CALGB 80802 (Alliance): Impact of Sorafenib with and without Doxorubicin on Hepatitis C Infection in Patients with Advanced Hepatocellular Carcinoma.

Sorafenib blocks nonstructural protein 5A (NS5A)-recruited c-Raf-mediated hepatitis C virus (HCV) replication and gene expression. Release of Raf-1-Ask-1 dimer and inhibition of Raf-1 via sorafenib putatively differ in the presence or absence of doxorubicin. Cancer and Leukemia Group B (CALGB) 80802 (Alliance) randomized phase III trial of doxorubicin plus sorafenib versus sorafenib in patients with advanced hepatocellular carcinoma (HCC), showed no improvement in median overall survival (OS). Whether HCV viral load impacts therapy and whether any correlation between HCV titers and outcome based on HCV was studied. In patients with HCV, HCV titer levels were evaluated at baseline and at multiple postbaseline timepoints until disease progression or treatment discontinuation. HCV titer levels were evaluated in relation to OS and progression-free survival (PFS). Among 53 patients with baseline HCV data, 12 patients had undetectable HCV (HCV-UN). Postbaseline HCV titer levels did not significantly differ between treatment arms. One patient in each arm went from detectable to HCV-UN with greater than 2 log-fold titer levels reduction. Aside from these 2 HCV-UN patients, HCV titers remained stable on treatment. Patients who had HCV-UN at baseline were 3.5 times more likely to progress and/or die from HCC compared with HCV detectable (HR = 3.51; 95% confidence interval: 1.58-7.78; P = 0.002). HCV titer levels remained unchanged, negating any sorafenib impact onto HCV titer levels. Although an overall negative phase III study, patients treated with doxorubicin plus sorafenib and sorafenib only, on CALGB 80802 had worse PFS if HCV-UN. Higher levels of HCV titers at baseline were associated with significantly improved PFS. SIGNIFICANCE: Sorafenib therapy for HCC may impact HCV replication and viral gene expression. In HCV-positive patients accrued to CLAGB 80802 phase III study evaluating the addition of doxorubicin to sorafenib, HCV titer levels were evaluated at baseline and different timepoints. Sorafenib did not impact HCV titer levels. Despite an improved PFS in patients with detectable higher level HCV titers at baseline, no difference in OS was noted.

[Distinguishing the Properties and Sources of the Dissolved Organic Matter in Karst Reservoir Water During Winter Using Three-Dimensional Fluorescence Spectrum Technology:A Case Study in Wulixia Reservoir of Guangxi Province].

In recent years, the fluorescence spectrum technology has been widely applied to study the physical and chemical properties of dissolved organic matter (DOM) in natural water. In order to reveal the properties of the dissolved organic matter in reservoir water, the three-dimensional fluorescence spectrum and the parallel factor analysis were used to determine the properties of DOM and its sources in the Wulixia reservoir during the winter of 2016. Moreover, the chemical characteristics of water and the relative proportion of DOM fluorescent components were estimated. Results show that:① Ca2+ and HCO3- are the main cations and anions in the Wulixia reservoir during winter. The water is mainly controlled by the carbonate balance system and dissolved organic carbon (DOC) accounted for about 91% of total organic carbon (TOC). ③ DOM from the Wulixia reservoir can be divided into three components:fulvic acid, humic acid, and tryptophan. ③ The parameters, fluorescence index, humification index, biological index, and freshness index show the existence of DOM in the Wulixia reservoir. Microorganisms have a significant effect on DOM composition.

Analysis of trace microcystins in vegetables using solid-phase extraction followed by high performance liquid chromatography triple-quadrupole mass spectrometry.

A selective and sensitive method for the simultaneous detection of three common and hazardous microcystins (microcystins-LR, -RR, and -YR) in various vegetables was established using solid-phase extraction followed by high performance liquid chromatography coupled with mass spectrometry. The methanol-water proportion ratio of the extraction solvent and its acidity, as well as the efficiencies of solid-phase extraction, were evaluated to optimize a pretreatment procedure for extracting the microcystins from 10 vegetable matrices. The limits of detection and quantitation were below 7.5 µg/kg (dw) and 25 µg/kg (dw), respectively, in different vegetable matrices. The recoveries of the microcystins in the 10 vegetable matrices ranged from 61.3 to 117.3%, with RSDs of 0.2-18.3%. The established method was used to analyze 28 field vegetable samples collected from the sides of Lake Dianchi, and microcystin-RR was found in almost all samples at concentrations of 36.4-2352.2 µg/kg (dw).