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preLekára.sk / Odborné časopisy / PLOS One / 2020 - 1

Soluble AXL as a marker of disease progression and survival in melanoma

English version

Autoři: Karine Flem-Karlsen aff001;  Marta Nyakas aff002;  Inger Nina Farstad aff001;  Erin McFadden aff001;  Patrik Wernhoff aff001;  Kari Dolven Jacobsen aff004;  Vivi Ann Flørenes aff001;  Gunhild Mari Mælandsmo aff003
Působiště autorů: Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway aff001;  Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway aff002;  Department of Tumor Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway aff003;  Department of Oncology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway aff004;  Institute of Medical Biology, Faculty of Health Sciences, UiT–Arctic University of Norway, Tromsø, Norway aff005
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pone.0227187

Souhrn

Receptor tyrosine kinase AXL is a one-pass transmembrane protein upregulated in cancers and associated with lower survival and therapy resistance. AXL can be cleaved by the A Disintegrin and Metalloproteinases (ADAM)10 and ADAM17, yielding a soluble version of the protein. Elevated soluble AXL (sAXL) has been reported to be associated with disease progression in hepatocellular carcinoma, renal cancer, neurofibromatosis type 1 and inflammatory diseases. In the present work, we analyzed sAXL levels in blood from melanoma patients and showed that sAXL increases with disease progression. Additionally, increased sAXL levels were found correlated with shorter two-year survival in stage IV patients treated with ipilimumab. Furthermore, we showed that sAXL levels were related to the percentage of cells expressing AXL in resected melanoma lymph node metastases. This finding was verified in vitro, where sAXL levels in the cell media corresponded to AXL expression in the cells. AXL inhibition using the small-molecular inhibitor BGB324 reduced sAXL levels, while the cellular expression was elevated through increased protein stability. Our findings signify that quantification of sAXL blood levels is a simple and easily assessable method to determine cellular AXL levels and should be further evaluated for its use as a biomarker of disease progression and treatment response.

Klíčová slova:

Blood plasma – Cancer treatment – Enzyme-linked immunoassays – Protein expression – Immunohistochemistry techniques – Lymph nodes – Melanoma cells – Melanomas

Zdroje

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Článek Dome-shaped macula in children and adolescents
Článek Targeted transcriptomic study of the implication of central metabolic pathways in mannosylerythritol lipids biosynthesis in Pseudozyma antarctica T-34
Článek Preliminary evidences of the presence of extracellular DNA single stranded forms in soil
Článek A comparison of quality of life between patients treated with different dialysis modalities in Taiwan
Článek Transcriptome analysis of Actinidia chinensis in response to Botryosphaeria dothidea infection
Článek Comparative study on skin protection activity of polyphenol-rich extract and polysaccharide-rich extract from Sargassum vachellianum
Článek Real-world data about emotional stress, disability and need for social care in a German IBD patient cohort
Článek The regenerative compatibility: A synergy between healthy ecosystems, environmental attitudes, and restorative experiences
Článek Perceptions of risk and influences of choice in pregnant women with obesity. An evidence synthesis of qualitative research
Článek Sexual risk classes among youth experiencing homelessness: Relation to childhood adversities, current mental symptoms, substance use, and HIV testing
Článek Effects of CK2β subunit down-regulation on Akt signalling in HK-2 renal cells
Článek Association between opioid analgesic therapy and initiation of buprenorphine management: An analysis of prescription drug monitoring program data
Článek Improvement project in higher education institutions: A BPEP-based model
Článek An updated evaluation of serum sHER2, CA15.3, and CEA levels as biomarkers for the response of patients with metastatic breast cancer to trastuzumab-based therapies
Článek Genome-wide association study of metabolic syndrome in Korean populations
Článek Drug therapy problems and treatment satisfaction among ambulatory patients with epilepsy in a specialized hospital in Ethiopia
Článek Intensified visual clutter induces increased sympathetic signalling, poorer postural control, and faster torsional eye movements during visual rotation
Článek Gut microbiota composition alterations are associated with the onset of diabetes in kidney transplant recipients
Článek Shock index and TIMI risk index as valuable prognostic tools in patients with acute coronary syndrome complicated by cardiogenic shock
Článek Merit overrules theory of mind when young children share resources with others
Článek Generalizing findings from a randomized controlled trial to a real-world study of the iLookOut, an online education program to improve early childhood care and education providers’ knowledge and attitudes about reporting child maltreatment
