Detection of methylated apoptosis-associated genes in urine sediments of bladder cancer patients.

PURPOSE: There is increasing evidence for a fundamental role for epigenetic silencing of apoptotic pathways in cancer. Changes in DNA methylation can be detected with a high degree of sensitivity, so we used the MethyLight assay to determine how methylation patterns of apoptosis-associated genes change during bladder carcinogenesis and whether DNA methylation could be detected in urine sediments. EXPERIMENTAL DESIGN: We analyzed the methylation status of the 5' regions of 12 apoptosis-associated genes (ARF, FADD, TNFRSF21, BAX, LITAF, DAPK, TMS-1, BCL2, RASSF1A, TERT, TNFRSF25, and EDNRB) in 18 bladder cancer cell lines, 127 bladder cancer samples, and 37 samples of adjacent normal bladder mucosa using the quantitative MethyLight assay. We also analyzed the methylation status in urine sediments of 20 cancer-free volunteers and 37 bladder cancer patients. RESULTS: The 5' regions of DAPK, BCL2, TERT, RASSFIA, and TNFRSF25 showed significant increases in methylation levels when compared with nonmalignant adjacent tissue (P < or = 0.01). Methylation levels of BCL2 were significantly associated with tumor staging and grading (P < or = 0.01), whereas methylation levels of RASSF1A and ARF were only associated with tumor stage (P < or = 0.04), and TERT methylation and EDNRB methylation were predictors of tumor grade (P < or = 0.02). To investigate clinical usefulness for noninvasive bladder cancer detection, we further analyzed the methylation status of the markers in urine samples of patients with bladder cancer. Methylation of DAPK, BCL2, and TERT in urine sediment DNA from bladder cancer patients was detected in the majority of samples (78%), whereas they were unmethylated in the urine sediment DNA from age-matched cancer-free individuals. CONCLUSIONS: Our results indicate that methylation of the 5' region of apoptosis-associated genes is a common finding in patients with bladder carcinoma. The ability to detect methylation not only in bladder tissue, but also in urine sediments, suggests that methylation markers are promising tools for noninvasive detection of bladder cancers. Our results also indicate that some methylation markers, such as those in regions of RASSF1A and TNFRSF25, might be of limited use for detection because they are also methylated in normal bladder tissues.     

Inhalative Vasodilatatoren in der kardiochirurgischen Intensivmedizin

Die Anwendung inhalativer Vasodilatatoren in der Intensivmedizin ist eine wirkungsvolle Therapieoption, um eine Senkung des pulmonalarteriellen Drucks bei stabilem arteriellem Druck zu erzielen. Stickstoffmonoxid (NO) war die erste diesbezüglich angewendete Substanz, die außerdem eine Verbesserung des Gasaustauschs bewirkte. Eine Vielzahl von Studien konnte die Wirksamkeit von inhaliertem NO, aber auch anderen aerosolierten Vasodilatatoren (z. B. Prostazyklin, Phosphodiesterasehemmer, Nitrate) bei der Behandlung von Patienten mit pulmonaler Hypertonie, Rechtsherzversagen und Hypoxämie belegen. Klinische Zulassungen liegen bisher für inhaliertes NO lediglich zur Behandlung der primär pulmonalen Hypertension des Neugeborenen und für das stabile Prostazyklin-Analogon Iloprost (Ventavis^®) zur inhalativen Behandlung der primär pulmonalen Hypertonie vor. Andererseits führt die gute klinische Wirksamkeit inhalierter Vasodilatatoren zu einem zunehmenden „Off-label-Gebrauch“ dieser Substanzen, besonders im Bereich der Intensivmedizin. Ziel der vorliegenden Übersicht ist es daher, nach einer Einführung in die pathophysiologischen und pharmakologischen Grundlagen des Therapiekonzepts die aktuelle Studienlage und praktische Anwendung, besonders in der kardiochirurgischen Intensivmedizin, zu erläutern.     

Zur Kenntnis der Osteoblastome

Ohne Zusammenfassung