SUMMARY:Epigenetic mechanisms including DNA methylation and histone deacetylation are thought to play important roles in gene transcriptional inactivation. Heterogenous expression of androgen receptor (AR), which appears to be related to variable responses to endocrine therapy in prostate cancer (PCa) may also be due to epigenetic factors. The methylation status of the 5Ј CpG island of the AR in 3 prostate cancer cell lines and 10 primary and 14 hormone-refractory PCa samples was determined using the bisulfite PCR methods. In DU145, CpG-rich regions of the AR were hypermethylated. By an immunohistochemical analysis, only one PCa sample had no AR expression, the others being heterogenous. Bisulfite sequencing and methylationspecific PCR analysis showed aberrant methylation of AR 5Ј-regulatory region in 20% of 10 primary and 28% of 14 hormone-refractory PCa samples. To clarify the effect of epigenetic regulation on AR expression, we treated three prostate cancer cell lines with a demethylating agent, 5-aza-2Ј-deoxycytidine (azaC), and a histone deacetylase inhibitor, Trichostatin A (TSA). In DU145, re-expression of AR mRNA was detected after treatment with azaC and/or TSA. Our results suggest that epigenetic regulations including CpG methylation and histone acetylation may play important roles in the regulation of the AR.
Abstract:Our objective was to determine the incidence of inguinal hernia (IH) after surgery for prostatic diseases. Medical records of 395 patients who underwent radical retropubic prostatectomy (RRP; n = 155), open simple prostatectomy (OP; n = 35), or transurethral resection of the prostate (TURP; n = 205) at the Chibaken Saiseikai Narashino Hospital from April 2000 to March 2007 were retrospectively evaluated. The incidence of IH was 23.9% in the RRP group, 18.9% in the OP group, and 2% in the TURP group. Overall, 91.9% in the RRP and 83.3% in the OP group developed an IH within 2 years postoperatively. The laterality of IH after open surgery was mainly on the right side. Subclinical IH were seen in 25% of RRP cases. The existence of subclinical IH was the only significant risk factor for postoperative IH in this analysis. Furthermore, OP and RRP procedures significantly increased the risk of postoperative IH compared with TURP. The hernia-free ratios were significantly lower after RRP and OP than after TURP (vs RRP: P < 0.001; vs OP: P < 0.001). Our findings confirm that a lower abdominal incision itself is associated with postoperative IH in patients undergoing prostate surgery. Attention must be paid to pre-existing subclinical IH through careful preoperative assessment. Patients should be followed for more than 2 years due to the high incidence of postoperative IH.
These results indicate an important role of CD44 methylation in the progression and metastasis of prostate cancer, although the amount of methylational heterogeneity is substantial among metastatic sites within the same patient.
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