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PMID: 24853380 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

Overactivated neddylation pathway as a therapeutic target in lung cancer.

Journal of the National Cancer Institute ·Vol. 106 ·No. 6 ·2014-06-00 ·Pages dju083

Li L, Wang M, Yu G, Chen P, Li H, Wei D, Zhu J, Xie L, Jia H, Shi J, Li C, Yao W, Wang Y, Gao Q, Jeong LS, Lee HW, Yu J, Hu F, Mei J, Wang P, Chu Y, Qi H, Yang M, Dong Z, Sun Y, Hoffman RM, Jia L

Abstract

A number of oncoproteins and tumor suppressors are known to be neddylated, but whether the neddylation pathway is entirely activated in human cancer remains unexplored. NEDD8-activating enzyme (NAE) (E1) and NEDD8-conjugating enzyme (E2) expression and global-protein neddylation were examined by immunohistochemistry, immunoblotting, and real-time polymerase chain reaction analysis. Cell proliferation, clonogenic survival, migration, and motility in vitro, as well as tumor formation and metastasis in vivo, were determined upon neddylation inhibition by MLN4924, an investigational NEDD8-activating enzyme inhibitor. Survival was analyzed with Kaplan-Meier methods and compared by the log-rank test. All statistical tests were two-sided. The entire neddylation pathway, including NEDD8-activating enzyme E1, NEDD8-conjugating enzyme E2, and global-protein neddylation, is overactivated in both lung adenocarcinoma and squamous-cell carcinoma. Compared with lung adenocarcinoma patients with low expression, those with high expression had worse overall survival (NEDD8-activating enzyme E1 subunit 1 [NAE1]: hazard ratio [HR] = 2.07, 95% confidence interval [CI] = 0.95 to 4.52, P = .07; ubiquitin-conjugating enzyme E2M (UBC12): HR = 13.26, 95% CI = 1.77 to 99.35, P = .01; global protein neddylation: HR = 3.74, 95% CI = 1.65 to 8.47, P = .002). Moreover, inhibition of neddylation by the NAE inhibitor MLN4924 statistically significantly suppressed proliferation, survival, migration, and motility of lung cancer cells in vitro and tumor formation and metastasis in vivo. At the molecular level, MLN4924 inactivated Cullin-RING E3 ligases, led to accumulation of tumor-suppressive Cullin-RING E3 ligase substrates and induced phorbol-12-myristate-13-acetate-induced protein 1 (NOXA)-dependent apoptosis or cellular senescence. Our study highlights the overactivated neddylation pathway in lung cancer development and as a promising therapeutic target.

MeSH Terms
Adenocarcinoma/drug therapy,enzymology Adenocarcinoma of Lung Antineoplastic Agents/pharmacology Carcinoma, Squamous Cell/drug therapy,enzymology Cell Line, Tumor Cell Movement/drug effects Cell Proliferation/drug effects Cell Survival/drug effects Cyclopentanes/pharmacology Flow Cytometry Gene Expression Regulation, Enzymologic/drug effects Gene Expression Regulation, Neoplastic/drug effects Humans Immunoblotting Immunohistochemistry Lung Neoplasms/drug therapy,enzymology,pathology Molecular Targeted Therapy/methods NEDD8 Protein Pyrimidines/pharmacology Real-Time Polymerase Chain Reaction Signal Transduction/drug effects Tumor Stem Cell Assay Ubiquitins/antagonists & inhibitors,metabolism
Chemicals
Antineoplastic Agents Cyclopentanes NEDD8 Protein NEDD8 protein, human Pyrimidines Ubiquitins pevonedistat
Authors & Affiliations
27 authors, click to expand affiliations / ORCID
Li Lihui
Affiliations of authors: Cancer Institute, Fudan University Shanghai Cancer Center (LL, GY, PC, DW, CL, WY, YW, LJ), Department of Oncology, Shanghai Medical College (LL, GY, PC, DW, CL, WY, YW, LJ), Department of Immunology, School of Basic Medical Sciences (LL, GY, CL, YW, YC, LJ), Clinical Statistics Center, Department of Radiation Oncology, Fudan University Shanghai Cancer Center (JZ, LX, HJ), and Liver Cancer Institute, Zhongshan Hospital (JS, QG), Fudan University, Shanghai, 200032, China; Department of Thoracic Cardiovascular Surgery, Xinhua Hospital of Shanghai Jiaotong University School of Medicine, Shanghai, China (MW, FH, JM); College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China (PC, ZD); Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China (HL, PW); College of Pharmacy, Seoul National University, Seoul, Korea (LSJ); College of Pharmacy, Ewha Womans University, Seoul, Korea (LSJ, HWL, JY); AntiCancer Biotech Beijing Co. Ltd., Beijing, China (HQ, MY); Division of Radiation and Cancer Biology, Department of Radiation Oncology, University of Michigan, Ann Arbor, MI (YS); Department of Surgery, University of California, San Diego, CA (RMH); AntiCancer, Inc., San Diego, CA (RMH, MY).
