A proprotein convertase subtilisin/kexin type 9 neutralizing antibody reduces serum cholesterol in mice and nonhuman primates.

PubWeight™: 3.39‹?› | Rank: Top 1%

🔗 View Article (PMC 2682542)

Published in Proc Natl Acad Sci U S A on May 14, 2009

Authors

Joyce C Y Chan1, Derek E Piper, Qiong Cao, Dongming Liu, Chadwick King, Wei Wang, Jie Tang, Qiang Liu, Jared Higbee, Zhen Xia, Yongmei Di, Susan Shetterly, Ziva Arimura, Heather Salomonis, William G Romanow, Stephen T Thibault, Richard Zhang, Ping Cao, Xiao-Ping Yang, Timothy Yu, Mei Lu, Marc W Retter, Gayle Kwon, Kirk Henne, Oscar Pan, Mei-Mei Tsai, Bryna Fuchslocher, Evelyn Yang, Lei Zhou, Ki Jeong Lee, Mark Daris, Jackie Sheng, Yan Wang, Wenyan D Shen, Wen-Chen Yeh, Maurice Emery, Nigel P C Walker, Bei Shan, Margrit Schwarz, Simon M Jackson

Author Affiliations

1: Department of Metabolic Disorders, Amgen Inc., South San Francisco, CA 94080, USA.

Articles citing this

How to improve R&D productivity: the pharmaceutical industry's grand challenge. Nat Rev Drug Discov (2010) 14.09

The biology and therapeutic targeting of the proprotein convertases. Nat Rev Drug Discov (2012) 3.18

A new method for measurement of total plasma PCSK9: clinical applications. J Lipid Res (2010) 1.64

High-dose atorvastatin causes a rapid sustained increase in human serum PCSK9 and disrupts its correlation with LDL cholesterol. J Lipid Res (2010) 1.56

The PCSK9 decade. J Lipid Res (2012) 1.50

Dissection of the endogenous cellular pathways of PCSK9-induced low density lipoprotein receptor degradation: evidence for an intracellular route. J Biol Chem (2009) 1.49

Malfolded protein structure and proteostasis in lung diseases. Am J Respir Crit Care Med (2014) 1.47

Increasing serum half-life and extending cholesterol lowering in vivo by engineering antibody with pH-sensitive binding to PCSK9. J Biol Chem (2012) 1.46

A proprotein convertase subtilisin-like/kexin type 9 (PCSK9) C-terminal domain antibody antigen-binding fragment inhibits PCSK9 internalization and restores low density lipoprotein uptake. J Biol Chem (2010) 1.32

A PCSK9-binding antibody that structurally mimics the EGF(A) domain of LDL-receptor reduces LDL cholesterol in vivo. J Lipid Res (2010) 1.29

Low density lipoprotein binds to proprotein convertase subtilisin/kexin type-9 (PCSK9) in human plasma and inhibits PCSK9-mediated low density lipoprotein receptor degradation. J Biol Chem (2013) 1.29

Fabs enable single particle cryoEM studies of small proteins. Structure (2012) 1.25

PCSK9 LNA antisense oligonucleotides induce sustained reduction of LDL cholesterol in nonhuman primates. Mol Ther (2011) 1.23

Pharmacological strategies for lowering LDL cholesterol: statins and beyond. Nat Rev Cardiol (2011) 1.20

Genome-wide significant loci: how important are they? Systems genetics to understand heritability of coronary artery disease and other common complex disorders. J Am Coll Cardiol (2015) 1.19

A locked nucleic acid antisense oligonucleotide (LNA) silences PCSK9 and enhances LDLR expression in vitro and in vivo. PLoS One (2010) 1.19

An anti-PCSK9 antibody reduces LDL-cholesterol on top of a statin and suppresses hepatocyte SREBP-regulated genes. Int J Biol Sci (2012) 1.15

