqKey="Jiang L" first="Liming" last="Jiang">Liming Jiang</name><affiliation wicri:level="4"><nlm:affiliation>Department of Medical Oncology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Medical Oncology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang</wicri:regionArea><orgName type="university">Université de Zhejiang</orgName><placeName><settlement type="city">Hangzhou</settlement><region type="province">Zhejiang</region></placeName></affiliation></author><author><name sortKey="Jing, Zhao" sort="Jing, Zhao" uniqKey="Jing Z" first="Zhao" last="Jing">Zhao Jing</name><affiliation wicri:level="4"><nlm:affiliation>Department of Medical Oncology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Medical Oncology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang</wicri:regionArea><orgName type="university">Université de Zhejiang</orgName><placeName><settlement type="city">Hangzhou</settlement><region type="province">Zhejiang</region></placeName></affiliation></author><author><name sortKey="Yao, Junlin" sort="Yao, Junlin" uniqKey="Yao J" first="Junlin" last="Yao">Junlin Yao</name><affiliation wicri:level="4"><nlm:affiliation>Department of Medical Oncology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Medical Oncology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang</wicri:regionArea><orgName type="university">Université de Zhejiang</orgName><placeName><settlement type="city">Hangzhou</settlement><region type="province">Zhejiang</region></placeName></affiliation></author><author><name sortKey="Li, Hongsen" sort="Li, Hongsen" uniqKey="Li H" first="Hongsen" last="Li">Hongsen Li</name><affiliation wicri:level="4"><nlm:affiliation>Department of Medical Oncology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Medical Oncology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang</wicri:regionArea><orgName type="university">Université de Zhejiang</orgName><placeName><settlement type="city">Hangzhou</settlement><region type="province">Zhejiang</region></placeName></affiliation></author><author><name sortKey="Xie, Jiansheng" sort="Xie, Jiansheng" uniqKey="Xie J" first="Jiansheng" last="Xie">Jiansheng Xie</name><affiliation wicri:level="4"><nlm:affiliation>Biomedical Research Center, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Biomedical Research Center, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang</wicri:regionArea><orgName type="university">Université de Zhejiang</orgName><placeName><settlement type="city">Hangzhou</settlement><region type="province">Zhejiang</region></placeName></affiliation></author><author><name sortKey="Wang, Zhanggui" sort="Wang, Zhanggui" uniqKey="Wang Z" first="Zhanggui" last="Wang">Zhanggui Wang</name><affiliation wicri:level="4"><nlm:affiliation>Department of Medical Oncology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Medical Oncology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang</wicri:regionArea><orgName type="university">Université de Zhejiang</orgName><placeName><settlement type="city">Hangzhou</settlement><region type="province">Zhejiang</region></placeName></affiliation></author><author><name sortKey="Pan, Qin" sort="Pan, Qin" uniqKey="Pan Q" first="Qin" last="Pan">Qin Pan</name><affiliation wicri:level="4"><nlm:affiliation>Department of Medical Oncology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Medical Oncology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang</wicri:regionArea><orgName type="university">Université de Zhejiang</orgName><placeName><settlement type="city">Hangzhou</settlement><region type="province">Zhejiang</region></placeName></affiliation></author><author><name sortKey="Pan, Hongming" sort="Pan, Hongming" uniqKey="Pan H" first="Hongming" last="Pan">Hongming Pan</name><affiliation wicri:level="4"><nlm:affiliation>Department of Medical Oncology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Medical Oncology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang</wicri:regionArea><orgName type="university">Université de Zhejiang</orgName><placeName><settlement type="city">Hangzhou</settlement><region type="province">Zhejiang</region></placeName></affiliation></author><author><name sortKey="Huang, Wendong" sort="Huang, Wendong" uniqKey="Huang W" first="Wendong" last="Huang">Wendong