Investigation of the association between C-X-C motif chemokine receptor subunits and tumor infiltration levels and prognosis in patients with early-stage pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is one of the malignancies with the highest morality rate due to postoperative local invasion and distant metastasis. Although C-X-C motif chemokine receptor (CXCR) subunits have been reported as prognostic indicators in gastric cancer, the prognostic value of CXCR subunits in PDAC remains poorly understood. In the present study, the expression levels and biological functions of CXCR subunits were investigated using multiple publicly accessible bioinformatic platforms and databases. Survival analysis was used to evaluate the prognostic value of CXCR subunits in 112 early-stage PDAC cases by setting the median expression levels as the cut-off values. A nomogram was constructed to combine CXCR subunit expression levels and clinical data for prognosis prediction. Moreover, the association between CXCR subunit expression levels and tumor infiltration levels were detected in PDAC. The expression levels of CXCR subunits were elevated in PDAC tumor tissues. In the multivariate Cox proportional risk regression model, high CXCR2, CXCR4 and CXCR6 expression levels in early-stage PDAC were associated with a more favorable prognosis. Further, it was demonstrated that the differential expression levels of CXCR subunits in PDAC for combined survival analysis could contribute to risk stratification. The nomogram model demonstrated the contribution of CXCR subunits and clinical features in the prognosis of PDAC. Gene Set Enrichment Analysis suggested that CXCR subunits serve a role in immunomodulatory functions. The expression levels and somatic copy number alterations of CXCR subunits were associated with tumor infiltration levels in PDAC. CXCR subunits were associated with prognosis in patients with early-stage PDAC and may be potential drug targets for the treatment of pancreatic cancer.

[9-nitrocamptothecin nanostructured lipid carrier system: in vitro releasing characteristics, uptake by cells, and tissue distribution in vivo].

AIM: To study the release and cell uptake characteristics of 9-nitrocamptothecin (9-NC) nanostructured lipid carrier system (NLC) in vitro and its tissue distribution characteristics in vivo. METHODS: Mouse peritoneal macrophages were used to investigate the uptake of nanoparticles by cells in vitro. The tissue distribution of 9-nitrocamptothecin solution and stealth nanostructured lipid carrier system (S-NLC) was determined after intravenous administration to mice at a single dose of 1.5 mg kg(-1). The release and crystalloid characteristics were also investigated. RESULTS: X-ray diffraction spectrum showed that 9-NC probably was amorphous in S-NLC. The liquid lipid did not change the characteristics of the solid matrix in nanoparticles. The in vitro release and cell uptake characteristics of stealth and non-stealth 9-NC-NLC were investigated, separately. The results showed that the stealth 9-NC-NLC had sustained-release characteristics and could resist the absorption effect of the additional plasmas to a certain extent. In addition, the cell uptake percentage of stealth 9-NC-NLC was much lower than that of the non-stealth ones. The tissues distribution results showed that 9-NC in the S-NLC was mainly found in the lung, liver, pancreas and ovary/uterus, while the quantity of 9-NC was much lower in heart and kidney. The AUQ(0-t), of S-NLC in blood, ovary/uterus, pancreas, liver and lung were higher than that of 9-nitrocamptothecin solution. The weight-average drug targeting efficiency (Te*) of S-NLC in liver and lung were significantly higher than that of 9-nitrocamptothecin solution. The mean residence times (MRT) of S-NLC was 44 h, while that of 9-nitrocamptothecin solution was 8 h. Therefore, S-NLC showed obvious targeting effects on liver and lung. CONCLUSION: S-NLC with PEG flexible chains has sustained-release characteristics and can prolong its circulation in blood and have good targeting efficiency on liver and lung.

[Studies on formulations of Panax notoginsenosides for intranasal administration].

AIM: To develop high bioavailability preparations without irritation for Panax notoginsenosides. METHODS: The effects of some additives such as microcrystalline cellulose, beta-cyclodextrin and hydroxypropyl cellulose on drug in the preparations were examined. RESULTS: Saponins of Panax notoginseng (PNS) was absorbed in rabbits more when administered intranasally than through other routines, and the formulations including MCC both gave high bioavailability and low irritation. CONCLUSION: Bioavailability of Panax notoginsenosides can be increased through changing routine of administration and formulations.