Related F-box proteins control cell death in Caenorhabditis elegans and human lymphoma.

Cell death is a common metazoan cell fate, and its inactivation is central to human malignancy. In Caenorhabditis elegans, apoptotic cell death occurs via the activation of the caspase CED-3 following binding of the EGL-1/BH3-only protein to the antiapoptotic CED-9/BCL2 protein. Here we report a major alternative mechanism for caspase activation in vivo involving the F-box protein DRE-1. DRE-1 functions in parallel to EGL-1, requires CED-9 for activity, and binds to CED-9, suggesting that DRE-1 promotes apoptosis by inactivating CED-9. FBXO10, a human protein related to DRE-1, binds BCL2 and promotes its degradation, thereby initiating cell death. Moreover, some human diffuse large B-cell lymphomas have inactivating mutations in FBXO10 or express FBXO10 at low levels. Our results suggest that DRE-1/FBXO10 is a conserved regulator of apoptosis.

Cardiothoracic MRI in the ICU: A 10-Year Experience.

RATIONALE AND OBJECTIVE: The objective of this study was to identify the feasibility and pitfalls of cardiothoracic magnetic resonance imaging (MRI) in intensive care unit (ICU) patients. MATERIALS AND METHODS: This retrospective study identified adult ICU patients scheduled for cardiothoracic MRIs during a 10-year study period. ICU patients scheduled for brain MRIs served as a comparison group. A chart review was performed to identify factors impacting a patient's ability to undergo an MRI. Differences between completed and canceled examinations for both cardiothoracic and brain MRIs were evaluated. For the cardiothoracic group, clinical indications and the diagnostic value of the study performed were also identified. RESULTS: A total of 143 cardiothoracic MRIs and 1011 brain MRIs were requested. Cardiothoracic MRI patients were less frequently completed (52% vs 62%), more frequently men (64% vs 43%), younger (55 vs 63 years), less likely mechanically ventilated (8% vs 29%), more likely to require intravenous contrast (83% vs 23%), and had longer examination times compared to brain MRI patients (64 vs 21 minutes). Successful completion of cardiothoracic MRI was associated with lower serum creatinine, higher glomerular filtration rate, and the absence of mechanical ventilation; significant differences were not seen with regard to gender and use of vasoactive agents. Cardiothoracic MRI results were diagnostic in 69% of examinations, most frequently when performed for myocardial disease (84%) and aortic disease (33%), and less frequently for viability (33%). CONCLUSIONS: In an ICU population, successful completion of cardiothoracic MRI is challenging but feasible in patients with intact renal function and the absence of mechanical ventilation. Examinations were most frequently diagnostic for myocardial and aortic disease indications.

Prostate-specific antigen decline during salvage radiation therapy following prostatectomy is associated with reduced biochemical failure.

PURPOSE: To evaluate the prognostic value of prostate-specific antigen (PSA) decline during salvage radiation therapy (SRT) after prostatectomy. METHODS AND MATERIALS: We reviewed an institutional database and identified all prostate cancer patients who were treated with SRT between the years 2003 and 2010, had at least 1 PSA measurement during their SRT course, and had no history of androgen deprivation therapy use prior to or during SRT. Disease characteristics, treatment information, and clinical outcomes data were tabulated for each patient. The PSA response during SRT was defined as a PSA decline of at least 0.2 ng/mL compared with the pretreatment PSA level. Bivariate and multivariate analyses using Cox proportional hazards modeling were performed to identify predictors of biochemical recurrence. RESULTS: Sixty-four patients met eligibility criteria for this analysis. Median PSA before SRT was 0.63 ng/mL (interquartile range: 0.42-1.00). With a median follow-up time of 70 months after SRT, 5-year actuarial rates for biochemical control and metastasis-free survival were 61% (95% confidence interval [CI], 48%-75%) and 88% (95% CI, 79%-97%), respectively. The median number of PSA measurements per patient during SRT was 3 (range, 1-5). On bivariate analysis, PSA response during SRT and positive surgical margins were significantly associated with a decreased risk of biochemical recurrence (BR), with hazard ratios of 0.160 (95% CI, 0.059-0.431, P < .001) and 0.396 (95% CI, 0.168-0.935, P = .035). On multivariate analysis, PSA response during SRT and positive surgical margin were independent, favorable predictors for BR, with hazard ratios of 0.171 (95% CI, 0.063-0.463, P < .001) and 0.411 (95% CI, 0.177-0.956, P = .039). The 5-year biochemical control rate for PSA responders was 81%, compared with 37% for nonresponders (P < .001). CONCLUSIONS: Prostate-specific antigen decline during SRT may be a valuable prognostic factor for subsequent clinical outcomes. Future studies should investigate the value of monitoring PSA during SRT and how PSA response may be used to personalize therapy.