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He, Lin,Bi, Juan-Juan,Guo, Qian,Yu, Yin,Ye, Xiu-Feng Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.4
To aim of this was to observe emodin-mediated cytotoxicity and its influence on Rad51 and ERCC1 expressionin non-small cell lung cancer (NSCLC). NSCLC cells were cultured in vitro with emodin at various concentrations (0, 25, 50, 75 and $100\;{\mu}mol/L$) for 48h and the proliferation inhibition rate was determined by the MTT method. Then, NSCLC were treated with emodin (SK-MES-1 $40\;{\mu}mol/L$, A549 $70\;{\mu}mol/L$) or $20\;{\mu}mol/L$ U0126 (an ERK inhibitor) for 48 h, or with various concentrations of emodin for 48 h and the protein and mRNA expressions of ERCC1 and Rad51 were determined by RT-PCR and Western blot assay, respectively. Emodin exerted a suppressive effect on the proliferation of NSCLC in a concentration dependent manner. Protein and mRNA expression of ERCC1 and Rad51 was also significantly decreased with the dose. Vacuolar degeneration was observed in A549 and SK-MES-1 cell lines after emodin treatment by transmission electron microscopy. Emodin may thus inhibited cell proliferation in NSCLC cells by downregulation ERCC1 and Rad51.
Identification of Halohydrin Dehalogenase Mutants that Resist COBE Inhibition
Shao-Yun Chen,Xiu-Juan He,Jian-ping Wu,Gang Xu,Li-Rong Yang 한국생물공학회 2014 Biotechnology and Bioprocess Engineering Vol.19 No.1
The biocatalytic cascade conversion of ethyl4-chloroacetoacetate (COBE) to ethyl (R)-4-cyano-3-hydroxybutyrate ((R)-HN) for the preparation of atorvastatinrepresents significant economic and environmental benefits,and is catalyzed by alcohol dehydrogenase and halohydrindehalogenase (HHDH). However, as the activity of HHDHis inhibited by COBE, the cascade reaction is an inefficientone-pot reaction. In this study, substrate inhibition kineticsanalysis was performed and the inhibition by COBE wasfound to be competitive reversible inhibition. Molecularsimulation analysis was used to determine the inhibitionmechanism by COBE. The results showed that COBEbound to the active center of HHDH via the formation ofhydrogen bonds with the OH groups of S132 and Y145. Site saturation mutagenesis of residues around the activesite and at the entrance of the access tunnel was performed,and two target mutant residues were identified, F136 andW249. Small focused mutagenesis on these two residueswas performed and the F136V/W249F mutant wassuccessfully found to relieve the activity inhibition ofHHDH by COBE. The half inhibiting concentration ofmutant F136V/W249F was found to be 20-fold higher thanwild-type HHDH. The efficiency of the multi-enzymaticone-pot system for the synthesis of (R)-HN from COBEusing mutant F136V/W249F was improved significantly.
Jiang, Chang,Liao, Fang-Xin,Rong, Yu-Ming,Yang, Qiong,Yin, Chen-Xi,He, Wen-Zhuo,Cai, Xiu-Yu,Guo, Gui-Fang,Qiu, Hui-Juan,Chen, Xu-Xian,Zhang, Bei,Xia, Liang-Ping Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.13
Objective: To compare the efficacy of taxane-based regimens in the first line setting retrospectively in Chinese patients with recurrent and/or metastatic esophageal cancer. Methods: We analyzed 102 recurrent and/or metastatic esophageal cancer patients who received taxanes-based regimens in a first-line setting from January 2009 to December 2013. Sixteen (15.7%) patients were administered Nab-PTX based chemotherapy and 86 patients (84.3%) received paclitaxel (PTX) or docetaxel (DTX) based chemotherapy. Patients in the PTX/DTX group could be further divided into TP (71 patients) and TPF (15 patients) groups. Results: The objective response rate (ORR) of all patients was 20.6%, and the disease control rate (DCR) was 67.6%. The median overall survival (OS) was 10.5 months (95% CI 10.1-16.4) and the median progression-free survival (PFS) was 6.04 months (95% CI 5.09-7.91). The DCR was higher in the TPF group than the TP group (93.3% vs. 59.1%; p = 0.015 ). There were no significant differences in ORR, OS, and PFS among Nab-PTX, TPF and TP groups. Conclusions: The three regimens of Nab-PTX based, TP and TPF proved active in a first line setting of Chinese patients with recurrent and/or metastatic esophageal cancer, and should thus be regarded as alternative treatments.