Noninvasive imaging at the molecular level is an emerging field in biomedical research. This paper introduces a new technology synergizing two leading imaging methodologies: positron emission tomography (PET) and magnetic resonance imaging (MRI). Although the value of PET lies in its high-sensitivity tracking of biomarkers in vivo, it lacks resolving morphology. MRI has lower sensitivity, but produces high soft-tissue contrast and provides spectroscopic information and functional MRI (fMRI). We have developed a three-dimensional animal PET scanner that is built into a 7-T MRI. Our evaluations show that both modalities preserve their functionality, even when operated isochronously. With this combined imaging system, we simultaneously acquired functional and morphological PET-MRI data from living mice. PET-MRI provides a powerful tool for studying biology and pathology in preclinical research and has great potential for clinical applications. Combining fMRI and spectroscopy with PET paves the way for a new perspective in molecular imaging.

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Matrix metalloproteinases (MMPs) play an important role in tumor progression and metastasis. Here, we investigated the prognostic relevance of MMP-7 in urinary bladder cancer. MMP-7 gene expression was measured in tissue samples of 101 patients using quantitative real-time PCR. Circulating MMP-7 serum levels of 98 individuals (79 patients and 19 controls) were analyzed by enzyme-linked immunosorbent assay. The results were compared with the clinical follow-up data, performing Kaplan-Meier logrank test as well as univariate and multivariate Cox analysis. In representative cases, immunohistochemical analysis for MMP-7 was performed. We detected significantly elevated MMP-7 levels both in tissue and serum samples of patients with metastatic disease (P = 0.001 and P = 0.002). Multivariate analysis revealed that high MMP-7 tissue expression and serum concentration are stageand grade-independent predictors of both metastasis-free (hazard ratio [HR] = 3.80, 95% confidence interval [CI], 1.29-11.23, P = 0.016, and HR = 2.53, 95% CI, 1.01-6.37, P = 0.048) and disease-specific survival (HR = 1.89, 95% CI, 1.00-3.55, P = 0.050 and HR = 1.95, 95% CI, 1.03-3.71, P = 0.041). Based on these findings, we conclude that MMP-7 is a promising marker to detect present and to predict future metastasis. Serum MMP-7 analysis provides information about the risk of metastasis before surgery which could help to optimize therapeutic procedures. Furthermore, high MMP-7 tissue and/or serum levels could identify patients most likely to benefit from early adjuvant chemotherapy. (Cancer Sci 2010; 101: 1300-1308 U rinary bladder cancer (UBC) is the most common malignancy of the urinary tract. Although the majority of patients present with superficial UBC, 20-40% of patients will either present or ultimately develop muscle-invasive disease. Radical cystectomy is the standard treatment for muscle-invasive UBC. However, this 'gold standard' only provides 5-year survival in about 50% of patients.(1) The most reliable prognostic factor in this cystectomy cohort is lymph node status. Patients with organ-confined muscle-invasive UBC enjoy longterm freedom from progression after radical cystectomy, while those with metastatic disease are at an increased risk for progression and mortality. The main cause of relapse is the presence of microscopic metastasis that remains undetected before surgery.(2) The role of conventional imaging modalities is limited due to their poor performance for detecting low-volume lymph node and/or distant metastases.(3) To date there are no markers in the daily routine to identify patients most likely to benefit from radical cystectomy. Therefore there is a clear need for novel prognostic biomarkers to ensure adequate risk stratification in muscle-invasive UBC.Matrix metalloproteinases (MMPs) are a family of zincdependent proteolytic enzymes capable of cleaving extracellular matrix proteins (ECMs). Degradation of ECM is an important step both in normal physiological processes (embryonic development, reproduction, and tissue re...

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Evidence continues to support a role for sleep in delayed learning without further practice. Here we demonstrate the beneficial influence of sleep on auditory skill learning. Fifty-six subjects were randomly assigned to two groups, trained and tested on a pitch memory task three times across 24 h. The morning group was trained at 09.00 h, retested 12 h later that same day, and again after 12 h sleep. The evening group was trained at 21.00 h, retested 12 h immediately after sleep, and again 12 h later the next day. At retesting, both groups combined showed significant delayed learning only after sleep, but not across equivalent periods of wake, regardless of which came first. These data add to the growing literature describing sleep-dependent learning throughout sensory and motor domains.

Molecular marker analyses aiming a more accurate disease characterization and risk stratification of cancer patients provided several promising marker candidates in the last few years. However, recent reviews underlined the paramount importance of validation, since many of the initially promising results could not be confirmed in independent patient cohorts. If serum or plasma is a more appropriate sample to test for prognostic markers is a matter of debate. We recently found serum MMP-7 levels to correlate with poor patients' prognosis in urinary bladder cancer. In this study, we examined associations of the MMP-7 plasma levels with clinical follow-up data in an independent cohort of bladder cancer patients to validate our former results and to assess if plasma is also suitable for MMP-7 analysis. Plasma levels of 97 patients and 22 controls were analyzed, using enzyme-linked immunosorbent assay. Associations between MMP-7 plasma concentrations and clinical data were assessed applying both univariate and multivariate analysis. Plasma MMP-7 levels were significantly higher in patients than in controls. Similarly to our former findings in sera, high MMP-7 plasma levels proved to be significant and independent predictors of both overall and disease-specific survival. In addition, we observed a metastasis-specific difference in MMP-7 levels between serum and plasma. In summary, we confirmed the prognostic relevance of circulating MMP-7 levels in an independent cohort of patients and concluded that circulating MMP-7 levels may help to identify bladder cancer patients at high-risk of disease progression who could benefit from an adjuvant chemotherapy or from an extended lymph node dissection.

Angiogenesis plays a critical role in tumor growth. VEGF, angiopoietins (Ang-1, Ang-2) and their tyrosine kinase receptor Tie2 are major regulators of angiogenesis. The aim of this study was to evaluate the prognostic value of the serum levels of these factors in bladder cancer. We analyzed the serum samples of 117 bladder cancer patients and 64 healthy volunteers by enzyme linked immunosorbent assay (ELISA) for Ang-1, Ang-2, VEGF and the extracellular domain of Tie2. The statistical evaluation of the obtained data was performed via Kaplan-Meier log-rank test, univariate Cox analyses as well as Cox proportional hazards regression model. Serum Ang-1 levels of bladder cancer patients were significantly higher (p < 0.001), while soluble Ang-2 and Tie2 levels were significantly lower (p = 0.016 and p = 0.001 respectively) in patients than those in controls. Cox univariate analysis revealed high sTie2 serum level as a risk factor for metastasis and as a borderline significant risk factor for disease related death (p = 0.022 and p = 0.081 respectively). These correlations were independent from tumor stage and grade in a Cox multivariate model (p = 0.016 and p = 0.069). These data indicate that the serum levels of analyzed angiogenic factors do change characteristically in bladder cancer. The soluble extracellular serum level of Tie2 may provide a stage and grade independent diagnostic tool to select a high risk group of bladder cancer patients.

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