Wang Mingsong
Affiliations of authors: Cancer Institute, Fudan University Shanghai Cancer Center (LL, GY, PC, DW, CL, WY, YW, LJ), Department of Oncology, Shanghai Medical College (LL, GY, PC, DW, CL, WY, YW, LJ), Department of Immunology, School of Basic Medical Sciences (LL, GY, CL, YW, YC, LJ), Clinical Statistics Center, Department of Radiation Oncology, Fudan University Shanghai Cancer Center (JZ, LX, HJ), and Liver Cancer Institute, Zhongshan Hospital (JS, QG), Fudan University, Shanghai, 200032, China; Department of Thoracic Cardiovascular Surgery, Xinhua Hospital of Shanghai Jiaotong University School of Medicine, Shanghai, China (MW, FH, JM); College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China (PC, ZD); Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China (HL, PW); College of Pharmacy, Seoul National University, Seoul, Korea (LSJ); College of Pharmacy, Ewha Womans University, Seoul, Korea (LSJ, HWL, JY); AntiCancer Biotech Beijing Co. Ltd., Beijing, China (HQ, MY); Division of Radiation and Cancer Biology, Department of Radiation Oncology, University of Michigan, Ann Arbor, MI (YS); Department of Surgery, University of California, San Diego, CA (RMH); AntiCancer, Inc., San Diego, CA (RMH, MY).
Yu Guangyang
Affiliations of authors: Cancer Institute, Fudan University Shanghai Cancer Center (LL, GY, PC, DW, CL, WY, YW, LJ), Department of Oncology, Shanghai Medical College (LL, GY, PC, DW, CL, WY, YW, LJ), Department of Immunology, School of Basic Medical Sciences (LL, GY, CL, YW, YC, LJ), Clinical Statistics Center, Department of Radiation Oncology, Fudan University Shanghai Cancer Center (JZ, LX, HJ), and Liver Cancer Institute, Zhongshan Hospital (JS, QG), Fudan University, Shanghai, 200032, China; Department of Thoracic Cardiovascular Surgery, Xinhua Hospital of Shanghai Jiaotong University School of Medicine, Shanghai, China (MW, FH, JM); College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China (PC, ZD); Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China (HL, PW); College of Pharmacy, Seoul National University, Seoul, Korea (LSJ); College of Pharmacy, Ewha Womans University, Seoul, Korea (LSJ, HWL, JY); AntiCancer Biotech Beijing Co. Ltd., Beijing, China (HQ, MY); Division of Radiation and Cancer Biology, Department of Radiation Oncology, University of Michigan, Ann Arbor, MI (YS); Department of Surgery, University of California, San Diego, CA (RMH); AntiCancer, Inc., San Diego, CA (RMH, MY).
Chen Ping
Affiliations of authors: Cancer Institute, Fudan University Shanghai Cancer Center (LL, GY, PC, DW, CL, WY, YW, LJ), Department of Oncology, Shanghai Medical College (LL, GY, PC, DW, CL, WY, YW, LJ), Department of Immunology, School of Basic Medical Sciences (LL, GY, CL, YW, YC, LJ), Clinical Statistics Center, Department of Radiation Oncology, Fudan University Shanghai Cancer Center (JZ, LX, HJ), and Liver Cancer Institute, Zhongshan Hospital (JS, QG), Fudan University, Shanghai, 200032, China; Department of Thoracic Cardiovascular Surgery, Xinhua Hospital of Shanghai Jiaotong University School of Medicine, Shanghai, China (MW, FH, JM); College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China (PC, ZD); Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China (HL, PW); College of Pharmacy, Seoul National University, Seoul, Korea (LSJ); College of Pharmacy, Ewha Womans University, Seoul, Korea (LSJ, HWL, JY); AntiCancer Biotech Beijing Co. Ltd., Beijing, China (HQ, MY); Division of Radiation and Cancer Biology, Department of Radiation Oncology, University of Michigan, Ann Arbor, MI (YS); Department of Surgery, University of California, San Diego, CA (RMH); AntiCancer, Inc., San Diego, CA (RMH, MY).
Li Hui
Affiliations of authors: Cancer Institute, Fudan University Shanghai Cancer Center (LL, GY, PC, DW, CL, WY, YW, LJ), Department of Oncology, Shanghai Medical College (LL, GY, PC, DW, CL, WY, YW, LJ), Department of Immunology, School of Basic Medical Sciences (LL, GY, CL, YW, YC, LJ), Clinical Statistics Center, Department of Radiation Oncology, Fudan University Shanghai Cancer Center (JZ, LX, HJ), and Liver Cancer Institute, Zhongshan Hospital (JS, QG), Fudan University, Shanghai, 200032, China; Department of Thoracic Cardiovascular Surgery, Xinhua Hospital of Shanghai Jiaotong University School of Medicine, Shanghai, China (MW, FH, JM); College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China (PC, ZD); Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China (HL, PW); College of Pharmacy, Seoul National University, Seoul, Korea (LSJ); College of Pharmacy, Ewha Womans University, Seoul, Korea (LSJ, HWL, JY); AntiCancer Biotech Beijing Co. Ltd., Beijing, China (HQ, MY); Division of Radiation and Cancer Biology, Department of Radiation Oncology, University of Michigan, Ann Arbor, MI (YS); Department of Surgery, University of California, San Diego, CA (RMH); AntiCancer, Inc., San Diego, CA (RMH, MY).
