Epigenetic silencing of miR-137 induces resistance to bicalutamide by targeting TRIM24 in prostate cancer cells.

Prostate cancer is an important hormone-dependent cancer affecting men. In the initial stages, prostate cancer is often treated using hormone therapy, including bicalutamide. Despite the initial effectiveness of this therapy, the tumor eventually acquires resistance, resulting in recurrence of castration-resistant prostate cancer (CRPC). Dysregulation of microRNA (miRNA) function is one of the putative underlying mechanisms of hormone therapy resistance. Reports have shown that miRNAs act as tumor suppressors in patients with prostate cancer, but the role of these molecules in bicalutamide resistance in prostate cancer cell lines remains unclear. We performed lentiviral miRNA library screening to identify novel miRNAs that modulate the response of human prostate cancer LNCaP cells to the antiandrogen bicalutamide. We found that the tumor suppressor miRNA miR-137 silenced signaling in a spectrum of human cancers and selectively targeted tripartite motif-containing 24 (TRIM24) to suppress tumor proliferation. Silencing of TRIM24 recapitulated the effect of miR-137 on cell proliferation, whereas overexpression of TRIM24 reversed this effect. Real-time reverse transcription PCR analysis revealed a reciprocal relationship between miR-137 and TRIM24 in prostate cancer cell lines and tissues. Mechanistic studies indicated that methyl CpG-binding protein 2 (MeCP2) and DNA methyltransferases (DNMTs) cooperate to promote methylation of the miR-137 promoter and the consequent decreased transcription, leading to enhanced TRIM24 expression and glutamine metabolism. These findings describe a novel mechanism that affects TRIM24 deregulation in human cancers and provide a molecular link between miR-137, TRIM24, and tumor proliferation in CRPC.

[Clinical efficacy and relative factors of dendritic cell-based tumor vaccination for prostate cancer: a systematic review and meta-analysis].

OBJECTIVE: To evaluate the efficacy and safety of dendritic cell (DC)-based vaccines in the treatment of prostate cancer, and investigate the factors that influence the clinical benefit rate (CBR) of the vaccines. METHODS: Based on pre-determined search criteria, we searched the Medline database for randomized controlled trials on DC-based vaccines immunotherapy of prostate cancer. We systematically analyzed the identified studies using RevMan 5.0 and SPSS 17.0 softwares. RESULTS: Ten randomized controlled trials involving 179 prostate cancer patients were identified and subjected to meta-analysis. The CBR of the DC vaccines for prostate cancer was 54.2% , and the objective response rate was 7.7%. Most adverse effects were local reactions at the injection site, fever and flu-like symptoms. The prostate cancer patients achieved cellular immune response (OR = 31.12, 95% CI = 5.52-175.6, P < 0.01) and reduction of log PSA slope (OR = 4.38, 95% CI = 1.17-16.35, P = 0.03) after administration of DC vaccines, which was positively correlated with CBR. The dose of DC vaccines had a significant correlation with CBR (OR = 5.98, 95% CI = 1.45-24.62, P = 0.01), but not the age of the patients (P = 0.53). Besides, density-enriched DCs achieved a higher CBR, while the route of administration had no effect on CBR. CONCLUSION: DC-based vaccines are effective, safe and well-tolerated in the treatment of prostate cancer. DC-mediated cellular immune response has a significant effect on CBR and can be used as an important index for the assessment of vaccines. More multi-centered randomized controlled trials of higher quality and larger sample size are needed to provide more valid evidence.

[Onset age and pathology of prostate cancer in Uygurs and Hans in Xinjiang].

OBJECTIVE: To investigate the differences in the onset age and pathology of prostate cancer between Uygurs and Hans in Xinjiang. METHODS: We enrolled in this study 518 patients (138 Uygurs and 380 Hans) with prostate cancer confirmed between January 2002 and December 2011. We conducted comparative analyses on their ages, years of diagnosis and Gleason scores. RESULTS: The incidence of prostate cancer increased year by year in both Uygur and Han people, but no statistically significant differences were found in the years of diagnosis between the two groups (chi2 = 1.063, P = 0.900). The median and mode ages of the Uygur patients were 70 and 63 years, and those of the Hans 73 and 71 years. The predilection age of prostate cancer was 70 -79 years in both the two groups. The Uygurs showed a significantly higher incidence of prostate cancer in the 50-59 yr and 60-69 yr groups than the Hans, but the results were just the opposite in the 80-89 yr group (chi2 = 40.375, P = 0.01). The median and mode of Gleason scores were 7 and 6 in the Uygurs, and 8 and 8 in the Hans, respectively, with no significant difference between the two groups (chi2 = 0.991, P = 0.01). CONCLUSION: The Uygurs differed from the Hans in the age of prostate cancer onset, but there were no significant differences in the annually increased incidence and pathological stage of prostate cancer between the Uygurs and Hans in Xinjiang.

[Oral mucosa for hypospadias repair: a report of 19 cases].

OBJECTIVE: To investigate the indications and clinical effect of using oral mucosa as the graft in hypospadias repair. METHODS: We performed hypospadias repair using oral mucosa for 19 patients, 10 with the urethral opening at the root of the penis, 7 at the scrotum and 2 at the perineum. Of these patients, 8 had received urethroplasty once, and 6 twice, unsuccessfully, and 7 of them were complicated by penile chordee. The lower lip mucosa was used as the graft for 14 cases, and the buccal mucosa for the other 5. Fifteen cases received autologous oral mucosa onlay for repair, with the new urethra covered by the dartos coat of the dorsal skin. For the other 4 cases, whose urethral plates had been damaged in the previous operations, oral mucosa strips were used to substitute the urethral plates to get the penis straightened, followed by urethroplasty 6 months later. RESULTS: Of the 19 patients, 17 (89.5%) achieved satisfactory results, with a desirable shape of the penis and a vertical slit-like meatus at the tip of the glans. Chordee was corrected in all the patients. No urethral stricture was found during the 3 - 18 months follow-up. Urethral fistula occurred in 2 cases because of infection, but cured by surgical repair 6 months later. CONCLUSION: Using oral mucosa as the graft is an effective surgical option for hypospadias repair.