Serine-arginine protein kinase 1 (SRPK1), a determinant of angiogenesis, is upregulated in prostate cancer and correlates with disease stage and invasion

Vascular endothelial growth factor (VEGF) undergoes alternative splicing to produce both proangiogenic and antiangiogenic isoforms. Preferential splicing of proangiogenic VEGF is determined by serine-arginine protein kinase 1 (SRPK1), which is upregulated in a number of cancers. In the present study, we aimed to investigate SRPK1 expression in prostate cancer (PCa) and its association with cancer progression. SRPK1 expression was assessed using immunohistochemistry of PCa tissue extracted from radical prostatectomy specimens of 110 patients. SRPK1 expression was significantly higher in tumour compared with benign tissue (p<0.00001) and correlated with higher pT stage (p=0.004), extracapsular extension (p=0.003) and extracapsular perineural invasion (p=0.008). Interestingly, the expression did not correlate with Gleason grade (p=0.21), suggesting that SRPK1 facilitates the development of a tumour microenvironment that favours growth and invasion (possibly through stimulating angiogenesis) while having little bearing on the morphology or function of the tumour cells themselves

Prostate cancer - evidence of exercise and nutrition trial (PrEvENT):Study protocol for a randomised controlled feasibility trial

Background: A growing body of observational evidence suggests that nutritional and physical activity interventions are associated with beneficial outcomes for men with prostate cancer, including brisk walking, lycopene intake, increased fruit and vegetable intake and reduced dairy consumption. However, randomised controlled trial data are limited. The ‘Prostate Cancer: Evidence of Exercise and Nutrition Trial’ investigates the feasibility of recruiting and randomising men diagnosed with localised prostate cancer and eligible for radical prostatectomy to interventions that modify nutrition and physical activity. The primary outcomes are randomisation rates and adherence to the interventions at 6 months following randomisation. The secondary outcomes are intervention tolerability, trial retention, change in prostate specific antigen level, change in diet, change in general physical activity levels, insulin-like growth factor levels, and a range of related outcomes, including quality of life measures. Methods/design: The trial is factorial, randomising men to both a physical activity (brisk walking or control) and nutritional (lycopene supplementation or increased fruit and vegetables with reduced dairy consumption or control) intervention. The trial has two phases: men are enrolled into a cohort study prior to radical prostatectomy, and then consented after radical prostatectomy into a randomised controlled trial. Data are collected at four time points (cohort baseline, true trial baseline and 3 and 6 months post-randomisation). Discussion: The Prostate Cancer: Evidence of Exercise and Nutrition Trial aims to determine whether men with localised prostate cancer who are scheduled for radical prostatectomy can be recruited into a cohort and subsequently randomised to a 6-month nutrition and physical activity intervention trial. If successful, this feasibility trial will inform a larger trial to investigate whether this population will gain clinical benefit from long-term nutritional and physical activity interventions post-surgery. Prostate Cancer: Evidence of Exercise and Nutrition Trial (PrEvENT) is registered on the ISRCTN registry, ref number ISRCTN99048944. Date of registration 17 November 2014.10 page(s

ELUM Year 2 report for Work Package 3 - Network of field sites to measure soil C dynamics and GHG emissions. Report V2

This report describes the second year of Work Package 3 (WP3) activities within the ETI’s Ecosystem Land Use Modelling Project (“ELUM”). It expands upon information reported in the first year and provides a forward look to WP3 activities for the remainder of the project. The soil C (carbon) and GHG (Greenhouse Gas) measurements recorded as part of WP3 are required to help reduce the uncertainty associated with the sustainability of bioenergy crop deployment across the UK. This data will be used to parameterise and test the underlying process models in the WP4 modelling work, as part of the development of the over-arching meta-model. A full review of all the data collected across the WP3 network sites will be reported in the D3.5 deliverable due in May 2014. Progress with the development and testing of novel methods for GHG measurement is also included in this report; these could offer means of improving monitoring resolution, thereby enhancing the collection of GHG flux data. A complete review of this work will follow in May 2014 with the D3.4 deliverable