Wei Dongping
Affiliations of authors: Cancer Institute, Fudan University Shanghai Cancer Center (LL, GY, PC, DW, CL, WY, YW, LJ), Department of Oncology, Shanghai Medical College (LL, GY, PC, DW, CL, WY, YW, LJ), Department of Immunology, School of Basic Medical Sciences (LL, GY, CL, YW, YC, LJ), Clinical Statistics Center, Department of Radiation Oncology, Fudan University Shanghai Cancer Center (JZ, LX, HJ), and Liver Cancer Institute, Zhongshan Hospital (JS, QG), Fudan University, Shanghai, 200032, China; Department of Thoracic Cardiovascular Surgery, Xinhua Hospital of Shanghai Jiaotong University School of Medicine, Shanghai, China (MW, FH, JM); College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China (PC, ZD); Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China (HL, PW); College of Pharmacy, Seoul National University, Seoul, Korea (LSJ); College of Pharmacy, Ewha Womans University, Seoul, Korea (LSJ, HWL, JY); AntiCancer Biotech Beijing Co. Ltd., Beijing, China (HQ, MY); Division of Radiation and Cancer Biology, Department of Radiation Oncology, University of Michigan, Ann Arbor, MI (YS); Department of Surgery, University of California, San Diego, CA (RMH); AntiCancer, Inc., San Diego, CA (RMH, MY).
Zhu Ji
Affiliations of authors: Cancer Institute, Fudan University Shanghai Cancer Center (LL, GY, PC, DW, CL, WY, YW, LJ), Department of Oncology, Shanghai Medical College (LL, GY, PC, DW, CL, WY, YW, LJ), Department of Immunology, School of Basic Medical Sciences (LL, GY, CL, YW, YC, LJ), Clinical Statistics Center, Department of Radiation Oncology, Fudan University Shanghai Cancer Center (JZ, LX, HJ), and Liver Cancer Institute, Zhongshan Hospital (JS, QG), Fudan University, Shanghai, 200032, China; Department of Thoracic Cardiovascular Surgery, Xinhua Hospital of Shanghai Jiaotong University School of Medicine, Shanghai, China (MW, FH, JM); College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China (PC, ZD); Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China (HL, PW); College of Pharmacy, Seoul National University, Seoul, Korea (LSJ); College of Pharmacy, Ewha Womans University, Seoul, Korea (LSJ, HWL, JY); AntiCancer Biotech Beijing Co. Ltd., Beijing, China (HQ, MY); Division of Radiation and Cancer Biology, Department of Radiation Oncology, University of Michigan, Ann Arbor, MI (YS); Department of Surgery, University of California, San Diego, CA (RMH); AntiCancer, Inc., San Diego, CA (RMH, MY).
Xie Li
Affiliations of authors: Cancer Institute, Fudan University Shanghai Cancer Center (LL, GY, PC, DW, CL, WY, YW, LJ), Department of Oncology, Shanghai Medical College (LL, GY, PC, DW, CL, WY, YW, LJ), Department of Immunology, School of Basic Medical Sciences (LL, GY, CL, YW, YC, LJ), Clinical Statistics Center, Department of Radiation Oncology, Fudan University Shanghai Cancer Center (JZ, LX, HJ), and Liver Cancer Institute, Zhongshan Hospital (JS, QG), Fudan University, Shanghai, 200032, China; Department of Thoracic Cardiovascular Surgery, Xinhua Hospital of Shanghai Jiaotong University School of Medicine, Shanghai, China (MW, FH, JM); College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China (PC, ZD); Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China (HL, PW); College of Pharmacy, Seoul National University, Seoul, Korea (LSJ); College of Pharmacy, Ewha Womans University, Seoul, Korea (LSJ, HWL, JY); AntiCancer Biotech Beijing Co. Ltd., Beijing, China (HQ, MY); Division of Radiation and Cancer Biology, Department of Radiation Oncology, University of Michigan, Ann Arbor, MI (YS); Department of Surgery, University of California, San Diego, CA (RMH); AntiCancer, Inc., San Diego, CA (RMH, MY).
Jia Huixun
Affiliations of authors: Cancer Institute, Fudan University Shanghai Cancer Center (LL, GY, PC, DW, CL, WY, YW, LJ), Department of Oncology, Shanghai Medical College (LL, GY, PC, DW, CL, WY, YW, LJ), Department of Immunology, School of Basic Medical Sciences (LL, GY, CL, YW, YC, LJ), Clinical Statistics Center, Department of Radiation Oncology, Fudan University Shanghai Cancer Center (JZ, LX, HJ), and Liver Cancer Institute, Zhongshan Hospital (JS, QG), Fudan University, Shanghai, 200032, China; Department of Thoracic Cardiovascular Surgery, Xinhua Hospital of Shanghai Jiaotong University School of Medicine, Shanghai, China (MW, FH, JM); College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China (PC, ZD); Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China (HL, PW); College of Pharmacy, Seoul National University, Seoul, Korea (LSJ); College of Pharmacy, Ewha Womans University, Seoul, Korea (LSJ, HWL, JY); AntiCancer Biotech Beijing Co. Ltd., Beijing, China (HQ, MY); Division of Radiation and Cancer Biology, Department of Radiation Oncology, University of Michigan, Ann Arbor, MI (YS); Department of Surgery, University of California, San Diego, CA (RMH); AntiCancer, Inc., San Diego, CA (RMH, MY).
