test, p < 0.05). Mitochondrial inhibitors did not significantly reduce Ca2+ clearance. A combination of glycolytic and mitochondrial inhibitors reduces Ca2+ clearance by 49.3% (p < 0.05). 3-BP and iodoacetate also reduced ATP levels to 0.82% and 75.0% of normal (T-test, p < 0.05), whereas there was no significant reduction when treated with mitochondrial inhibitors. 3-BP at a concentration of 300mM increases the rate of Panc-1 cell necrosis measured at 3 h and 6 h (p < 0.01), suggesting a timedependent and dose-dependent response. CCCP has no effect on cell necrosis. Conclusions: Our data suggests inhibition of glycolytic ATP to PMCA is an effective therapeutic target that could represent a new strategy for selectively killing PDAC cells and sparing normal, healthy cells.
guidelines suggest that patients who have undergone potentially curative treatment for colorectal cancer (CRC) should be followed up for 3 years. The primary aim of this study was to investigate whether the time to presentation with colorectal liver metastases (CRLM) has changed over time. This information, which is currently unknown, may inform future decisions regarding follow-up. A secondary aim was to identify any variables associated with the timing of presentation with CRLM. Methods: Patients presenting with metachronous isolated liver metastases between 1997 and 2011 were included. Timings of presentation with CRLM, rates of liver resection, survival data and factors associated with delayed presentation were investigated. Results: 269 patients were included in the study. Those having their primary CRC resection between 1997 and 2007 presented earlier with liver metastases over time (r = À0.33, 95% CI À0.45 to À0.20). However, 26% of patients who developed CRLM did so beyond 3 years. There was no significant difference in rates of liver resections for those presenting within, or beyond, 3 years (p = 0.21). There was no significant difference in survival for those presenting with resectable CRLM within, or beyond, 3 years (Exp(b) = 0.60, 95% CI 0.28e1.28). No factors associated with late presentation were identified. Conclusions: Despite a trend towards earlier presentation with CRLM after primary CRC resection, a significant proportion of patients present beyond 3 years. Time to presentation with CRLM seems independent of resectability rates. In addition, for those presenting with resectable disease time to presentation does not influence survival. These results suggest that CRC follow-up should be extended to 5 years. Follow-up interventions should be more frequent in the early stages reflecting the trend towards earlier presentation with CRLM. The economic implications of extending follow-up compare favourably to other NHS funded initiatives.
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