Regulation of hepatic LDL receptors by mTORC1 and PCSK9 in mice. J Clin Invest (2012) 1.14

Inhibition of PCSK9: a powerful weapon for achieving ideal LDL cholesterol levels. Proc Natl Acad Sci U S A (2009) 1.12

A two-step binding model of PCSK9 interaction with the low density lipoprotein receptor. J Biol Chem (2010) 1.10

Molecular Validation of PACE4 as a Target in Prostate Cancer. Transl Oncol (2011) 1.05

Effects of the prosegment and pH on the activity of PCSK9: evidence for additional processing events. J Biol Chem (2010) 1.04

Annexin A2 is a natural extrahepatic inhibitor of the PCSK9-induced LDL receptor degradation. PLoS One (2012) 1.04

Effects of currently prescribed LDL-C-lowering drugs on PCSK9 and implications for the next generation of LDL-C-lowering agents. Lipids Health Dis (2011) 1.03

On the cutting edge of proprotein convertase pharmacology: from molecular concepts to clinical applications. Biomol Concepts (2011) 1.02

Improved efficacy for ezetimibe and rosuvastatin by attenuating the induction of PCSK9. J Lipid Res (2011) 1.01

Furin-cleaved proprotein convertase subtilisin/kexin type 9 (PCSK9) is active and modulates low density lipoprotein receptor and serum cholesterol levels. J Biol Chem (2012) 0.99

A common polymorphism in the LDL receptor gene has multiple effects on LDL receptor function. Hum Mol Genet (2013) 0.96

Characterization of proprotein convertase subtilisin/kexin type 9 (PCSK9) trafficking reveals a novel lysosomal targeting mechanism via amyloid precursor-like protein 2 (APLP2). J Biol Chem (2013) 0.96

The biology of PCSK9 from the endoplasmic reticulum to lysosomes: new and emerging therapeutics to control low-density lipoprotein cholesterol. Drug Des Devel Ther (2013) 0.94

PCSK9 reduces the protein levels of the LDL receptor in mouse brain during development and after ischemic stroke. J Lipid Res (2011) 0.93

The discovery of PCSK9 inhibitors: A tale of creativity and multifaceted translational research. Glob Cardiol Sci Pract (2013) 0.93

Fenofibrate treatment increases human serum proprotein convertase subtilisin kexin type 9 levels. J Lipid Res (2009) 0.93

PCSK9 is not involved in the degradation of LDL receptors and BACE1 in the adult mouse brain. J Lipid Res (2010) 0.91

PCSK9 and LDLR degradation: regulatory mechanisms in circulation and in cells. Curr Opin Lipidol (2014) 0.91

The Sirt1 activator SRT3025 provides atheroprotection in Apoe-/- mice by reducing hepatic Pcsk9 secretion and enhancing Ldlr expression. Eur Heart J (2014) 0.91

Identification of a small peptide that inhibits PCSK9 protein binding to the low density lipoprotein receptor. J Biol Chem (2013) 0.90

Novel domain interaction regulates secretion of proprotein convertase subtilisin/kexin type 9 (PCSK9) protein. J Biol Chem (2011) 0.90

Bile acid and sterol metabolism with combined HMG-CoA reductase and PCSK9 suppression. J Lipid Res (2013) 0.90

Relation of plasma PCSK9 levels to lipoprotein subfractions in patients with stable coronary artery disease. Lipids Health Dis (2014) 0.89

Efficacy and safety of alirocumab, a fully human PCSK9 monoclonal antibody, in high cardiovascular risk patients with poorly controlled hypercholesterolemia on maximally tolerated doses of statins: rationale and design of the ODYSSEY COMBO I and II trials. BMC Cardiovasc Disord (2014) 0.88

PCSK9 inhibition-mediated reduction in Lp(a) with evolocumab: an analysis of 10 clinical trials and the LDL receptor's role. J Lipid Res (2016) 0.88

