No abstract

The small GTPases Rab4, Rab5 and Rab7 are endosomal proteins which play important roles in the regulation of various stages of endosomal trafficking. Rab4 and Rab5 have both been localized to early endosomes and have been shown to control recycling and endosomal fusion, respectively. Rab7, a marker of the late endosomal compartment, is involved in the regulation of the late endocytic pathway. Here, we compare the role of Rab4, Rab5 and Rab7 in early and late endosomal trafficking in HeLa cells monitoring ligand uptake, recycling and degradation. Expression of the Rab4 dominant negative mutant (Rab4AS22N) leads to a significant reduction in both recycling and degradation while, as expected, Rab7 mutants exclusively affect epidermal growth factor (EGF) and low density lipoprotein degradation. As also expected, expression of the dominant negative Rab5 mutant perturbs internalization kinetics and affects both recycling and degradation. Expression of Rab4WT and dominant positive mutant (Rab4AQ67L) changes dramatically the morphology of the transferrin compartment leading to the formation of membrane tubules. These transferrin positive tubules display swellings (varicosities) some of which are positive for early endosomal antigen-1 and contain EGF. We propose that the Rab4GTPase is important for the function of the early sorting endosomal compartment, affecting trafficking along both recycling and degradative pathways. ß

Population-based information regarding statistically and clinically significant treatment effects on long-term global HRQoL, symptom burden and functionality should be provided during treatment decision-making. Screening for symptoms and utilising interventions during long-term follow-up may improve survivors' HRQoL.

1Objective: Preventive strategies are known to reduce cancer risk and incidence and improve 2 prognosis. Men seldom seek medical information about cancer prevention and risk reduction. 3The aim of this meta-narrative systematic review was to critically appraise evidence from 4 qualitative, quantitative, and mixed-methods studies that explored men's information-seeking 5 behaviours in relation to cancer prevention and risk reduction. qualitative studies, nine quantitative studies, and one mixed-methods study). The 11 methodological quality of the studies was appraised using different tools. 12Results: Most studies focused on screening for prostate (n=18) and colorectal cancer (n=7). 13The majority of men were passive information-gatherers rather than active information-

Cancer-related symptoms significantly predict psychological wellbeing among prostate cancer survivors. Greater use of interventions and medications and to alleviate symptoms might improve psychological wellbeing of prostate cancer survivors.

ObjectiveTo investigate the prevalence of physical symptoms that were ‘ever’ and ‘currently’ experienced by survivors of prostate cancer at a population level, to assess burden and thus inform policy to support survivors.Patients and MethodsThe study included 3 348 men surviving prostate cancer for 2–18 years after diagnosis. A cross‐sectional, postal survey of 6 559 survivors diagnosed 2–18 years ago with primary, invasive prostate cancer (ICD10‐C61) identified via national, population‐based cancer registries in Northern Ireland and Republic of Ireland. Questions included symptoms at diagnosis, primary treatments and physical symptoms (erectile dysfunction [ED]/urinary incontinence [UI]/bowel problems/breast changes/loss of libido/hot flashes/fatigue) experienced ‘ever’ and at questionnaire completion (‘current’). Symptom proportions were weighted by age, country and time since diagnosis. Bonferroni corrections were applied for multiple comparisons.ResultsAdjusted response rate 54%; 75% reported at least one ‘current’ physical symptom (‘ever’ 90%), with 29% reporting at least three. Prevalence varied by treatment. Overall, 57% reported current ED and this was highest after radical prostatectomy (RP, 76%) followed by external beam radiotherapy with concurrent hormone therapy (HT, 64%). UI (overall ‘current’ 16%) was highest after RP (‘current’ 28%; ‘ever’ 70%). While 42% of brachytherapy patients reported no ‘current’ symptoms, 43% reported ‘current’ ED and 8% ‘current’ UI. ‘Current’ hot flashes (41%), breast changes (18%) and fatigue (28%) were reported more often by patients on HT.ConclusionSymptoms after prostate cancer treatment are common, often multiple, persist long‐term and vary by treatment method. They represent a significant health burden. An estimated 1.6% of men aged >45 years are survivors of prostate cancer and currently experiencing an adverse physical symptom. Recognition and treatment of physical symptoms should be prioritised in patient follow‐up. This information should facilitate men and clinicians when deciding about treatment as differences in survival between radical treatments is minimal.

Low bone mineral density (BMD) is a major risk factor for the development of osteoporosis and there is strong evidence to suggest that the procurement and preservation of peak BMD is genetically determined. In an effort to identify factors responsible for susceptibility to low BMD in the Irish population, we investigated its possible association with polymorphisms in the Osteoprotegerin (OPG) gene, Type I collagen alpha 1 (COLIA1) Sp1 binding site and vitamin D receptor (VDR) start codon. Following a systematic screening of the regulatory and coding regions of the OPG gene, we identified a novel G1181C polymorphism in exon 1 and a T950C polymorphism in the promoter region of the OPG gene. Participants were recruited from the Bone Densitometry Unit of Cork University Hospital, including 381 postmenopausal women aged 61.26 +/- 8.50 (mean +/- SD) and 130 premenopausal women aged 46.30 +/- 6.50 (mean +/- SD). Following association analysis using both the premenopausal and postmenopausal cohorts we found that postmenopausal women carrying one or more C alleles of the G1181C polymorphism had 14.8% lower BMD (P = 0.05) at the lumbar spine and 14.4% lower BMD (P = 0.04) at the FN. However, both were nonsignificant when the Bonferroni correction factor (0.01 significance level) was applied to correct for multiple hypothesis testing. We found no association between alleles of the T950C OPG polymorphism and BMD. Similarly, we have found a lack of association between the VDR (fok1) polymorphism or COLIA1 Sp1 polymorphism and low BMD in either postmenopausal or premenopausal women in this population.

Background: Increased use of prostate specific antigen (PSA) has been associated with increased prostate cancer incidence. Ireland is estimated to have one of the highest prostate cancer incidences in Europe and has no national guidelines for prostate cancer screening. GPs have a pivotal role in influencing PSA testing, therefore, our aim was to describe GP testing practices and to identify factors influencing these.