Visible-Light-Promoted Deoxygenative Alkylation of Quinoxalin-2(1H)-ones with Activated Alcohols.

A one-pot strategy for deoxygenative alkylation of alcohols with quinoxalin-2(1H)-ones was developed by using xanthate salts as alcohol-activating groups for radical generation in the presence of tricyclohexylphosphine under visible-light-promoted conditions. The remarkable features of this reaction include a broad substrate scope, excellent functional group tolerance, mild conditions, and simple operation. Moreover, the synthetic utility of this reaction was validated by the success of two-step one-pot reactions, scale-up synthesis, and chemoselective radical monodeoxygenation of diols.

Phototriggered Fluoroalkylation/Cyclization of Unactivated 1-Acryloyl-2-cyanoindoles: Synthesis of RCOCF2-Substituted Pyrrolo[1,2-a]indolediones.

A photochemical approach toward RCOCF2-substituted pyrrolo[1,2-a]indolediones was developed by the radical cascade difluoroalkylation/cyclization reaction of unactivated 1-acryloyl-2-cyanoindoles with ethyl iododifluoroacetate or iododifluoramides under visible-light irradiation. This transition-metal- and photosensitizer-free protocol afforded diverse difluoroalkylated pyrrolo[1,2-a]indolediones in moderate to good yields under mild reaction conditions. Most appealingly, the reaction can proceed smoothly under sunlight irradiation, which opens a new avenue toward difluoroalkylated pyrrolo[1,2-a]indolediones.

Investigation of the Effect of Graphene Oxide on the Properties and Microstructure of Clay-Cement Composite Grouting Materials.

Reductions in bleeding rates and bulk shrinkage of grouting repair materials comprise the key to solving the leakage of earth-rock dams. In this paper, an anti-seepage grouting material for earth-rock dam was developed by introducing mineral admixtures and graphene oxide (GO) nano sheets into low-cost clay-cement grouting materials and by adding polycarboxylate superplasticizers (PCs) to improve slurry viscosity. The experimental results show that the shear stress and viscosity of the slurry increase with the increase in GO concentration, and the slurry has a certain thixotropy. GO can provide a platform to promote the formation of hydration products and fill the pores of clay particles due to its high specific surface area and low volume; in this paper, the microstructure of clay-cement-graphene oxide (CCGO) grouting materials were improved. Therefore, the bleeding rate, bulk shrinkage rate, setting time and unconfined compressive strength (UCS) of the sample were macroscopically improved. In particular, the bleeding rate and bulk shrinkage rate were shown to be 0% when the content of GO reached 1.08 g/kg. Thus, the grouting anti-seepage and reinforcement performance of CCGO grouting materials were improved.

Magnesium Isoglycyrrhizinate Induces an Inhibitory Effect on Progression and Epithelial-Mesenchymal Transition of Laryngeal Cancer via the NF-κB/Twist Signaling.

BACKGROUND: Magnesium isoglycyrrhizinate (MI) was extracted from roots of the plant Glycyrrhiza glabra, which displays multiple pharmacological activities such as anti-inflammation, anti-apoptosis, and anti-tumor. Here, we aimed to investigate the effect of MI on the progression and epithelial-mesenchymal transition (EMT) of laryngeal cancer. METHODS: Forty laryngeal cancer clinical samples were used. The role of MI in the proliferation of laryngeal cancer cells was assessed by MTT assay, Edu assay and colony formation assay. The function of MI in the migration and invasion of laryngeal cancer cells was tested by transwell assays. The effect of MI on apoptosis of laryngeal cancer cells was determined by cell apoptosis assay. The impact of MI on tumor growth in vivo was analyzed by tumorigenicity analysis using Balb/c nude mice. qPCR and Western blot analysis were performed to measure the expression levels of gene and protein, respectively. RESULTS: We identified that EMT-related transcription factor Twist was significantly elevated in the laryngeal cancer tissues. The expression of Twist was also enhanced in the human laryngeal carcinoma HEP-2 cells compared with that in the primary laryngeal epithelial cells. The high expression of Twist was remarkably correlated with poor overall survival of patients with laryngeal cancer. Meanwhile, our data revealed that MI reduced cell proliferation, migration and invasion and enhanced apoptosis of laryngeal cancer cells in vitro. Moreover, MI decreased transcriptional activation and the expression levels of NF-κB and Twist, and alleviated EMT in vitro and in vivo. MI remarkably inhibited tumor growth and EMT of laryngeal cancer cells in vivo. CONCLUSION: MI restrains the progression of laryngeal cancer and induces an inhibitory effect on EMT in laryngeal cancer by modulating the NF-κB/Twist signaling. Our finding provides new insights into the mechanism by which MI inhibits laryngeal carcinoma development, enriching the understanding of the anti-tumor function of MI.

Lenalidomide in treating patients with castration-resistant prostate cancer.