Peroxisome Proliferator-activated receptor γ activation by ligands and dephosphorylation induces proprotein convertase subtilisin kexin type 9 and low density lipoprotein receptor expression. J Biol Chem (2012) 0.87

Cholesterol-lowering Action of BNA-based Antisense Oligonucleotides Targeting PCSK9 in Atherogenic Diet-induced Hypercholesterolemic Mice. Mol Ther Nucleic Acids (2012) 0.86

Familial hypercholesterolemia: present and future management. Curr Cardiol Rep (2011) 0.86

PCSK9 inhibition fails to alter hepatic LDLR, circulating cholesterol, and atherosclerosis in the absence of ApoE. J Lipid Res (2014) 0.86

Molecular and cellular function of the proprotein convertase subtilisin/kexin type 9 (PCSK9). Basic Res Cardiol (2015) 0.85

Profile of evolocumab and its potential in the treatment of hyperlipidemia. Drug Des Devel Ther (2015) 0.85

Age-Related Hypercholesterolemia and HMG-CoA Reductase Dysregulation: Sex Does Matter (A Gender Perspective). Curr Gerontol Geriatr Res (2010) 0.85

Discovery and validation of new molecular targets in treating dyslipidemia: the role of human genetics. Trends Cardiovasc Med (2009) 0.84

A mathematical analysis of rebound in a target-mediated drug disposition model: I.without feedback. J Math Biol (2013) 0.84

Delineation of molecular pathways that regulate hepatic PCSK9 and LDL receptor expression during fasting in normolipidemic hamsters. Atherosclerosis (2012) 0.83

New developments in atherosclerosis: clinical potential of PCSK9 inhibition. Vasc Health Risk Manag (2015) 0.83

Mipomersen: evidence-based review of its potential in the treatment of homozygous and severe heterozygous familial hypercholesterolemia. Core Evid (2012) 0.82

Plasma levels of PCSK9 and phenotypic variability in familial hypercholesterolemia. J Lipid Res (2012) 0.82

A cholesterol-lowering VLP vaccine that targets PCSK9. Vaccine (2015) 0.82

Decreased APOE-containing HDL subfractions and cholesterol efflux capacity of serum in mice lacking Pcsk9. Lipids Health Dis (2013) 0.82

Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Single Domain Antibodies Are Potent Inhibitors of Low Density Lipoprotein Receptor Degradation. J Biol Chem (2016) 0.81

Annexin A2 reduces PCSK9 protein levels via a translational mechanism and interacts with the M1 and M2 domains of PCSK9. J Biol Chem (2014) 0.80

Common Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Epitopes Mediate Multiple Routes for Internalization and Function. PLoS One (2015) 0.80

Proprotein convertases in high-density lipoprotein metabolism. Biomark Res (2013) 0.80

Lowering plasma cholesterol by raising LDL receptors--revisited. N Engl J Med (2012) 0.80

Qualification of a free ligand assay in the presence of anti-ligand antibody Fab fragments. MAbs (2013) 0.80

Immunization against proprotein convertase subtilisin-like/kexin type 9 lowers plasma LDL-cholesterol levels in mice. J Lipid Res (2012) 0.79

PCSK9 inhibitors in the prevention of cardiovascular disease. J Thromb Thrombolysis (2016) 0.79

PCSK9 as a therapeutic target in atherosclerosis. Curr Atheroscler Rep (2010) 0.78

PCSK9 inhibitors - mechanisms of action. Aust Prescr (2016) 0.78

Impact of 3'UTR genetic variants in PCSK9 and LDLR genes on plasma lipid traits and response to atorvastatin in Brazilian subjects: a pilot study. Int J Clin Exp Med (2015) 0.77

Characterization of a quantitative method to measure free proprotein convertase subtilisin/kexin type 9 in human serum. MAbs (2014) 0.77

PCSK9 inhibition in the management of hyperlipidemia: focus on evolocumab. Vasc Health Risk Manag (2016) 0.77

