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  • 1
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    Clinical course and progression-free survival of adult intracranial and spinal ependymoma patients (2015)
    Oxford University Press
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    Publication Date: 2015-02-26
    Description: Background Ependymomas are rare CNS tumors. Previous studies describing the clinical course of ependymoma patients were restricted to small sample sizes, often with patients at a specific institution. Methods Clinically annotated ependymoma tissue samples from 19 institutions were centrally reviewed. Patients were all adults aged 18 years or older at the time of diagnosis. Potential prognostic clinical factors identified on univariate analysis were included in a multivariate Cox proportional hazards model with backwards selection to model progression-free survival. Results The 282 adult ependymoma patients were equally male and female with a mean age of 43 years (range, 18–80y) at diagnosis. The majority were grade II (78%) with the tumor grade for 20 cases being reclassified on central review (half to higher grade). Tumor locations were spine (46%), infratentorial (35%), and supratentorial (19%). Tumor recurrence occurred in 26% ( n = 74) of patients with a median time to progression of 14 years. A multivariate Cox proportional hazards model identified supratentorial location ( P 〈 .01), grade III (anaplastic; P 〈 .01), and subtotal resection, followed or not by radiation ( P 〈 .01), as significantly increasing risk of early progression. Conclusions We report findings from an ongoing, multicenter collaboration from a collection of clinically annotated adult ependymoma tumor samples demonstrating distinct predictors of progression-free survival. This unique resource provides the opportunity to better define the clinical course of ependymoma for clinical and translational studies.
    Print ISSN: 1522-8517
    Electronic ISSN: 1523-5866
    Topics: Medicine
    Published by Oxford University Press on behalf of The Society for Neuro-Oncology (SNO).
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  • 2
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    Circulating C-reactive protein and colorectal cancer risk: a report from the Shanghai Men's Health Study (2013)
    Oxford University Press
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    Publication Date: 2013-12-01
    Description: Chronic inflammation has been implicated in the pathogenesis of colorectal cancer. The objective of this study was to evaluate the association of prediagnostic circulating levels of C-reactive protein (CRP), a biomarker of systemic inflammation, with subsequent development of colorectal cancer. Prediagnostic plasma CRP levels were examined among 288 colorectal cancer cases and 576 individually-matched controls nested within the Shanghai Men’s Health Study (2002–06), a population-based cohort study of 61 482 Chinese men. The association between CRP levels and colorectal cancer risk was investigated. Baseline plasma CRP levels were 53% higher among men who subsequently developed colorectal cancer than among those who remained free of the disease (1.15 versus 0.75 μg/ml; P 〈 0.001). Multivariate analyses showed a dose-dependent relationship between CRP and colorectal cancer risk ( P trend = 0.003); men in the highest tertile (CRP 〉 1.19 μg/ml) had 1.88-fold (95% confidence interval (CI): 1.24–2.86) increased odds of developing colorectal cancer compared with men in the lowest tertile (CRP 〈 0.45 μg/ml). The association was only significant for colon cancer, when cancer site was considered, and was predominantly seen for cases diagnosed within 4 years of blood collection; adjusted odds ratios for the highest versus the lowest tertiles were 3.28 (95% CI: 1.28–8.37), 3.68 (95% CI: 1.62–8.38) and 1.05 (95% CI: 0.56–1.97), respectively, for cases diagnosed 〈2, 2–4 and 〉4 years after blood collection. The findings from our study suggest that circulating CRP level is positively associated with colorectal cancer risk in Chinese men, and this association, at least in part, is explained by inflammation-related cancerous or precancerous processes.
