Androgen receptor modulatory miR-1271-5p can promote hormone sensitive prostate cancer cell growth.

In most patients with advanced prostate cancer treated with hormonal therapy, androgen independence eventually emerges, leading to death. Androgen receptor signalling remains an important prostate cancer driver, even in the advanced disease stage. MicroRNAs (miRs), non-coding RNAs that regulate gene expression by inhibiting translation and/or promoting degradation of target mRNAs, can act as tumour suppressors or "oncomiRs" and modulate tumour growth.

Handheld ISFET Lab-on-Chip detection of TMPRSS2-ERG and AR mRNA for prostate cancer prognostics.

Ion-sensitive field-effect transistors (ISFETs) in combination with unmodified complementary metal oxide semiconductors present a point-of-care platform for clinical diagnostics and prognostics. This work illustrates the sensitive and specific detection of two circulating mRNA markers for prostate cancer, the androgen receptor and the TMPRSS2-ERG fusion using a target-specific loop-mediated isothermal amplification method. TMPRSS2-ERG and androgen receptor RNA were detected down to 3x10 and 5x10 copies respectively in under 30 minutes.

Detection of YAP1 and AR-V7 mRNA for Prostate Cancer Prognosis Using an ISFET Lab-On-Chip Platform.

Prostate cancer (PCa) is the second most common cause of male cancer-related death worldwide. The gold standard of treatment for advanced PCa is androgen deprivation therapy (ADT). However, eventual failure of ADT is common and leads to lethal metastatic castration-resistant PCa.

Coordinated AR and microRNA regulation in prostate cancer.

The androgen receptor (AR) remains a key driver of prostate cancer (PCa) progression, even in the advanced castrate-resistant stage, where testicular androgens are absent. It is therefore of critical importance to understand the molecular mechanisms governing its activity and regulation during prostate tumourigenesis. MicroRNAs (miRs) are small ∼22 nt non-coding RNAs that regulate target gene, often through association with 3' untranslated regions (3'UTRs) of transcripts.

Qualitative Analysis of Factors Influencing Patient Persistence and Adherence to Prescribed Overactive Bladder Medication in UK Primary Care.

Introduction: Pharmacotherapy for overactive bladder (OAB) is generally associated with low rates of persistence and adherence. This study was conducted to explore the patient journey in a UK primary care setting (experiences, perceptions, attitudes, and levels of engagement and expectations) and identify self-reported reasons for patient non-adherence and/or non-persistence to medications for OAB.

Methods: This was a qualitative, non-interventional study involving one-to-one semi-structured, face-to-face or phone interviews with individuals aged 40-80 years, diagnosed with OAB, and currently taking, or having taken, either antimuscarinic or β-adrenoceptor agonist medications within the last 12 months.

Conceptualizing the 'whole university' approach: an international qualitative study.

Focusing on the conceptualization of a whole university approach, this paper reports on an international qualitative study that explored vice-chancellors' and network members' understanding of and commitment to Health Promoting Universities, examined perspectives on leadership and investigated the Okanagan Charter's potential to catalyse whole university leadership and change. A multi-method qualitative approach was used: semi-structured interviews and focus groups were conducted face-to-face with vice-chancellors (n = 12) and Health Promoting University co-ordinators who were members of the UK Healthy Universities Network (n = 8); telephone interviews were conducted with a mix of UK and non-UK Health Promoting University co-ordinators (n = 5) and two online questionnaires were distributed to non-UK network co-ordinators (n = 6) and non-UK Health Promoting University co-ordinators (n = 10). Through thematic analysis, a number of key themes emerged that build a new conceptualization of the whole university approach (see Figure 1): building a broad understanding and framing of health; developing a supportive ethos and culture; embedding health into the university and joining up areas of work; focusing on the whole population and facing challenges and seizing opportunities.

WOMEN IN CANCER THEMATIC REVIEW: New roles for nuclear receptors in prostate cancer.

Prostate cancer has, for decades, been treated by inhibiting androgen signalling. This is effective in the majority of patients, but inevitably resistance develops and patients progress to life-threatening metastatic disease - hence the quest for new effective therapies for 'castrate-resistant' prostate cancer (CRPC). Studies into what pathways can drive tumour recurrence under these conditions has identified several other nuclear receptor signalling pathways as potential drivers or modulators of CRPC.

Antiandrogens act as selective androgen receptor modulators at the proteome level in prostate cancer cells.

Current therapies for prostate cancer include antiandrogens, inhibitory ligands of the androgen receptor, which repress androgen-stimulated growth. These include the selective androgen receptor modulators cyproterone acetate and hydroxyflutamide and the complete antagonist bicalutamide. Their activity is partly dictated by the presence of androgen receptor mutations, which are commonly detected in patients who relapse while receiving antiandrogens, i.

Engineered repressors are potent inhibitors of androgen receptor activity.

Prostate cancer growth is dependent upon the Androgen Receptor (AR) pathway, hence therapies for this disease often target this signalling axis. Such therapies are successful in the majority of patients but invariably fail after a median of 2 years and tumours progress to a castrate resistant stage (CRPC). Much evidence exists to suggest that the AR remains key to CRPC growth and hence remains a valid therapeutic target.

Role of the HSP90-associated cochaperone p23 in enhancing activity of the androgen receptor and significance for prostate cancer.

Prostate tumor growth initially depends on androgens, which act via the androgen receptor (AR). Despite androgen ablation therapy, tumors eventually progress to a castrate-resistant stage in which the AR remains active. The mechanisms are poorly understood but it may be that changes in levels or activity of AR coregulators affect trafficking and activation of the receptor.

FUS/TLS is a novel mediator of androgen-dependent cell-cycle progression and prostate cancer growth.

Progression of prostate cancer is highly dependent upon the androgen receptor pathway, such that knowledge of androgen-regulated proteins is vital to understand and combat this disease. Using a proteomic screen, we found the RNA-binding protein FUS/TLS (Fused in Ewing's Sarcoma/Translocated in Liposarcoma) to be downregulated in response to androgen. FUS has recently been shown to be recruited by noncoding RNAs to the regulatory regions of target genes such as cyclin D1, in which it represses transcription by disrupting complex formation.

Hey1, a mediator of notch signaling, is an androgen receptor corepressor.

Hey1 is a member of the basic helix-loop-helix-Orange family of transcriptional repressors that mediate Notch signaling. Here we show that transcription from androgen-dependent target genes is inhibited by Hey1 and that expression of a constitutively active form of Notch is capable of repressing transactivation by the endogenous androgen receptor (AR). Our results indicate that Hey1 functions as a corepressor for AF1 in the AR, providing a mechanism for cross talk between Notch and androgen-signaling pathways.

Analysis of stromal-epithelial interactions in prostate cancer identifies PTPCAAX2 as a potential oncogene.

A PCR-based subtractive hybridisation technique was used to identify genes involved in stromal-epithelial interactions in prostate cancer. Eight genes were identified as being differentially expressed in benign prostatic fibroblast cells after stimulation with tumourigenic LNCaP conditioned media. One of these genes, protein tyrosine phosphatase CAAX2 (PTPCAAX2; also described as PTP4A and OV-1), has recently been shown to be oncogenic in hamster pancreatic epithelial cells.