Molecular landscape and clinical significance of exon 11 mutations in KIT gene among patients with gastrointestinal stromal tumor: a retrospective exploratory study

ObjectiveThis aim of this study was to investigate the prognostic significance of KIT exon 11 mutation subtypes in patients with GISTs.MethodsA total of 233 consecutive patients diagnosed with GISTs at the First Affiliated Hospital of Zhengzhou University from January 2013 to August 2018 were included in this study. The prevalence and mutation landscape of exon 11 in KIT was presented. The clinicopathological characteristics and prognosis among the different mutation subtypes were analyzed. All the statistical analyses were performed by SPSS22.0.ResultsSomatic mutational analysis indicated that point mutations were the most frequently detected mutations followed by deletions & compound mutations and insertion and tandem duplication mutations in the stomach. Point mutations showed a low mitotic count and a high risk of recurrence, and deletions and compound mutations have a high mitotic count while insertions and tandem duplication mutations showed a low mitotic count with an intermediate recurrence risk. Point mutations and deletions frequently occurred in sequence region codons 550-560 of exon 11, while compound mutations, insertion, and tandem duplication were mainly detected in codons 557-559, 572-580, and 577-581, respectively. The multi-variation analysis demonstrated that tumor diameter and high recurrence risk groups had worse prognostic values. However, mutation types were not significant predictors of relapse-free survival (RFS) in GISTs. Survival analysis suggested no significant difference in RFS between the 557/558 deletion and the other deletions.ConclusionThis study suggested that mutations in exon 11 of the KIT gene were common with intermediate/high recurrence risk in GISTs patients. Tumor diameter ≥5 cm, and deletions mutations might predict a worse prognosis

One-Step Preparation of Nitrogen-Doped Platinum-Based Catalysts for Electrocatalytic Oxidation of Ethanol

Pt/nitrogen-doped reduced graphene oxide (N-GO) catalysts were prepared by one-step microwave-assisted ethylene glycol reduction using N-methyl-2-pyrrolidone (NMP) as the nitrogen source. Nitrogen doping in GO and the deposition of highly dispersed platinum nanoparticles were completed at the same time. The effect of adding NMP on the microstructure and the electrocatalytic performance of Pt/N-GO catalysts were studied. The results show that Pt/N-GO catalysts have better particle size distribution and electrocatalytic performance than undoped catalysts. When the ratio of GO to NMP reaches 1:200, the peak current density of the catalyst is about 3 times that of the non-nitrogen-doped Pt/GO and Pt/C(JM) catalysts, indicating that the electrocatalytic performance of this catalyst is the best. Therefore, the development of a one-step synthesis of Pt/N-GO catalysts has a broad application prospects in direct ethanol fuel cells (DEFCs)

Protein kinase C is involved in arsenic trioxide-induced apoptosis and inhibition of proliferation in human bladder cancer cells

Objective: Arsenic trioxide (ATO) is a potent antitumor agent used to treat acute promyelocytic leukemia, and recently solid tumors including bladder cancers. However, a mechanism to explain its antitumor activity in bladder cancers is unclear. Here, we investigated the role of protein kinase C (PKC) in ATO-induced apoptosis and inhibition of proliferation in bladder cancer cells. Methods: T24 human bladder carcinoma cells were incubated with different concentrations of ATO in the presence or absence of PMA (PKC activator) or H7 (PKC inhibitor). Cell proliferation was assessed by MTT assay, and apoptosis by TUNEL and electron microscopy. Flow cytometry was used to analyze cell cycle distribution, radioimmunoassay to measure PKC activity, and Western blot analysis to detect caspase-3. Results: ATO inhibited proliferation and induced apoptosis of T24 cells in a dose-dependent manner, caused an increase of percentage of cells in the G1 phase and a decrease in the S and G2 phases, and upregulated the expression of activated caspase-3 and reduced PKC activity. These effects were abrogated by PMA, but enhanced by H7. Conclusions: PKC is involved in the anticancer activity of ATO for T24 bladder cancer cells, suggesting that targeting the PKC pathway may represent a potential approach to enhance the efficacy of ATO to treat bladder cancers

One-Pot Synthesis of Pt High Index Facets Catalysts for Electrocatalytic Oxidation of Ethanol

Direct ethanol fuel cell (DEFC) has attracted wide attention due to its wide range of fuel sources, cleanliness, and high efficiency. However, the problems of low catalytic efficiency and poor catalyst stability still exist in DEFC catalysts, which restrict its rapid development. With chloroplatinic acid (H2PtCl6·6H2O) as the precursor, Polyvinylpyrrolidone (PVP) plays the role of surfactant, stabilizer, and reducing agent in the experiment. Glycine is the surface control agent and co-reducing agent. Pt high-index facets nanocatalyst was prepared with the one-pot hydrothermal method by adjusting the amount of PVP and glycine. X-Ray Diffraction (XRD), transmission electron microscope (TEM), and scanning electron microscope (SEM) were used to characterize the micro-structure of the nanocatalyst, and the influence of PVP and glycine on the synthesis of high-index facets catalyst was studied. The electrocatalytic performance of the catalyst was tested with an electrochemical workstation, and it was found that the performance of the prepared catalyst was better than that of the commercial catalyst. When the mass ratio of PVP and Pt was 50:1 and the molar ratio of glycine and Pt was 24:1, Pt nanocatalysts with {310}, {520} and {830} high exponential facets were prepared. The electrochemical test results showed that the peak current density of ethanol oxidation was 2.194 m2/g, and the steady-state current density was 0.241 mA/cm2, which was 5.7 times higher than that of commercial catalyst. The results of this paper show that due to the defects such as steps and kinks on the surface of the high-index facets, the active sites are increased, thus showing excellent electrocatalytic performance. This study provides a theoretical basis for the development and commercial application of high index facets nanocatalysts