15 research outputs found

    Of mice and men: molecular genetics of congenital heart disease

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    A role for STEAP2 in prostate cancer progression

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    Prostate adenocarcinoma is the second most frequent cancer worldwide and is one of the leading causes of male cancer-related deaths. However, it varies greatly in its behaviour, from indolent non-progressive disease to metastatic cancers with high associated mortality. The aim of this study was to identify predictive biomarkers for patients with localised prostate tumours most likely to progress to aggressive disease, to facilitate future tailored clinical treatment and identify novel therapeutic targets. The expression of 602 genes was profiled using oligoarrays, across three prostate cancer cell lines: CA-HPV-10, LNCaP and PC3, qualitatively identifying several potential prognostic biomarkers. Of particular interest was six transmembrane epithelial antigen of the prostate (STEAP) 1 and STEAP 2 which was subsequently analysed further in prostate cancer tissue samples following optimisation of an RNA extraction method from laser captured cells isolated from formalin-fixed paraffin-embedded biopsy samples. Quantitative analysis of STEAP1 and 2 gene expression were statistically significantly associated with the metastatic cell lines DU145 and PC3 as compared to the normal prostate epithelial cell line, PNT2. This expression pattern was also mirrored at the protein level in the cells. Furthermore, STEAP2 up-regulation was observed within a small patient cohort and was associated with those that had locally advanced disease. Subsequent mechanistic studies in the PNT2 cell line demonstrated that an over-expression of STEAP2 resulted in these normal prostate cells gaining an ability to migrate and invade, suggesting that STEAP2 expression may be a crucial molecule in driving the invasive ability of prostate cancer cells

    Continuous, non-invasive techniques to determine cardiac output in children after cardiac surgery: evaluation of transesophageal Doppler and electric velocimetry

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    BACKGROUND: Continuous and non-invasive measurement of cardiac output (CO) may contribute helpful information to the care and treatment of the critically ill pediatric patient. Different methods are available but their clinical verification is still a major problem. AIM: Comparison of reliability and safety of two continuous non-invasive methods with transthoracic echocardiography (TTE) for CO measurement: electric velocimetry technique (EV, Aesculon) and transesophageal Doppler (TED, CardioQP). METHODS/MATERIAL: In 26 infants and children who had undergone corrective cardiac surgery at a median age of 3.5 (1-17) years CO and stroke volume (SV) were obtained by EV, TED and TTE. Each patient had five measurements on the first day after surgery, during mechanical ventilation and sedation. RESULTS: Values for CO and SV from TED and EV correlated well with those of TTE (r = 0.85 and r = 0.88), but mean values were significantly lower than the values of TTE for TED (P = 0.02) and EV (P = 0.001). According to Bland-Altman analysis, bias was 0.36 l/min with a precision of 1.67 l/min for TED vs. TTE and 0.87 l/min (bias) with a precision of 3.26 l/min for EV vs. TTE. No severe adverse events were observed and the handling of both systems was easy in the sedated child. CONCLUSIONS: In pediatric patients non-invasive measurement of CO and SV with TED and EV is useful for continuous monitoring after heart surgery. Both new methods seem to underestimate cardiac output in terms of absolute values. However, TED shows tolerable bias and precision and may be helpful for continuous CO monitoring in a deeply sedated and ventilated pediatric patient, e.g. in the operating room or intensive care unit
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