Research

Research News

Download the Breast Cancer Research Newsletter - 2011

Interview with Professor Michael Kerin - Ireland AM on TV3, October 27th,  2010
(scroll down and click on Finding Cancer video)

Galway Breast Cancer Research Breakthrough - The Irish Times, December 22nd, 2009

External Conference Schedule (Abstract Submission Deadlines) 2011/2012

Introduction to our research

Research at the Department of Surgery provides a facility for medical students and surgical personnel wishing to undertake clinical research projects or postgraduate courses. Current research areas includes Breast Cancer, Gastrointestinal/Colorectal cancer, Orthopaedics and Vascular Surgery.

The research laboratory is also home to full-time scientific researchers focusing primarilly on cancer research.

Research facilities include the Surgical Research laboratories in the Clinical Science Institute, REMEDI, NCBES at NUI Galway and the Western Vascular Institute at University Hospital, Galway.

Research is conducted in collaboration with national and international research instituions, e.g.  the Mayo Clinic and Yale Unversity in the USA and Nottingham Trent University in the UK. 

Professor Michael Kerin and Anna O'Coinne (NBCRI Chairperson) with members of the Research Team

Cancer Research Projects

Molecular Profiling of Breast and Colon Cancer: mRNA and microRNA expression

As part of an ongoing HRB-funded departmental project entitled "Gene expression profiling to predict response to tamoxifen treatment in axillary node-negative breast cancer patients" , mRNA derived from early-stage breast cancer patients has been hybridised to whole genome expression arrays. The purpose of this study is to develop a new predictive tool that will have clinical utility in tailoring treatment options for axillary node negative breast cancer patients and out-perform currently available predictive markers. To do this breast tumour samples from patients with early stage breast carcinomas, treated with the anti-oestrogenic agent tamoxifen, have been divided into good prognosis and poor prognosis groups based on patient follow-up data.

MicroRNAs ( miRNAs) are non-coding regulatory genetic elements expressed in a tissue-specific and developmentally regulated manner. Their expression has been implicated in critical biological processes including development, cell differentiation and oncogenesis. miRNAs have the ability to regulate activity of other genes. Recent findings have demonstrated that miRNA expression is frequently abnormal in breast cancer. We are currently investigating the hypothesis that that miRNAs are key regulators of cancer metastasis and progression and could act as novel biomarkers to improve cancer diagnosis and prognostication. miRNA realtime PCR is currently being used to investigate the expression profiles of cancer-associated miRNAs in fresh frozen, paraffin embedded tissue and peripheral blood. In 2007 researchers were awarded a Health Research Board grant for the study of microRNAs in breast cancer.

(In collaboration with Dr. Vladimir Benes, European Molecular Biology Laboratory, Heidelberg, NCBES, NUI Galway and Professor Frank Slack, Yale University, USA)

MicroRNA expression profiling has been performed using Taqman Low Density Arrays in colorectal tumours to identify signatures that predict disease aggressiveness, risk of recurrence and response to adjuvant therapy. Aberrantly expressed miRNAs are validated by real-time PCR. To further elucidate the miRNA-mRNA regulatory mechanisms, expression of potential gene and downstream protein targets of dysregulated miRNAs are investigated by PCR and immunohistochemistry.

Mesenchymal Stem Cells and Breast Cancer

Adult Mesenchymal Stem Cells (MSCs) have the proven ability to specifically home to the site of tumours and their metastases, and also appear to bypass the host immune system. As a result of these remarkable traits, research is ongoing to determine the potential of these cells for tumour-targeted delivery of therapeutic genes. Further understanding the biology of MSCs and their interactions with breast cancer cells will be fundamental to determining whether these cells can be safely harnessed for tumour-targeted delivery of therapeutic agents. There are two central aims of the Breast Cancer- MSC program

1. To investigate the potential of MSCs for tumour targeted delivery of therapeutic genes in the setting of metastatic breast cancer

2. To understand the prevalence, role and fate of native MSCs in the primary breast tumour microenvironment

(In collaboration with REMEDI, NUI Galway and Professor John Morris,  Mayo Clinic College of Medicine, Rochester, USA)

To better understand the underlying causes of breast cancer we currently involved in a large collaborative study to investigate the hereditary component to breast cancer in the west of Ireland population in patients with a family history of the disease. Among the Irish breast cancer population there are many women with a significant family history of breast cancer who do not carry germline mutations in either of the 2 breast cancer susceptibility genes: BRCA1 and BRCA2 mutations by current diagnostic methods. For these women and their families risk analysis and heritability calculations remain elusive. It is thought that several common low penetrance genes account for the non- BRCA associated genetic susceptibility to breast cancer. These genes are likely to be inherited not as autosomal dominant traits or their penetrance would be obvious; but as complex traits that need to interact with each other and with the environment to induce their cancer causing effects. In order to identify these genes we are performing an association study to compare DNA from 1000 breast cancer patients in the West of Ireland with 1000 matched controls from the same ethnic and regional background.

(In collaboration with Professor Ian Tomlinson et al., Cancer Research UK)

Other Research

microRNAs in Obesity (Helen Heneghan)

Quality of Life Study & Economics of Cancer Management (Helen Heneghan in collaboration with Ciaran O'Neill, Economics, NUI Galway)

Bibliometric Study (Ronan Glynn)

Efficacy of a cognitive-behavioural intervention for women with recently diagnosed breast cancer: a randomised control trial
(In collaboration with the Department of Psychology, NUI Galway)

Research Methodologies

Primary Tissue Culture

Primary cell culture of fresh breast tumour tissue is an established technique in our laboratory. Following surgical excision and pathological review, fresh tumour tissue is placed in antibiotic PBS and subjected to collagenase digestion to generate organoid, epithelial and stromal cell fractions. Epithelial and stromal cell fractions are cultured separately, and monitored for adherence and proliferation. Breast tumour sub-type differentiation into cytoplasmic epithelial, nuclear myoepithelial and membranous fibroblastic fractions is verified by IHC staining using specific antibodies. Fractions of pure breast epithelial cells are used to determine the effects of potential chemopreventive agents such as bisphosphanates on tumour cell function. This technique is currently being employed to investigate the role of breast cancer fibroblast and epithelial cell interactions in tumour progression. 

Real Time Quantitative PCR (RQ-PCR)

We currently employ this technique to quantify gene expression in RNA derived from fresh-frozen normal and diseased breast tissue in several studies listed below. In addition we have begun to use RQ-PCR in the analysis of RNA extracted from formalin-fixed paraffin embedded tissue.

Immunohistochemistry

The Department houses a Ventana Discovery Autostainer instrument facilitating high throughput automated immunohistochemistry. This instrument has been used to assess the expression and prognostic significance of proteins of interest in many research projects. 

Vascular Research

Western Vascular Institute http://www.vascular.ie/

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