ABCC6- a new player in cellular cholesterol and lipoprotein metabolism? Lipids Health Dis (2014) 0.77

Proprotein convertase subtilisin/kexin type 9: from the discovery to the development of new therapies for cardiovascular diseases. Scientifica (Cairo) (2012) 0.76

Improving the predictive value of interventional animal models data. Drug Discov Today (2014) 0.76

Acute intake of plant stanol esters induces changes in lipid and lipoprotein metabolism-related gene expression in the liver and intestines of mice. Lipids (2015) 0.75

Retargeting the management of hypercholesterolemia - focus on evolocumab. Ther Clin Risk Manag (2016) 0.75

An inhibitory antibody against dipeptidyl peptidase IV improves glucose tolerance in vivo. J Biol Chem (2012) 0.75

Selection of DNA aptamers with two modified bases. Proc Natl Acad Sci U S A (2017) 0.75

Lowering serum lipids via PCSK9-targeting drugs: current advances and future perspectives. Acta Pharmacol Sin (2017) 0.75

Effect of evolocumab on cholesterol synthesis and absorption. J Lipid Res (2016) 0.75

The PCSK9 revolution and the potential of PCSK9-based therapies to reduce LDL-cholesterol. Glob Cardiol Sci Pract (2017) 0.75

PCSK9 Inhibitors: Treating the Right Patients in Daily Practice. Curr Cardiol Rep (2017) 0.75

Low PCSK9 levels are correlated with mortality in patients with end-stage liver disease. PLoS One (2017) 0.75

Articles cited by this

The CCP4 suite: programs for protein crystallography. Acta Crystallogr D Biol Crystallogr (1994) 187.88

Crystallography & NMR system: A new software suite for macromolecular structure determination. Acta Crystallogr D Biol Crystallogr (1998) 169.28

Continuous cultures of fused cells secreting antibody of predefined specificity. Nature (1975) 83.56

Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med (2006) 23.83

Low LDL cholesterol in individuals of African descent resulting from frequent nonsense mutations in PCSK9. Nat Genet (2005) 12.12

Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet (2003) 11.67

Therapeutic RNAi targeting PCSK9 acutely lowers plasma cholesterol in rodents and LDL cholesterol in nonhuman primates. Proc Natl Acad Sci U S A (2008) 4.57

Decreased plasma cholesterol and hypersensitivity to statins in mice lacking Pcsk9. Proc Natl Acad Sci U S A (2005) 4.56

Adenoviral-mediated expression of Pcsk9 in mice results in a low-density lipoprotein receptor knockout phenotype. Proc Natl Acad Sci U S A (2004) 4.27

Statins upregulate PCSK9, the gene encoding the proprotein convertase neural apoptosis-regulated convertase-1 implicated in familial hypercholesterolemia. Arterioscler Thromb Vasc Biol (2004) 4.08

Post-transcriptional regulation of low density lipoprotein receptor protein by proprotein convertase subtilisin/kexin type 9a in mouse liver. J Biol Chem (2004) 3.93

PCSK9: a convertase that coordinates LDL catabolism. J Lipid Res (2008) 3.92

Role of liver in the maintenance of cholesterol and low density lipoprotein homeostasis in different animal species, including humans. J Lipid Res (1993) 3.64

Secreted PCSK9 decreases the number of LDL receptors in hepatocytes and in livers of parabiotic mice. J Clin Invest (2006) 3.54

Binding of proprotein convertase subtilisin/kexin type 9 to epidermal growth factor-like repeat A of low density lipoprotein receptor decreases receptor recycling and increases degradation. J Biol Chem (2007) 3.45

Molecular characterization of loss-of-function mutations in PCSK9 and identification of a compound heterozygote. Am J Hum Genet (2006) 3.38

Structural and biophysical studies of PCSK9 and its mutants linked to familial hypercholesterolemia. Nat Struct Mol Biol (2007) 2.76