Shi Jieyi
Affiliations of authors: Cancer Institute, Fudan University Shanghai Cancer Center (LL, GY, PC, DW, CL, WY, YW, LJ), Department of Oncology, Shanghai Medical College (LL, GY, PC, DW, CL, WY, YW, LJ), Department of Immunology, School of Basic Medical Sciences (LL, GY, CL, YW, YC, LJ), Clinical Statistics Center, Department of Radiation Oncology, Fudan University Shanghai Cancer Center (JZ, LX, HJ), and Liver Cancer Institute, Zhongshan Hospital (JS, QG), Fudan University, Shanghai, 200032, China; Department of Thoracic Cardiovascular Surgery, Xinhua Hospital of Shanghai Jiaotong University School of Medicine, Shanghai, China (MW, FH, JM); College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China (PC, ZD); Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China (HL, PW); College of Pharmacy, Seoul National University, Seoul, Korea (LSJ); College of Pharmacy, Ewha Womans University, Seoul, Korea (LSJ, HWL, JY); AntiCancer Biotech Beijing Co. Ltd., Beijing, China (HQ, MY); Division of Radiation and Cancer Biology, Department of Radiation Oncology, University of Michigan, Ann Arbor, MI (YS); Department of Surgery, University of California, San Diego, CA (RMH); AntiCancer, Inc., San Diego, CA (RMH, MY).
Li Chunjie
Affiliations of authors: Cancer Institute, Fudan University Shanghai Cancer Center (LL, GY, PC, DW, CL, WY, YW, LJ), Department of Oncology, Shanghai Medical College (LL, GY, PC, DW, CL, WY, YW, LJ), Department of Immunology, School of Basic Medical Sciences (LL, GY, CL, YW, YC, LJ), Clinical Statistics Center, Department of Radiation Oncology, Fudan University Shanghai Cancer Center (JZ, LX, HJ), and Liver Cancer Institute, Zhongshan Hospital (JS, QG), Fudan University, Shanghai, 200032, China; Department of Thoracic Cardiovascular Surgery, Xinhua Hospital of Shanghai Jiaotong University School of Medicine, Shanghai, China (MW, FH, JM); College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China (PC, ZD); Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China (HL, PW); College of Pharmacy, Seoul National University, Seoul, Korea (LSJ); College of Pharmacy, Ewha Womans University, Seoul, Korea (LSJ, HWL, JY); AntiCancer Biotech Beijing Co. Ltd., Beijing, China (HQ, MY); Division of Radiation and Cancer Biology, Department of Radiation Oncology, University of Michigan, Ann Arbor, MI (YS); Department of Surgery, University of California, San Diego, CA (RMH); AntiCancer, Inc., San Diego, CA (RMH, MY).
Yao Wantong
Affiliations of authors: Cancer Institute, Fudan University Shanghai Cancer Center (LL, GY, PC, DW, CL, WY, YW, LJ), Department of Oncology, Shanghai Medical College (LL, GY, PC, DW, CL, WY, YW, LJ), Department of Immunology, School of Basic Medical Sciences (LL, GY, CL, YW, YC, LJ), Clinical Statistics Center, Department of Radiation Oncology, Fudan University Shanghai Cancer Center (JZ, LX, HJ), and Liver Cancer Institute, Zhongshan Hospital (JS, QG), Fudan University, Shanghai, 200032, China; Department of Thoracic Cardiovascular Surgery, Xinhua Hospital of Shanghai Jiaotong University School of Medicine, Shanghai, China (MW, FH, JM); College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China (PC, ZD); Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China (HL, PW); College of Pharmacy, Seoul National University, Seoul, Korea (LSJ); College of Pharmacy, Ewha Womans University, Seoul, Korea (LSJ, HWL, JY); AntiCancer Biotech Beijing Co. Ltd., Beijing, China (HQ, MY); Division of Radiation and Cancer Biology, Department of Radiation Oncology, University of Michigan, Ann Arbor, MI (YS); Department of Surgery, University of California, San Diego, CA (RMH); AntiCancer, Inc., San Diego, CA (RMH, MY).