Huang</name><affiliation wicri:level="2"><nlm:affiliation>Division of Molecular Diabetes Research, Department of Diabetes and Metabolic Diseases Research, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Molecular Diabetes Research, Department of Diabetes and Metabolic Diseases Research, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Han, Weidong" sort="Han, Weidong" uniqKey="Han W" first="Weidong" last="Han">Weidong Han</name><affiliation wicri:level="4"><nlm:affiliation>Department of Medical Oncology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Medical Oncology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang</wicri:regionArea><orgName type="university">Université de Zhejiang</orgName><placeName><settlement type="city">Hangzhou</settlement><region type="province">Zhejiang</region></placeName></affiliation></author></analytic><series><title level="j">Oncotarget</title><idno type="eISSN">1949-2553</idno><imprint><date when="2015" type="published">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Autophagy (drug effects)</term><term>Cell Line, Tumor</term><term>Cell Survival (drug effects)</term><term>Crizotinib</term><term>Drug Synergism</term><term>Eukaryotic Initiation Factor-2 (metabolism)</term><term>Female</term><term>Humans</term><term>Hydroxychloroquine (pharmacology)</term><term>Immunoblotting</term><term>Lung Neoplasms (drug therapy)</term><term>Lung Neoplasms (metabolism)</term><term>Mice, Inbred BALB C</term><term>Mice, Nude</term><term>Microscopy, Electron, Transmission</term><term>Microscopy, Fluorescence</term><term>Microtubule-Associated Proteins (metabolism)</term><term>Phagosomes (drug effects)</term><term>Phagosomes (metabolism)</term><term>Phagosomes (ultrastructure)</term><term>Phosphorylation (drug effects)</term><term>Proto-Oncogene Proteins c-bcl-2 (metabolism)</term><term>Pyrazoles (pharmacology)</term><term>Pyridines (pharmacology)</term><term>STAT3 Transcription Factor (metabolism)</term><term>Signal Transduction (drug effects)</term><term>Xenograft Model Antitumor Assays</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Autophagie ()</term><term>Facteur de transcription STAT-3 (métabolisme)</term><term>Facteur-2 d'initiation eucaryote (métabolisme)</term><term>Femelle</term><term>Humains</term><term>Hydroxychloroquine (pharmacologie)</term><term>Immunotransfert</term><term>Lignée cellulaire tumorale</term><term>Microscopie de fluorescence</term><term>Microscopie électronique à transmission</term><term>Phagosomes ()</term><term>Phagosomes (métabolisme)</term><term>Phagosomes (ultrastructure)</term><term>Phosphorylation ()</term><term>Protéines associées aux microtubules (métabolisme)</term><term>Protéines proto-oncogènes c-bcl-2 (métabolisme)</term><term>Pyrazoles (pharmacologie)</term><term>Pyridines (pharmacologie)</term><term>Souris de lignée BALB C</term><term>Souris nude</term><term>Survie cellulaire ()</term><term>Synergie des médicaments</term><term>Tests d'activité antitumorale sur modèle de xénogreffe</term><term>Transduction du signal ()</term><term>Tumeurs du poumon (métabolisme)</term><term>Tumeurs du poumon (traitement médicamenteux)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Eukaryotic Initiation Factor-2</term><term>Microtubule-Associated Proteins</term><term>Proto-Oncogene Proteins c-bcl-2</term><term>STAT3 Transcription Factor</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Hydroxychloroquine</term><term>Pyrazoles</term><term>Pyridines</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>Crizotinib</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Autophagy</term><term>Cell Survival</term><term>Phagosomes</term><term>Phosphorylation</term><term>Signal Transduction</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Lung Neoplasms</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Lung Neoplasms</term><term>Phagosomes</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Facteur de transcription STAT-3</term><term>Facteur-2 d'initiation eucaryote</term><term>Phagosomes</term><term>Protéines associées aux microtubules</term><term>Protéines proto-oncogènes c-bcl-2</term><term>Tumeurs du poumon</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Hydroxychloroquine</term><term>Pyrazoles</term><term>Pyridines</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Tumeurs