Whether blood transfusion exacerbates cancer outcomes after surgery in humans remains inconclusive. We utilized a large cohort to investigate the effect of perioperative blood transfusion on cancer prognosis following colorectal cancer (CRC) resection. Patients with stage I through III CRC undergoing tumour resection at a tertiary medical center between 2005 and 2014 were identified and evaluated through August 2016. Propensity score matching was used to cancel out imbalances in patient characteristics. Postoperative disease-free survival (DFS) and overall survival (OS) were analysed using Cox regression model. A total of 4,030 and 972 patients were analysed before and after propensity score matching. Cox regression analyses demonstrated blood transfusion associated with shorter DFS and OS before and after matching (hazard ratio: 1.41, 95% CI: 1.2–1.66 for DFS; 1.97, 95% CI: 1.6–2.43 for OS). Larger transfusion volume was linked to higher overall mortality (≤4 units vs. nil, HR = 1.58; >4 units vs. nil, HR = 2.32) but not more cancer recurrence. Preoperative anemia was not associated with decreased survival after adjusting covariates. Perioperative blood transfusion was associated with worse cancer prognosis after curative colorectal resection, independently of anemia status. Strategies aimed at minimizing transfusion requirements should be further developed.

Celecoxib, a COX-2 inhibitor and non-steroidal anti-inflammatory drug, can prevent several types of cancer, including hepatocellular carcinoma (HCC). Here we show that celecoxib suppressed the self-renewal and drug-pumping functions in HCC cells. Besides, celecoxib depleted CD44 + /CD133 + hepatic cancer stem cells (hCSC). Prostaglandin E2 (PGE2) and CD133 overexpression did not reverse the celecoxib-induced depletion of hCSC. Also, celecoxib inhibited progression of rat Novikoff hepatoma. Moreover, a 60-day celecoxib program increased the survival rate of rats with hepatoma. Histological analysis revealed that celecoxib therapy reduced the abundance of CD44 + /CD133 + hCSCs in hepatoma tissues. Besides, the hCSCs depletion was associated with elevated apoptosis and blunted proliferation and angiogenesis in hepatoma. Celecoxib therapy activated peroxisome proliferator-activated receptor γ (PPARγ) and up-regulated PTEN, thereby inhibiting Akt and disrupting hCSC expansion. PTEN gene delivery by adenovirus reduced CD44/CD133 expression in vitro and hepatoma formation in vivo. This study suggests that celecoxib suppresses cancer stemness and progression of HCC via activation of PPARγ/PTEN signaling.

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BackgroundInformation is limited about the effect of restricted carbapenem use on clearance of multi-drug resistant Acinetobacter baumannii (MDRAB). We sought to determine the time effect of antibiotic exposure on multi-drug resistant Acinetobacter baumannii (MDRAB) acquisition and clearance.MethodsWe conducted a retrospective observational study at the intensive care units of a tertiary medical center. Forty-two of a cohort of previously healthy young adults who were concurrently burned by a dust explosion was included. Cases consisted of those from whom MDRAB was isolated during hospitalization. Controls consisted of patients from whom MDRAB was not isolated in the same period. Use of antimicrobial agents was compared based on days of therapy per 1,000 patient-days (DOT/1,000PD). A 2-state Markov multi-state model was used to estimate the risk of acquisition and clearance of MDRAB.ResultsMDRAB was discovered in 9/42 (21.4%) individuals. The cases had significantly higher use of carbapenem (652 DOT/1,000PD vs. 385 DOT/1,000PD, P < 0.001) before MDRAB isolation. For the cases, clearance of MDRAB was associated with lower use of carbapenem (469 DOT/1,000PD vs. 708 DOT/1,000PD, P = 0.003) and higher use of non-carbapenem beta-lactam (612 DOT/1,000PD vs. 246 DOT/1,000PD, P <0.001). In multi-state model, each additional DOT of carbapenem increased the hazard of acquiring MDRAB (hazard ratio (HR), 1.08; 95% confidence interval (CI) 1.01–1.16) and each additional DOT of non-carbapenem beta-lactam increased the protection of clearing MDRAB (HR, 1.25; 95% CI 1.07–1.46).ConclusionsBoth acquisition and clearance of MDRAB were related to antibiotic exposure in a homogeneous population. Our findings suggest that early discontinuation of carbapenem could be an effective measure in antibiotic stewardship for the control of MDRAB spreading.

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Clinical and pathological predictors have proved to be insufficient in identifying high-risk patients who develop cancer recurrence after tumour resection. We aimed to compare the prognostic ability of various inflammation markers in patients undergoing surgical resection of lung cancer. We consecutively included 2,066 patients with stage I–III non-small-cell lung cancer undergoing surgical resection at the center between 2005 and 2015. We evaluated prognostic nutritional index, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio along with their perioperative changes. We conducted stepwise backward variable elimination and internal validation to compare the selected markers’ predictive performance for postoperative recurrence-free survival and overall survival. Preoperative neutrophil-to-lymphocyte ratio independently predicts recurrence-free survival (HR: 1.267, 95% CI 1.064–1.509, p = 0.0079, on base-2 logarithmic scale) and overall survival (HR: 1.357, 95% CI 1.070–1.721, p = 0.0117, on base-2 logarithmic scale). The cut-off value is 2.3 for predicting both recurrence (sensitivity: 46.1% and specificity: 66.7%) and mortality (sensitivity: 84.2% and specificity: 40.4%). Advanced cancer stage, poor tumour differentiation, and presence of perineural infiltration were significantly correlated with higher preoperative neutrophil-to-lymphocyte ratio. We concluded that preoperative neutrophil-to-lymphocyte ratio is superior to prognostic nutritional index and platelet-to-lymphocyte ratio in predicting postoperative recurrence and mortality of patients undergoing surgical resection of non-small-cell lung cancer.

Antimicrobial peptides play an important role in the innate immune response and host defense mechanism. In the present study, we employed phage display technique to screen for inhibitors which may block the phosphoenolpyruvatedependent phosphotransferase system (PTS) pathway and hence retard cell growth. The recombinant histidine-containing phosphocarrier HPr protein was prepared as the target to screen for the tight binders from the phage-displayed random peptide library Ph.D.-12. The biopanning processes were performed and the binding capabilities of the selected phage were further estimated by enzyme-linked immunosorbent assay (ELISA). The single-stranded DNAs of the 20 selected phages were isolated, sequenced, and five corresponding peptides were synthesized. Only one of the five peptides, AP1 (YQVTQSK VMSHR) was found to inhibit the growth of Escherichia coli cells efficiently (IC₅₀~50 μM). Molecular modeling reveals that AP1 may block the EI-HPr interaction and phosphotransfer. Interestingly, AP1 was also found to induce cell aggregation in a concentration-dependent manner. Since glycogen accumulation has been attributed to biofilm formation, the effects of AP1 on the intracellular glycogen levels were measured. The results strongly indicate that the cell aggregation may be caused by the binding of peptide AP1 with HPr to block the interaction of dephosphorylated HPr with glycogen phosphorylase (GP). Because glycogen phosphorylase activity can be activated by HPr-GP interaction, the binding of AP1 to HPr would cause a decreasing rate of glycogen breakdown in M9 medium and accumulation of glycogen, which may lead to eventual cell aggregation. To the best of our knowledge, this is the first study to demonstrate that an inhibitor bound to a dephosphorylated HPr can decouple its regulatory function and induce cell aggregation.