A pilot study of blood epinephrine levels and CREB phosphorylation in men undergoing prostate biopsies

Purpose

In mouse models of prostate cancer, increased epinephrine levels accelerated tumor growth via the beta2-adrenoreceptor/PKA signaling pathway. It is unknown, however, whether men experience increased epinephrine levels sufficient to activate the beta2-adrenoreceptor/PKA pathway in the prostate gland. We measured epinephrine levels in blood samples collected immediately prior to prostate biopsies and measured phosphorylation of S133CREB (PKA site), S112BAD, T202/Y204ERK, and S473 Akt in prostate biopsy tissue samples.

Methods

Tissue samples and 3 ml of blood were obtained from men (n = 20) recruited from the patients scheduled for prostate biopsies. Epinephrine levels were measured by ELISA. Proteins were extracted from biopsied tissue, and protein phosphorylation was measured by Western blotting with phospho-specific antibodies. Pearson and Spearman’s rank correlations were analyzed to assess relationships between blood epinephrine levels and phosphorylation of CREB, BAD, AKT, and ERK.

Results

Epinephrine levels above 1 nM were detected in 5 of 20 patients. A strong positive correlation was observed between increased epinephrine levels and CREB phosphorylation. In contrast, no correlation was observed between epinephrine levels and phosphorylation of ERK, BAD, or AKT.

Conclusion

Our results suggest that increased blood epinephrine levels activate the beta2-adrenoreceptor/PKA signaling pathway in human prostate glands. These results will inform future studies to examine whether beta2-selective blockers can inhibit activation of the epinephrine/ADRB2/PKA pathway in prostate tumors of men with increased epinephrine levels and explore the use of beta2-selective blockers as adjuvant therapy for prostate cancer.     

Retropubic versus transobturator tension‐free vaginal tape (TVT vs TVT‐O): Five‐year results of the Austrian randomized trial

Aims

To compare outcomes of the retropubic versus the transobturator tension‐free vaginal tape (TVT vs TVT‐O) at 5 years.

Methods

A total of 569 women undergoing surgery for primary stress incontinence were randomized to receive a retropubic or a transobturator tensionfree vaginal tape (TVT or TVT‐O). Follow‐up at 5 years included clinical examination, urodynamic studies and quality of life. The primary outcome measure was continence defined as a negative cough stress test at a volume of 300 mL. Secondary outcomes included urodynamic parameters, complications and quality of life. ClinicalTrials.gov (NCT 0041454).

Results

Three hundred and thirty‐one patients (59%) were evaluated at 5 years (277 were seen, examined and completed questionnaires; 54 only completed questionnaires). No significant differences were seen in rates of a negative cough stress test (83% vs 76%, respectively), urodynamic parameters and complications. Quality‐of‐life improved significantly in both groups, without significant differences between the groups. Erosion rates were 5.2% and 4.5%, and reoperation rates were 4.1% and 3.2% respectively.

Conclusions

At 5 years, subjective and objective results after TVT and TVT‐O are stable and similar, without statistical significant differences between the procedures. Major long‐term problems appear rare.     

Consensus Recommendations for the Diagnosis and Management of Pancreatic Neuroendocrine Tumors: Guidelines from a Canadian National Expert Group

Annals of Surgical Oncology - Pancreatic neuroendocrine tumors (pNETs) are rare heterogeneous tumors that have been steadily increasing in both incidence and prevalence during the past few decades....