Wang Yanchun
Affiliations of authors: Cancer Institute, Fudan University Shanghai Cancer Center (LL, GY, PC, DW, CL, WY, YW, LJ), Department of Oncology, Shanghai Medical College (LL, GY, PC, DW, CL, WY, YW, LJ), Department of Immunology, School of Basic Medical Sciences (LL, GY, CL, YW, YC, LJ), Clinical Statistics Center, Department of Radiation Oncology, Fudan University Shanghai Cancer Center (JZ, LX, HJ), and Liver Cancer Institute, Zhongshan Hospital (JS, QG), Fudan University, Shanghai, 200032, China; Department of Thoracic Cardiovascular Surgery, Xinhua Hospital of Shanghai Jiaotong University School of Medicine, Shanghai, China (MW, FH, JM); College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China (PC, ZD); Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China (HL, PW); College of Pharmacy, Seoul National University, Seoul, Korea (LSJ); College of Pharmacy, Ewha Womans University, Seoul, Korea (LSJ, HWL, JY); AntiCancer Biotech Beijing Co. Ltd., Beijing, China (HQ, MY); Division of Radiation and Cancer Biology, Department of Radiation Oncology, University of Michigan, Ann Arbor, MI (YS); Department of Surgery, University of California, San Diego, CA (RMH); AntiCancer, Inc., San Diego, CA (RMH, MY).
Gao Qiang
Affiliations of authors: Cancer Institute, Fudan University Shanghai Cancer Center (LL, GY, PC, DW, CL, WY, YW, LJ), Department of Oncology, Shanghai Medical College (LL, GY, PC, DW, CL, WY, YW, LJ), Department of Immunology, School of Basic Medical Sciences (LL, GY, CL, YW, YC, LJ), Clinical Statistics Center, Department of Radiation Oncology, Fudan University Shanghai Cancer Center (JZ, LX, HJ), and Liver Cancer Institute, Zhongshan Hospital (JS, QG), Fudan University, Shanghai, 200032, China; Department of Thoracic Cardiovascular Surgery, Xinhua Hospital of Shanghai Jiaotong University School of Medicine, Shanghai, China (MW, FH, JM); College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China (PC, ZD); Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China (HL, PW); College of Pharmacy, Seoul National University, Seoul, Korea (LSJ); College of Pharmacy, Ewha Womans University, Seoul, Korea (LSJ, HWL, JY); AntiCancer Biotech Beijing Co. Ltd., Beijing, China (HQ, MY); Division of Radiation and Cancer Biology, Department of Radiation Oncology, University of Michigan, Ann Arbor, MI (YS); Department of Surgery, University of California, San Diego, CA (RMH); AntiCancer, Inc., San Diego, CA (RMH, MY).
Jeong Lak Shin
Affiliations of authors: Cancer Institute, Fudan University Shanghai Cancer Center (LL, GY, PC, DW, CL, WY, YW, LJ), Department of Oncology, Shanghai Medical College (LL, GY, PC, DW, CL, WY, YW, LJ), Department of Immunology, School of Basic Medical Sciences (LL, GY, CL, YW, YC, LJ), Clinical Statistics Center, Department of Radiation Oncology, Fudan University Shanghai Cancer Center (JZ, LX, HJ), and Liver Cancer Institute, Zhongshan Hospital (JS, QG), Fudan University, Shanghai, 200032, China; Department of Thoracic Cardiovascular Surgery, Xinhua Hospital of Shanghai Jiaotong University School of Medicine, Shanghai, China (MW, FH, JM); College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China (PC, ZD); Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China (HL, PW); College of Pharmacy, Seoul National University, Seoul, Korea (LSJ); College of Pharmacy, Ewha Womans University, Seoul, Korea (LSJ, HWL, JY); AntiCancer Biotech Beijing Co. Ltd., Beijing, China (HQ, MY); Division of Radiation and Cancer Biology, Department of Radiation Oncology, University of Michigan, Ann Arbor, MI (YS); Department of Surgery, University of California, San Diego, CA (RMH); AntiCancer, Inc., San Diego, CA (RMH, MY).
Lee Hyuk Woo
Affiliations of authors: Cancer Institute, Fudan University Shanghai Cancer Center (LL, GY, PC, DW, CL, WY, YW, LJ), Department of Oncology, Shanghai Medical College (LL, GY, PC, DW, CL, WY, YW, LJ), Department of Immunology, School of Basic Medical Sciences (LL, GY, CL, YW, YC, LJ), Clinical Statistics Center, Department of Radiation Oncology, Fudan University Shanghai Cancer Center (JZ, LX, HJ), and Liver Cancer Institute, Zhongshan Hospital (JS, QG), Fudan University, Shanghai, 200032, China; Department of Thoracic Cardiovascular Surgery, Xinhua Hospital of Shanghai Jiaotong University School of Medicine, Shanghai, China (MW, FH, JM); College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China (PC, ZD); Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China (HL, PW); College of Pharmacy, Seoul National University, Seoul, Korea (LSJ); College of Pharmacy, Ewha Womans University, Seoul, Korea (LSJ, HWL, JY); AntiCancer Biotech Beijing Co. Ltd., Beijing, China (HQ, MY); Division of Radiation and Cancer Biology, Department of Radiation Oncology, University of Michigan, Ann Arbor, MI (YS); Department of Surgery, University of California, San Diego, CA (RMH); AntiCancer, Inc., San Diego, CA (RMH, MY).
