Feasibility and acceptability of breath research in primary care: a prospective, cross-sectional, observational study.

Objectives: To examine the feasibility and acceptability of breath research in primary care.

Design: Non-randomised, prospective, mixed-methods cross-sectional observational study.

Setting: Twenty-six urban primary care practices.

Development of a north-west London paracentesis simulation course for core medical trainees.

We designed, implemented and evaluated a near-peer simulation training programme teaching diagnostic and therapeutic abdominal paracentesis to core medical trainees (CMTs). We taught diagnostic and therapeutic abdominal paracentesis to 77 north-west London CMTs over 8 training days over 4 years, 2015 to 2019. The programme was optimised by use of plan, do, study, act (PDSA) cycles and the content was evaluated by anonymous pre- and post-course questionnaires.

Bronchiectasis in yellow nail syndrome.

Background And Objective: Yellow nail syndrome (YNS) is a rare and poorly described disease process. In this case-control study, clinical features and findings on HRCT were compared with idiopathic bronchiectasis (IBx).

Methods: A review of all patients attending an adult bronchiectasis clinic between 2007 and 2013 identified 25 YNS patients.

EGFR Is Regulated by TFAP2C in Luminal Breast Cancer and Is a Target for Vandetanib.

Expression of TFAP2C in luminal breast cancer is associated with reduced survival and hormone resistance, partially explained through regulation of RET. TFAP2C also regulates EGFR in HER2 breast cancer. We sought to elucidate the regulation and functional role of EGFR in luminal breast cancer.

Receptor Tyrosine Kinase Expression Predicts Response to Sunitinib in Breast Cancer.

Background: Preliminary data indicate that tyrosine kinase inhibitors (TKIs) function through rearranged during transfection (RET) in breast cancer. However, TKIs are not specific and can block several receptor tyrosine kinases (RTKs). This study used cell lines and primary breast cancer specimens to determine factors associated with TKI response.

The role of Tcfap2c in tumorigenesis and cancer growth in an activated Neu model of mammary carcinogenesis.

TFAP2C/AP-2γ influences development of the mammary gland and regulates patterns of gene expression in luminal and HER2-amplified breast cancer. The roles of TFAP2C in mammary gland tumorigenesis and in pathways critical to cancer progression remain poorly understood. To gain greater insight into oncogenic mechanisms regulated by TFAP2C, we examined mammary tumorigenesis in MMTV-Neu transgenic female mice with or without conditional knockout (KO) of Tcfap2c, the mouse homolog of TFAP2C.

Sumoylation pathway is required to maintain the basal breast cancer subtype.

The TFAP2C/AP-2γ transcription factor regulates luminal breast cancer genes, and loss of TFAP2C induces epithelial-mesenchymal transition. By contrast, the highly homologous family member, TFAP2A, lacks transcriptional activity at luminal gene promoters. A detailed structure-function analysis identified that sumoylation of TFAP2A blocks its ability to induce the expression of luminal genes.

Clinical teaching fellows: everyone's a winner.

Background: The principle teachers of the undergraduate medical curriculum are junior doctors and consultants, who may not necessarily be trained to teach. In addition, pressurised clinical environments may limit teaching time and decrease teaching quality. Clinical teaching fellows (CTFs) are doctors employed to teach, often undergoing a teaching qualification.

Inhibition of RET increases the efficacy of antiestrogen and is a novel treatment strategy for luminal breast cancer.

Purpose: Recent findings suggest that combination treatment with antiestrogen and anti-RET may offer a novel treatment strategy in a subset of patients with breast cancer. We investigated the role of RET in potentiating the effects of antiestrogen response and examined whether RET expression predicted the ability for tyrosine kinase inhibitor (TKI) to affect extracellular signal-regulated kinase 1/2 (ERK1/2) activation in primary breast cancer.

Experimental Design: Growth response, ERK1/2 activation, Ki-67, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling were assessed in breast cancer cell lines in vitro and in xenografts with vandetanib and/or tamoxifen.

TFAP2C governs the luminal epithelial phenotype in mammary development and carcinogenesis.

Molecular subtypes of breast cancer are characterized by distinct patterns of gene expression that are predictive of outcome and response to therapy. The luminal breast cancer subtypes are defined by the expression of estrogen receptor-alpha (ERα)-associated genes, many of which are directly responsive to the transcription factor activator protein 2C (TFAP2C). TFAP2C participates in a gene regulatory network controlling cell growth and differentiation during ectodermal development and regulating ESR1/ERα and other luminal cell-associated genes in breast cancer.

Using simulation for prescribing: an evaluation.

Background: Drug errors are a major cause of patient morbidity. The UK General Medical Council has highlighted that prescribing teaching should be prioritised. How should medical teachers best teach the practical aspects of prescribing?

Method: We piloted a set of eight prescribing simulation tutorials for 35 final-year undergraduate medical students in Great Western Hospital, Swindon, UK.

Distinct pathways regulated by RET and estrogen receptor in luminal breast cancer demonstrate the biological basis for combination therapy.

Objective: We investigated directed therapy based on TFAP2C-regulated pathways to inform new therapeutic approaches for treatment of luminal breast cancer.

