Development of a conceptual framework to improve sexual wellbeing communication in routine prostate cancer care.

Objective: To systematically develop a framework to improve sexual wellbeing communication in routine prostate cancer care.

Methods: The Theoretical Domains Framework was used to guide a multi-phase process used to identify components of the framework based on evidence reviews, semi-structured interviews and stakeholder workshops. 'Think-aloud' testing was used to explore usability, potential barriers and other factors relevant to implementation.

Multifocal breast cancers are more prevalent in BRCA2 versus BRCA1 mutation carriers.

Multifocal (MF)/multicentric (MC) breast cancer is generally considered to be where two or more breast tumours are present within the same breast, and is seen in ~10% of breast cancer cases. This study investigates the prevalence of multifocality/multicentricity in a cohort of BRCA1/2 mutation carriers with breast cancer from Northern Ireland via cross-sectional analysis. Data from 211 women with BRCA1/2 mutations (BRCA1-91, BRCA2-120) and breast cancer were collected including age, tumour focality, size, type, grade and receptor profile.

The association between erosive toothwear and gastro-oesophageal reflux-related symptoms and disease: A systematic review and meta-analysis.

Objectives: To conduct a systematic review and meta-analysis to explore the association between erosive toothwear and gastro-oesophageal reflux disease or symptoms (GERD/S).

Sources: Electronic searches were performed in Scopus, Embase, and Web of Science databases for the identification of relevant studies, from 1980 until 2nd August 2019.

Study Selection: The review protocol was registered on PROSPERO (CRD42018096959) and the review was conducted according to PRISMA guidelines.

Management of Patients with Advanced Prostate Cancer: Report of the Advanced Prostate Cancer Consensus Conference 2019.

Background: Innovations in treatments, imaging, and molecular characterisation in advanced prostate cancer have improved outcomes, but there are still many aspects of management that lack high-level evidence to inform clinical practice. The Advanced Prostate Cancer Consensus Conference (APCCC) 2019 addressed some of these topics to supplement guidelines that are based on level 1 evidence.

Objective: To present the results from the APCCC 2019.

Machine learning to predict early recurrence after oesophageal cancer surgery.

Background: Early cancer recurrence after oesophagectomy is a common problem, with an incidence of 20-30 per cent despite the widespread use of neoadjuvant treatment. Quantification of this risk is difficult and existing models perform poorly. This study aimed to develop a predictive model for early recurrence after surgery for oesophageal adenocarcinoma using a large multinational cohort and machine learning approaches.

Author Correction: Acute and chronic hypoxia differentially predispose lungs for metastases.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

New targets for therapy: antigen identification in adults with B-cell acute lymphoblastic leukaemia.

Acute lymphoblastic leukaemia (ALL) in adults is a rare and difficult-to-treat cancer that is characterised by excess lymphoblasts in the bone marrow. Although many patients achieve remission with chemotherapy, relapse rates are high and the associated impact on survival devastating. Most patients receive chemotherapy and for those whose overall fitness supports it, the most effective treatment to date is allogeneic stem cell transplant that can improve overall survival rates in part due to a 'graft-versus-leukaemia' effect.

A network analysis to identify mediators of germline-driven differences in breast cancer prognosis.

Identifying the underlying genetic drivers of the heritability of breast cancer prognosis remains elusive. We adapt a network-based approach to handle underpowered complex datasets to provide new insights into the potential function of germline variants in breast cancer prognosis. This network-based analysis studies ~7.

ICI-RS 2019 nocturia think tank: How can experimental science guide us in understanding the pathophysiology of nocturia?

Introduction: The following is a report on the proceedings of the 2019 International Consultation on Incontinence-Research Society nocturia think tank (NTT).

Objectives: The objectives of the 2019 NTT were as follows: (a) to evaluate the role of urothelium in the pathophysiology of nocturia; (b) to determine whether nocturia is a circadian disorder; (c) to discuss the role of melatonin in nocturia; (d) to consider ambulatory urodynamic monitoring in evaluating patients with nocturia; (e) to explore studies of water handling in human compartments utilizing heavy water; and (f) to explore whether basic science is the key to understanding the treatment options for diminished bladder capacity in patients with nocturia.

