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    ABSTRACT: Epstein Barr virus (EBV) is a highly prevalent human gamma 1 lymphocryptovirus which infects both B lymphocytes and epithelial cells. In the healthy host, infection of these different cell lineages broadly reflects the different phases of the virus lifecycle. Memory B cells are the reservoir for latent EBV, in which viral gene expression is highly restricted to maintain an asymptomatic lifelong infection. In contrast, epithelial cells may be a major site of the virus lytic cycle, where infectious virus is propagated and transmitted via saliva to uninfected hosts. To achieve this dual tropism, EBV has evolved a unique set of glycoproteins in addition to a highly conserved set, which interact with cell lineage-specific receptors and switch cellular tropism during infection.
    No preview · Article · Feb 2014
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    ABSTRACT: Background Malignant brain tumors in children generally have a very poor prognosis when they relapse and improvements are required in their management. It can be difficult to accurately diagnose abnormalities detected during tumor surveillance, and new techniques are required to aid this process. This study investigates how metabolite profiles measured noninvasively by (1)H magnetic resonance spectroscopy (MRS) at relapse reflect those at diagnosis and may be used in this monitoring process.Methods Single-voxel MRS (1.5 T, point-resolved spectroscopy, echo time 30 ms, repetition time 1500 ms was performed on 19 children with grades II-IV brain tumors during routine MRI scans prior to treatment for a suspected brain tumor and at suspected first relapse. MRS was analyzed using TARQUIN software to provide metabolite concentrations. Paired Student's t-tests were performed between metabolite profiles at diagnosis and at first relapse.ResultsThere was no significant difference (P > .05) in the level of any metabolite, lipid, or macromolecule from tumors prior to treatment and at first relapse. This was true for the whole group (n = 19), those with a local relapse (n = 12), and those with a distant relapse (n = 7). Lipids at 1.3 ppm were close to significance when comparing the level at diagnosis with that at distant first relapse (P = .07, 6.5 vs 12.9). In 5 cases the MRS indicative of tumor preceded a formal diagnosis of relapse.Conclusions Tumor metabolite profiles, measured by MRS, do not change greatly from diagnosis to first relapse, and this can aid the confirmation of the presence of tumor.
    No preview · Article · Dec 2013 · Neuro-Oncology
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    ABSTRACT: Background: Epithelial cell adhesion molecule is overexpressed in bladder tumours and released from bladder cancer cells in vitro. We test the hypotheses that urinary EpCAM could act as a biomarker for primary bladder cancer detection and risk stratification. Methods: Epithelial cell adhesion molecule was measured by ELISA in urine from 607 patients with primary bladder tumours and in urine from 53 non-cancer controls. Mann–Whitney tests and ROC analyses were used to determine statistical significance and discrimination between non-cancer controls and different stages and grades of disease. Multivariable modelling and Kaplan–Meier analyses were used to determine prognostic significance. The structure of urinary EpCAM was investigated by western blotting and mass spectrometry. Results: Urinary EpCAM levels increase with stage and grade of bladder cancer. Alongside grade and stage, elevated urinary EpCAM is an independent indicator of poor prognosis with a hazard ratio of 1.76 for bladder cancer-specific mortality. The soluble form of EpCAM in urine is the extracellular domain generated by cleavage between ala243 and gly244. Further studies are required to define the influence of other urinary tract malignancies and benign urological conditions on urinary EpCAM. Conclusion: The extracellular domain of EpCAM is shed into urine by bladder tumours. Urinary EpCAM is a strong indicator of bladder cancer-specific survival, and may be useful within a multi-marker panel for disease detection or as a stand-alone marker to prioritise the investigation and treatment of patients. The mechanisms and effects of EpCAM cleavage in bladder cancer are worthy of further investigation, and may identify novel therapeutic targets.
    No preview · Article · Nov 2013 · British Journal of Cancer
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