Článek When and what to test for: A cost-effectiveness analysis of febrile illness test-and-treat strategies in the era of responsible antibiotic use
Článek Comparison of effects and safety in providing controlled hypotension during surgery between dexmedetomidine and magnesium sulphate: A meta-analysis of randomized controlled trials
Článek The gene encoding the ketogenic enzyme HMGCS2 displays a unique expression during gonad development in mice
Článek Efficacy of a mitochondrion-targeting agent for reducing the level of urinary protein in rats with puromycin aminonucleoside-induced minimal-change nephrotic syndrome
Článek Association of endothelial nitric oxide synthase (NOS3) gene polymorphisms with primary open-angle glaucoma in a Saudi cohort
Článek Antitrust analysis with upward pricing pressure and cost efficiencies
Článek Pyramiding QTLs controlling tolerance against drought, salinity, and submergence in rice through marker assisted breeding
Článek The virulence domain of Shigella IcsA contains a subregion with specific host cell adhesion function
Článek Sequencing artifacts derived from a library preparation method using enzymatic fragmentation
Článek Quantitative analysis of adsorption and desorption of volatile organic compounds on reusable zeolite filters using gas chromatography
Článek Quo vadis Pantanal? Expected precipitation extremes and drought dynamics from changing sea surface temperature
Článek The Brief Measure of Emotional Preoperative Stress (B-MEPS) as a new predictive tool for postoperative pain: A prospective observational cohort study
Článek Morphological adjustment in free-living Steinernema feltiae infective juveniles to increasing concentration of Nemafric-BL phytonematicide
Článek Key necroptotic proteins are required for Smac mimetic-mediated sensitization of cholangiocarcinoma cells to TNF-α and chemotherapeutic gemcitabine-induced necroptosis
Článek Concurrent lipidomics and proteomics on malignant plasma cells from multiple myeloma patients: Probing the lipid metabolome
Článek Retraction: SDR9C7 Promotes Lymph Node Metastases in Patients with Esophageal Squamous Cell Carcinoma
Článek Bioluminescent imaging of Arabidopsis thaliana using an enhanced Nano-lantern luminescence reporter system
Článek Biosynthetic pathway of indole-3-acetic acid in ectomycorrhizal fungi collected from northern Thailand
Článek Sex-specific and opposite modulatory aspects revealed by PPI network and pathway analysis of ischemic stroke in humans
Článek Role of donor genotype in RT-QuIC seeding activity of chronic wasting disease prions using human and bank vole substrates
Článek Sleep quality and sex modify the relationships between trait energy and fatigue on state energy and fatigue
Článek Availability, prices and affordability of selected antibiotics and medicines against non-communicable diseases in western Cameroon and northeast DR Congo
Článek Educators’ perceptions of organisational readiness for implementation of a pre-adolescent transdisciplinary school health intervention for inter-generational outcomes
Článek The effects of sport expertise and shot results on basketball players’ action anticipation
Článek Framework and algorithms for identifying honest blocks in blockchain
Článek Multiplex real-time PCR for the detection of Clavibacter michiganensis subsp. michiganensis, Pseudomonas syringae pv. tomato and pathogenic Xanthomonas species on tomato plants
Článek Hyper-spectral response and estimation model of soil degradation in Kenli County, the Yellow River Delta
Článek Construction of a high-density genetic map and fine mapping of a candidate gene locus for a novel branched-spike mutant in barley
Článek Natural hybridization between Phyllagathis and Sporoxeia species produces a hybrid without reproductive organs
Článek From seed to flour: Sowing sustainability in the use of cantaloupe melon residue (Cucumis melo L. var. reticulatus)
Článek Core Scientific Dataset Model: A lightweight and portable model and file format for multi-dimensional scientific data
Článek Accounting for measurement error to assess the effect of air pollution on omic signals
Článek Leucine zipper transcription factor-like 1 binds adaptor protein complex-1 and 2 and participates in trafficking of transferrin receptor 1
Článek Barriers for tuberculosis case finding in Southwest Ethiopia: A qualitative study
Článek Genetic predisposition to celiac disease in Kazakhstan: Potential impact on the clinical practice in Central Asia
Článek A lower psoas muscle volume was associated with a higher rate of recurrence in male clear cell renal cell carcinoma
Článek Two angles of overqualification-the deviant behavior and creative performance: The role of career and survival job
Článek Cost-utility analysis of de-escalating biological disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis
Článek Efficient estimation of stereo thresholds: What slope should be assumed for the psychometric function?
