Ablative therapy for people with localised prostate cancer : a systematic review and economic evaluation

The research reported in this issue of the journal was funded by the HTA programme as project number 10/136/01. The contractual start date was in April 2012. The draft report began editorial review in October 2013 and was accepted for publication in April 2014. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The HTA editors and publisher have tried to ensure the accuracy of the authors’ report and would like to thank the reviewers for their constructive comments on the draft document. However, they do not accept liability for damages or losses arising from material published in this report. Acknowledgements We thank l the people recruited from the local UCAN for providing valuable consumer insight and advice through their participation as members of the project focus group: - Mark Emberton (Professor of Interventional Oncology), Damian Greene (consultant urologist), Axel Heidenreich (Professor and Director of Department of Urology), Christoph von Klot (specialist in brachytherapy), Roger Kockelbergh (BAUS chairman and Clinical Director of Urology) and Axel Merserburger (Deputy Clinical Director of Urology and Urologic Oncology) for providing their clinical expertise as members of the project advisory group - Edgar Paez (consultant urologist) and Gill Lawrence (Head of Radiotherapy Physics) for providing a list of staff time by grade and specialty involved in EBRT - Debbie Bennett (Radiotherapy Service Manager) for providing estimates for the expected number of uses for EBRT - Ian Pedley (clinical director/clinical oncologist) and Gill Lawrence for providing a list of all resource inputs relevant to brachytherapy - Steve Locks (Consultant Clinical Scientist in Radiotherapy) for providing a list of reusable equipment and consumables used during brachytherapy, along with their unit costs - Sue Asterling (urology research nurse) and Mark Kelly (Acting Divisional General Manager – Theatres) for providing a list of all resource inputs relevant to cryotherapy - Lara Kemp for providing secretarial support. The Health Services Research Unit is core funded by the Chief Scientist Office of the Scottish Government Health Directorates.Peer reviewedPublisher PD

Role of voiding and storage symptoms for the quality of life before and after treatment in men with voiding dysfunction

Previous studies on associations between voiding dysfunction and quality of life (QoL) have largely been limited to baseline data. Therefore, we have explored associations between Q (max) and voiding and storage sub-scores of the International Prostate Symptom Score (IPSS) before and after treatment with QoL. Analysis of a single-center database of 2,316 men with voiding dysfunction attributed to benign prostatic hyperplasia undergoing various medical and surgical treatment forms. Q (max) exhibited little correlation with QoL before or after treatment. IPSS inversely correlated with QoL at baseline and after treatment, and IPSS improvements correlated with those of QoL. The associations applied to both the voiding and storage sub-score of the IPSS, with the latter consistently exhibiting somewhat tighter associations. Our post-treatment data support the idea of a cause-effect relationship between voiding symptoms and QoL irrespective of treatment form. While both voiding and storage symptoms contribute to this relationship, storage symptoms play a somewhat greater rol

Similar NF-κB Gene Signatures in TNF-α Treated Human Endothelial Cells and Breast Tumor Biopsies

BACKGROUND: Endothelial dysfunction has been implicated in the pathogenesis of diverse pathologies ranging from vascular and immune diseases to cancer. TNF-α is one of the mediators of endothelial dysfunction through the activation of transcription factors, including NF-κB. While HUVEC (macrovascular cells) have been largely used in the past, here, we documented an NF-κB gene signature in TNFα-stimulated microvascular endothelial cells HMEC often used in tumor angiogenesis studies. METHODOLOGY/PRINCIPAL FINDINGS: We measured mRNA expression of 55 NF-κB related genes using quantitative RT-PCR in HUVEC and HMEC. Our study identified twenty genes markedly up-regulated in response to TNFα, including adhesion molecules, cytokines, chemokines, and apoptosis regulators, some of them being identified as TNF-α-inducible genes for the first time in endothelial cells (two apoptosis regulators, TNFAIP3 and TNFRSF10B/Trail R2 (DR5), the chemokines GM-CSF/CSF2 and MCF/CSF1, and CD40 and TNF-α itself, as well as NF-κB components (RELB, NFKB1 or 50/p105 and NFKB2 or p52/p100). For eight genes, the fold induction was much higher in HMEC, as compared to HUVEC. Most importantly, our study described for the first time a connection between NF-κB activation and the induction of most, if not all, of these genes in HMEC as evaluated by pharmacological inhibition and RelA expression knock-down by RNA interference. Moreover, since TNF-α is highly expressed in tumors, we further applied the NF-κB gene signature documented in TNFα-stimulated endothelial cells to human breast tumors. We found a significant positive correlation between TNF and the majority (85 %) of the identified endothelial TNF-induced genes in a well-defined series of 96 (48 ERα positive and 48 ERα negative) breast tumors. CONCLUSION/SIGNIFICANCE: Taken together these data suggest the potential use of this NF-κB gene signature in analyzing the role of TNF-α in the endothelial dysfunction, as well as in breast tumors independently of the presence of ERα

A Host Defense Mechanism Involving CFTR-Mediated Bicarbonate Secretion in Bacterial Prostatitis

BACKGROUND: Prostatitis is associated with a characteristic increase in prostatic fluid pH; however, the underlying mechanism and its physiological significance have not been elucidated. METHODOLOGY/PRINCIPAL FINDINGS: In this study a primary culture of rat prostatic epithelial cells and a rat prostatitis model were used. Here we reported the involvement of CFTR, a cAMP-activated anion channel conducting both Cl(-) and HCO(3)(-), in mediating prostate HCO(3)(-) secretion and its possible role in bacterial killing. Upon Escherichia coli (E. coli)-LPS challenge, the expression of CFTR and carbonic anhydrase II (CA II), along with several pro-inflammatory cytokines was up-regulated in the primary culture of rat prostate epithelial cells. Inhibiting CFTR function in vitro or in vivo resulted in reduced bacterial killing by prostate epithelial cells or the prostate. High HCO(3)(-) content (>50 mM), rather than alkaline pH, was found to be responsible for bacterial killing. The direct action of HCO(3)(-) on bacterial killing was confirmed by its ability to increase cAMP production and suppress bacterial initiation factors in E. coli. The relevance of the CFTR-mediated HCO(3)(-) secretion in humans was demonstrated by the upregulated expression of CFTR and CAII in human prostatitis tissues. CONCLUSIONS/SIGNIFICANCE: The CFTR and its mediated HCO(3)(-) secretion may be up-regulated in prostatitis as a host defense mechanism