Methods: A compendium of discussions of the role of experimental science in understanding the pathophysiology of nocturia is described herein.

Deletion of iRhom2 protects against diet-induced obesity by increasing thermogenesis.

Objective: Obesity is the result of positive energy balance. It can be caused by excessive energy consumption but also by decreased energy dissipation, which occurs under several conditions including when the development or activation of brown adipose tissue (BAT) is impaired. Here we evaluated whether iRhom2, the essential cofactor for the Tumour Necrosis Factor (TNF) sheddase ADAM17/TACE, plays a role in the pathophysiology of metabolic syndrome.

in the Colorectum and Its Association with Cancer Risk and Survival: A Systematic Review and Meta-analysis.

Background: The gut microbiome, in particular , has been reported to play a role in colorectal cancer development and in patient prognosis. We aimed to perform a systematic review and meta-analysis of published studies to assess the prevalence of in colorectal tumors and evaluate the association between and colorectal cancer development and prognosis.

Methods: MEDLINE, EMBASE, and Web of Science databases were systematically searched for studies published until January 2019.

Fine-mapping of 150 breast cancer risk regions identifies 191 likely target genes.

Genome-wide association studies have identified breast cancer risk variants in over 150 genomic regions, but the mechanisms underlying risk remain largely unknown. These regions were explored by combining association analysis with in silico genomic feature annotations. We defined 205 independent risk-associated signals with the set of credible causal variants in each one.

The NeST (neoadjuvant systemic therapy in breast cancer) study - Protocol for a prospective multi-centre cohort study to assess the current utilization and short-term outcomes of neoadjuvant systemic therapies in breast cancer.

Introduction: Neoadjuvant systemic therapy (NST) has several potential advantages in the treatment of breast cancer. However, there is currently considerable variation in NST use across the UK. The NeST study is a national, prospective, multicentre cohort study that will investigate current patterns of care with respect to NST in the UK.

miR-191 promotes radiation resistance of prostate cancer through interaction with RXRA.

Radiation therapy is a common treatment for prostate cancer, however recurrence remains a problem. MicroRNA expression is altered in prostate cancer and may promote therapy resistance. Through bioinformatic analyses of TCGA and CPC-GENE patient cohorts, we identified higher miR-191 expression in tumor versus normal tissue, and increased expression in higher Gleason scores.

Pathways, Processes, and Candidate Drugs Associated with a Cluster-Dependency Model of Leukemia.

High expression of the cluster correlates with poor clinical outcome in acute myeloid leukemias, particularly those harboring rearrangements of the mixed-lineage-leukemia gene (). Whilst decreased expression acts as a readout for candidate experimental therapies, the necessity of the cluster for leukemia maintenance has not been fully explored. Primary leukemias were generated in hematopoietic stem/progenitor cells from responsive transgenic mice for conditional deletion of the locus.

Induction of an Alternative mRNA 5' Leader Enhances Translation of the Ciliopathy Gene Inpp5e and Resistance to Oncolytic Virus Infection.

Residual cell-intrinsic innate immunity in cancer cells hampers infection with oncolytic viruses. Translational control of mRNA is an important feature of innate immunity, yet the identity of translationally regulated mRNAs functioning in host defense remains ill-defined. We report the translatomes of resistant murine "4T1" breast cancer cells infected with three of the most clinically advanced oncolytic viruses: herpes simplex virus 1, reovirus, and vaccinia virus.

Raptor-Mediated Proteasomal Degradation of Deamidated 4E-BP2 Regulates Postnatal Neuronal Translation and NF-κB Activity.

The translation initiation repressor 4E-BP2 is deamidated in the brain on asparagines N99/N102 during early postnatal brain development. This post-translational modification enhances 4E-BP2 association with Raptor, a central component of mTORC1 and alters the kinetics of excitatory synaptic transmission. We show that 4E-BP2 deamidation is neuron specific, occurs in the human brain, and changes 4E-BP2 subcellular localization, but not its disordered structure state.