Acid-dependent ligand dissociation and recycling of LDL receptor mediated by growth factor homology region. Nature (1987) 2.74

Molecular basis for LDL receptor recognition by PCSK9. Proc Natl Acad Sci U S A (2008) 2.42

Atorvastatin increases human serum levels of proprotein convertase subtilisin/kexin type 9. J Lipid Res (2007) 2.15

Proprotein convertase subtilisin/kexin type 9 (PCSK9): hepatocyte-specific low-density lipoprotein receptor degradation and critical role in mouse liver regeneration. Hepatology (2008) 2.07

The crystal structure of PCSK9: a regulator of plasma LDL-cholesterol. Structure (2007) 1.99

Antisense inhibition of proprotein convertase subtilisin/kexin type 9 reduces serum LDL in hyperlipidemic mice. J Lipid Res (2007) 1.99

The C679X mutation in PCSK9 is present and lowers blood cholesterol in a Southern African population. Atherosclerosis (2006) 1.99

Plasma PCSK9 preferentially reduces liver LDL receptors in mice. J Lipid Res (2008) 1.98

Catalytic activity is not required for secreted PCSK9 to reduce low density lipoprotein receptors in HepG2 cells. J Biol Chem (2007) 1.97

Structural requirements for PCSK9-mediated degradation of the low-density lipoprotein receptor. Proc Natl Acad Sci U S A (2008) 1.86

Secreted PCSK9 downregulates low density lipoprotein receptor through receptor-mediated endocytosis. J Lipid Res (2007) 1.82

Functional transplant of megabase human immunoglobulin loci recapitulates human antibody response in mice. Nat Genet (1997) 1.67

Antagonism of secreted PCSK9 increases low density lipoprotein receptor expression in HepG2 cells. J Biol Chem (2009) 1.65

Secreted PCSK9 promotes LDL receptor degradation independently of proteolytic activity. Biochem J (2007) 1.48

PCSK9 binds to multiple receptors and can be functionally inhibited by an EGF-A peptide. Biochem Biophys Res Commun (2008) 1.47

The proprotein convertases are potential targets in the treatment of dyslipidemia. J Mol Med (Berl) (2007) 1.40

Antibody-mediated disruption of the interaction between PCSK9 and the low-density lipoprotein receptor. Biochem J (2009) 1.24

FGF21 N- and C-termini play different roles in receptor interaction and activation. FEBS Lett (2008) 1.24

Mouse models of hyperlipidemia and atherosclerosis. Front Biosci (2001) 1.20

Antibody discovery: the use of transgenic mice to generate human monoclonal antibodies for therapeutics. Curr Opin Biotechnol (2002) 1.10

Role of liver in the synthesis of cholesterol and the clearance of low density lipoproteins in the cynomolgus monkey. J Lipid Res (1995) 1.06

ApoE distribution among lipoproteins of rhesus monkeys is modulated by dietary fat and cholesterol. J Nutr (1986) 0.81

Articles by these authors

A second generation human haplotype map of over 3.1 million SNPs. Nature (2007) 85.39

A novel heterocyclic compound: catena-poly[[[diaquasodium(I)]-di-mu-aqua] hemi(1,5-dihydroxy-4,8,9-trioxa-2,6-diazabicyclo[3.3.1]nona-2,6-diene-3,7-diolate)]. Acta Crystallogr C (2007) 65.39

Scalable molecular dynamics with NAMD. J Comput Chem (2005) 59.49

The diploid genome sequence of an Asian individual. Nature (2008) 46.29

Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome. Nat Genet (2007) 32.41

Human infection with a novel avian-origin influenza A (H7N9) virus. N Engl J Med (2013) 24.88

Genome-wide detection and characterization of positive selection in human populations. Nature (2007) 17.27

Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials. Lancet (2004) 12.92

Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci. Nat Genet (2008) 12.51

piggyBac transposition reprograms fibroblasts to induced pluripotent stem cells. Nature (2009) 11.27

