• Breast cancer cell migration is regulated through junctional adhesion molecule-A-mediated activation of Rap1 GTPase

      McSherry, Elaine A; Brennan, Kieran; Hudson, Lance; Hill, Arnold DK; Hopkins, Ann M (2011-03-23)
      Abstract Introduction The adhesion protein junctional adhesion molecule-A (JAM-A) regulates epithelial cell morphology and migration, and its over-expression has recently been linked with increased risk of metastasis in breast cancer patients. As cell migration is an early requirement for tumor metastasis, we sought to identify the JAM-A signalling events regulating migration in breast cancer cells. Methods MCF7 breast cancer cells (which express high endogenous levels of JAM-A) and primary cultures from breast cancer patients were used for this study. JAM-A was knocked down in MCF7 cells using siRNA to determine the consequences for cell adhesion, cell migration and the protein expression of various integrin subunits. As we had previously demonstrated a link between the expression of JAM-A and β1-integrin, we examined activation of the β1-integrin regulator Rap1 GTPase in response to JAM-A knockdown or functional antagonism. To test whether JAM-A, Rap1 and β1-integrin lie in a linear pathway, we tested functional inhibitors of all three proteins separately or together in migration assays. Finally we performed immunoprecipitations in MCF7 cells and primary breast cells to determine the binding partners connecting JAM-A to Rap1 activation. Results JAM-A knockdown in MCF7 breast cancer cells reduced adhesion to, and migration through, the β1-integrin substrate fibronectin. This was accompanied by reduced protein expression of β1-integrin and its binding partners αV- and α5-integrin. Rap1 activity was reduced in response to JAM-A knockdown or inhibition, and pharmacological inhibition of Rap1 reduced MCF7 cell migration. No additive anti-migratory effect was observed in response to simultaneous inhibition of JAM-A, Rap1 and β1-integrin, suggesting that they lie in a linear migratory pathway. Finally, in an attempt to elucidate the binding partners putatively linking JAM-A to Rap1 activation, we have demonstrated the formation of a complex between JAM-A, AF-6 and the Rap1 activator PDZ-GEF2 in MCF7 cells and in primary cultures from breast cancer patients. Conclusions Our findings provide compelling evidence of a novel role for JAM-A in driving breast cancer cell migration via activation of Rap1 GTPase and β1-integrin. We speculate that JAM-A over-expression in some breast cancer patients may represent a novel therapeutic target to reduce the likelihood of metastasis.
    • Breast cancer management: clinical guidelines.

      Walsh, T. N.; O'Higgins, N.; Royal College of Surgeons in Ireland. Clinical Guidelines Committee. (Royal College of Sugeons in Ireland, 2000-11)
    • Breast cancer research output, 1945-2008: a bibliometric and density-equalizing analysis

      Glynn, Ronan W; Scutaru, Cristian; Kerin, Michael J; Sweeney, Karl J (2010-12-22)
      Abstract Introduction Breast cancer is the most common form of cancer among women, with an estimated 194,280 new cases diagnosed in the United States in 2009 alone. The primary aim of this work was to provide an in-depth evaluation of research yield in breast cancer from 1945 to 2008, using large-scale data analysis, the employment of bibliometric indicators of production and quality, and density-equalizing mapping. Methods Data were retrieved from the Web of Science (WOS) Science Citation Expanded database; this was searched using the Boolean operator, 'OR', with different terms related to breast cancer, including "breast cancer", "mammary ductal carcinoma" and "breast tumour". Data were then extracted from each file, transferred to Excel charts and visualised as diagrams. Mapping was performed as described by Groneberg-Kloft et al. in 2008. Results A total of 180,126 breast cancer-associated items were produced over the study period; these had been cited 4,136,224 times. The United States returned the greatest level of output (n = 77,101), followed by the UK (n = 18,357) and Germany (n = 12,529). International cooperation peaked in 2008, with 3,127 entries produced as a result; relationships between the United States and other countries formed the basis for the 10 most common forms of bilateral cooperation. Publications from nations with high levels of international cooperation were associated with greater average citation rates. A total of 4,096 journals published at least one item on breast cancer, although the top 50 most prolific titles together accounted for over 43% (77,517/180,126) of the total output. Conclusions Breast cancer-associated research output continues to increase annually. In an era when bibliometric indicators are increasingly being employed in performance assessment, these findings should provide useful information for those tasked with improving that performance.
    • Breast cancer subtype discordance: impact on post-recurrence survival and potential treatment options

