Direct oxidative C-H alkynylation of N-carbamoyl tetrahydroisoquinolines and dihydroisoquinolines.

An efficient oxidative C-H alkynylation of N-carbamoyl tetrahydroisoquinolines mediated by a TEMPO oxoammonium salt has been established. A variety of electronically varied N-carbamoyl tetrahydroisoquinolines reacted with a range of alkynyl potassium trifluoroborates smoothly under mild metal-free conditions. Dihydroisoquinolines were also suitable components for the reaction. The synthetic applicability of the method for facile access to structurally diverse bioactive molecules was further demonstrated.

Endoscopic submucosal dissection vs endoscopic mucosal resection for colorectal tumors: a meta-analysis.

AIM: To compare the efficacy and safety of endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR) for the treatment of colorectal tumors. METHODS: Databases, such as PubMed, EMBASE, Cochrane Library and Science Citation Index updated to 2013 were searched to include eligible articles. In the meta-analysis, the main outcome measurements were the en bloc resection rate, the histological resection rate and the local recurrence rate. Meanwhile, we also compared the operation time and the incidence of procedure-related complications. RESULTS: Six trials were identified and a total of 1642 lesions were included. The en bloc resection rate was higher and the local recurrence rate was lower in the ESD group compared with the EMR group (OR = 7.94; 95%CI: 3.96-15.91; OR = 0.09; 95%CI: 0.04-0.19). There was no significant difference in histological resection rate(OR = 1.65; 95%CI: 0.29-9.30) and procedure-related complication rate between the two groups (OR = 1.59; 95%CI: 0.92-2.73). The meta-analysis also showed that ESD was more time consuming than EMR. CONCLUSION: Compared with EMR, ESD results in higher en bloc resection rate and lower local recurrence rate for the treatment of colorectal tumors, without increasing the procedure-related complications.

Endoscopic submucosal dissection versus endoscopic mucosal resection for the treatment of early esophageal carcinoma: a meta-analysis.

Endoscopic submucosal dissection (ESD) was originally developed for en bloc resection of large, flat gastrointestinal lesions. Compared with endoscopic mucosal resection (EMR), ESD is considered to be more time consuming and have more complications for treatment of early esophageal carcinoma, such as bleeding, stenosis and perforation. The objective of this study was to compare the efficacy and safety of ESD and EMR for such lesions. We searched databases, such as PubMed, EMBASE, Cochrane Library and Science Citation Index updated to 2013 for related trials. In the meta-analysis, the main outcome measurements were the en bloc resection rate, the histologically resection rate and the local recurrence rate. We also compared the operation time and the incidences of procedure-related complications. Five trials were identified, and a total of 710 patients and 795 lesions were included. The en bloc and histologically complete resection rates were higher in the ESD group compared with the EMR group (odds ratio (OR) 27.3; 95% CI, 11.5-64.8; OR 18.4; 95% CI, 8.82-38.59). The local recurrence rate was lower in the ESD group (OR 0.13, 95 % CI 0.04-0.43). The meta-analysis also showed ESD was more time consuming, but did not increase the complication rate (P=0.76). The results implied that compared with EMR, ESD showed better en bloc and histologically resection rates, and lower local recurrence, without increasing the incidence of procedure-related complications in the treatment of early esophageal carcinoma.

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone induces retinoic acid receptor ß hypermethylation through DNA methyltransferase 1 accumulation in esophageal squamous epithelial cells.

Overexpression of DNA methyltransferase 1 (DNMT1) has been detected in many cancers. Tobacco exposure is known to induce genetic and epigenetic changes in the pathogenesis of malignancy. 4-(Methylnitrosamino)- 1-(3-pyridyl)-1-butanone (NNK) is an important carcinogen present in tobacco smoke; however the detailed molecular mechanism of how NNK induces esophageal carcinogenesis is still unclear. We found that DNMT1 was overexpressed in ESCC tissues compared with paired non-cancerous tissues, the overexpression being correlated with smoking status and low expression of RARß. The latter could be upregulated by NNK treatment in Het-1A cells, and the increased DNMT1 expression level reflected promoter hypermethylation and downregulation of retinoic acid receptor ß (RARß). RNA interference mediated knockdown of DNMT1 resulted in promoter demethylation and upregulation of RARß in KYSE30 and TE-1 cells. 3-(4,5-Dimethyl-thiazol-2yl)- 2,5-diphenyltetrazolium bromide (MTT) and flow cytometric analysis demonstrated that NNK treatment in Het- 1A cells could enhance cell proliferation and inhibit cell apoptosis in a dose-dependent manner. In conclusion, DNMT1 overexpression is correlated with smoking status and low expression of RARß in esophageal SCC patients. NNK could induce RARß promoter hypermethylation through upregulation of DNMT1 in esophageal squamous epithelial cells, finally leading to enhancement of cell proliferation and inhibition of apoptosis.

Effects of DNA methyltransferase 1 inhibition on esophageal squamous cell carcinoma.

To explore the role of DNA methyltransferase 1 (DNMT1) in esophageal squamous cell carcinoma (ESCC) and the potential of DNMT1-targeted small interfering RNA as ESCC therapy, we examined expression changes of DNMT1 in ESCC and investigated the effect of DNMT1 knockdown by RNA interference in a human ESCC cell line, KYSE30. DNMT1 messenger RNA was over-expressed in seven out of 12 ESCC samples, and the percentage of cells expressing DNMT1 was significantly higher in ESCC tissues compared with paired non-cancerous tissues. DNMT1 protein levels correlated with lymph node metastasis, but exhibited no correlation with sex, age, tumor site, or tumor differentiation. Knockdown of DNMT1 in KYSE30 cells using RNA interference resulted in a reduction of promoter methylation and re-expression of methyl-guanine methyl-transferase and retinoic acid receptors beta, inhibition of cell proliferation/viability and induction of cell apoptosis. These results indicate that DNMT1 over-expression is involved in ESCC and correlated with lymph node metastasis. Knockdown of DNMT1 led to promoter demethylation and re-expression of several tumor suppressor genes thereby inhibiting cell proliferation/viability and inducing cell apoptosis.

Perchloric acid catalyzed homogeneous and heterogeneous addition of beta-dicarbonyl compounds to alcohols and alkenes and investigation of the mechanism.

The direct addition of various beta-dicarbonyl compounds to a series of secondary alcohols and alkenes has been achieved using 1 mol % perchloric acid (HClO(4)) as the catalyst. The HClO(4)-catalyzed reactions could be conveniently conducted in commercial solvent and gave moderate to excellent yields. Moreover, the silica gel-supported HClO(4) could also catalyze the heterogeneous addition for a series of substrates with similar or even higher yields in comparison with the homogeneous ones. The supported catalyst could be readily recovered and reused for four runs. Furthermore, the mechanism of the HClO(4)-catalyzed addition of the beta-diketone to alcohol was investigated, and an S(N)1 mechanism was proved unambiguously for the first time through a series of experiments. The discrimination of catalytic abilities among different Brønsted acids was also rationalized by DFT calculations.

Upper gastrointestinal hemorrhage caused by superwarfarin poisoning.

Superwarfarins are a class of rodenticides. Gastrointestinal hemorrhage is a fatal complication of superwarfarin poisoning, requiring immediate treatment. Here, we report a 55-year-old woman with tardive upper gastrointestinal hemorrhage caused by superwarfarin poisoning after endoscopic cold mucosal biopsy.