Sequencing of 50 human exomes reveals adaptation to high altitude. Science (2010) 11.27

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in children and adolescents. Ann Neurol (2009) 9.25

Distinct epigenomic landscapes of pluripotent and lineage-committed human cells. Cell Stem Cell (2010) 8.74

The genome of the mesopolyploid crop species Brassica rapa. Nat Genet (2011) 8.23

A two-gene expression ratio predicts clinical outcome in breast cancer patients treated with tamoxifen. Cancer Cell (2004) 8.06

Automatic atom type and bond type perception in molecular mechanical calculations. J Mol Graph Model (2006) 7.93

Celecoxib for the prevention of sporadic colorectal adenomas. N Engl J Med (2006) 7.62

Targeted bisulfite sequencing reveals changes in DNA methylation associated with nuclear reprogramming. Nat Biotechnol (2009) 7.59

Prior image constrained compressed sensing (PICCS): a method to accurately reconstruct dynamic CT images from highly undersampled projection data sets. Med Phys (2008) 7.52

Epidemiology of human infections with avian influenza A(H7N9) virus in China. N Engl J Med (2013) 7.52

Oncogenic Kras maintains pancreatic tumors through regulation of anabolic glucose metabolism. Cell (2012) 7.36

Acute renal failure and sepsis. N Engl J Med (2004) 7.18

The MicroArray Quality Control (MAQC)-II study of common practices for the development and validation of microarray-based predictive models. Nat Biotechnol (2010) 7.08

High-performance neuroprosthetic control by an individual with tetraplegia. Lancet (2012) 6.66

LPS/TLR4 signal transduction pathway. Cytokine (2008) 6.60

Cellular and synaptic mechanisms of anti-NMDA receptor encephalitis. J Neurosci (2010) 6.44

Publication of NIH funded trials registered in ClinicalTrials.gov: cross sectional analysis. BMJ (2012) 6.39

Celecoxib for the prevention of colorectal adenomatous polyps. N Engl J Med (2006) 6.15

The dog genome: survey sequencing and comparative analysis. Science (2003) 5.84

Imaging iron stores in the brain using magnetic resonance imaging. Magn Reson Imaging (2005) 5.83

New loci associated with kidney function and chronic kidney disease. Nat Genet (2010) 5.58

Antitumor activity of rapamycin in a Phase I trial for patients with recurrent PTEN-deficient glioblastoma. PLoS Med (2008) 5.54

The draft genome of the transgenic tropical fruit tree papaya (Carica papaya Linnaeus). Nature (2008) 5.54

Specific ablation of the apoptotic functions of cytochrome C reveals a differential requirement for cytochrome C and Apaf-1 in apoptosis. Cell (2005) 5.37

Predictive value for the Chinese population of the Framingham CHD risk assessment tool compared with the Chinese Multi-Provincial Cohort Study. JAMA (2004) 5.34

The oyster genome reveals stress adaptation and complexity of shell formation. Nature (2012) 5.30

De novo mutations in histone-modifying genes in congenital heart disease. Nature (2013) 5.15

DNA-binding specificity of the ERF/AP2 domain of Arabidopsis DREBs, transcription factors involved in dehydration- and cold-inducible gene expression. Biochem Biophys Res Commun (2002) 5.14

Evidence for HIV-associated B cell exhaustion in a dysfunctional memory B cell compartment in HIV-infected viremic individuals. J Exp Med (2008) 5.14

CD24 and Siglec-10 selectively repress tissue damage-induced immune responses. Science (2009) 5.00

MicroRNA-34b and MicroRNA-34c are targets of p53 and cooperate in control of cell proliferation and adhesion-independent growth. Cancer Res (2007) 4.95

Attenuated cold sensitivity in TRPM8 null mice. Neuron (2007) 4.73

AMPA receptor antibodies in limbic encephalitis alter synaptic receptor location. Ann Neurol (2009) 4.49