    Print ISSN: 0143-3334
    Electronic ISSN: 1460-2180
    Topics: Medicine
    Published by Oxford University Press
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  • 3
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    GPR48, a poor prognostic factor, promotes tumor metastasis and activates {beta}-catenin/TCF signaling in colorectal cancer (2013)
    Oxford University Press
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    Publication Date: 2013-12-01
    Description: G-protein-coupled receptor 48 (GPR48) is an orphan receptor belonging to the G-protein-coupled receptors family, which plays an important role in the development of various organs and cancer development and progression such as gastric cancer and colorectal cancer (CRC). However, the prognostic value of GPR48 expression in patients with CRC has not been reported. In this study, we observed that GPR48 was overexpressed in primary CRC and metastatic lymph nodes and closely correlated with tumor invasion and metastasis. Multivariate analysis indicated that high GPR48 expression was a poor prognostic factor for overall survival in CRC patients. In vitro and in vivo assays demonstrated that enforced expression of GPR48 contributed to enhance migration and invasion of cancer cells and tumor metastasis. In addition, we found that GPR48 increased nuclear β-catenin accumulation, T-cell factor 4 (TCF4) transcription activity, and expression of its target genes including Cyclin D1 and c-Myc in CRC cells. Correlation analysis showed that GPR48 expression in CRC tissues was positively associated with β-catenin expression. Upregulation of GPR48 resulted in increased phosphorylation of glycogen synthase kinase 3β, Akt and extracellular signal-regulated kinase 1/2 (ERK1/2) in CRC cells, while inhibition of PI3K/Akt and mitogen-activated protein kinase /ERK1/2 pathways was sufficient to abolish the effect of GPR48 on β-catenin/TCF signaling. Taken together, GPR48 could serve as both a prognostic biomarker and a therapeutic target for resectable CRC patients.
    Print ISSN: 0143-3334
    Electronic ISSN: 1460-2180
    Topics: Medicine
    Published by Oxford University Press
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  • 4
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    The effect of interaction ratio in a chemical reaction (2013)
    Oxford University Press
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    Publication Date: 2013-11-26
    Description: This paper is concerned with the effect of interaction ratio in a chemical reaction with zero-flux boundary condition. Treating the interaction ratio as a parameter, the existence of non-constant positive steady states is discussed by the bifurcation theory. Especially, the steady-state bifurcation from the double eigenvalue is derived. The Hopf bifurcation analysis to both ordinary differential equations and partial differential equations systems is investigated in detail. Examples of numerical simulations are shown to support and complement the analytical conclusions.
    Print ISSN: 0272-4960
    Electronic ISSN: 1464-3634
    Topics: Mathematics
    Published by Oxford University Press
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  • 5
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    DNA Priming Prior to Inactivated Influenza A(H5N1) Vaccination Expands the Antibody Epitope Repertoire and Increases Affinity Maturation in a Boost-Interval-Dependent Manner in Adults (2013)
    Oxford University Press
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    Publication Date: 2013-07-03
    Description: DNA priming improves the response to inactivated influenza A(H5N1) vaccination. We compared the immunogenicity of an H5 DNA prime (using strain A/Indonesia/5/2005) followed by an H5N1 monovalent inactivated vaccine boost at 4, 8, 12, 16, or 24 weeks to that of 2 doses of H5N1 monovalent inactivated vaccine in adults. Antibody epitope repertoires were elucidated by genome-fragment phage-display library analysis, and antibody avidities for HA1 and HA2 domains were measured by surface plasmon resonance. H5 DNA priming expanded the H5-specific antibody epitope repertoire and enhanced antibody avidity to the HA1 (but not the HA2) domain in an interval-dependent manner. Enhanced HA1 binding and avidity after an interval of ≥12 weeks between prime and boost correlated with improved neutralization of homologous and heterologous H5N1 strains. Clinical trials registration NCT01086657.
    Print ISSN: 0022-1899
    Electronic ISSN: 1537-6613
    Topics: Medicine
    Published by Oxford University Press on behalf of The Infectious Diseases Society of America (IDSA).
