Background:Recent evidence suggests that bone-related parameters are the main prognostic factors for overall survival in advanced prostate cancer (PCa), with elevated circulating levels of alkaline phosphatase (ALP) thought to reflect the dysregulated bone formation accompanying distant metastases. We have identified that PCa cells express ALPL, the gene that encodes for tissue nonspecific ALP, and hypothesised that tumour-derived ALPL may contribute to disease progression.Methods:Functional effects of ALPL inhibition were investigated in metastatic PCa cell lines. ALPL gene expression was analysed from published PCa data sets, and correlated with disease-free survival and metastasis.Results:ALPL expression was increased in PCa cells from metastatic sites. A reduction in tumour-derived ALPL expression or ALP activity increased cell death, mesenchymal-to-epithelial transition and reduced migration. Alkaline phosphatase activity was decreased by the EMT repressor Snail. In men with PCa, tumour-derived ALPL correlated with EMT markers, and high ALPL expression was associated with a significant reduction in disease-free survival.Conclusions:Our studies reveal the function of tumour-derived ALPL in regulating cell death and epithelial plasticity, and demonstrate a strong association between ALPL expression in PCa cells and metastasis or disease-free survival, thus identifying tumour-derived ALPL as a major contributor to the pathogenesis of PCa progression.

Bladder cancers are a leading cause of death from malignancy. Molecular markers might predict disease progression and behaviour more accurately than the available prognostic factors. Here we use whole-genome sequencing to identify somatic mutations and chromosomal changes in 14 bladder cancers of different grades and stages. As well as detecting the known bladder cancer driver mutations, we report the identification of recurrent protein-inactivating mutations in CDKN1A and FAT1. The former are not mutually exclusive with TP53 mutations or MDM2 amplification, showing that CDKN1A dysfunction is not simply an alternative mechanism for p53 pathway inactivation. We find strong positive associations between higher tumour stage/grade and greater clonal diversity, the number of somatic mutations and the burden of copy number changes. In principle, the identification of sub-clones with greater diversity and/or mutation burden within early-stage or low-grade tumours could identify lesions with a high risk of invasive progression.

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We have evaluated the usefulness of electrical capacitance tomography (ECT) as a tool for monitoring pneumatic conveying in horizontal ducts. Power spectra of solids concentration fluctuations obtained from single-plane ECT data were used to identify the various flow regimes, and these were confirmed through visual observation. From single-plane ECT data, the instantaneous and time-averaged distributions of particle concentration over the cross section of the conveying pipe have been determined in various flow regimes. Propagation velocities of patterns were evaluated from cross correlation of twin-plane ECT data. The solids mass flow rate, determined independently by load cell measurements, was found to be roughly proportional to the product of the pattern velocity, the particle density, and the average solids holdup in the pipe, and the proportionality factor depended on the material being transported through the pipe. In our experiments involving flows past a 90°smooth bend, ECT was able to detect significant temporal and spatial nonuniformity in particle concentration in the postbend region.