Structural basis of toll-like receptor 3 signaling with double-stranded RNA. Science (2008) 4.41

Hepatocyte growth factor induces gefitinib resistance of lung adenocarcinoma with epidermal growth factor receptor-activating mutations. Cancer Res (2008) 4.30

Intravenous administration of human bone marrow stromal cells induces angiogenesis in the ischemic boundary zone after stroke in rats. Circ Res (2003) 4.29

Probable limited person-to-person transmission of highly pathogenic avian influenza A (H5N1) virus in China. Lancet (2008) 4.17

EpCAM and alpha-fetoprotein expression defines novel prognostic subtypes of hepatocellular carcinoma. Cancer Res (2008) 4.17

Pharmacological rescue of synaptic plasticity, courtship behavior, and mushroom body defects in a Drosophila model of fragile X syndrome. Neuron (2005) 4.11

Evidence for antibody-mediated pathogenesis in anti-NMDAR encephalitis associated with ovarian teratoma. Acta Neuropathol (2009) 3.97

Noncanonical NF-kappaB activation requires coordinated assembly of a regulatory complex of the adaptors cIAP1, cIAP2, TRAF2 and TRAF3 and the kinase NIK. Nat Immunol (2008) 3.91

Pelvic Organ Support Study (POSST): the distribution, clinical definition, and epidemiologic condition of pelvic organ support defects. Am J Obstet Gynecol (2005) 3.85

Association between adverse clinical outcome in human disease caused by novel influenza A H7N9 virus and sustained viral shedding and emergence of antiviral resistance. Lancet (2013) 3.83

Epigenomic analysis of multilineage differentiation of human embryonic stem cells. Cell (2013) 3.81

Epidemiological transition of stroke in China: twenty-one-year observational study from the Sino-MONICA-Beijing Project. Stroke (2008) 3.81

Natural selection on EPAS1 (HIF2alpha) associated with low hemoglobin concentration in Tibetan highlanders. Proc Natl Acad Sci U S A (2010) 3.78

Acute renal failure: definitions, diagnosis, pathogenesis, and therapy. J Clin Invest (2004) 3.75

Severe impairment of interleukin-1 and Toll-like receptor signalling in mice lacking IRAK-4. Nature (2002) 3.74

Discovery and annotation of functional chromatin signatures in the human genome. PLoS Comput Biol (2009) 3.61

Residential proximity to naturally occurring asbestos and mesothelioma risk in California. Am J Respir Crit Care Med (2005) 3.55

Clinical application of massively parallel sequencing-based prenatal noninvasive fetal trisomy test for trisomies 21 and 18 in 11,105 pregnancies with mixed risk factors. Prenat Diagn (2012) 3.54

Statins induce angiogenesis, neurogenesis, and synaptogenesis after stroke. Ann Neurol (2003) 3.54

Surgical treatment of giant coronary artery aneurysm. J Thorac Cardiovasc Surg (2005) 3.53

The therapeutic effect of anti-HER2/neu antibody depends on both innate and adaptive immunity. Cancer Cell (2010) 3.52

ChromaSig: a probabilistic approach to finding common chromatin signatures in the human genome. PLoS Comput Biol (2008) 3.46

Gradient-index meta-surfaces as a bridge linking propagating waves and surface waves. Nat Mater (2012) 3.42

Characteristics associated with differences in survival among black and white women with breast cancer. JAMA (2013) 3.35

Effects of acupuncture on pregnancy rates in women undergoing in vitro fertilization: a systematic review and meta-analysis. Fertil Steril (2012) 3.33

CCL18 from tumor-associated macrophages promotes breast cancer metastasis via PITPNM3. Cancer Cell (2011) 3.31

Structural snapshots of human HDAC8 provide insights into the class I histone deacetylases. Structure (2004) 3.31