BACKGROUND: This analysis was conducted to evaluate the efficacy and safety of lenalidomide based regimen in treating patients with castration-resistant prostate cancer. MATERIALS AND METHODS: Clinical studies evaluating the efficacy and safety of lenalidomide based regimens on response and safety for patients with castration-resistant prostate cancer were identified using a predefined search strategy. A pooled response rate (rate of PSA level decline of ≥50%) to treatment was calculated. RESULTS: In lenalidomide based regimen, 3 clinical studies which including 98 patients with castration-resistant prostate cancer were considered eligible for inclusion. These lenalidomide based regimens included cisplatin, doxorubicin, or GM-CSF. Pooled analysis suggested that, in all patients, the pooled PSA level decline of ≥50% was 13.3% (13/98) in lenalidomide based regimens. Fatigue, nausea and vomitting were the main side effects. No grade III or IV renal or liver toxicity were observed. No treatment related death occurred in patients with lenalidomide based regimens. CONCLUSIONS: This evidence based analysis suggests that lenalidomide based regimens are associated with mild response rate and acceptable toxicities for treating patients with castration-resistant prostate cancer.

Association of NAT2, GSTM1, GSTT1, CYP2A6, and CYP2A13 gene polymorphisms with susceptibility and clinicopathologic characteristics of bladder cancer in Central China.

OBJECTIVE: To explore the association of polymorphisms in N-acetyltransferase 2 (NAT2), glutathione S-transferase (GST), cytochrome P450 (CYP) 2A6, and CYP 2A13 genes with susceptibility and clinicopathologic characteristics of bladder cancer in a Chinese population. METHODS: In a hospital-based case-control study of 208 cases and 212 controls matched on age and gender, genotypes were determined by PCR-based methods. Risks were evaluated by unconditional logistic regression analysis. RESULTS: It was found that significant associations of the NAT2 slow-acetylator genotype (odds ratio, OR: 2.42; 95% confidence interval, CI: 1.47-3.99), GSTM1 null genotype (OR: 1.64; 95% CI: 1.11-2.42) and GSTM1/GSTT1-double null genotype (OR: 1.72; 95% CI: 1.00-2.95) with increased risk of bladder cancer. Conversely, carriers with at least one CYP2A6*4 allele showed lower risk than the non-carriers (OR: 0.47; 95% CI: 0.28-0.79). The adjusted ORs (95% CI) for smokers with NAT2 slow-acetylator, GSTM1 null, GSTM1/GSTT1-double null genotype, and variant CYP2A6 genotypes were 2.99 (1.44-6.25), 1.98 (1.13-3.48), 2.66 (1.22-5.81) and 0.41 (0.20-0.86), respectively. Furthermore, NAT2 slow-acetylator, GSTM1 null, and GSTM1/GSTT1-double null genotypes were associated with higher tumor grade (P=0.001, 0.022, and 0.036, respectively), and only NAT2 slow-acetylator genotype was associated with higher tumor stage (P=0.007). CYP2A13 was not associated with risk or tumor characteristics. CONCLUSION: It is suggested that NAT2 slow-acetylator, GSTM1 null, GSTM1/GSTT1-double null, and variant CYP2A6 genotypes may play important roles in the development of bladder cancer in Henan area, China.

Efficient screening method of the thiopurine methyltransferase polymorphisms for patients considering taking thiopurine drugs in a Chinese Han population in Henan Province (central China).

BACKGROUND: Thiopurine S-methyltransferase (TPMT) is an enzyme that catalyzed the S-methylation of thiopurine drugs. TPMT activity exhibits an interindividual variability, mainly as a result of genetic polymorphism. Patients with intermediate or deficient TPMT activity are at risk for toxicity after receiving standard doses of thiopurine drugs. We determined a cut-off concentration of the TPMT activity assay less than which genotyping of the TPMT gene should be performed. In addition, the influence of hemodialysis on TPMT activity in uremic patients was examined. METHODS: In 248 healthy subjects and 30 uremic patients, PCR-based methods were used to analyze the most common functional mutations TPMT2, 3A, 3B and 3C. A HPLC assay was used to measure erythrocyte TPMT activity in the whole population. RESULTS: Seven TPMT3C heterozygotes were identified, while TPMT2, 3A and 3B alleles were not detected in 248 healthy subjects. The frequency of TPMT3C allele was 1.4% (7/496). The TPMT activity in healthy subjects was normally distributed, ranged from 6.09 to 28.65 nmol/h/ml pRBC with a mean of 16.03 +/- 4.16 nmol/h/ml pRBC. The cut-off for high TPMT activity and intermediate TPMT activity was 10.07 nmol/h/ml pRBC. There were 19 intermediate activity healthy subjects (7.7%) and 229 high activity healthy subjects (92.3%), and no TPMT deficiency subject was found. All of the 229 healthy subjects with high activity had no mutant alleles, while 7 of the 19 subjects with intermediate activity had a mutant allele. Phenotypes were in good agreement with genotypes for 95% of subjects. The uremic patients were all homozygous for the wild-type allele whose TPMT activity was activated significantly before hemodialysis compared with TPMT activity after hemodialysis. CONCLUSIONS: We defined the cut-off values for the TPMT phenotyping assay at 10.07 nmol/h/ml pRBC, less than which additional genotyping elucidates the individual risk for drug therapy. In uremic patients, TPMT activity is increased by some uremic factors, and dialysis shifted their TPMT activity close to that of a healthy control group.