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  • 6
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    Ex vivo acidic preconditioning enhances bone marrow ckit+ cell therapeutic potential via increased CXCR4 expression (2013)
    Oxford University Press
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    Publication Date: 2013-07-08
    Description: Aims The chemokine receptor CXCR4 modulates endothelial progenitor cell migration, homing, and differentiation, and plays a key role in cardiovascular regeneration. Here we examined the effect of ex vivo acidic preconditioning (AP) on CXCR4 expression and on the regenerative potential of mouse bone marrow (BM) ckit + cells. Methods and results Acidic preconditioning was achieved by exposing BM ckit + cells to hypercarbic acidosis (pH 7.0) for 24 h; control cells were kept at pH 7.4. Acidic preconditioning enhanced CXCR4 and stromal cell-derived factor 1 (SDF-1) mRNA levels, as well as CXCR4 phosphorylation. Acidic preconditioning ability to modulate CXCR4 expression depended on cytosolic calcium [Ca 2+ ] i mobilization and on nitric oxide (NO), as determined by [Ca 2+ ] i buffering with BAPTA, and by treatment with the NO donor (DETA/NO) and the NO synthase inhibitor (L-NAME). Further, AP increased SDF-1-driven chemotaxis, transendothelial migration, and differentiation toward the endothelial lineage in vitro . In a mouse model of hindlimb ischaemia, control and AP ckit + cells were transplanted into the ischaemic muscle; AP cells accelerated blood flow recovery, increased capillary, and arteriole number as well as the number of regenerating muscle fibres vs. control. These effects were abolished by treating AP cells with L-NAME. Conclusion Acidic preconditioning represents a novel strategy to enhance BM ckit + cell therapeutic potential via NO-dependent increase in CXCR4 expression.
    Print ISSN: 0195-668X
    Electronic ISSN: 1522-9645
    Topics: Medicine
    Published by Oxford University Press
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  • 7
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    AuthorReward: increasing community curation in biological knowledge wikis through automated authorship quantification (2013)
    Oxford University Press
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    Publication Date: 2013-07-06
    Description: : Community curation—harnessing community intelligence in knowledge curation, bears great promise in dealing with the flood of biological knowledge. To exploit the full potential of the scientific community for knowledge curation, multiple biological wikis (bio-wikis) have been built to date. However, none of them have achieved a substantial impact on knowledge curation. One of the major limitations in bio-wikis is insufficient community participation, which is intrinsically because of lack of explicit authorship and thus no credit for community curation. To increase community curation in bio-wikis, here we develop AuthorReward , an extension to MediaWiki, to reward community-curated efforts in knowledge curation. AuthorReward quantifies researchers’ contributions by properly factoring both edit quantity and quality and yields automated explicit authorship according to their quantitative contributions. AuthorReward provides bio-wikis with an authorship metric, helpful to increase community participation in bio-wikis and to achieve community curation of massive biological knowledge. Availability: http://cbb.big.ac.cn/software . Contact: zhangzhang@big.ac.cn Supplementary information: Supplementary data are available at Bioinformatics online.
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
    Published by Oxford University Press
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  • 8
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    MiR-106a is an independent prognostic marker in patients with glioblastoma (2013)
    Oxford University Press
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    Publication Date: 2013-05-23
    Description: Background Very little is known regarding correlation of micro RNA (miR)–106a with clinical outcomes of patients with glioblastoma multiforme (GBM). This study determined whether miR-106a could be used as an independent prognostic biomarker in those patients. Methods A total of 156 GBM patients were divided into 2 cohorts. In the first cohort, matched fresh frozen and formalin-fixed paraffin-embedded (FFPE) samples were collected from 24 GBM patients, while in the second cohort, only FFPE samples were collected from 132 GBM patients. MiR-106a expression levels were examined by quantitative real-time PCR in the 2 cohorts and further validated by in situ hybridization assay in the second cohort. The correlation between miR-106a expression levels and overall survival was evaluated in the second cohort of 114 GBM patients available for follow-up by a log-rank test and a multivariate Cox proportional hazards model. Results Our data showed a very good correlation of miR-106a or U6 expression between fresh frozen and FFPE GBM specimens, with Pearson's correlation coefficients of 0.849 and 0.823, respectively ( P 〈 .001). Their expression levels in archival FFPE samples were quite stable for at least 7 years when stored at room temperature. Multivariate analysis revealed that the expression level of miR-106a was an independent and significant predictor of overall survival in GBM patients ( P = .011). Conclusions MiR-106a expression was relatively abundant and stable in a large cohort of archival FFPE GBM specimens and could be used as an independent prognostic biomarker in those patients. Thus, miR-106a can be used to predict prognosis and treatment response in individual GBM patients.