Quantitative analysis of ERG expression and its splice isoforms in formalin-fixed, paraffin-embedded prostate cancer samples: Association with seminal vesicle invasion and biochemical recurrence

© American Society for Clinical Pathology. Objectives: The proto-oncogene ETS-related gene (ERG) is consistently overexpressed in prostate cancer. Alternatively spliced isoforms of ERG have variable biological activities; inclusion of exon 11 (72 base pairs [bp]) is associated with aggressiveness and progression of disease. Exon 10 (81 bp) has also been shown to be alternatively spliced. Within this study, we assess whether ERG protein, messenger RNA (mRNA), and ERG splice isoform mRNA expression is altered as prostate cancer progresses. Methods: Detection of the TMPRSS2-ERG fusion was done using direct methods (reverse transcription polymerase chain reaction [PCR] and fluorescence in situ hybridization) and indirect methods for ERG mRNA and protein expression using quantitative PCR and immunohistochemistry, respectively. A linear equation method was used to quantitatively determine relative proportions of ERG variants (ERG72/Δ72, ERG81/Δ81) for each sample. Results: ERG mRNA and protein expression is increased in patients with advanced prostate cancer, with higher levels of ERG expression significantly associated with seminal vesicle invasion (stage pT3b) and biochemical recurrence. Genes involved in cell migration and invasiveness (matrix metalloproteinase 7, osteopontin, and septin 9) are increased in prostate cancers that overexpress ERG. In addition, there is a clear indication of increased retention of exons 10 and 11 in prostate cancer. Conclusions: Analysis of ERG and its variants may be valuable in determining prognosis and development of prostate cancer

NeuroSAFE PROOF randomised controlled feasibility study: brief report of perioperative outcomes, histological concordance, and feasibility

No abstract available

Prostate-Specific Antigen Screening and 15-year Prostate Cancer Mortality:A Secondary Analysis of the CAP Randomized Clinical Trial

Key PointsQuestion  In men aged 50 to 69 years, does a single invitation for a prostate-specific antigen (PSA) screening test reduce prostate cancer mortality at 15-year follow-up compared with no invitation for testing?Findings  In this secondary analysis of a randomized clinical trial of 415 357 men aged 50 to 69 years randomized to a single invitation for PSA screening (n = 195 912) or a control group without PSA screening (n = 219 445) and followed up for a median of 15 years, risk of death from prostate cancer was lower in the group invited to screening (0.69% vs 0.78%; mean difference, 0.09%) compared with the control group.Meaning  Compared with no invitation for routine PSA testing, a single invitation for a PSA screening test reduced prostate cancer mortality at a median follow-up of 15 years, but the absolute mortality benefit was small.AbstractIMPORTANCE The Cluster randomized trial of PSA testing for Prostate cancer (CAP) reported no effect of prostate specific antigen (PSA) screening on prostate cancer mortality at median 10-year follow-up (primary outcome), but the long-term effects of PSA screening on prostate cancer mortality remain unclear.OBJECTIVE To evaluate the effect of a single invitation for PSA screening on the pre-specified secondary outcome of prostate cancer-specific mortality at a median of 15 years’ follow-up, compared to a control group not invited for screening. DESIGN, SETTING, PARTICIPANTS Cluster randomized trial of men aged 50-69 identified from 573 primary-care practices in England and Wales. Primary-care practices were randomized between 09/25/2001 and 08/24/2007 and men were enrolled between 01/08/2002 and 01/20/2009. Follow-up was completed on 03/31/2021. INTERVENTION A single invitation for a PSA screening test with subsequent diagnostic tests if PSA≥3.0ng/ml, compared to standard practice (control). MAIN OUTCOMES AND MEASURES The primary outcome was reported previously. Of eight prespecified secondary outcomes, results of four were reported previously. The four remaining pre-specified secondary outcomes at 15-year follow-up were prostate cancer-specific mortality, all-cause mortality, and prostate cancer stage and Gleason grade at diagnosis.RESULTS Of 415,357 randomized men (mean [SD] age: 59.0 [5.6] years), 98% were analyzed in these analyses. Overall, 12,013 and 12,958 men with prostate cancers were diagnosed in the intervention and control groups (15-year cumulative risks 7.1% and 6.9% respectively). At a median 15-year follow-up, 1,199 (0.69%) men in the intervention group and 1,451 (0.78%) men in the control group died of prostate cancer (rate ratio [RR] 0.92 [95% CI 0.85, 0.99]; p=0.03). Compared to the control group, the PSA screening intervention increased detection of low-grade (Gleason score [GS]≤6; 2.2% versus 1.6%;p&lt;0.001) and localized (T1/T2; 3.6% versus 3.1%;p&lt;0.001) disease, but not intermediate (GS=7), high-grade (GS≥8), locally-advanced (T3) or distally-advanced (T4/N1/M1) tumors. There were 45,084 all-cause deaths (23.2%) in the intervention group and 50,336 deaths (23.3%) in the control group respectively (RR 0.97 [95% CI 0.94, 1.01]; p=0.11). Eight deaths in the intervention and seven deaths in the control group were related to a diagnostic biopsy or prostate cancer treatment.CONCLUSIONS AND RELEVANCE A single invitation for PSA screening, compared to standard practice without routine screening, reduced the secondary outcome of prostate cancer deaths at a median follow-up of 15-years. However, the absolute reduction in deaths was small.<br/

