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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.

Purpose Minimally invasive surgery (MIS) has become the standard for many surgical procedures as it minimizes trauma, reduces infection rates and shortens hospitalization. However, the manipulation of objects in the surgical workspace can be difficult due to the unintuitive handling of instruments and limited range of motion. Apart from the advantages of robot-assisted systems such as augmented view or improved dexterity, both robotic and MIS techniques introduce drawbacks such as limited haptic perception and their major reliance on visual perception. Methods In order to address the above-mentioned limitations, a perception study was conducted to investigate whether the transmission of intra-abdominal acoustic signals can potentially improve the perception during MIS. To investigate whether these acoustic signals can be used as a basis for further automated analysis, a large audio data set capturing the application of electrosurgery on different types of porcine tissue was acquired. A sliding window technique was applied to compute log-mel-spectrograms, which were fed to a pre-trained convolutional neural network for feature extraction. A fully connected layer was trained on the intermediate feature representation to classify instrument–tissue interaction. Results The perception study revealed that acoustic feedback has potential to improve the perception during MIS and to serve as a basis for further automated analysis. The proposed classification pipeline yielded excellent performance for four types of instrument–tissue interaction (muscle, fascia, liver and fatty tissue) and achieved top-1 accuracies of up to 89.9%. Moreover, our model is able to distinguish electrosurgical operation modes with an overall classification accuracy of 86.40%. Conclusion Our proof-of-principle indicates great application potential for guidance systems in MIS, such as controlled tissue resection. Supported by a pilot perception study with surgeons, we believe that utilizing audio signals as an additional information channel has great potential to improve the surgical performance and to partly compensate the loss of haptic feedback.

Pancreatic cancer is a disease with high resistance to most common therapies and therefore has a poor prognosis, which is partly due to a lack of reaction to apoptotic stimuli. Signal transduction of such stimuli includes a death receptor-mediated extrinsic pathway as well as an intrinsic pathway linked to the mitochondria. Defects in apoptotic pathways and the deregulation of apoptotic proteins, such as Survivin, Bcl-2, Bcl-xL and Mcl-1, play decisive roles in the development of pancreatic cancer. Investigation of the molecular mechanism allowing tumors to resist apoptotic cell death would lead to an improved understanding of the physiology and the development of new molecular strategies in pancreatic cancer.

The validity of the 8th edition of the Union for International Cancer Control (UICC) staging system for gastric cancer has been evaluated only in Asian cohorts and not in European cohorts. The aim of this study was to evaluate the prognostic performance of the 8th edition of the UICC staging system in German and Korean cohorts independently and compare it with that of the 7th edition. A total of 6121 patients (526 from Germany and 5595 from Korea) who underwent upfront surgery for gastric cancer were retrospectively reclassified according to the 8th edition. Survival according to the UICC stages was estimated by the Kaplan-Meier method and compared by log-rank tests. A Cox proportional hazards model was fitted after adjusting for clinicopathological factors, and receiver operating characteristics analysis was conducted. The 8th edition showed significant differences in survival between each adjacent stage in the Korean cohort but not in the German cohort. Multivariate analyses revealed that the 8th edition staging was an independent prognostic factor, and its C-statistics were >0.76 in both German and Korean patients. The results were comparable to those observed with the UICC seventh edition (C-statistics was 0.768 vs 0.767 in the German cohort and 0.789 vs 0.785 in the Korean cohort for the 7th vs the 8th edition). The 8th edition showed prognostic value in predicting the survival of gastric cancer patients in both German and Korean cohorts. However, the predictive ability of the 8th and 7th edition was similar.

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