Genetic analysis of complex traits in the emerging Collaborative Cross. Genome Res (2011) 3.25

Effects of a universal classroom behavior management program in first and second grades on young adult behavioral, psychiatric, and social outcomes. Drug Alcohol Depend (2008) 3.22

Allele-specific methylation is prevalent and is contributed by CpG-SNPs in the human genome. Genome Res (2010) 3.17

Transcriptome profiling of human and murine ESCs identifies divergent paths required to maintain the stem cell state. Stem Cells (2005) 3.16

A recalibrated molecular clock and independent origins for the cholera pandemic clones. PLoS One (2008) 3.16

Effectiveness of strengthened stimulation during acupuncture for the treatment of Bell palsy: a randomized controlled trial. CMAJ (2013) 3.15

Responsiveness to reduced dosage of rituximab in Chinese patients with neuromyelitis optica. Neurology (2013) 3.13

Methods for testing theory and evaluating impact in randomized field trials: intent-to-treat analyses for integrating the perspectives of person, place, and time. Drug Alcohol Depend (2008) 3.09

Quantum-sized carbon dots for bright and colorful photoluminescence. J Am Chem Soc (2006) 3.08

Adverse metabolic consequences in humans of prolonged sleep restriction combined with circadian disruption. Sci Transl Med (2012) 3.08

Oxidative damage targets complexes containing DNA methyltransferases, SIRT1, and polycomb members to promoter CpG Islands. Cancer Cell (2011) 3.07

Assessing the performance of the MM/PBSA and MM/GBSA methods. 1. The accuracy of binding free energy calculations based on molecular dynamics simulations. J Chem Inf Model (2010) 3.04

Epidemiology of Alzheimer's disease and other forms of dementia in China, 1990-2010: a systematic review and analysis. Lancet (2013) 3.02

The molecular mechanism governing the oncogenic potential of SOX2 in breast cancer. J Biol Chem (2008) 3.01

Long non-coding RNA H19 increases bladder cancer metastasis by associating with EZH2 and inhibiting E-cadherin expression. Cancer Lett (2013) 2.99

Abnormal TNF activity in Timp3-/- mice leads to chronic hepatic inflammation and failure of liver regeneration. Nat Genet (2004) 2.96

Genome-wide association study of esophageal squamous cell carcinoma in Chinese subjects identifies susceptibility loci at PLCE1 and C20orf54. Nat Genet (2010) 2.95

U1 snRNP determines mRNA length and regulates isoform expression. Cell (2012) 2.92

Role of a transductional-transcriptional processor complex involving MyD88 and IRF-7 in Toll-like receptor signaling. Proc Natl Acad Sci U S A (2004) 2.89

Melamine related bilateral renal calculi in 50 children: single center experience in clinical diagnosis and treatment. J Urol (2010) 2.83

The polymorphism architecture of mouse genetic resources elucidated using genome-wide resequencing data: implications for QTL discovery and systems genetics. Mamm Genome (2007) 2.82

Structure and function of Nurr1 identifies a class of ligand-independent nuclear receptors. Nature (2003) 2.81

Sleep restriction for 1 week reduces insulin sensitivity in healthy men. Diabetes (2010) 2.81

Differential requirement for TANK-binding kinase-1 in type I interferon responses to toll-like receptor activation and viral infection. J Exp Med (2004) 2.80

Characterizing the appearance and growth of amyloid plaques in APP/PS1 mice. J Neurosci (2009) 2.76

NPR3 and NPR4 are receptors for the immune signal salicylic acid in plants. Nature (2012) 2.76

Potent immunogenicity and efficacy of a universal influenza vaccine candidate comprising a recombinant fusion protein linking influenza M2e to the TLR5 ligand flagellin. Vaccine (2007) 2.76

Autophosphorylation of the catalytic subunit of the DNA-dependent protein kinase is required for efficient end processing during DNA double-strand break repair. Mol Cell Biol (2003) 2.74