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Dundee, United Kingdom

Kotronoulas G.,University of Surrey | Kearney N.,University of Surrey | Maguire R.,University of Surrey | Harrow A.,Dundee Cancer Center | And 3 more authors.
Journal of Clinical Oncology | Year: 2014

Purpose: The systematic use of patient-reported outcome measures (PROMs) has been advocated as an effective way to standardize cancer practice. Yet, the question of whether PROMs can lead to actual improvements in the quality of patient care remains under debate. This review examined whether inclusion of PROM in routine clinical practice is associated with improvements in patient outcomes, processes of care, and health service outcomes during active anticancer treatment. Methods: A systematic review of five electronic databases (Medline, EMBASE, CINAHL [Cumulative Index to Nursing and Allied Health Literature], PsycINFO, and Psychology and Behavioral Sciences Collection [PBSC]) was conducted from database inception to May 2012 to locate randomized and nonrandomized controlled trials of patients receiving active anticancer treatment or supportive care irrespective of type of cancer. Results: Based on prespecified eligibility criteria, we included 26 articles that reported on 24 unique controlled trials. Wide variability in the design and use of interventions delivered, outcomes evaluated, and cancer- and modality-specific context was apparent. Health service outcomes were only scarcely included as end points. Overall, the number of statistically significant findings were limited and PROMs' intervention effect sizes were predominantly small-to-moderate. Conclusion: The routine use of PROMs increases the frequency of discussion of patient outcomes during consultations. In some studies, PROMs are associated with improved symptom control, increased supportive care measures, and patient satisfaction. Additional effort is required to ensure patient adherence, as well as additional support to clinicians who will respond to patient concerns and issues, with clear system guidelines in place to guide their responses. More research is required to support PROM cost-benefit in terms of patient safety, clinician burden, and health services usage. © 2014 by American Society of Clinical Oncology. Source

Sawers L.,Cancer Research UK Research Institute | Ferguson M.J.,Dundee Cancer Center | Ihrig B.R.,Cancer Research UK Research Institute | Young H.C.,Cancer Research UK Research Institute | And 3 more authors.
British journal of cancer | Year: 2014

Chemotherapy response in ovarian cancer patients is frequently compromised by drug resistance, possibly due to altered drug metabolism. Platinum drugs are metabolised by glutathione S-transferase P1 (GSTP1), which is abundantly, but variably expressed in ovarian tumours. We have created novel ovarian tumour cell line models to investigate the extent to which differential GSTP1 expression influences chemosensitivity. Glutathione S-transferase P1 was stably deleted in A2780 and expression significantly reduced in cisplatin-resistant A2780DPP cells using Mission shRNA constructs, and MTT assays used to compare chemosensitivity to chemotherapy drugs used to treat ovarian cancer. Differentially expressed genes in GSTP1 knockdown cells were identified by Illumina HT-12 expression arrays and qRT-PCR analysis, and altered pathways predicted by MetaCore (GeneGo) analysis. Cell cycle changes were assessed by FACS analysis of PI-labelled cells and invasion and migration compared in quantitative Boyden chamber-based assays. Glutathione S-transferase P1 knockdown selectively influenced cisplatin and carboplatin chemosensitivity (2.3- and 4.83-fold change in IC50, respectively). Cell cycle progression was unaffected, but cell invasion and migration was significantly reduced. We identified several novel GSTP1 target genes and candidate platinum chemotherapy response biomarkers. Glutathione S-transferase P1 has an important role in cisplatin and carboplatin metabolism in ovarian cancer cells. Inter-tumour differences in GSTP1 expression may therefore influence response to platinum-based chemotherapy in ovarian cancer patients. Source

Elsberger B.,Dundee Cancer Center
Critical Reviews in Oncology/Hematology | Year: 2014

