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| Open AccessNon-CG DNA methylation is a biomarker for assessing endodermal differentiation capacity in pluripotent stem cells
The methylation of non-CpG residues is a poorly understood marker of pluripotent cells, gradually lost as cells differentiate. Here the authors show non-CG methylation can be used as a marker of differentiation potential.
- Lee M. Butcher
- , Mitsuteru Ito
- & Stephan Beck
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| Open AccessFrequent alterations in cytoskeleton remodelling genes in primary and metastatic lung adenocarcinomas
Despite lung adenocarcinoma having a high global mortality, the genetic mutations present in Asian patients are uncharacterized. Here the authors use genomic and transcriptomic analysis to identify thirteen significantly affected genes, including RHPN2, GLI3, MRC2, TP53 and IQGAP3.
- Kui Wu
- , Xin Zhang
- & Jianxing He
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| Open AccessFibrocyte-like cells mediate acquired resistance to anti-angiogenic therapy with bevacizumab
Acquired resistance to anti-angiogenic drugs, including bevacizumab, may occur in cancer patients. In this study the authors identify in the tumour microenvironment, fibrocyte-like cells derived from the bone marrow that mediate the resistance to bevacizumab through the production of FGF2.
- Atsushi Mitsuhashi
- , Hisatsugu Goto
- & Yasuhiko Nishioka
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| Open AccessCerebrospinal fluid-derived circulating tumour DNA better represents the genomic alterations of brain tumours than plasma
DNA circulating in the plasma of cancer patients carries features of the primary tumour, however such DNA is found in low levels in brain cancer patients. Here, the authors show that circulating tumour DNA can be detected in the cerebral spinal fluid of cancer patients and that this better recapitulates the primary tumour compared to DNA from the plasma.
- Leticia De Mattos-Arruda
- , Regina Mayor
- & Joan Seoane
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| Open AccessMAP3K8/TPL-2/COT is a potential predictive marker for MEK inhibitor treatment in high-grade serous ovarian carcinomas
The identification of pharmaceutically targetable biomarkers is essential for improving therapeutic options for cancer patients. In this study, the authors identify MAP3K8 as a potential predictive marker for MEK inhibitor treatment in patients with aggressive ovarian cancer.
- Tina Gruosso
- , Camille Garnier
- & Fatima Mechta-Grigoriou
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| Open AccessImmunological biomarkers predict HIV-1 viral rebound after treatment interruption
In some HIV-1-infected individuals, viraemia remains undetectable after antiretroviral treatment, but which of these patients will experience viral rebound is difficult to predict. Here the authors show that T cell exhaustion markers before treatment are predictive of shorter time to viral rebound.
- Jacob Hurst
- , Matthias Hoffmann
- & John Frater
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Article
| Open AccessEZH2-mediated loss of miR-622 determines CXCR4 activation in hepatocellular carcinoma
Chemokines and their receptors have key roles in tumorigenesis. Here, the authors demonstrate that CXRC4 is overexpressed in hepatocellular carcinoma and is associated with poor prognosis and, mechanistically CXCR4 is increased in expression via EZH2 repression of microRNA-622.
- Haiou Liu
- , Yidong Liu
- & Jiejie Xu
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| Open AccessSTAT3 regulated ARF expression suppresses prostate cancer metastasis
IL6-STAT3 signaling is activated in prostate cancer, however inhibiting this pathway has not lead to a survival advantage in patients. Here, Pencik et al.show that loss of the IL6-STAT3 axis in mice and humans leads to metastasis due to loss of ARF, unravelling STAT3 and ARF as potential prognostic markers in prostate cancer.
- Jan Pencik
- , Michaela Schlederer
- & Lukas Kenner
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Article
| Open AccessDesialylation is a mechanism of Fc-independent platelet clearance and a therapeutic target in immune thrombocytopenia
Immune thrombocytopenia (ITP) is caused by autoantibody-mediated platelet clearance, but refractoriness to current immunomodulatory therapies is common. Here the authors show that desialylated platelets can be cleared via hepatic Ashwell–Morell receptor, a process that can be attenuated by sialidase inhibitors, suggesting a new therapy for ITP.