      McAnena, Peter F; Brown, James A; Ramli, A.; Curran, C.; Malone, C.; McLaughlin, R.; Barry, K.; JAL, Brown; Kerin, M. J (2018-02-20)
      Abstract Background Recent studies have shown that breast cancer subtype can change from the primary tumour to the recurrence. Discordance between primary and recurrent breast cancer has implications for further treatment and ultimately prognosis. The aim of the study was to determine the rate of change between primary and recurrence of breast cancer and to assess the impact of these changes on survival and potential treatment options. Methods Patient demographics were collected on those who underwent surgery for breast cancer between 2001 and 2014 and had a recurrence with biopsy results and pathology scoring of both the primary and recurrence. Results One hundred thirty two consecutive patients were included. There were 31 (23.5%) changes in subtype. Discordance occurred most frequently in luminal A breast cancer (n = 20), followed by triple negative (n = 4), luminal B (n = 3) and HER2 (n = 3). Patients who changed from luminal A to triple negative (n = 18) had a significantly worse post-recurrence survival (p < 0.05) with overall survival approaching significance (p = 0.064) compared to concordant luminal A cases (n = 46). Overall receptor discordance rates were: estrogen receptor 20.4% (n = 27), progesterone receptor 37.7% (n = 50) and HER2 3% (n = 4). Loss of estrogen receptor and progesterone receptor was more common than gain (21 vs. 6 (p = 0.04) and 44 vs. 6 (p = 0.01) respectively). Nine patients (6.8%) gained receptor status potentially impacting treatment options. Conclusion Discordance in subtype and receptor status occurs between primary and recurrent breast cancer, ultimately affecting survival and potentially impacting treatment options.
    • Breast clinic referrals &#8211; should mastalgia be managed in primary care?

      Alamiri, Jamal; Lowery, AJ; Rajendran, S; Hill, AD (2013-01-30)
    • Breast self-examination and breast cancer awareness in women in developing countries: a survey of women in Buea, Cameroon

      Suh, Mary Atanga B; Atashili, Julius; Fuh, Eunice A; Eta, Vivian A (2012-11-09)
      Abstract Background Breast cancer is one of the leading causes of cancer morbidity and mortality worldwide. In Cameroon, breast cancer causes as many as 10.7 deaths per 100,000 women making it the second cause of cancer mortality. Better documenting women’s knowledge and practices on breast cancer and breast self-exam (BSE) would be useful in the design of interventions aimed at preventing breast cancer. This study sought to 1. describe Cameroonian women’s knowledge of breast self-examination (BSE); 2. assess their impression on the practice of BSE and 3. describe their perceptions on the causes, risk factors and prevention of breast cancer. Methods A cross-sectional survey was conducted in a volunteer sample of 120 consenting women in Buea, Cameroon. Data were collected using a structured questionnaire self-administered by study participants. Results The sample was fairly educated with close to three quarters (70.83%) having completed high school. Nearly three quarters (74.17%) of participants had previously heard about BSE, however as many as 40% had never done a BSE. Although 95% of participants believed that breast cancer could be prevented, only 36.67% recognized breast examination as a prevention method. A substantial 13.33% thought that breast cancer could be prevented with a vaccine while 45% thought that dieting or exercising would prevent breast cancer. Similarly, 70% of participants thought that breast cancer could be treated, with 35.83% thinking that it could be treated medically while 34.17% thought it could be treated traditionally or spiritually. Conclusions The practice of BSE while perceived as being important is not frequent in these women in Buea, Cameroon. Health education campaigns are imperative to elucidate the public on the causes, risk factors and prevention of breast cancer. Further studies need to explore what interventions could be best used to improve the uptake and practice of BSE.
    • BreastMark: an integrated approach to mining publicly available transcriptomic datasets relating to breast cancer outcome

