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    ABSTRACT: Bladder cancer is the seventh most common malignancy worldwide, with almost 14,000 patients dying from this disease in the USA alone. Because of the need for long-term and frequent follow-up, as well as the paucity of sensitive and specific noninvasive tests, bladder cancer management has the highest cost per patient among all cancer types. Several molecular markers, especially members of the cell cycle regulation and apoptosis pathways, have been investigated. However, no individual marker has been prognostically powerful enough to change clinical management. The combined analysis of a panel of markers spanning different pathways is the most promising approach. We give an overview of the most important molecular markers functioning in crucial pathways and focus on their role in multimarker analysis.
    Expert Review of Anti-infective Therapy 01/2008; 7(12):1717-27. · 2.07 Impact Factor
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    ABSTRACT: Bladder cancer is a model tumor progressing from superficial to locally invasive and finally metastatic disease. The likelihood of progression is determined to a large extent by the molecular profile of the tumor. From the pre-genomic era only p53 emerged as the molecular prognostic factor able to add value to existing clinical and pathological features of bladder cancer, however it was not introduced to the clinic. Microarray technologies enable us to study expression of thousands of genes in the tumor tissue. This method has already proven to add information to clinical classifiers, to find new tumor suppressor genes and to define p53 related pathways of cell-cycle regulation. In the last decade, progress in the treatment of locally invasive and metastatic bladder cancer was minimal; large Phase III trials with neo/adjuvant chemotherapy were inconclusive. The new paradigm of treatment tailored to an individual patient could be realized in bladder cancer for his chronic clinical course with opportunities to obtain tumor samples for microarray studies. Molecular profiling of two samples taken at the superficial stage and at cystectomy should enable us to study the microevolution of the tumor, to tailor existing treatment options, and to introduce new biologicals to the clinic.Introduction
    Pharmacogenomics 04/2003; 4(2):179-89. · 3.86 Impact Factor
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    ABSTRACT: Despite the crucial role of the brain in the control of the human lower urinary tract, little is known about the supraspinal mechanisms regulating micturition. To investigate the central regulatory mechanisms activated during micturition initiation and actual micturition, we used an alternating sequence of micturition imitation/imagination, micturition initiation, and actual micturition in 22 healthy males undergoing functional magnetic resonance imaging. Subjects able to micturate (voiders) showed the most prominent supraspinal activity during the final phase of micturition initiation whereas actual micturition was associated with significantly less such activity. Initiation of micturition in voiders induced significant activity in the brainstem (periaqueductal gray, pons), insula, thalamus, prefrontal cortex, parietal operculum and cingulate cortex with significant functional connectivity between the forebrain and parietal operculum. Subjects unable to micturate (nonvoiders) showed less robust activation during initiation of micturition, with activity in the forebrain and brainstem particularly lacking. Our findings suggest that micturition is controlled by a specific supraspinal network which is essential for the voluntary initiation of micturition. Once this network triggers the bulbospinal micturition reflex via brainstem centers, micturition continues automatically without further supraspinal input. Unsuccessful micturition is characterized by a failure to activate the periaqueductal gray and pons during initiation.
    European Urology Supplements 03/2013; 12(1):e70–e71. · 3.37 Impact Factor