Results of a phase II clinical trial of 6-mercaptopurine (6MP) and methotrexate in patients with BRCA-defective tumours.

Background: Tumour cells with BRCA1/2 gene mutations demonstrate increased sensitivity to platinum and poly (ADP-ribose) polymerase (PARP) inhibitors. 6-mercaptopurine (6MP) was found to selectively kill BRCA-defective cells in a xenograft model as effectively as the PARP inhibitor AG014699, even after these cells acquired resistance to a PARP inhibitor or cisplatin.

Methods: This phase II single-arm trial investigated the activity of 6MP 55-75 mg/m per day, and methotrexate 15-20 mg/m per week in advanced breast or platinum-resistant ovarian cancer patients with a BRCA1/2 germline mutation, who had progressed after ≥1 previous line of chemotherapy.

Alcohol intake, tobacco smoking, and esophageal adenocarcinoma survival: a molecular pathology epidemiology cohort study.

Purpose: To investigate the association between cigarette smoking, alcohol consumption, and esophageal adenocarcinoma survival, including stratified analysis by selected prognostic biomarkers.

Methods: A population-representative sample of 130 esophageal adenocarcinoma patients (n = 130) treated at the Northern Ireland Cancer Centre between 2004 and 2012. Cox proportional hazards models were applied to evaluate associations between smoking status, alcohol intake, and survival.

Dual Erb B Inhibition in Oesophago-gastric Cancer (DEBIOC): A phase I dose escalating safety study and randomised dose expansion of AZD8931 in combination with oxaliplatin and capecitabine chemotherapy in patients with oesophagogastric adenocarcinoma.

Background: AZD8931 has equipotent activity against epidermal growth factor receptor, erbB2, and erbB3. Primary objectives were to determine the recommended phase II dose (RP2D) of AZD8931 + chemotherapy, and subsequently assess safety/preliminary clinical activity in patients with operable oesophagogastric cancer (OGC).

Methods: AZD8931 (20 mg, 40 mg or 60 mg bd) was given with Xelox (oxaliplatin + capecitabine) for eight 21-day cycles, continuously or with intermittent schedule (4 days on/3 off every week; 14 days on/7 off, per cycle) in a rolling-six design.

Statin Use Is Associated with Lower Risk of PTEN-Null and Lethal Prostate Cancer.

Purpose: Statins are associated with lower risk of aggressive prostate cancer, but lethal prostate cancer is understudied and contributing mechanisms are unclear. We prospectively examined statins and lethal prostate cancer risk in the Health Professionals Follow-up Study (HPFS), tested associations with molecular subtypes, and integrated gene expression profiling to identify putative mechanisms.

Experimental Design: Our study included 44,126 men cancer-free in 1990, followed for prostate cancer incidence through 2014, with statin use recorded on biennial questionnaires.

Borderline Estrogen Receptor-Positive Breast Cancers in Black and White Women.

Background: Some breast tumors expressing greater than 1% and less than 10% estrogen receptor (ER) positivity (ER-borderline) are clinically aggressive; others exhibit luminal biology. Prior ER-borderline studies included few black participants.

Methods: Using the Carolina Breast Cancer Study (phase I: 1993-1996; 2: 1996-2001; 3: 2008-2013), a population-based study that oversampled black women, we compared ER-borderline (n = 217) to ER-positive (n = 1885) and ER-negative (n = 757) tumors.

Endothelial cells and organ function: applications and implications of understanding unique and reciprocal remodelling.

The microvasculature is a heterogeneous, dynamic and versatile component of the systemic circulation, with a unique ability to locally self-regulate and to respond to organ demand and environmental stimuli. Endothelial cells from different organs display considerable variation, but it is currently unclear to what extent functional properties of organ-specific endothelial cells are intrinsic, acquired and/or reprogrammable. Vascular function is a fundamental pillar of homeostasis, and dysfunction results in systemic consequences for the organism.