Článek Learning efficient haptic shape exploration with a rigid tactile sensor array
Článek Effects of dietary supplementation with a microalga (Schizochytrium sp.) on the hemato-immunological, and intestinal histological parameters and gut microbiota of Nile tilapia in net cages
Článek Regional versus local wind speed and direction at a narrow beach with a high and steep foredune
Článek Fragmented QRS complex in patients with systemic lupus erythematosus at the time of diagnosis and its relationship with disease activity
Článek Severe thiamine deficiency in eastern Baltic cod (Gadus morhua)
Článek Transfer entropy as a variable selection methodology of cryptocurrencies in the framework of a high dimensional predictive model
Článek Psychometric validation of Czech version of the Sport Motivation Scale
Článek Correction: Multiple innate antibacterial immune defense elements are correlated in diverse ungulate species
Článek Recognition of personality disorder and anxiety disorder comorbidity in patients treated for depression in secondary psychiatric care
Článek Correction: Strategies for achieving high sequencing accuracy for low diversity samples and avoiding sample bleeding using illumina platform
Článek ETAPOD: A forecast model for prediction of black pod disease outbreak in Nigeria
Článek Number of days required to estimate physical activity constructs objectively measured in different age groups: Findings from three Brazilian (Pelotas) population-based birth cohorts
Článek Exploring the mechanism of olfactory recognition in the initial stage by modeling the emission spectrum of electron transfer
Článek Risk of complications among diabetics self-reporting oral health status in Canada: A population-based cohort study
Článek Practical considerations in the use of a porcine model (Sus scrofa domesticus) to assess prevention of postoperative peritubal adhesions
Článek Identifying maintenance hosts for infection with Dichelobacter nodosus in free-ranging wild ruminants in Switzerland: A prevalence study
Článek The impact of a wireless audio system on communication in robotic-assisted laparoscopic surgery: A prospective controlled trial
Článek Post-transcriptional regulation of Rad51c by miR-222 contributes cellular transformation
Článek Repository-based plasmid design
Článek Patient perceived value of teleophthalmology in an urban, low income US population with diabetes
Článek Evidence in support of chromosomal sex influencing plasma based metabolome vs APOE genotype influencing brain metabolome profile in humanized APOE male and female mice
Článek Dense carbon-nanotube coating scaffolds stimulate osteogenic differentiation of mesenchymal stem cells
Článek Gamma Knife radiosurgery for vestibular schwannomas: Evaluation of planning using the sphericity degree of the target volume
Článek Purification and molecular characterization of phospholipase, antigen 5 and hyaluronidases from the venom of the Asian hornet (Vespa velutina)
Článek A study to better understand under-utilization of laboratory tests for antenatal care in Senegal
Článek Physicians’ perspectives regarding non-medical switching of prescription medications: Results of an internet e-survey
Článek Effectiveness of information technology–enabled ‘SMART Eating’ health promotion intervention: A cluster randomized controlled trial
Článek Cauda Equina Syndrome Core Outcome Set (CESCOS): An international patient and healthcare professional consensus for research studies
Článek Long term conjugated linoleic acid supplementation modestly improved growth performance but induced testicular tissue apoptosis and reduced sperm quality in male rabbit
Článek A new approach to the temporal significance of house orientations in European Early Neolithic settlements
Článek Effect of classroom intervention on student food selection and plate waste: Evidence from a randomized control trial
Článek Color image segmentation using adaptive hierarchical-histogram thresholding
Článek Potential socioeconomic impacts from ocean acidification and climate change effects on Atlantic Canadian fisheries
Článek Female finches prefer courtship signals indicating male vigor and neuromuscular ability
Článek The impact of translated reminder letters and phone calls on mammography screening booking rates: Two randomised controlled trials
Článek Design and evaluation of a laboratory-based wheelchair castor testing protocol using community data
