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BackgroundPancreatic ductal adenocarcinoma shows a distinct apoptosis resistance, which contributes significantly to the aggressive nature of this tumor and constrains the effectiveness of new therapeutic strategies. Apoptosis resistance is determined by the net balance of the cells pro-and anti-apoptotic "control mechanisms". Numerous dysregulated anti-apoptotic genes have been identified in pancreatic cancer and seem to contribute to the high anti-apoptotic buffering capacity. We aimed to compare the benefit of simultaneous gene silencing (SGS) of several candidate genes with conventional gene silencing of single genes.MethodsFrom literature search we identified the anti-apoptotic genes XIAP, Survivin and Bcl-2 as commonly upregulated in pancreatic cancer. We performed SGS and silencing of single candidate genes using siRNA molecules in two pancreatic cancer cell lines. Effectiveness of SGS was assessed by qRT-PCR and western blotting. Apoptosis induction was measured by flow cytometry and caspase activation.ResultsSimultaneous gene silencing reduced expression of the three target genes effectively. Compared to silencing of a single target or control, SGS of these genes resulted in a significant higher induction of apoptosis in pancreatic cancer cells.ConclusionsIn the present study we performed a subliminal silencing of different anti-apoptotic target genes simultaneously. Compared to silencing of single target genes, SGS had a significant higher impact on apoptosis induction in pancreatic cancer cells. Thereby, we give further evidence for the concept of an anti-apoptotic buffering capacity of pancreatic cancer cells.

BackgroundNeoadjuvant therapy may increase the rate of radical tumour resection in patients with pancreatic cancer. Its impact on tumour recurrence has not been investigated fully. This study aimed to assess the impact of neoadjuvant therapy on patterns of recurrence.MethodsA systematic review was performed of articles identified through the PubMed, Scopus, Embase, Ovid and Google Scholar databases that analysed the relationship between neoadjuvant therapy and recurrence published to January 2016. The main endpoint was overall tumour recurrence. Other endpoints included local recurrence, any kind of distant, hepatic, pulmonary or peritoneal metastasis.ResultsA total of 4257 citations were reviewed. Twelve observational studies comprising 1365 patients were analysed. Neoadjuvant therapy significantly reduced the risk of overall (risk ratio (RR) 0·82, 95 per cent c.i. 0·74 to 0·90; P < 0·001) and local (RR 0·42, 0·32 to 0·55; P < 0·001) recurrence. Neoadjuvant therapy did not reduce the risk of any kind of distant (RR 1·02, 0·91 to 1·14; P = 0·78), hepatic (RR 0·86, 0·68 to 1·10; P = 0·23), pulmonary (RR 0·99, 0·37 to 2·66; P = 0·98) or peritoneal (RR 0·88, 0·57 to 1·38; P = 0·58) metastasis.ConclusionNeoadjuvant therapy reduced the risk of local recurrence but not that of distant metastasis.