Background: TFAP2C regulates the expression of genes characterizing the luminal phenotype including ESR1 and RET, but pathway cross talk and potential for distinct elements have not been characterized.

Methods: Activation of extracellular signal-regulated kinases (ERK) and AKT was assessed using phosphorylation-specific Western blot.

Human Melanoma cells over-express extracellular matrix 1 (ECM1) which is regulated by TFAP2C.

Extracellular matrix 1 (ECM1) is over-expressed in multiple epithelial malignancies. However, knowledge regarding the expression of ECM1 in melanomas and the mechanisms of ECM1 regulation is limited. In this study, we found that ECM1 is over-expressed in several melanoma cell lines, when compared to primary melanocytes, and furthermore, that ECM1 expression paralleled that of TFAP2C levels in multiple cell lines.

Transcriptional regulation of the GPX1 gene by TFAP2C and aberrant CpG methylation in human breast cancer.

The complexity of gene regulation has created obstacles to defining mechanisms that establish the patterns of gene expression characteristic of the different clinical phenotypes of breast cancer. TFAP2C is a transcription factor that has a critical role in the regulation of both estrogen receptor-alpha (ERα) and c-ErbB2/HER2 (Her2). Herein, we performed chromatin immunoprecipitation and direct sequencing (ChIP-seq) for TFAP2C in four breast cancer cell lines.

Expression of the RET proto-oncogene is regulated by TFAP2C in breast cancer independent of the estrogen receptor.

Background: The RET proto-oncogene is expressed as part of the estrogen receptor (ER) cluster in breast cancer. We sought to determine if TFAP2C regulates Ret expression directly or indirectly through ER.

Methods: Chromatin immunoprecipitation sequencing (ChIP-Seq) and gel-shift assay were used to identify TFAP2C binding sites in the RET promoter in four breast cancer cell lines.

Discovery of SMAD4 promoters, transcription factor binding sites and deletions in juvenile polyposis patients.

Inactivation of SMAD4 has been linked to several cancers and germline mutations cause juvenile polyposis (JP). We set out to identify the promoter(s) of SMAD4, evaluate their activity in cell lines and define possible transcription factor binding sites (TFBS). 5'-rapid amplification of cDNA ends (5'-RACE) and computational analyses were used to identify candidate promoters and corresponding TFBS and the activity of each was assessed by luciferase vectors in different cell lines.

Discovery of the BMPR1A promoter and germline mutations that cause juvenile polyposis.

Juvenile polyposis (JP) is an autosomal dominant hamartomatous polyposis syndrome where affected individuals are predisposed to colorectal and upper gastrointestinal cancer. Forty-five percent of JP patients have mutations or deletions involving the coding regions of SMAD4 and BMPR1A, but the genetic basis of other cases is unknown. We set out to identify the JP gene in a large kindred having 10 affected members without SMAD4 or BMPR1A coding sequence mutations or deletions.

Identification of primary gene targets of TFAP2C in hormone responsive breast carcinoma cells.

The TFAP2C transcription factor is involved in mammary development, differentiation, and oncogenesis. Previous studies established a role for TFAP2C in the regulation of ESR1 (ERalpha) and ERBB2 (Her2) in breast carcinomas. However, the role of TFAP2C in different breast cancer phenotypes has not been examined in detail.

The evolution of immunohematology in South Asian countries.

Many factors have resulted in the slow development of transfusion services in some South Asian countries. Despite difficulties, there have been some excellent developments and the outlook for the future is very positive. The biggest problems relate to the availability of the truly voluntary altruistic blood donors and considerable work is still needed to upgrade this aspect of the work.

Interaction of TFAP2C with the estrogen receptor-alpha promoter is controlled by chromatin structure.

Purpose: Transcriptional regulation of estrogen receptor-alpha (ERalpha) involves both epigenetic mechanisms and trans-active factors, such as TFAP2C, which induces ERalpha transcription through an AP-2 regulatory region in the ERalpha promoter. Attempts to induce endogenous ERalpha expression in ERalpha-negative breast carcinomas by forced overexpression of TFAP2C have not been successful. We hypothesize that epigenetic chromatin structure alters the activity of TFAP2C at the ERalpha promoter.

TFAP2C controls hormone response in breast cancer cells through multiple pathways of estrogen signaling.

Breast cancers expressing estrogen receptor-alpha (ERalpha) are associated with a favorable biology and are more likely to respond to hormonal therapy. In addition to ERalpha, other pathways of estrogen response have been identified including ERbeta and GPR30, a membrane receptor for estrogen, and the key mechanisms regulating expression of ERs and hormone response remain controversial. Herein, we show that TFAP2C is the key regulator of hormone responsiveness in breast carcinoma cells through the control of multiple pathways of estrogen signaling.

An immunohematological 'Wet' workshop.

A practical workshop on 'Immunohematology' was conducted in conjunction with the Indian Society of Blood Transfusion and Immunohaematology annual scientific program. The participants, from many parts of India, were able to obtain valuable practice in key areas of blood group serology and by the end of the workshop were able to carry out 'tube' techniques for antibody detection and identification. Column agglutination methods were also demonstrated.