      Madden, Stephen F; Clarke, Colin; Gaule, Patricia; Aherne, Sinead T; O'Donovan, Norma; Clynes, Martin; Crown, John; Gallagher, William M (2013-07-02)
      Abstract Introduction Breast cancer is a complex heterogeneous disease for which a substantial resource of transcriptomic data is available. Gene expression data have facilitated the division of breast cancer into, at least, five molecular subtypes, namely luminal A, luminal B, HER2, normal-like and basal. Once identified, breast cancer subtypes can inform clinical decisions surrounding patient treatment and prognosis. Indeed, it is important to identify patients at risk of developing aggressive disease so as to tailor the level of clinical intervention. Methods We have developed a user-friendly, web-based system to allow the evaluation of genes/microRNAs (miRNAs) that are significantly associated with survival in breast cancer and its molecular subtypes. The algorithm combines gene expression data from multiple microarray experiments which frequently also contain miRNA expression information, and detailed clinical data to correlate outcome with gene/miRNA expression levels. This algorithm integrates gene expression and survival data from 26 datasets on 12 different microarray platforms corresponding to approximately 17,000 genes in up to 4,738 samples. In addition, the prognostic potential of 341 miRNAs can be analysed. Results We demonstrated the robustness of our approach in comparison to two commercially available prognostic tests, oncotype DX and MammaPrint. Our algorithm complements these prognostic tests and is consistent with their findings. In addition, BreastMark can act as a powerful reductionist approach to these more complex gene signatures, eliminating superfluous genes, potentially reducing the cost and complexity of these multi-index assays. Known miRNA prognostic markers, mir-205 and mir-93, were used to confirm the prognostic value of this tool in a miRNA setting. We also applied the algorithm to examine expression of 58 receptor tyrosine kinases in the basal-like subtype, identifying six receptor tyrosine kinases associated with poor disease-free survival and/or overall survival (EPHA5, FGFR1, FGFR3, VEGFR1, PDGFRβ, and TIE1). A web application for using this algorithm is currently available. Conclusions BreastMark is a powerful tool for examining putative gene/miRNA prognostic markers in breast cancer. The value of this tool will be in the preliminary assessment of putative biomarkers in breast cancer. It will be of particular use to research groups with limited bioinformatics facilities.
    • Bridging the digital disconnect

      Clarke, Aleisha M; Kuosmanen, Tuuli; Chambers, Derek; Barry, Margaret M; National University of Ireland (2014-10)
    • Brief communication: dentists’ reproducibility in scoring the plaque index using a fluorescent colouring agent

      Nishi, Makiko; Oral Health Services Research Centre, University College Cork, Cork (Irish Dental Association, 2017-08)
    • Brighten up

      Densem, Julia (Irish Dental Association, 2013-02)
    • Bronchoplastic procedure for an unusual indication--Wegener's granulomatosis.

      Soo, Alan; Aziz, Rasheed; Buckley, Mella; Young, Vincent; Department of Cardiothoracic Surgery, Crest Directorate, St James's Hospital, James Street, Dublin 8, Ireland. alan.soo@ucd.ie (2009-09)
      Wegener's granulomatosis (WG) is a systemic vasculitic condition that commonly affects the lung and kidneys. With improvement in medical therapy, airway complications are increasingly encountered and are difficult to manage. Here, we present a case whereby a patient presenting with airway complication is successfully treated with surgery.
    • Building Irish families through surrogacy: medical and judicial issues for the advanced reproductive technologies.

      Sills, Eric Scott; Healy, Clifford M; Sims International Fertility Clinic, Dublin, Ireland. escottsills@yahoo.com; Clifford M. Healy; Compton Aylmer Solicitors clifford@comptonaylmer.ie (2008)
      Surrogacy involves one woman (surrogate mother) carrying a child for another person/s (commissioning person/couple), based on a mutual agreement requiring the child to be handed over to the commissioning person/couple following birth. Reasons for seeking surrogacy include situations where a woman has non-functional or absent reproductive organs, or as a remedy for recurrent pregnancy loss. Additionally, surrogacy may find application in any medical context where pregnancy is contraindicated, or where a couple consisting of two males seek to become parents through oocyte donation. Gestational surrogacy is one of the main issues at the forefront of bioethics and the advanced reproductive technologies, representing an important challenge to medical law. This analysis reviews the history of surrogacy and clinical and legal issues pertaining to this branch of reproductive medicine. Interestingly, the Medical Council of Ireland does not acknowledge surrogacy in its current practice guidelines, nor is there specific legislation addressing surrogacy in Ireland at present. We therefore have developed a contract-based model for surrogacy in which, courts in Ireland may consider when confronted with a surrogacy dispute, and formulated a system to resolve any potential dispute arising from a surrogacy arrangement. While the 2005 report by the Commission on Assisted Human Reproduction (CAHR) is an expert opinion guiding the Oireachtas' development of specific legislation governing assisted human reproduction and surrogacy, our report represents independent scholarship on the contractual elements of surrogacy with particular focus on how Irish courts might decide on surrogacy matters in a modern day Ireland. This joint medico-legal collaborative also reviews the contract for services arrangement between the commissioning person/s and the surrogate, and the extent to which the contract may be enforced.
    • Burden of injury in childhood and adolescence in 8 European countries.