    Print ISSN: 1522-8517
    Electronic ISSN: 1523-5866
    Topics: Medicine
    Published by Oxford University Press on behalf of The Society for Neuro-Oncology (SNO).
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  • 9
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    Non-invasive indices of right ventricular function are markers of ventricular-arterial coupling rather than ventricular contractility: insights from a porcine model of chronic pressure overload (2013)
    Oxford University Press
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    Publication Date: 2013-11-08
    Description: Aims To investigate the physiological correlates of indices of RV function in a model of chronic pressure overload. Methods and results Chronic pulmonary hypertension (PH) was induced in piglets by ligation of the left pulmonary artery (PA) followed by weekly embolization of right lower lobe arteries for 5 weeks (the PH group, n = 11). These animals were compared with sham-operated animals (controls, n = 6). At 6 weeks, a subgroup of five PH pigs underwent surgical reperfusion of the left lung and four others were followed until 12 weeks without treatment. Right ventricular function was assessed using echocardiography and conductance catheter measurements. At 6 weeks, mean PA pressure was higher in PH group compared with controls (35 ± 9 vs. 14 ± 2 mmHg, P 〈 0.01). Although RV elastance (Ees) increased at 6 weeks in the PH group (0.55 ± 0.09 vs. 0.38 ± 0.05mmHg/mL, P 〈 0.001), ventricular–arterial coupling measured by the ratio of Ees on PA elastance (Ea) was decreased (0.68 ± 0.17 vs. 1.18 ± 0.18, P 〈 0.001). There was a strong direct relationship between Ees/Ea and indices of RV function, while relationship between Ees and indices of RV function was moderate. Changes in indices of RV function with time and after left lung reperfusion were associated with changes in Ees/Ea. Conclusion Usual indices of RV function are associated with ventricular–arterial coupling rather than with ventricular contractility in a model of chronic pressure overload.
    Print ISSN: 1525-2167
    Electronic ISSN: 1532-2114
    Topics: Medicine
    Published by Oxford University Press
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  • 10
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    Colitis-accelerated colorectal cancer and metabolic dysregulation in a mouse model (2013)
    Oxford University Press
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    Publication Date: 2013-08-03
    Description: The connection between inflammation and colorectal cancer (CRC) has been well recognized, and numerous related molecular mechanisms have been uncovered. To gain further insight, we used BALB/c mice treated with azoxymethane (AOM) and dextran sulfate sodium salt (DSS) to establish a colitis-associated CRC model recapitulating tubulovillous adenoma with high-grade dysplasia at week 14. We evaluated the mice in four groups: a control group fed a standard diet; a group given DSS, in which we observed no tumor or dysplasia; a group given AOM, in which we observed few dysplastic foci despite repeated administrations of the carcinogen and a group given both AOM and DSS, in which our observations agreed with those of other studies that found accelerated colorectal carcinogenesis following DSS-induced colitis. We examined the messenger RNA and micro RNA (miRNA) expression profiles of the four groups. In colitis-associated CRC, we observed the dysregulation of many pathways, including the upregulation of Wnt signaling and CRC pathways and the downregulation of apoptosis. Also, most differentially expressed genes were significantly enriched in metabolic rather than immune/inflammation pathways/processes. Additionally, we demonstrated that the expression of several important miRNAs involved in both the inflammatory response and metabolism was dramatically altered during colitis-associated CRC. Gene network analysis and gene profile analysis confirmed a close relationship between metabolic and inflammatory genes in colitis-associated CRC. Thus, our study may provide a framework for identifying metabolic genes as targets of novel molecular-based therapies against CRC.
    Print ISSN: 0143-3334
    Electronic ISSN: 1460-2180
    Topics: Medicine
    Published by Oxford University Press
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