- June Li
- , Dianne E. van der Wal
- & Heyu Ni
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| Open AccessUCHL1 provides diagnostic and antimetastatic strategies due to its deubiquitinating effect on HIF-1α
When stabilized, HIF-1 can activate adaptation to hypoxia and metastasis. Here the authors show that upregulation of Ubiquitin C-terminal hydrolase-L1 in human cancers promotes metastasis and correlates with poor prognosis because of its role in opposing ubiquitin-mediated degradation of HIF-1.
- Yoko Goto
- , Lihua Zeng
- & Hiroshi Harada
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Low MITF/AXL ratio predicts early resistance to multiple targeted drugs in melanoma
Increased expression of MITF transcription factor is thought to promote melanoma progression and kinase inhibitor resistance. Here Muller et al. show that MITF loss is also common in melanomas and confers kinase inhibitor resistance due to upregulation of AXL and other receptor tyrosine kinases.
- Judith Müller
- , Oscar Krijgsman
- & Daniel S. Peeper
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Article
| Open AccessStrong effects of genetic and lifestyle factors on biomarker variation and use of personalized cutoffs
Protein biomarkers could play an important role in the diagnosis and management of diseases. Here the authors investigate the impact of genetic, clinical and lifestyle factors on 92 protein biomarkers for cancer and inflammation and suggest that personalized biomarker thresholds should be used in cancer management.
- Stefan Enroth
- , Åsa Johansson
- & Ulf Gyllensten
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| Open AccessAlarmin S100A8/S100A9 as a biomarker for molecular imaging of local inflammatory activity
Alarmins are locally released during inflammation and are early amplifiers of inflammation. Here Vogl et al.show that the alarmin S100A8/S100A9 can be used as a sensitive marker to detect subclinical inflammation and follow disease progression in a variety of disease models.
- Thomas Vogl
- , Michel Eisenblätter
- & Johannes Roth
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Angiotensin II plasma levels are linked to disease severity and predict fatal outcomes in H7N9-infected patients
An avian influenza H7N9 virus causes severe human disease, including acute and often lethal respiratory failure. Here, the authors report that plasma levels of angiotensin II, a regulatory peptide of the renin–angiotensin system, are associated with disease severity and fatal outcome in infected patients.
- Fengming Huang
- , Jing Guo
- & Lanjuan Li
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| Open AccessMaternal nutrition at conception modulates DNA methylation of human metastable epialleles
Maternal diet affects DNA methylation in the developing offspring, leading to phenotypic changes. Here, Dominguez-Salas et al. exploit seasonal variation in the diet of Gambian women to show that maternal methyl donor nutrient status around the time of conception predicts methylation levels at metastable epialleles in infants.
- Paula Dominguez-Salas
- , Sophie E. Moore
- & Branwen J. Hennig
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| Open AccessExhaustion of nucleus pulposus progenitor cells with ageing and degeneration of the intervertebral disc
Back pain and sciatica are often caused by intervertebral disc degeneration. Sakai and colleagues identify a subset of nucleus pulposus progenitor cells from the intervertebral disc and show that loss of these progenitor cells correlates with ageing and intervertebral disc degeneration.
- Daisuke Sakai
- , Yoshihiko Nakamura
- & Joji Mochida
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Alternative α-synuclein transcript usage as a convergent mechanism in Parkinson's disease pathology
The protein α-synuclein is implicated in Parkinson's disease. Rhinn and colleagues perform gene expression analysis and find that specific α-synuclein transcripts are preferentially associated with Parkinson's disease, and that they potentiate the accumulation of α-synuclein protein.
- Herve Rhinn
- , Liang Qiang
- & Asa Abeliovich
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| Open AccessIdentification of high-quality cancer prognostic markers and metastasis network modules
There has been great interest in attempting to identify gene expression signatures that predict cancer survival. In this study a new algorithm is developed to analyse gene expression datasets that accurately classify both ER+ and ER− breast cancers into low- and high-risk groups.
- Jie Li
- , Anne E.G. Lenferink
- & Edwin Wang