Článek Evaluation of the predictive ability of ultrasound-based assessment of breast cancer using BI-RADS natural language reporting against commercial transcriptome-based tests
Článek Recovery of health-related quality of life after burn injuries: An individual participant data meta-analysis
Článek Modeling aggressive market order placements with Hawkes factor models
Článek High expression of olfactomedin-4 is correlated with chemoresistance and poor prognosis in pancreatic cancer
Článek Complex patterns of cell growth in the placenta in normal pregnancy and as adaptations to maternal diet restriction
Článek Temporal ordering of input modulates connectivity formation in a developmental neuronal network model of the cortex
Článek Healthy lifestyle index and its association with hypertension among community adults in Sri Lanka: A cross-sectional study
Článek Effects of Allium hookeri on gut microbiome related to growth performance in young broiler chickens
Článek Novel imaging biomarkers for mapping the impact of mild mitochondrial uncoupling in the outer retina in vivo
Článek Comparison of post-transplantation diabetes mellitus incidence and risk factors between kidney and liver transplantation patients
Článek A definition-by-example approach and visual language for activity patterns in engineering disciplines
Článek Use of conventional cardiac troponin assay for diagnosis of non-ST-elevation myocardial infarction: ‘The Ottawa Troponin Pathway’
Článek Identification and characterization of miRNAs involved in cold acclimation of zebrafish ZF4 cells
Článek Research on motion planning for an indoor spray arm based on an improved potential field method
Článek Detailed analysis of the transverse arch of hallux valgus feet with and without pain using weightbearing ultrasound imaging and precise force sensors
Článek Diagnostic differences in respiratory breathing patterns and work of breathing indices in children with Duchenne muscular dystrophy
Článek Single-modal and multi-modal false arrhythmia alarm reduction using attention-based convolutional and recurrent neural networks
Článek Eye-gaze information input based on pupillary response to visual stimulus with luminance modulation
Článek Were ancient foxes far more carnivorous than recent ones?—Carnassial morphological evidence
Článek Disruption in daily eating-fasting and activity-rest cycles in Indian adolescents attending school
Článek The Shapley value for a fair division of group discounts for coordinating cooling loads
Článek Pancreatic secretory trypsin inhibitor reduces multi-organ injury caused by gut ischemia/reperfusion in mice
Článek Biochemical characterization of Ty1 retrotransposon protease
Článek The validation of the Beijing version of the Montreal Cognitive Assessment in Chinese patients undergoing hemodialysis
Článek Inflammasome expression is higher in ovarian tumors than in normal ovary
Článek Clinical, cytogenetic and molecular genetic characterization of a tandem fusion translocation in a male Holstein cattle with congenital hypospadias and a ventricular septal defect
Článek Estimating the basic reproduction number of a pathogen in a single host when only a single founder successfully infects
Článek Community- and trophic-level responses of soil nematodes to removal of a non-native tree at different stages of invasion
Článek Association of ECG parameters with late gadolinium enhancement and outcome in patients with clinical suspicion of acute or subacute myocarditis referred for CMR imaging
Článek Catchment-scale export of antibiotic resistance genes and bacteria from an agricultural watershed in central Iowa
Článek Impact of multi-drug resistant bacteria on economic and clinical outcomes of healthcare-associated infections in adults: Systematic review and meta-analysis
Článek Characterization of a universal screening approach for congenital CMV infection based on a highly-sensitive, quantitative, multiplex real-time PCR assay
Článek Intraoperative computed tomography imaging for dose calculation in intraoperative electron radiation therapy: Initial clinical observations
Článek Simple non-mydriatic retinal photography is feasible and demonstrates retinal microvascular dilation in Chronic Obstructive Pulmonary Disease (COPD)
Článek Maternal depressive symptoms and children’s cognitive development: Does early childcare and child’s sex matter?