Src kinase is a member of a non-receptor tyrosine kinase family. It has been implicated as a regulator of cell proliferation and survival and plays a complex role in cell adhesion and motility. In vitro evidence for a role for Src in breast cancer is compelling. However, only a few translational clinical studies have been undertaken in this field. This review summarises translational evidence on expression and activation of Src kinase in breast cancer patient cohorts exploring clinical significance and the possibility of identifying key biomarkers. There is strengthened translational proof for a definitive role of Src in breast cancer. Nevertheless, there remains a need to find a robust biomarker to identify patients responsive to Src inhibitors for clinical trials. © 2013 Elsevier Ireland Ltd. Source

Mackenzie I.S.,University of Dundee | MacDonald T.M.,University of Dundee | Thompson A.,Dundee Cancer Center | Morant S.,University of Dundee | Wei L.,University of Dundee
BMJ (Online) | Year: 2012

Objective: To investigate whether exposure to spironolactone treatment affects the risk of incident breast cancer in women over 55 years of age. Design: Retrospective, matched cohort study. Setting: General Practice Research Database, a primary care anonymised database representative of the general population in the United Kingdom. Participants: 1 290 625 female patients, older than 55 years and with no history of breast cancer, from 557 general practices with a total follow-up time of 8.4 million patient years. We excluded patients with poor quality data and those with no contacts with their general practitioner after their current registration date. Intervention: Exposed cohort included women who received at least two prescriptions of spironolactone after age 55 years, who were followed up from the first prescription (index date). We randomly selected two unexposed female controls for every exposed patient, matched by practice, year of birth, and socioeconomic scores (if information was available), and followed up from the same date. Main outcome measure: New cases of breast cancer, using Read codes to confirm diagnoses. Results: Index dates for study patients ranged from 1987 to 2010, and 29 491 new cases of breast cancer were recorded in the study population (incidence rate 0.35% per year). The exposed cohort of 28 032 patients and control cohort of 55 961 patients had unadjusted incidence rates of 0.39% and 0.38% per year, respectively, over a mean follow-up time of 4.1 years. Time-to-event analysis, adjusting for potential risk factors, provided no evidence of an increased incidence of breast cancer in patients exposed to spironolactone (hazard ratio 0.99, 95% confidence interval 0.87 to 1.12). Conclusions: These data suggest that the long term management of cardiovascular conditions with spironolactone does not increase the risk of breast cancer in women older than 55 years with no history of the disease. Source

Bruce J.,University of Warwick | Thornton A.J.,University of Aberdeen | Scott N.W.,University of Aberdeen | Marfizo S.,Dundee Cancer Center | And 5 more authors.
British Journal of Cancer | Year: 2012

Background: Few epidemiological studies have prospectively investigated preoperative and surgical risk factors for acute postoperative pain after surgery for breast cancer. We investigated demographic, psychological, pain-related and surgical risk factors in women undergoing resectional surgery for breast cancer. Methods :Primary outcomes were pain severity, at rest (PAR) and movement-evoked pain (MEP), in the first postoperative week.Results:In 338 women undergoing surgery, those with chronic preoperative pain were three times more likely to report moderate to severe MEP after breast cancer surgery (OR 3.18, 95% CI 1.45-6.99). Increased psychological robustness, a composite variable representing positive affect and dispositional optimism, was associated with lower intensity acute postoperative PAR (OR 0.63, 95% CI 0.48-0.82) and MEP (OR 0.71, 95% CI 0.54-0.93). Sentinel lymph node biopsy (SLNB) and intraoperative nerve division were associated with reduced postoperative pain. No relationship was found between preoperative neuropathic pain and acute pain outcomes; altered sensations and numbness postoperatively were more common after axillary sample or clearance compared with SLNB. Conclusion :Chronic preoperative pain, axillary surgery and psychological robustness significantly predicted acute pain outcomes after surgery for breast cancer. Preoperative identification and targeted intervention of subgroups at risk could enhance the recovery trajectory in cancer survivors. © 2012 Cancer Research UK All rights reserved. Source

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