Yu Jinha
Affiliations of authors: Cancer Institute, Fudan University Shanghai Cancer Center (LL, GY, PC, DW, CL, WY, YW, LJ), Department of Oncology, Shanghai Medical College (LL, GY, PC, DW, CL, WY, YW, LJ), Department of Immunology, School of Basic Medical Sciences (LL, GY, CL, YW, YC, LJ), Clinical Statistics Center, Department of Radiation Oncology, Fudan University Shanghai Cancer Center (JZ, LX, HJ), and Liver Cancer Institute, Zhongshan Hospital (JS, QG), Fudan University, Shanghai, 200032, China; Department of Thoracic Cardiovascular Surgery, Xinhua Hospital of Shanghai Jiaotong University School of Medicine, Shanghai, China (MW, FH, JM); College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China (PC, ZD); Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China (HL, PW); College of Pharmacy, Seoul National University, Seoul, Korea (LSJ); College of Pharmacy, Ewha Womans University, Seoul, Korea (LSJ, HWL, JY); AntiCancer Biotech Beijing Co. Ltd., Beijing, China (HQ, MY); Division of Radiation and Cancer Biology, Department of Radiation Oncology, University of Michigan, Ann Arbor, MI (YS); Department of Surgery, University of California, San Diego, CA (RMH); AntiCancer, Inc., San Diego, CA (RMH, MY).
Hu Fengqing
Affiliations of authors: Cancer Institute, Fudan University Shanghai Cancer Center (LL, GY, PC, DW, CL, WY, YW, LJ), Department of Oncology, Shanghai Medical College (LL, GY, PC, DW, CL, WY, YW, LJ), Department of Immunology, School of Basic Medical Sciences (LL, GY, CL, YW, YC, LJ), Clinical Statistics Center, Department of Radiation Oncology, Fudan University Shanghai Cancer Center (JZ, LX, HJ), and Liver Cancer Institute, Zhongshan Hospital (JS, QG), Fudan University, Shanghai, 200032, China; Department of Thoracic Cardiovascular Surgery, Xinhua Hospital of Shanghai Jiaotong University School of Medicine, Shanghai, China (MW, FH, JM); College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China (PC, ZD); Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China (HL, PW); College of Pharmacy, Seoul National University, Seoul, Korea (LSJ); College of Pharmacy, Ewha Womans University, Seoul, Korea (LSJ, HWL, JY); AntiCancer Biotech Beijing Co. Ltd., Beijing, China (HQ, MY); Division of Radiation and Cancer Biology, Department of Radiation Oncology, University of Michigan, Ann Arbor, MI (YS); Department of Surgery, University of California, San Diego, CA (RMH); AntiCancer, Inc., San Diego, CA (RMH, MY).
Mei Ju
Affiliations of authors: Cancer Institute, Fudan University Shanghai Cancer Center (LL, GY, PC, DW, CL, WY, YW, LJ), Department of Oncology, Shanghai Medical College (LL, GY, PC, DW, CL, WY, YW, LJ), Department of Immunology, School of Basic Medical Sciences (LL, GY, CL, YW, YC, LJ), Clinical Statistics Center, Department of Radiation Oncology, Fudan University Shanghai Cancer Center (JZ, LX, HJ), and Liver Cancer Institute, Zhongshan Hospital (JS, QG), Fudan University, Shanghai, 200032, China; Department of Thoracic Cardiovascular Surgery, Xinhua Hospital of Shanghai Jiaotong University School of Medicine, Shanghai, China (MW, FH, JM); College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China (PC, ZD); Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China (HL, PW); College of Pharmacy, Seoul National University, Seoul, Korea (LSJ); College of Pharmacy, Ewha Womans University, Seoul, Korea (LSJ, HWL, JY); AntiCancer Biotech Beijing Co. Ltd., Beijing, China (HQ, MY); Division of Radiation and Cancer Biology, Department of Radiation Oncology, University of Michigan, Ann Arbor, MI (YS); Department of Surgery, University of California, San Diego, CA (RMH); AntiCancer, Inc., San Diego, CA (RMH, MY).
Wang Ping
Affiliations of authors: Cancer Institute, Fudan University Shanghai Cancer Center (LL, GY, PC, DW, CL, WY, YW, LJ), Department of Oncology, Shanghai Medical College (LL, GY, PC, DW, CL, WY, YW, LJ), Department of Immunology, School of Basic Medical Sciences (LL, GY, CL, YW, YC, LJ), Clinical Statistics Center, Department of Radiation Oncology, Fudan University Shanghai Cancer Center (JZ, LX, HJ), and Liver Cancer Institute, Zhongshan Hospital (JS, QG), Fudan University, Shanghai, 200032, China; Department of Thoracic Cardiovascular Surgery, Xinhua Hospital of Shanghai Jiaotong University School of Medicine, Shanghai, China (MW, FH, JM); College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China (PC, ZD); Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China (HL, PW); College of Pharmacy, Seoul National University, Seoul, Korea (LSJ); College of Pharmacy, Ewha Womans University, Seoul, Korea (LSJ, HWL, JY); AntiCancer Biotech Beijing Co. Ltd., Beijing, China (HQ, MY); Division of Radiation and Cancer Biology, Department of Radiation Oncology, University of Michigan, Ann Arbor, MI (YS); Department of Surgery, University of California, San Diego, CA (RMH); AntiCancer, Inc., San Diego, CA (RMH, MY).