Článek Prevalence and characteristics of Livestock-Associated Methicillin-Resistant Staphylococcus aureus (LA-MRSA) isolated from chicken meat in the province of Quebec, Canada
Článek Using machine learning methods to determine a typology of patients with HIV-HCV infection to be treated with antivirals
Článek Gender differences influence over insomnia in Korean population: A cross-sectional study
Článek Impact of scion/rootstock reciprocal effects on metabolomics of fruit juice and phloem sap in grafted Citrus reticulata
Článek Adapting cognitive diagnosis computerized adaptive testing item selection rules to traditional item response theory
Článek Umbilical cord separation time, predictors and healing complications in newborns with dry care
Článek Analysis of attitudinal components towards statistics among students from different academic degrees
Článek An integrated vitamin E-coated polymer hybrid nanoplatform: A lucrative option for an enhanced in vitro macrophage retention for an anti-hepatitis B therapeutic prospect
Článek The effect of strontium and silicon substituted hydroxyapatite electrochemical coatings on bone ingrowth and osseointegration of selective laser sintered porous metal implants
Článek Molecular prevalence of Bartonella, Babesia, and hemotropic Mycoplasma species in dogs with hemangiosarcoma from across the United States
Článek Comparisons of recurrence-free survival and overall survival between microwave versus radiofrequency ablation treatment for hepatocellular carcinoma: A multiple centers retrospective cohort study with propensity score matching
Článek Oral misoprostol, low dose vaginal misoprostol, and vaginal dinoprostone for labor induction: Randomized controlled trial
Článek The association between dietary patterns before and in early pregnancy and the risk of gestational diabetes mellitus (GDM): Data from the Malaysian SECOST cohort
Článek Molecular evidence for horizontal transmission of chelonid alphaherpesvirus 5 at green turtle (Chelonia mydas) foraging grounds in Queensland, Australia
Článek cagA gene EPIYA motif genetic characterization from Colombian Helicobacter pylori isolates: Standardization of a molecular test for rapid clinical laboratory detection
Článek Spectral characteristics of urine from patients with end-stage kidney disease analyzed using Raman Chemometric Urinalysis (Rametrix)
Článek Comparison of Monocyte Distribution Width (MDW) and Procalcitonin for early recognition of sepsis
Článek Morphological association between the muscles and bones in the craniofacial region
Článek Antenatal depression and its association with adverse birth outcomes in low and middle-income countries: A systematic review and meta-analysis
Článek The role of refugee and migrant migration status on medication adherence: Mediation through illness perceptions
Článek Novel broad-spectrum activity-based probes to profile malarial cysteine proteases
Článek Effect of a community-based approach of iron and folic acid supplementation on compliance by pregnant women in Kiambu County, Kenya: A quasi-experimental study
Článek Plasma kynurenines and prognosis in patients with heart failure
Článek Occurrence and distribution of anthropogenic persistent organic pollutants in coastal sediments and mud shrimps from the wetland of central Taiwan
Článek Metabolic analysis of amino acids and vitamin B6 pathways in lymphoma survivors with cancer related chronic fatigue
Článek Immunopathogenesis of canine chronic ulcerative stomatitis
Článek Natural selection contributes to food web stability
Článek Diversity and plant growth-promoting functions of diazotrophic/N-scavenging bacteria isolated from the soils and rhizospheres of two species of Solanum
Článek Sofosbuvir-based regimen for genotype 2 HCV infected patients in Taiwan: A real world experience
Článek Cloud-computing and machine learning in support of country-level land cover and ecosystem extent mapping in Liberia and Gabon
Článek The impact of diabetes mellitus medication on the incidence of endogenous endophthalmitis
Článek Correction: Chl1 DNA helicase and Scc2 function in chromosome condensation through cohesin deposition
Článek Clinical and pathological features of thrombotic microangiopathy influencing long-term kidney transplant outcomes
Článek Occupational exposure to particulate matter from air pollution in the outdoor workplaces in Almaty during the cold season
Článek Association between tuberculosis and depression on negative outcomes of tuberculosis treatment: A systematic review and meta-analysis
Článek Control of the microsporidian parasite Nosema ceranae in honey bees (Apis mellifera) using nutraceutical and immuno-stimulatory compounds
Článek Oral magnesium supplementation for leg cramps in pregnancy—An observational controlled trial