      Polinder, Suzanne; Haagsma, Juanita A; Toet, Hidde; Brugmans, Marco J P; van Beeck, Ed F; Department of Public Health, Erasmus Medical Centre, University Medical Centre Rotterdam, The Netherlands. s.polinder@erasmusmc.nl (2010)
      BACKGROUND: Injury is the major cause of death and suffering among children and adolescents, but awareness of the problem and political commitment for preventive actions remain unacceptably low. We have assessed variation in the burden of injuries in childhood and adolescence in eight European countries. METHODS: Hospital, emergency department, and mortality databases of injury patients aged 0-24 years were analyzed for Austria, Denmark, Ireland, Latvia, Netherlands, Norway, Slovenia and the United Kingdom (England, Wales). Years lost due to premature mortality (YLL), years lived with disability (YLD), and disability adjusted life years (DALYs) were calculated. RESULTS: Differences in the burden of injury in childhood and adolescence are large, with a fourfold gap between the safest countries (Netherlands and UK) in western-Europe and the relatively unsafe countries (Latvia and Slovenia) in the east. Variation between countries is attributable to high variation in premature mortality (YLL varied from 14-58 per 1000 persons) and disability (YLD varied from 3-10 per 1000 persons). Highest burden is observed among males ages 15-24. If childhood and adolescence injuries are reduced to the level of current best injury prevention practices, 6 DALYs per 1000 child years can be avoided. CONCLUSIONS: Injuries in childhood and adolescence cause a high disability and mortality burden in Europe. In all developmental stages large inequalities between west and east are observed. Potential benefits up to almost 1 million healthy child years gained across Europe are possible, if proven ways for prevention are more widely implemented. Our children deserve action now.
    • The Burden of Severe Lactational Mastitis in Ireland from 2006 to 2015

      Cooney, F; Petty-Saphon, N; Department of Public Health, Dr Steevens' Hospital (irish Medical Journal, 2019-01-15)
    • Burnout and Physical Activity in Medical Students

      Macilwraith, P; Bennett, D (Irish Medical Journal, 2018-03)
    • The Buteyko breathing technique in effective asthma management

      Ruth, Alan (Nursing in General Practice, 2014-03)
    • Caesarean delivery and subsequent pregnancy interval: a systematic review and meta-analysis

      O’Neill, Sinéad M; Kearney, Patricia M; Kenny, Louise C; Henriksen, Tine B; Lutomski, Jennifer E; Greene, Richard A; Khashan, Ali S (2013-08-27)
      Abstract Background Caesarean delivery has increased worldwide, however, the effects on fertility are largely unknown. This systematic review aims to compare subsequent sub-fertility (time to next pregnancy or birth) among women with a Caesarean delivery to women with a vaginal delivery. Methods Systematic review of the literature including seven databases: CINAHL; the Cochrane Library; Embase; Medline; PubMed; SCOPUS and Web of Knowledge (1945 - October 2012), using detailed search-strategies and reference list cross-checking. Cohort, case–control and cross-sectional studies were included. Two assessors reviewed titles, abstracts, and full articles using standardised data abstraction forms and assessed study quality. Results 11 articles were eligible for inclusion in the systematic review, of these five articles which adjusted for confounders were combined in a meta-analysis, totalling 750,407 women using fixed-effect models. Previous Caesarean delivery was associated with an increased risk of sub-fertility [pooled odds ratio (OR) 0.90; 95% CI 0.86, 0.93]. Subgroup analyses by parity [primiparous women: OR 0.91; 95% CI 0.87, 0.96; not limited to primiparous women: OR 0.81; 95% CI 0.73, 0.90]; by publication date (pre-2000: OR 0.80, 95% CI 0.68, 0.94; post-2000: OR 0.90, 95% CI 0.86, 0.94); by length of follow-up (<10 years: OR 0.81, 95% CI 0.73, 0.90; >10 years: OR 0.91, 95% CI 0.87, 0.96); by indication for mode of delivery (specified: 0.92, 95% CI 0.88, 0.97; not specified: OR 0.81, 95% CI 0.73, 0.90); by cohort size (<35,000: OR 0.79, 95% CI 0.67, 0.92; >35,000: OR 0.90, 95% CI 0.87, 0.95), by definition of sub-fertility used divided into (birth interval [BI]: OR 0.89, 95% CI 0.84, 0.94; inter-pregnancy interval [IPI]: OR 0.91, 95% CI 0.85, 0.97; and categorical measures: OR 0.81, 95% CI 0.73, 0.90); continuous measures: OR 0.91, 95% CI 0.87, 0.96) were performed. Results of the six studies not included in the meta-analysis (which did not adjust for confounders) are presented individually. Conclusions The meta-analysis shows an increased waiting time to next pregnancy and risk of sub-fertility among women with a previous Caesarean delivery. However, included studies are limited by poor epidemiological methods such as variations in the definition of time to next pregnancy, lack of confounding adjustment, or details of the indication for Caesarean delivery. Further research of a more robust methodological quality to better explore any underlying causes of sub-fertility and maternal intent to delay childbearing is warranted.