Chu Yiwei
Affiliations of authors: Cancer Institute, Fudan University Shanghai Cancer Center (LL, GY, PC, DW, CL, WY, YW, LJ), Department of Oncology, Shanghai Medical College (LL, GY, PC, DW, CL, WY, YW, LJ), Department of Immunology, School of Basic Medical Sciences (LL, GY, CL, YW, YC, LJ), Clinical Statistics Center, Department of Radiation Oncology, Fudan University Shanghai Cancer Center (JZ, LX, HJ), and Liver Cancer Institute, Zhongshan Hospital (JS, QG), Fudan University, Shanghai, 200032, China; Department of Thoracic Cardiovascular Surgery, Xinhua Hospital of Shanghai Jiaotong University School of Medicine, Shanghai, China (MW, FH, JM); College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China (PC, ZD); Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China (HL, PW); College of Pharmacy, Seoul National University, Seoul, Korea (LSJ); College of Pharmacy, Ewha Womans University, Seoul, Korea (LSJ, HWL, JY); AntiCancer Biotech Beijing Co. Ltd., Beijing, China (HQ, MY); Division of Radiation and Cancer Biology, Department of Radiation Oncology, University of Michigan, Ann Arbor, MI (YS); Department of Surgery, University of California, San Diego, CA (RMH); AntiCancer, Inc., San Diego, CA (RMH, MY).
Qi Hui
Affiliations of authors: Cancer Institute, Fudan University Shanghai Cancer Center (LL, GY, PC, DW, CL, WY, YW, LJ), Department of Oncology, Shanghai Medical College (LL, GY, PC, DW, CL, WY, YW, LJ), Department of Immunology, School of Basic Medical Sciences (LL, GY, CL, YW, YC, LJ), Clinical Statistics Center, Department of Radiation Oncology, Fudan University Shanghai Cancer Center (JZ, LX, HJ), and Liver Cancer Institute, Zhongshan Hospital (JS, QG), Fudan University, Shanghai, 200032, China; Department of Thoracic Cardiovascular Surgery, Xinhua Hospital of Shanghai Jiaotong University School of Medicine, Shanghai, China (MW, FH, JM); College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China (PC, ZD); Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China (HL, PW); College of Pharmacy, Seoul National University, Seoul, Korea (LSJ); College of Pharmacy, Ewha Womans University, Seoul, Korea (LSJ, HWL, JY); AntiCancer Biotech Beijing Co. Ltd., Beijing, China (HQ, MY); Division of Radiation and Cancer Biology, Department of Radiation Oncology, University of Michigan, Ann Arbor, MI (YS); Department of Surgery, University of California, San Diego, CA (RMH); AntiCancer, Inc., San Diego, CA (RMH, MY).
Yang Meng
Affiliations of authors: Cancer Institute, Fudan University Shanghai Cancer Center (LL, GY, PC, DW, CL, WY, YW, LJ), Department of Oncology, Shanghai Medical College (LL, GY, PC, DW, CL, WY, YW, LJ), Department of Immunology, School of Basic Medical Sciences (LL, GY, CL, YW, YC, LJ), Clinical Statistics Center, Department of Radiation Oncology, Fudan University Shanghai Cancer Center (JZ, LX, HJ), and Liver Cancer Institute, Zhongshan Hospital (JS, QG), Fudan University, Shanghai, 200032, China; Department of Thoracic Cardiovascular Surgery, Xinhua Hospital of Shanghai Jiaotong University School of Medicine, Shanghai, China (MW, FH, JM); College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China (PC, ZD); Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China (HL, PW); College of Pharmacy, Seoul National University, Seoul, Korea (LSJ); College of Pharmacy, Ewha Womans University, Seoul, Korea (LSJ, HWL, JY); AntiCancer Biotech Beijing Co. Ltd., Beijing, China (HQ, MY); Division of Radiation and Cancer Biology, Department of Radiation Oncology, University of Michigan, Ann Arbor, MI (YS); Department of Surgery, University of California, San Diego, CA (RMH); AntiCancer, Inc., San Diego, CA (RMH, MY).
Dong Ziming
Affiliations of authors: Cancer Institute, Fudan University Shanghai Cancer Center (LL, GY, PC, DW, CL, WY, YW, LJ), Department of Oncology, Shanghai Medical College (LL, GY, PC, DW, CL, WY, YW, LJ), Department of Immunology, School of Basic Medical Sciences (LL, GY, CL, YW, YC, LJ), Clinical Statistics Center, Department of Radiation Oncology, Fudan University Shanghai Cancer Center (JZ, LX, HJ), and Liver Cancer Institute, Zhongshan Hospital (JS, QG), Fudan University, Shanghai, 200032, China; Department of Thoracic Cardiovascular Surgery, Xinhua Hospital of Shanghai Jiaotong University School of Medicine, Shanghai, China (MW, FH, JM); College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China (PC, ZD); Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China (HL, PW); College of Pharmacy, Seoul National University, Seoul, Korea (LSJ); College of Pharmacy, Ewha Womans University, Seoul, Korea (LSJ, HWL, JY); AntiCancer Biotech Beijing Co. Ltd., Beijing, China (HQ, MY); Division of Radiation and Cancer Biology, Department of Radiation Oncology, University of Michigan, Ann Arbor, MI (YS); Department of Surgery, University of California, San Diego, CA (RMH); AntiCancer, Inc., San Diego, CA (RMH, MY).
