BACKGROUND:Predicting survival is uniquely difficult in patients with pancreatic cancer who receive chemotherapy. The authors developed a systemic inflammation response index (SIRI) based on peripheral neutrophil, monocyte, and lymphocyte counts and evaluated the ability of the SIRI to predict the survival of patients with pancreatic cancer who received chemotherapy. METHODS: The SIRI was developed in a training set of 177 patients who had advanced pancreatic cancer and received palliative chemotherapy. The ability of the SIRI to predict a patient's survival after chemotherapy was validated in 2 independent cohorts (n 5 397). RESULTS: Compared with patients who had an SIRI <1.8, patients in the training cohort who had an SIRI 1.8 had a shorter time to progression (TTP) (hazard ratio [HR], 2.348; 95% confidence interval, 1.559-3.535; P 5 .003) and shorter overall survival (OS) (HR, 2.789; 95% confidence interval, 1.897-4.121; P < .001). Comparable TTP and OS findings were observed in 2 independent validation cohorts. Multivariate analysis confirmed that the SIRI was an independent prognostic factor for both TTP and OS. In addition, compared with no change, an increase in the SIRI at week 8 was associated with poor TTP and OS, whereas a decrease in the SIRI was associated with improved outcomes. In addition, high SIRI scores were correlated with higher serum levels of interleukin 10, C-C motif chemokine ligand 17 (CCL17), CCL18, and CCL22 and with a shortened TTP. CONCLUSIONS: The SIRI can be used to predict the survival of patients with pancreatic adenocarcinomas who receive chemotherapy, potentially allowing clinicians to improve treatment outcomes by identifying candidates for aggressive therapy. Cancer 2016;122:2158-67.

No abstract

CXCR1, a receptor for CXCL8/IL-8, has recently been demonstrated to be associated with cancer stem cell (CSC) populations in certain types of human cancers. However, the effect of CXCR1 on CSC and its prognostic value in human pancreatic cancer remain unknown. In this study, we evaluated the expression of CXCR1 in human pancreatic duct adenocarcinoma (PDAC) and found that positive CXCR1 expression correlated with lymph node metastasis (P = 0.017) and a poor survival rate (HR, 3.748; 95% CI, 1.822 to 7.712; P < 0.001) in patients with PDAC. In addition, we identified significant positive correlations between CXCR1 and CD44 (P = 0.002) and CD133 (P = 0.017). Further functional studies confirmed that IL-8 addition increased sphere formation, CSC populations, and cell invasion of pancreatic cancer cells and that these effects could be reversed by antagonizing CXCR1 with a CXCR1-specific antibody. Therefore, our study demonstrated that the IL-8/CXCR1 axis is associated with the CSC-like properties of pancratic cancer cells and prognosis in human pancreatic cancer. This suggested a way of targeting pancreatic CSCs by disrupting IL-8/CXCR1 axis.

To develop and validate a radiomics signature for the prediction of gastric cancer (GC) survival and chemotherapeutic benefits. In this multicenter retrospective analysis, we analyzed the radiomics features of portal venous-phase computed tomography in 1591 consecutive patients. A radiomics signature was generated by using the Lasso-Cox regression model in 228 patients and validated in internal and external validation cohorts. Radiomics nomograms integrating the radiomics signature were constructed, demonstrating the incremental value of the radiomics signature to the traditional staging system for individualized survival estimation. The performance of the nomograms was assessed with respect to calibration, discrimination, and clinical usefulness. The radiomics signature consisted of 19 selected features and was significantly associated with DFS (disease-free survival) and OS (overall survival). Multivariate analysis demonstrated that the radiomics signature was an independent prognostic factor. Incorporating the radiomics signature into the radiomics-based nomograms resulted in better performance for the estimation of DFS and OS than the clinicopathological nomograms and TNM staging system, with improved accuracy of the classification of survival outcomes. Further analysis showed that stage II and III patients with higher radiomics scores exhibited a favorable response to chemotherapy. In conclusion, the newly developed radiomics signature is a powerful predictor of DFS and OS, and it may predict which patients with stage II and III GC benefit from chemotherapy.

