PMEPA1 was identified originally as a highly androgen-inducible gene with prostate-abundant expression that was restricted to prostatic epithelial cells. PMEPA1 protein is a NEDD4 (ubiquitin-protein isopeptide ligase)-binding protein, which negatively regulates prostate cancer cell growth. In this study we establish that PMEPA1 is a direct transcriptional target of the androgen receptor (AR). We also demonstrate that PMEPA1 negatively regulates AR protein levels in different cell culture models. Transient expression of PMEPA1 down-regulates AR protein levels and AR transcriptional targets in prostate cancer cells. Conversely, knockdown of PMEPA1 leads to elevated levels of AR protein, AR transcriptional targets (prostatespecific antigen), and increased cell cycle S phase. We define that the PMEPA1-dependent down-regulation of AR is because of AR ubiquitination and proteasome-mediated degradation. The mutant PMEPA1 (PY1/2 motif mutation) that is impaired in NEDD4 recruitment shows attenuated AR ubiquitination and AR protein down-regulation. These data support the hypothesis that PMEPA1 negatively regulates the stability of AR protein by enhancing AR ubiquitination and proteasome-mediated degradation through NEDD4. The effect of PMEPA1 on AR ubiquitination and degradation appears to be MDM2-independent. Thus, the PMEPA1-AR degradation pathway may represent a new androgen-dependent mechanism for regulating AR levels in prostate epithelial cells. These findings underscore that the decreased PMEPA1 expression frequently noted in prostate cancers may lead to increased AR functions and strengthen the biological role of PMEPA1 in prostate cancers.
Patients with higher body mass index, greater stone burden, nonbranched stones and multiple nephrostomy access tracts are at risk for increased radiation exposure during percutaneous nephrolithotomy. Urologists must seek alternative strategies to minimize radiation exposure, such as tighter collimation to the region of interest, judicious use of magnification and the acquisition of as few images as possible during stone removal.
Study Type – Therapy (outcomes research) Level of Evidence 2c What’s known on the subject? and What does the study add? While epidemiological studies have shown a significantly lower incidence of adenocarcinoma of the prostate in Asia than the United States, several studies have demonstrated that Asian Americans present with more advanced stages, higher tumour grades, and worse mortality‐incidence ratios than Caucasian Americans. This study, conducted in an equal access military healthcare system, reveals improved pathological and survival outcomes in Asian Americans compared to other races. This may indicate that worsened outcomes previously reported among Asian Americans diagnosed with adenocarcinoma of the prostate may be related to access to care, language barriers, socioeconomic status, or cultural factors. OBJECTIVE • To characterize the incidence, management and clinicopathological characteristics of prostate cancer (CaP) in a population of Asian Americans undergoing mandatory annual screening in an equal access healthcare system. PATIENTS AND METHODS • Men registered into the military‐based Center for Prostate Disease Research multi‐institutional database from 1989–2007 with biopsy‐proven CaP and categorized as Asian American, Caucasian or African American were included. • Demographic information, treatment modality, clinicopathological characteristics and outcomes were compared. RESULTS • In total, there were 10 964 patients; 583 (5.3%) were Asian Americans. Asian Americans had lower clinical stage (P < 0.001) but worse biopsy grade (P < 0.001) than other groups. They were more likely to choose radical prostatectomy (RP) (P < 0.001) and showed a higher percentage of organ‐confined disease (P < 0.001). • Asian Americans had improved biochemical recurrence free (P < 0.01) and overall survival (P < 0.001) rates compared to African Americans or Caucasians treated with RP or external radiation therapy. CONCLUSIONS • Asian Americans with CaP treated in an equal access healthcare system have improved pathological outcomes and survival characteristics compared to other races. • Asian ethnicity’s negative impact on survival noted by others appears to be the result of factors other than the tumour’s intrinsic behaviour, such as language barriers, socioeconomic status and cultural norms.
NSS offered shorter hospital stay but had increased risk of recurrence. Therefore, extreme care should be made to rule out occult invasive tumors preoperatively. Patients being managed endoscopically must be informed of the necessity for close follow-up.
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