Sun Yi
Affiliations of authors: Cancer Institute, Fudan University Shanghai Cancer Center (LL, GY, PC, DW, CL, WY, YW, LJ), Department of Oncology, Shanghai Medical College (LL, GY, PC, DW, CL, WY, YW, LJ), Department of Immunology, School of Basic Medical Sciences (LL, GY, CL, YW, YC, LJ), Clinical Statistics Center, Department of Radiation Oncology, Fudan University Shanghai Cancer Center (JZ, LX, HJ), and Liver Cancer Institute, Zhongshan Hospital (JS, QG), Fudan University, Shanghai, 200032, China; Department of Thoracic Cardiovascular Surgery, Xinhua Hospital of Shanghai Jiaotong University School of Medicine, Shanghai, China (MW, FH, JM); College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China (PC, ZD); Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China (HL, PW); College of Pharmacy, Seoul National University, Seoul, Korea (LSJ); College of Pharmacy, Ewha Womans University, Seoul, Korea (LSJ, HWL, JY); AntiCancer Biotech Beijing Co. Ltd., Beijing, China (HQ, MY); Division of Radiation and Cancer Biology, Department of Radiation Oncology, University of Michigan, Ann Arbor, MI (YS); Department of Surgery, University of California, San Diego, CA (RMH); AntiCancer, Inc., San Diego, CA (RMH, MY).
Hoffman Robert M
Affiliations of authors: Cancer Institute, Fudan University Shanghai Cancer Center (LL, GY, PC, DW, CL, WY, YW, LJ), Department of Oncology, Shanghai Medical College (LL, GY, PC, DW, CL, WY, YW, LJ), Department of Immunology, School of Basic Medical Sciences (LL, GY, CL, YW, YC, LJ), Clinical Statistics Center, Department of Radiation Oncology, Fudan University Shanghai Cancer Center (JZ, LX, HJ), and Liver Cancer Institute, Zhongshan Hospital (JS, QG), Fudan University, Shanghai, 200032, China; Department of Thoracic Cardiovascular Surgery, Xinhua Hospital of Shanghai Jiaotong University School of Medicine, Shanghai, China (MW, FH, JM); College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China (PC, ZD); Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China (HL, PW); College of Pharmacy, Seoul National University, Seoul, Korea (LSJ); College of Pharmacy, Ewha Womans University, Seoul, Korea (LSJ, HWL, JY); AntiCancer Biotech Beijing Co. Ltd., Beijing, China (HQ, MY); Division of Radiation and Cancer Biology, Department of Radiation Oncology, University of Michigan, Ann Arbor, MI (YS); Department of Surgery, University of California, San Diego, CA (RMH); AntiCancer, Inc., San Diego, CA (RMH, MY).
Jia Lijun
Affiliations of authors: Cancer Institute, Fudan University Shanghai Cancer Center (LL, GY, PC, DW, CL, WY, YW, LJ), Department of Oncology, Shanghai Medical College (LL, GY, PC, DW, CL, WY, YW, LJ), Department of Immunology, School of Basic Medical Sciences (LL, GY, CL, YW, YC, LJ), Clinical Statistics Center, Department of Radiation Oncology, Fudan University Shanghai Cancer Center (JZ, LX, HJ), and Liver Cancer Institute, Zhongshan Hospital (JS, QG), Fudan University, Shanghai, 200032, China; Department of Thoracic Cardiovascular Surgery, Xinhua Hospital of Shanghai Jiaotong University School of Medicine, Shanghai, China (MW, FH, JM); College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China (PC, ZD); Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China (HL, PW); College of Pharmacy, Seoul National University, Seoul, Korea (LSJ); College of Pharmacy, Ewha Womans University, Seoul, Korea (LSJ, HWL, JY); AntiCancer Biotech Beijing Co. Ltd., Beijing, China (HQ, MY); Division of Radiation and Cancer Biology, Department of Radiation Oncology, University of Michigan, Ann Arbor, MI (YS); Department of Surgery, University of California, San Diego, CA (RMH); AntiCancer, Inc., San Diego, CA (RMH, MY). [email protected].
Article Info
Journal
Journal of the National Cancer Institute
Abbr.
J Natl Cancer Inst
ISSN
1460-2105
DOI
10.1093/jnci/dju083
Email
[email protected]
Published
2014-06-00
Epub
2014-00-22
Pages
dju083
Language
English
Region
United States
NLM ID
7503089
Subset
IM
External Links
PubMed source DOI: 10.1093/jnci/dju083 View journal details
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