Článek Health care professionals’ knowledge of commonly used sedative, analgesic and neuromuscular drugs: A single center (Rambam Health Care Campus), prospective, observational survey
Článek Campylobacter portucalensis sp. nov., a new species of Campylobacter isolated from the preputial mucosa of bulls
Článek Transgenic interleukin 11 expression causes cross-tissue fibro-inflammation and an inflammatory bowel phenotype in mice
Článek The role of peer, parental, and school norms in predicting adolescents’ attitudes and behaviours of majority and different minority ethnic groups in Croatia
Článek The effect of mutations derived from mouse-adapted H3N2 seasonal influenza A virus to pathogenicity and host adaptation
Článek Detection of posttraumatic pneumothorax using electrical impedance tomography—An observer-blinded study in pigs with blunt chest trauma
Článek Beyond the heterodimer model for mineralocorticoid and glucocorticoid receptor interactions in nuclei and at DNA
Článek Exploring the impact of terminology differences in blood and organ donor decision making
Článek Platelet indices significantly correlate with liver fibrosis in HCV-infected patients
Článek The nitrate content of fresh and cooked vegetables and their health-related risks
Článek Bioreactor for mobilization of mesenchymal stem/stromal cells into scaffolds under mechanical stimulation: Preliminary results
Článek Non-gradient and genotype-dependent patterns of RSV gene expression
Článek The 24-hour urinary cortisol in post-traumatic stress disorder: A meta-analysis
Článek Drug-eluting versus bare-metal stents for first myocardial infarction in patients with atrial fibrillation: A nationwide population-based cohort study
Článek Health-related quality of life among patients with type 2 diabetes mellitus in Eastern Province, Saudi Arabia: A cross-sectional study
Článek “I like the way I am, but I feel like I could get a little bit bigger”: Perceptions of body image among adolescents and youth living with HIV in Durban, South Africa
Článek Nanoparticle-based ‘turn-on’ scattering and post-sample fluorescence for ultrasensitive detection of water pollution in wider window
Článek Insights into the strategy of micro-environmental adaptation: Transcriptomic analysis of two alvinocaridid shrimps at a hydrothermal vent
Článek Thirty-day readmission after medical-surgical hospitalization for people who experience imprisonment in Ontario, Canada: A retrospective cohort study
Článek The association of telomere length and telomerase activity with adverse outcomes in older patients with non-ST-elevation acute coronary syndrome
Článek Alterations of aqueous humor Aβ levels in Aβ-infused and transgenic mouse models of Alzheimer disease
Článek The impact of peer attachment on prosocial behavior, emotional difficulties and conduct problems in adolescence: The mediating role of empathy
Článek Diagnostic performance of serum interferon gamma, matrix metalloproteinases, and periostin measurements for pulmonary tuberculosis in Japanese patients with pneumonia
Článek Characterization of black patina from the Tiber River embankments using Next-Generation Sequencing
Článek Problem gambling, associations with comorbid health conditions, substance use, and behavioural addictions: Opportunities for pathways to treatment
Článek Nanosheet wrapping-assisted coverslip-free imaging for looking deeper into a tissue at high resolution
Článek Validity of cerebrovascular ICD-9-CM codes in healthcare administrative databases. The Umbria Data-Value Project
Článek Torque teno virus viral load is related to age, CMV infection and HLA type but not to Alzheimer's disease
Článek Associations of cigarette smoking and burden of thoracic aortic calcification in asymptomatic individuals: A dose-response relationship
Článek Transforming assessment of speech in children with cleft palate via online crowdsourcing
Článek Human-raptor conflict in rural settlements of Colombia
Článek Assessment of peritoneal microbial features and tumor marker levels as potential diagnostic tools for ovarian cancer
Článek Deficiency syndromes in top predators associated with large-scale changes in the Baltic Sea ecosystem
Článek Perceived relative social status and cognitive load influence acceptance of unfair offers in the Ultimatum Game
Článek Hepatitis B and C virus infection among HIV patients within the public and private healthcare systems in Chile: A cross-sectional serosurvey
Článek Retraction: Oncogenic Fibulin-5 Promotes Nasopharyngeal Carcinoma Cell Metastasis through the FLJ10540/AKT Pathway and Correlates with Poor Prognosis
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2020 Číslo 1
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Autori: MUDr. Tomáš Ürge, PhD.
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