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Chen, Jia,Zheng, Xin,Liu, Dong-Yang,Zhao, Qian,Wu, Yi-Wen,Tan, Fen-Lai,Wang, Yin-Xiang,Jiang, Ji,Hu, Pei Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.17
Background: The aim of this study was to evaluate how CYP2C19 affects icotinib and metabolite' exposure, and to determine whether the exposure and EGFR genotype influences survival time, tumor metastasis and adverse drug reactions. Materials and Methods: 274 NSCLC patients who accepted 125mg icotinib/t.i.d. were chosen from a phase III study. Blood samples were obtained in $672^{nd}$ ($4^{th}$ week) and $1,680^{th}$ hours ($10^{th}$ week), and plasma was used to quantify the concentration of icotinib and blood cells were sampled to check the genotypes. Clinical data were also collected at the same time, including EGFR genotypes. Plasma concentrations were assessed by HPLC-MS/MS and genotype by sequencing. All data were analyzed through SPSS 17.0 and SAS 9.2. Results: CYP 2C19 genotypes affected bio-transformation from icotinib to M24 and M26, especially in poor-metabolisers. Higher icotinib concentrations (>1000 ng/mL) not only increased patient PFS and OS but also reduced tumor metastasis. Patients with mutant EGFR experienced a higher median PFS and OS (234 and 627 days), especially those with the 19del genotype demonstrating higher PR ratio. Patients who suffered grade II skin toxicity had a higher icotinib exposure than those with grade I skin toxicity or no adverse effects. Liver toxic reactions might occur in patients with greater M20 and M23 plasma concentrations. Conclusions: CYP2C19 polymorphisms significantly affect icotinib, M24 and M26 exposure. Patients with mutant EGFR genotype and higher icotinib concentration might have increased PFS and OS and lower tumor metastasis. Liver ADR events and serious skin effects might be respectively induced by greater M20, M23 and icotinib concentrations.
Yu Wang,Pei-Sheng Lee,Yi-Fen Chen,Chi-Tang Ho,Min-Hsiung Pan 한국식품영양과학회 2016 Journal of medicinal food Vol.19 No.9
We reported previously that hydroxylated polymethoxyflavones (HPMFs) effectively suppressed obesity in high-fat-induced mouse. In this study, we further investigated the molecular mechanism of action of 5-hydroxy-3,6,7,8,3′,4′-hexamethoxyflavone (5-OH-HxMF), one of major HPMFs in orange peel. Treatment of 5-OH-HxMF effectively inhibited lipid accumulation by 55–60% in a dose-dependent manner. The 5-OH-HxMF attenuated adipogenesis through downregulating adipogenesis-related transcription factors such as peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding proteins (C/EBPs), as well as downstream target fatty acid synthase and acetyl-CoA carboxylase (ACC). 5-OH-HxMF activated adenosine monophosphate-activated protein kinase signaling and silent mating type information regulation 1 (SIRTUIN 1 or SIRT1) in 3T3-L1 adipocytes to decrease lipid accumulation. In addition, the inhibition rate of lipid accumulation was compared between 5-OH-HxMF and 3,5,6,7,8,3′,4′-heptamethoxyflavone (HpMF). 5-OH-HxMF inhibited lipid accumulation 15–20% more than HpMF did, indicating that hydroxyl group at position 5 can be a key factor in the suppression of adipogenesis.
Yi-Chuan Hsieh,Su-Fen Cheng,Pei-Kwei Tsay,Wen-Jen Su,Yen-Hua Cho,Chi-Wen Chen 한국간호과학회 2017 Asian Nursing Research Vol.11 No.4
Purpose: This study aimed to evaluate the effects of cognitive-behavioral program on pain and medical fear in hospitalized school-aged children receiving intravenous (IV) placement. Methods: This study used an quasi-experimental design. Thirty-five participants were assigned to the experimental group and 33 to the control group in the acute internal medicine ward of a children's hospital. The cognitive-behavioral program entailed having the patients read an educational photo book about IV placement before the procedure and having them watch their favorite music video during the procedure. The outcome measures were numeric rating scales for pain intensity and fear during the procedure. Results: After applying the cognitive-behavioral program, the mean scores on pain and fear decreased in the experimental group. However, the difference in pain intensity between these two groups was nonsignificant. The intensity of fear in the experimental group was significantly lower than that in the control group. Conclusion: In this study, the cognitive-behavioral program used with school-aged hospitalized children promoted less fear during IV placement. The results of this study can serve as a reference for empirical nursing care and as care guidance for clinical IV injections involving children.
CHIEN-CHIANG LEE,Meng-Fen Hsieh,Pei-Fen Chen,Shih-Jui Yang 한국증권학회 2013 Asia-Pacific Journal of Financial Studies Vol.42 No.5
This paper examines the impact of bank diversification on stability, using bank-level data for 22 Asian countries over the period from 1995 to 2009. We empirically investigate whether country characteristics, economic structure, regulatory and governance environments, and globalization have affected the degree of banking stability in Asia. This study takes on two measures for banking diversification - asset and income diversities - and adopts a broad set of variables as a proxy for bank stability. We apply dynamic panel data techniques and show different results from the U.S. and Europe. Our results first reveal that in Asia asset diversity is not sufficient enough to improve bank stability. However, bank stability can be enhanced through a strategy of income diversity. Second, a higher degree of globalization decreases bank stability through income diversity, but stability rises through asset diversity. Third, a country with a higher level of corporate governance reduces the agency problem, thus further increasing stability through diversity. Finally, a country with a higher level of economic development will support asset diversity so that banks can obtain higher profit accompanied by lower risk.
Tian-Hao Weng,Min-Ya Yao,Xiang-Ming Xu,Chen-Yu Hu,Shu-Hao Yao,Yi-Zhi Liu,Zhi-Gang Wu,Tao-Ming Tang,Pei-Fen Fu,Ming-Hai Wang,Hang-Ping Yao 대한암학회 2020 Cancer Research and Treatment Vol.52 No.3
Purpose Triple-negative breast cancer (TNBC) is highly malignant and has poor prognosis and a high mortality rate. The lack of effective therapy has spurred our investigation of new targets for treating this malignant cancer. Here, we identified RON (macrophage-stimulating 1 receptor) and MET (MET proto-oncogene, receptor tyrosine kinase) as a prognostic biomarker and therapeutic targets for potential TNBC treatment. Materials and Methods We analyzed RON and MET expression in 187 primary TNBC clinical samples with immunohistochemistry. We validated the targeted therapeutic effects of RON and MET in TNBC using three tyrosine kinase inhibitors (TKIs): BMS-777607, INCB28060, and tivantinib. The preclinical therapeutic efficacy of the TKIs was mainly estimated using a TNBC xenograft model. Results Patients with TNBC had widespread, abnormal expression of RON and MET. There was RON overexpression, MET overexpression, and RON and MET co-overexpression in 63 (33.7%), 63 (33.7%), and 43 cases (23.0%), respectively, which had poor prognosis and short survival. In vivo, the TKI targeting RON ant MET inhibited the activation of the downstream signaling molecules, inhibited TNBC cell migration and proliferation, and increased TNBC cell apoptosis; in the xenograft model, they significantly inhibited tumor growth and shrank tumor volumes. The TKI targeting RON and Met, such as BMS-777607 and tivantinib, yielded stronger anti-tumor effects than INCB28060. Conclusion RON and MET co-overexpression can be significant pathological characteristics in TNBC for poor prognosis. TKIs targeting RON and MET have stronger drug development potential for treating TNBC.