Recent studies have revealed that long non-coding RNAs (lncRNAs) play important roles in cancer biology and that lncRNA gas5 (growth arrest-specific 5) regulates breast cancer cell growth. However, the role of gas5 in pancreatic cancer progression remains largely unknown. In the current study, we assay the expression level of gas5 in pancreatic cancer tissues and define the role of gas5 in the regulation of pancreatic cancer cell proliferation. We verify that the expression level of gas5 is significantly decreased in pancreatic cancer tissues compared with normal control. Overexpression of gas5 in pancreatic cancer cells inhibits cell proliferation, whereas gas5 inhibition induces a significant decrease in G0/G1 phase and an increase in S phase. We further demonstrate that gas5 negatively regulates CDK6 (cyclin-dependent kinase 6) expression in vitro and in vivo. More importantly, knockdown of CDK6 partially abrogates gas5-siRNA-induced cell proliferation. These data suggest an important role of gas5 in the molecular etiology of pancreatic cancer and implicate the potential application of gas5 in pancreatic cancer therapy.

Nonhealing chronic wounds on foot are one of the most dreaded complications of diabetes, and biomedical scaffolds remain an attractive option for repairing or regenerating tissues. Accelerating angiogenesis in the early stage after injury is critical to wound healing process; however, the scaffolds accelerate the angiogenesis in the beginning but with the acceleration of vessel network formation the scaffold network hinders the process. In this study, the water soluble drugs-loaded hydrogel nanofibrous scaffolds are designed for rapidly recruiting angiogenesis relative cells and promoting wound healing. The sustained release profile of desferrioxamine (DFO), which continues for about 72 h, leads to significantly increase of neovascularization. The majority of the scaffold is degraded in 14 d, leaving enough space for cell proliferation and vessel formation. The in vitro results show that the scaffolds upregulate the expression of Hif-1α and vascular endothelial growth factor, and enhance the interaction between fibroblasts and endothelial cells. The in vivo studies show a higher expression of angiogenesis related cytokines. This study demonstrates that the DFO released from hydrogel nanofibrous scaffolds of quick degradation can interfere with the required prolyl-hydroxylases cofactors by acting as Fe(2+) chelator and upregulate the expression of Hif-1α, leading to a significant increase of the neovascularization.

Single‐atom nanozyme (SAzyme) with peroxidase‐like activity can alter cellular redox balance and shows promising potential for tumor therapy. However, the “cold” immune microenvironment and limited amount of hydrogen peroxide (H2O2) in solid tumors severely restrict its efficacy. Herein, a light‐controlled oxidative stress amplifier system is designed by co‐encapsulating Pd‐C SAzymes and camptothecin in agarose hydrogel, which exhibits enhanced synergistic antitumor activity by self‐producing H2O2 and transforming “cold” tumors. In this nanozyme hydrogel system, the Pd‐C SAzyme converts near‐infrared laser into heat, resulting in agarose degradation and consequent camptothecin release. The camptothecin increases H2O2 level in tumors by activating nicotinamide adenine dinucleotide phosphate oxidase, improving the catalytic performance of SAzymes with peroxidase‐like activity. Moreover, the combination of photothermal therapy, chemotherapy, and nanozyme‐based catalytic therapy further facilitates tumor immunogenic death and enhanced antitumor immunity. The results reveal the synergistic antitumor potential of the novel SAzyme/chemotherapeutics‐based hydrogel system.

Serum lactate dehydrogenase (LDH) concentrations correlate with tumor progression and poor outcome. We evaluated the predictive value of serum LDH level for overall survival (OS) of patients with advanced pancreatic cancer after gemcitabine-based chemotherapy. We retrospectively enrolled 364 patients with locally advanced or metastatic pancreatic adenocarcinoma who were then allocated to training (n = 139) and validation cohorts (n = 225). We evaluated the association between serum LDH levels and OS as well as with markers of systemic inflammation, including neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) and lymphocyte/monocyte ratio (LMR). Kaplan–Meier analyses revealed that low serum LDH levels in the training cohort significantly correlated with longer OS. Multivariate analysis identified the serum LDH levels as an independent prognostic predictor of OS (p = 0.005). Serum LDH levels correlated positively with NLR and PLR and correlated negatively with LMR. Similar results were obtained for the validation cohort, except that multivariate analysis identified the serum LDH level as a significant prognostic predictor and only a statistical trend for OS (p = 0.059). We conclude that serum LDH levels were associated with the systemic inflammatory response and served as a significant prognostic predictor of OS. Serum LDH levels predicted OS in patients with advanced pancreatic cancer after gemcitabine-based palliative chemotherapy.