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Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer
Smith, Matthew R.,Saad, Fred,Chowdhury, Simon,Oudard, Sté,phane,Hadaschik, Boris A.,Graff, Julie N.,Olmos, David,Mainwaring, Paul N.,Lee, Ji Youl,Uemura, Hiroji,Lopez-Gitlitz, Angela,Trudel, G&e New England Journal of Medicine 2018 The New England journal of medicine Vol.378 No.15
<P>Among men with nonmetastatic castration-resistant prostate cancer, metastasis-free survival and time to symptomatic progression were significantly longer with apalutamide than with placebo.</P>
Keogh Cian,Moore Julie,Cossio Danica,Smith Nick,Clark David A. 대한대장항문학회 2024 Annals of Coloproctolgy Vol.40 No.3
Purpose: Stenting is a useful treatment option for malignant colonic obstruction, but its role remains unclear. This study was designed to establish how stents have been used in Queensland, Australia, and to review outcomes. Methods: Patients diagnosed with colorectal cancer in Queensland from January 1, 2008, to December 31, 2014, who underwent colonic stent insertion were reviewed. Primary outcomes of 5-year survival, 30-day mortality, and overall length of survival were calculated. The secondary outcomes included patient and tumor factors, and stoma rates. Results: In total, 319 patients were included, and distant metastases were identified in 183 patients (57.4%). The 30-day mortality rate was 6.6% (n=21), and the 5-year survival was 11.9% (n=38). Median survival was 11 months (interquartile range, 4–27 months). A further operation (hazard ratio [HR], 0.19; P<0.001) and chemotherapy and/or radiotherapy (HR, 0.718; P=0.046) reduced the risk of 5-year mortality. The presence of distant metastases (HR, 2.052; P<0.001) and a comorbidity score of 3 or more (HR, 1.572; P=0.20) increased mortality. Surgery was associated with a reduced risk of mortality even in patients with metastatic disease (HR, 0.14; P<0.001). Twenty-two patients (6.9%) ended the study period with a stoma. Conclusion: Colorectal stenting was used in Queensland in several diverse scenarios, in both localized and metastatic disease. Surgery had a survival advantage, even in patients with metastatic disease. There was no survival difference according to whether patients were socioeconomically disadvantaged, diagnosed in a major city or not, or treated at private or public hospitals. Stenting proved a valid treatment option with low stoma rates.
Katie Pricola Fehnel,David L. Penn,Micah Duggins-Warf,Maxwell Gruber,Steven Pineda,Julie Sesen,Alexander Moses-Gardner,Nishali Shah,Jessica Driscoll,David Zurakowski,Darren B. Orbach,Edward R. Smith 생화학분자생물학회 2020 Experimental and molecular medicine Vol.52 No.-
We investigated (1) EphrinB2 and EphB4 receptor expression in cerebral AVMs, (2) the impact of an altered EphrinB2: EphB4 ratio on brain endothelial cell function and (3) potential translational applications of these data. The following parameters were compared between AVM endothelial cells (AVMECs) and human brain microvascular endothelial cells (HBMVECs): quantified EphrinB2 and EphB4 expression, angiogenic potential, and responses to manipulation of the EphrinB2:EphB4 ratio via pharmacologic stimulation/inhibition. To investigate the clinical relevance of these in vitro data, Ephrin expression was assessed in AVM tissue (by immunohistochemistry) and urine (by ELISA) from pediatric patients with AVM (n=30), other cerebrovascular disease (n=14) and control patients (n=29), and the data were subjected to univariate and multivariate statistical analyses. Compared to HBMVECs, AVMECs demonstrated increased invasion (p=0.04) and migration (p=0.08), impaired tube formation (p=0.06) and increased EphrinB2:EphB4 ratios. Altering the EphrinB2:EphB4 ratio (by increasing EphrinB2 or blocking EphB4) in HBMVECs increased invasion (p=0.03 and p<0.05, respectively). EphrinB2 expression was increased in AVM tissue, which correlated with increased urinary EphrinB2 levels in AVM patients. Using the optimal urinary cutoff value (EphrinB2>25.7pg/μg), AVMs were detected with high accuracy (80% vs. controls) and were distinguished from other cerebrovascular disease (75% accuracy). Posttreatment urinary EphrinB2 levels normalized in an index patient. In summary, AVMECs have an EphrinB2:EphB4 ratio that is increased compared to that of normal HBMVECs. Changing this ratio in HBMVECs induces AVMEC-like behavior. EphrinB2 is clinically relevant, and its levels are increased in AVM tissue and patient urine. This work suggests that dysregulation of the EphrinB2:EphB4 signaling cascade and increases in EphrinB2 may play a role in AVM development, with potential utility as a diagnostic and therapeutic target.