ABSTRACT
CONTEXT: Gemcitabine (GEM) and Baicalein (BCL) are reported to have anti-tumor effects including pancreatic cancer. Hyaluronic acid (HA) can bind to over-expressed receptors in various kinds of cancer cells. OBJECTIVE: The aim of this study is to develop prodrugs containing HA, BCL and GEM, and construct nanomedicine incorporate GEM and BCL in the core and HA on the surface. This system could target the cancer cells and co-deliver the drugs. METHODS: GEM-stearic acid lipid prodrug (GEM-SA) and hyaluronic acid-amino acid-baicalein prodrug (HA-AA-BCL) were synthesized. Then, GEM and BCL prodrug-based targeted nanostructured lipid carriers (HA-GEM-BCL NLCs) were prepared by the nanoprecipitation technique. The in vitro cytotoxicity studies of the NLCs were evaluated on AsPC1 pancreatic cancer cell line. In vivo anti-tumor effects were observed on the murine-bearing pancreatic cancer model. RESULTS: HA-GEM-BCL NLCs were effective in entering pancreatic cancer cells over-expressing HA receptors, and showed cytotoxicity of tumor cells in vitro. In vivo study revealed significant tumor growth inhibition ability of HA-GEM-BCL NLCs in murine pancreatic cancer model. CONCLUSION: It could be concluded that HA-GEM-BCL NLCs could be featured as promising co-delivery, tumor-targeted nanomedicine for the treatment of cancers.
Subject(s)
Antineoplastic Agents/administration & dosage , Drug Carriers/administration & dosage , Hyaluronic Acid/administration & dosage , Nanostructures/administration & dosage , Pancreatic Neoplasms/drug therapy , Prodrugs/administration & dosage , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacokinetics , Cell Line, Tumor , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Deoxycytidine/chemistry , Deoxycytidine/pharmacokinetics , Drug Carriers/chemistry , Drug Carriers/pharmacokinetics , Flavanones/administration & dosage , Flavanones/chemistry , Flavanones/pharmacokinetics , Humans , Hyaluronic Acid/chemistry , Hyaluronic Acid/metabolism , Lipids/administration & dosage , Lipids/chemistry , Lipids/pharmacokinetics , Mice , Mice, Inbred C57BL , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/pathology , Prodrugs/chemistry , Prodrugs/pharmacokinetics , Tumor Burden/drug effects , Tumor Burden/physiology , Xenograft Model Antitumor Assays/methods , GemcitabineABSTRACT
A rapid, sensitive and high-throughput liquid chromatography-tandem mass spectrometry (LC-MS-MS) method was established and validated to assay the concentration of nardosinone, a main active compound isolated from Nardostachys chinensis, in rat plasma. Plasma samples were processed by protein precipitation with acetonitrile and separated on a Venusil MP-C18 column (50 × 2.1 mm, 5 µm) at an isocratic flow rate of 0.6 mL/min using methanol-0.1% formic acid in water (55 : 45, v/v) as mobile phase, and total run time was 2.5 min. MS-MS detection was accomplished in selected reaction monitoring mode with positive electrospray ionization. The calibration curve was linear over the concentration range of 9.60-320 ng/mL with lower limit of quantification of 9.60 ng/mL. The intra- and inter-day precisions were below 12.3% in terms of relative standard deviation, and the accuracy was within ±9.0% in terms of relative error. Extraction recovery, matrix effect and stability were also satisfactory in rat plasma. The developed method was successfully applied to a pharmacokinetic study of nardosinone following an intravenous injection at a dose of 1.04 mg/kg to Sprague-Dawley rats.
Subject(s)
Chromatography, Liquid/methods , Mass Spectrometry/methods , Sesquiterpenes/blood , Animals , Female , Limit of Detection , Male , Polycyclic Sesquiterpenes , Rats , Rats, Sprague-Dawley , Reproducibility of Results , Sesquiterpenes/pharmacokineticsABSTRACT
Whether or not p16 promoter hypermethylation has any prognostic value on the survival of patients with colorectal cancer (CRC) is uncertain. A meta-analysis was therefore conducted on the overall survival involving 16 studies with 3968 patients and disease-free survival involving six studies with 1091 cases, respectively. The promoter hypermethylation was found to be significantly associated with shorter survival compared to controls, which was not only stable according to influence analysis and cumulative meta-analysis but also conclusive according to trial sequential meta-analysis. The meta-analysis supports the hypermethylation as an independent adverse prognostic factor for CRC.
Subject(s)
Colorectal Neoplasms/genetics , DNA Methylation , Genes, p16 , Neoplasm Proteins/genetics , Cyclin-Dependent Kinase Inhibitor p16 , Gene Expression Regulation, Neoplastic , Humans , Prognosis , Promoter Regions, Genetic , Prospective Studies , Survival AnalysisABSTRACT
Spatial distribution patterns of total mercury (THg) in 36 surficial sediment samples representing five regions of Lake Taihu were assessed using the ArcGis geostatistical analyst module. The pollution levels of THg were also evaluated from the same five lake regions. Concentrations of THg were in a ranged of 23-168 ng/g (mean 55 ng/g) in surfical sediments, which was significantly higher than those established baseline levels of the lake. Results of THg indicated that the northern region exhibited notably higher values, the bay regions showed elevated values relative to open areas, and the lakeside regions were higher than those observed in the central area. Lake Taihu suffered moderate to high Hg pollution, and expressed clear Hg enrichment status according to monomial pollution index I(geo) and human activity factors. The concentrations of THg in the surficial sediments of Lake Taihu showed moderate-strong variation (coefficient of variation 52%). Geostatistical analysis indicated a weak spatial self-correlation, suggesting the contamination of Hg in Lake Taihu is primarily the result of anthropogenic activities.