10-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Localized Prostate Cancer.

Background The comparative effectiveness of treatments for prostate cancer that is detected by prostate-specific antigen (PSA) testing remains uncertain. Methods We compared active monitoring, radical prostatectomy, and external-beam radiotherapy for the treatment of clinically localized prostate cancer. Between 1999 and 2009, a total of 82,429 men 50 to 69 years of age received a PSA test; 2664 received a diagnosis of localized prostate cancer, and 1643 agreed to undergo randomization to active monitoring (545 men), surgery (553), or radiotherapy (545). The primary outcome was prostate-cancer mortality at a median of 10 years of follow-up. Secondary outcomes included the rates of disease progression, metastases, and all-cause deaths. Results There were 17 prostate-cancer-specific deaths overall: 8 in the active-monitoring group (1.5 deaths per 1000 person-years; 95% confidence interval [CI], 0.7 to 3.0), 5 in the surgery group (0.9 per 1000 person-years; 95% CI, 0.4 to 2.2), and 4 in the radiotherapy group (0.7 per 1000 person-years; 95% CI, 0.3 to 2.0); the difference among the groups was not significant (P=0.48 for the overall comparison). In addition, no significant difference was seen among the groups in the number of deaths from any cause (169 deaths overall; P=0.87 for the comparison among the three groups). Metastases developed in more men in the active-monitoring group (33 men; 6.3 events per 1000 person-years; 95% CI, 4.5 to 8.8) than in the surgery group (13 men; 2.4 per 1000 person-years; 95% CI, 1.4 to 4.2) or the radiotherapy group (16 men; 3.0 per 1000 person-years; 95% CI, 1.9 to 4.9) (P=0.004 for the overall comparison). Higher rates of disease progression were seen in the active-monitoring group (112 men; 22.9 events per 1000 person-years; 95% CI, 19.0 to 27.5) than in the surgery group (46 men; 8.9 events per 1000 person-years; 95% CI, 6.7 to 11.9) or the radiotherapy group (46 men; 9.0 events per 1000 person-years; 95% CI, 6.7 to 12.0) (P<0.001 for the overall comparison). Conclusions At a median of 10 years, prostate-cancer-specific mortality was low irrespective of the treatment assigned, with no significant difference among treatments. Surgery and radiotherapy were associated with lower incidences of disease progression and metastases than was active monitoring. (Funded by the National Institute for Health Research; Current Controlled Trials number, ISRCTN20141297 ; ClinicalTrials.gov number, NCT02044172 .)