Showing papers by "Donal J. Brennan published in 2007"

CENP-F expression is associated with poor prognosis and chromosomal instability in patients with primary breast cancer

Abstract: DNA microarrays have the potential to classify tumors according to their transcriptome. Tissue microarrays (TMAs) facilitate the validation of biomarkers by offering a high-throughput approach to sample analysis. We reanalyzed a high profile breast cancer DNA microarray dataset containing 96 tumor samples using a powerful statistical approach, between group analyses. Among the genes we identified was centromere protein-F (CENP-F), a gene associated with poor prognosis. In a published follow-up breast cancer DNA microarray study, comprising 295 tumour samples, we found that CENP-F upregulation was significantly associated with worse overall survival (p<0.001) and reduced metastasis-free survival (p<0.001). To validate and expand upon these findings, we used 2 independent breast cancer patient cohorts represented on TMAs. CENP-F protein expression was evaluated by immunohistochemistry in 91 primary breast cancer samples from cohort I and 289 samples from cohort II. CENP-F correlated with markers of aggressive tumor behavior including ER negativity and high tumor grade. In cohort I, CENP-F was significantly associated with markers of CIN including cyclin E, increased telomerase activity, c-Myc amplification and aneuploidy. In cohort II, CENP-F correlated with VEGFR2, phosphorylated Ets-2 and Ki67, and in multivariate analysis, was an independent predictor of worse breast cancer-specific survival (p=0.036) and overall survival (p=0.040). In conclusion, we identified CENP-F as a biomarker associated with poor outcome in breast cancer and showed several novel associations of biological significance.

routine Mobilization of the Splenic Flexure is not Necessary During Anterior Resection for Rectal Cancer

Abstract: Splenic flexure mobilization is widely considered to be an essential component of anterior resection for rectal cancer. It was our hypothesis that selective splenic flexure mobilization would reduce operative times without increasing morbidity or affecting cure. A total of 100 consecutive patients with rectal cancer (mean 8 (range, 4–15) cm from anal verge) who underwent anterior resection for cure between 1996 and 2002 had splenic flexure mobilization only as required to achieve a tension-free anastomosis. Operative time, postoperative morbidity, pathologic findings, and recurrence rates were recorded. There were no clinicopathologic differences between those who had splenic flexure mobilization (n = 26) and those who did not (n = 74). Mean operative time in the splenic flexure mobilization group was longer, 167 (range, 130–200) minutes vs. 120 (range, 95–180) minutes in the nonmobilized group (P = 0.023). Mean length of specimen resected was longer in the splenic flexure mobilization group: 36 vs. 18 cm (P = 0.008). Anastomotic complications (4 percent), local recurrence (7 percent, median follow-up, 38 months), perioperative morbidity (32 percent) and mortality (2 percent), and survival did not differ between the two groups. Routine splenic flexure mobilization is not required for safe anterior resection in patients with rectal cancer. Avoiding splenic flexure mobilization results in shorter operative times and does not increase postoperative morbidity, anastomotic leakage, or local recurrence.

Contribution of DNA and Tissue Microarray Technology to the Identification and Validation of Biomarkers and Personalised Medicine in Breast Cancer

Abstract: Completion of the human genome project has revolutionised translational medicine. High-throughput technology now permits investigators to systematically interrogate the genome, transcriptome, proteome and metabolome. It is expected that these advances will eventually be translated into new more sensitive diagnostic tests and less toxic therapeutics. A major shift is expected in clinical oncology over the next few decades as we start to move away from currently practiced, population-based approaches to personalised medicine. In this emerging approach, the molecular and pathophysiological characteristics of an individual patient and tumour will be measured and tailored therapeutic regimens will be administered based on these profiles. One of the key steps in this process will be the identification and validation of biomarkers. Whilst great advances have been made in the discovery of putative biomarkers, disappointingly few have been translated into clinically applicable assays. It is widely believed that this is due to a lack of well-designed, thorough validation studies. Here, we review the role of DNA microarrays and tissue microarrays in the validation of biomarkers in breast cancer, with emphasis on their potential application to determine mode of personalised therapy in the future.

Breast cancer proteomics: clinical perspectives.

Abstract: Breast cancer is the one of leading causes of cancer-related deaths in women within economically developed regions of the world. A major focus of present research into this malignancy is the identification of new biomarkers and drug targets to improve detection and treatment. Proteomics represents one of the latest technological developments in this context. It aims to analyse the complex circuitry of the breast cancer proteome. Here, the authors review how breast cancer proteomics has progressed so far, with emphasis on its potential application to clinically relevant scenarios.