Overexpression of GOLPH3 is associated with poor prognosis and clinical progression in pancreatic ductal adenocarcinoma.

BACKGROUND: Golgi phosphoprotein 3 (GOLPH3) has been identified as an oncoprotein in various human cancers; however, its role in pancreatic ductal adenocarcinoma (PDAC) is unknown. We examined GOLPH3 expression levels and relationship with survival in patients with PDAC to establish the significance of GOLPH3 in the development and progression of PDAC. METHODS: Real-time qPCR and Western blotting were performed to analyze the expression levels of GOLPH3 mRNA and protein in paired PDAC tumor and adjacent non-tumor tissues. Immunohistochemistry was used to analyze the expression levels of GOLPH3 protein in paraffin-embedded tissues from 109 cases of PDAC. Univariate and multivariate analyses were performed to identify correlations between the immunohistochemical data for GOLPH3 expression and the clinicopathologic characteristics in PDAC. RESULTS: Expression levels of GOLPH3 mRNA and protein were upregulated in PDAC lesions compared to paired adjacent noncancerous tissues. Expression of GOLPH3 was significantly correlated with clinical stage (P = 0.006), T classification (P = 0.021), N classification (P = 0.049) and liver metastasis (P = 0.035). Patients with high GOLPH3 expression had shorter overall survival times compared to those with low GOLPH3 expression (P = 0.007). Multivariate analysis revealed that GOLPH3 overexpression was an independent prognostic factor in PDAC. CONCLUSIONS: Our findings suggest that GOLPH3 expression status may be a potential prognostic biomarker and therapeutic target in PCAC.

MicroRNA-362 induces cell proliferation and apoptosis resistance in gastric cancer by activation of NF-κB signaling.

BACKGROUND: According to cancer-related microRNA (miRNA) expression microarray research available in public databases, miR-362 expression is elevated in gastric cancer. However, the expression and biological role of miR-362 in gastric progression remain unclear. METHODS: miR-362 expression levels in gastric cancer tissues and cell lines were determined using real-time PCR. The roles of miR-362, in promoting gastric cancer cell proliferation and apoptosis resistance, were assessed by different biological assays, such as colony assay, flow cytometry and TUNEL assay. The effect of miR-362 on NF-κB activation was investigated using the luciferase reporter assay, fluorescent immunostaining. RESULTS: MiR-362 overexpression induced cell proliferation, colony formation, and resistance to cisplatin-induced apoptosis in BGC-823 and SGC-7901 gastric cancer cells. MiR-362 increased NF-κB activity and relative mRNA expression of NF-κB-regulated genes, and induced nuclear translocation of p65. Expression of the tumor suppressor CYLD was inhibited by miR-362 in gastric cancer cells; miR-362 levels were inversely correlated with CYLD expression in gastric cancer tissue. MiR-362 downregulated CYLD expression by binding its 3' untranslated region. NF-κB activation was mechanistically associated with siRNA-mediated downregulation of CYLD. MiR-362 inhibitor reversed all the effects of miR-362. CONCLUSION: The results suggest that miR-362 plays an important role in repressing the tumor suppressor CYLD and present a novel mechanism of miRNA-mediated NF-κB activation in gastric cancer.

Modified apical dissection of the prostate improves early continence in laparoscopic radical prostatectomy: technique and initial results.

OBJECTIVES: Incontinence after radical retropubic prostatectomy (RRP) is one of the greatest worries for all patients. One of the possible reasons for this urinary incontinence is a postoperative deficiency of the external striated urethral sphincter (EUS) complex and continence nerves. This study evaluated the application of a modified simple technique to dissection of the apical prostate in laparoscopic radical prostatectomy (LRP) and assessed the rate of urinary continence. METHODS: A total of 104 patients were randomly selected using envelopes and enrolled in this study. A standard LRP was performed in 52 patients (standard LRP group) and a modified technique for simple dissection of the apical prostate in LRP was performed in another 52 patients (modified LRP group). The urethra was dissected and transected at the apex of the prostate, proximal to the nerve-distributing rhabdosphincter using sharp scissors to avoid damage to the EUS complex and continence nerves. In all patients, a pad test was performed on 3, 30 and 90 days postoperatively and correlated with urinary continence. Continence was defined as zero pads or a liner used for security reasons only. RESULTS: After catheter removal, the continence rates were regained in 66, 85 and 96% of patients in the modified LRP group compared with 28, 55 and 91% of the patients in the standard LRP group at 3, 30 and 90 days, respectively. A statistically significant difference was present at 3 and 30 days (p < 0.01, respectively). At 90 days, the difference, although still present, was not statistically significant (p > 0.05). CONCLUSIONS: In this preliminary study, the technique of simplified apical dissection of the prostate in LRP appears to be an easy and feasible technique in early recovery of urinary continence. Further long-term and larger sample studies are necessary to elucidate the modified technique in LRP on early restoration of urinary continence.