We applied protein-complex purification strategies and identified PRAME as a substrate recognition subunit of a Cullin2-based E3 ubiquitin ligase. PRAME can be recruited to DNA in vitro, and genome-wide chromatin immunoprecipitation experiments revealed that PRAME is specifically enriched at transcriptionally active promoters that are also bound by NFY and at enhancers. Our results are consistent with
a role for the PRAME ubiquitin ligase complex in NFY-mediated transcriptional regulation. The EMBO Journal (2011) 30, 3786-3798. doi: 10.1038/emboj.2011.262; Published online 5 August 2011″
“BACKGROUND. Active surveillance followed by selective treatment for men who have evidence of disease progression may be an option for select patients with early-stage prostate cancer. In this article, the authors report their experience in a contemporary cohort of men with prostate cancer who CA3 Stem Cells & Wnt inhibitor were managed with active surveillance.\n\nMETHODS. All men who were managed initially with active surveillance were identified through the authors’ institutional database. Selection criteria for active surveillance included: prostate-specific antigen (PSA) <10 ng/mL, biopsy Gleason sum <= 6 with no pattern 4 or 5, cancer involvement of <33% of biopsy cores, and clinical stage T1/T2a tumor.
Patients were followed with PSA measurements and digital rectal examination every 3 to 6 months and with transrectal ultrasound at 6- to 12-month intervals. Beginning in 2003, selleck chemical patients also underwent repeat prostate biopsy at 12 to 24 months. The primary outcome measured was active treatment. Evidence of disease progression, defined as an increase in rebiopsy Gleason sum or significant PSA velocity changes (>0.75
ng/mL per year), was a secondary outcome. Chi-square and log-rank tests were used to compare groups. The association between clinical characteristics and receipt of active treatment was analyzed by using Cox proportional hazards regression.\n\nRESULTS. Three hundred twenty-one men (mean age [+/- standard deviation]: 63.4 +/- 8.5 years) selected active surveillance as their initial management. The overall median follow-up was 3.6 years (range, 1-17 years). VX-809 mouse The initial mean PSA level was 6.5 +/- 3.9 ng/mL. One hundred twenty men (37%) met at least I criterion for progression. Overall, 38% of men had higher grade on repeat biopsy, and 26% of men had a PSA velocity >0.75 ng/mL per year. Seventy-eight men (24%) received secondary treatment at a median 3 years (range, 1-17 years) after diagnosis. Approximately 13% of patients with no disease progression elected to obtain treatment. PSA density at diagnosis and rise in Gleason score on repeat biopsy were associated significantly with receipt of secondary treatment. The disease-specific survival rate was 100%.\n\nCONCLUSIONS.