du poumon</term></keywords><keywords scheme="MESH" qualifier="ultrastructure" xml:lang="en"><term>Phagosomes</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cell Line, Tumor</term><term>Drug Synergism</term><term>Female</term><term>Humans</term><term>Immunoblotting</term><term>Mice, Inbred BALB C</term><term>Mice, Nude</term><term>Microscopy, Electron, Transmission</term><term>Microscopy, Fluorescence</term><term>Xenograft Model Antitumor Assays</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Autophagie</term><term>Femelle</term><term>Humains</term><term>Immunotransfert</term><term>Lignée cellulaire tumorale</term><term>Microscopie de fluorescence</term><term>Microscopie électronique à transmission</term><term>Phagosomes</term><term>Phosphorylation</term><term>Souris de lignée BALB C</term><term>Souris nude</term><term>Survie cellulaire</term><term>Synergie des médicaments</term><term>Tests d'activité antitumorale sur modèle de xénogreffe</term><term>Transduction du signal</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Autophagy is an evolutionarily conserved survival pathway in eukaryote and is frequently upregulated in cancer cells after chemotherapy or targeted therapy. Thus induction of autophagy has emerged as a drug resistance mechanism. In this study, we found that crizotinib induced a high level of autophagy in lung cancer cells through inhibition of STAT3. Ectopic expression of wild-type or constitutive activated STAT3 significantly suppressed the effect of crizotinib on autophagy. Interestingly, crizotinib-mediated inhibition of STAT3 is in a step-wise manner. Firstly it inhibited cytoplasmic STAT3, which leads to the phosphorylation of EIF2A, then inhibited nuclear STAT3, which leads to the downregulation of BCL-2. Cell death induced by crizotinib was greatly enhanced after the inhibition of autophagy by the pharmacological inhibitors or shRNAs against Beclin-1. Moreover, the autophagy inhibitor HCQ significantly augmented the anti-tumor effect of crizotinib in a mouse xenograft model. In conclusion, crizotinib can induce cytoprotective autophagy by suppression of STAT3 in lung cancer cells. Thus, autophagy inhibition represents a promising approach to improve the efficacy of crizotinib in the treatment of targeted lung cancer patients. </div></front></TEI><affiliations><list><country><li>République populaire de Chine</li><li>États-Unis</li></country><region><li>Californie</li><li>Zhejiang</li></region><settlement><li>Hangzhou</li></settlement><orgName><li>Université de Zhejiang</li></orgName></list><tree><country name="République populaire de Chine"><region name="Zhejiang"><name sortKey="You, Liangkun" sort="You, Liangkun" uniqKey="You L" first="Liangkun" last="You">Liangkun You</name></region><name sortKey="Deng, Danchen" sort="Deng, Danchen" uniqKey="Deng D" first="Danchen" last="Deng">Danchen Deng</name><name sortKey="Han, Weidong" sort="Han, Weidong" uniqKey="Han W" first="Weidong" last="Han">Weidong Han</name><name sortKey="Jiang, Liming" sort="Jiang, Liming" uniqKey="Jiang L" first="Liming" last="Jiang">Liming Jiang</name><name sortKey="Jing, Zhao" sort="Jing, Zhao" uniqKey="Jing Z" first="Zhao" last="Jing">Zhao Jing</name><name sortKey="Li, Hongsen" sort="Li, Hongsen" uniqKey="Li H" first="Hongsen" last="Li">Hongsen Li</name><name sortKey="Pan, Hongming" sort="Pan, Hongming" uniqKey="Pan H" first="Hongming" last="Pan">Hongming Pan</name><name sortKey="Pan, Qin" sort="Pan, Qin" uniqKey="Pan Q" first="Qin" last="Pan">Qin Pan</name><name sortKey="Shou, Jiawei" sort="Shou, Jiawei" uniqKey="Shou J" first="Jiawei" last="Shou">Jiawei Shou</name><name sortKey="Wang, Zhanggui" sort="Wang, Zhanggui" uniqKey="Wang Z" first="Zhanggui" last="Wang">Zhanggui Wang</name><name sortKey="Xie, Jiansheng" sort="Xie, Jiansheng" uniqKey="Xie J" first="Jiansheng" last="Xie">Jiansheng Xie</name><name sortKey="Yao, Junlin" sort="Yao, Junlin" uniqKey="Yao J" first="Junlin" last="Yao">Junlin Yao</name></country><country name="États-Unis"><region name="Californie"><name sortKey="Huang, Wendong" sort="Huang, Wendong" uniqKey="Huang W" first="Wendong" last="Huang">Wendong Huang</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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