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div>Finally, we propose that the TRAIL pathway might be severely dysregulated in prostate cancer, as virtually all tissue samples on our TMA demonstrated aberrations that eventually lead to TRAIL resistance. Our findings also suggest that most of these aberrations take place at the level of TRAIL receptors or its immediate downstream complex, the DISC, which is inhibited by FLIP. Although, in this study, we cannot rule out additional effects of downstream pathway components on TRAIL sensitivity, nor even investigate the functional impact of these aberrations on apoptosis in vitro or in vivo, the sheer percentage of patients displaying either death receptor downregulation and/or FLIPL overexpression is startling. Hence, we conclude that TRAIL-based therapy might benefit from an analysis of TRAIL resistance factors before treatment initiation. A therapeutic approach targeting Dabrafenib these resistance factors might complement TRAIL and possibly increase its efficacy. To summarize, we measured protein expression of TRAIL, its receptors DR4, DR5, DcR1, and DcR2, as well as FLIPL on a prostate cancer tissue microarray in a large cohort. On the basis of correlations with several clinical parameters as well as survival analyses, we suggest that TRAIL pathway plays an important role in prostate cancer pathogenesis and TRAIL expression, in particular, is of high prognostic value. We discovered that stromal expression selleck inhibitor of TRAIL is lost during transformation from normal prostate to prostate cancer, and this loss is further associated with poor recurrence-free Venetoclax survival of prostate cancer patients. Special thanks to Thomas Pangerl for excellent technical support. FWF Grant P20715-B12, HEC Pakistan Scholarship to M.A. ""It is common practice to hold anthracycline induction chemotherapy in children with high-risk acute lymphoblastic leukemia (HR-ALL) until an echocardiogram is performed and interpreted. It is unclear whether withholding therapy in HR-ALL children is justified by echocardiogram findings. We reviewed the initial echocardiograms in a cohort of children with HR-ALL to determine the incidence of contraindications for anthracycline treatment. We identified 50 consecutive children (<21 years old) with HR-ALL presenting at our institution over a 10-year period. One didn't have an initial echocardiogram, 39 had pre-therapy studies, and 10 were studied within 6 days of beginning chemotherapy. These 49 studies were reviewed to determine the incidence and clinical significance of abnormalities. All 49 patients had normal cardiac function. Initial echocardiogram findings had no impact on induction chemotherapy administration in any patient. However, only 22(45%) of the studies were completely normal. Echocardiographic abnormalities included pericardial effusion (17/49), trivial or mild mitral or aortic insufficiency (13/49), left ventricular enlargement (3/49), and structural heart disease (4/49).