RON and MET Co-overexpression Are Significant Pathological Characteristics of Poor Survival and Therapeutic Targets of Tyrosine Kinase Inhibitors in Triple-Negative Breast Cancer

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.

Evaluating the effects of programs for reducing achievement gaps: a case study in Taiwan

Yao-Ting Sung,Fen-Lan Tseng,Nien-Ping Kuo,Tien-Ying Chang,Jia-Min Chiou 서울대학교 교육연구소 2014 Asia Pacific Education Review Vol.15 No.1

Considering that achievement gaps have become a serious educational problem worldwide, the Ministry of Education in Taiwan has been addressing a series of policies to reduce achievement gaps, but the effect of these policies has not yet been carefully examined. Therefore, the present study investigated current educational policies, achievement gap phenomenon, and its changing trends in the use of national standardized tests in Taiwan and evaluated the degree to which these policies are reducing the achievement gaps among Taiwanese students. Junior high school graduates who took the high school entrance examination between 2004 and 2010 were recruited to examine the associations between their academic achievements and variables such as socioeconomic status (SES), ethnicity, and school district. Time series analyses were conducted to determine the longitudinal trends for the achievement gaps. The results revealed that achievement gaps are decreasing among different ethnicities, but they are increasing among different SESs and school districts. These findings demonstrate some positive effects of the educational policies introduced in Taiwan, but also the need for further modification and precise implementation of these policies. Suggestions for implementing educational programs and policies to reduce achievement gaps are also presented.

Effects of lycopene on number and function of human peripheral blood endothelial progenitor cells cultivated with high glucose

Yao-Chi Zeng,Gui-Ping Mu,Shu-Fen Huang,Xue-Hui Zeng,Hong Cheng,Zhong-Xin Li 한국영양학회 2014 Nutrition Research and Practice Vol.8 No.4

BACKGROUND/OBJECTIVES: The objectives of this study were to investigate the effects of lycopene on the migration, adhesion, tube formation capacity, and p38 mitogen-activated protein kinase (p38 MAPK) activity of endothelial progenitor cells (EPCs) cultivated with high glucose (HG) and as well as explore the mechanism behind the protective effects of lycopene on peripheral blood EPCs. MATERIALS/METHODS: Mononuclear cells were isolated from human peripheral blood by Ficoll density gradient centrifugation. EPCs were identified after induction of cellular differentiation. Third generation EPCs were incubated with HG (33 mmol/L) or 10, 30, and 50 μg/mL of lycopene plus HG. MTT assay and flow cytometry were performed to assess proliferation and apoptosis of EPCs. EPC migration was assessed by MTT assay with a modified boyden chamber. Adhesion assay was performed by replating EPCs on fibronectin-coated dishes, after which adherent cells were counted. In vitro vasculogenesis activity was assayed by Madrigal network formation assay. Western blotting was performed to analyze protein expression of both phosphorylated and non-phosphorylated p38 MAPK. RESULTS: The proliferation, migration, adhesion, and in vitro vasculogenesis capacity of EPCs treated with 10, 30, and 50 μg/mL of lycopene plus HG were all significantly higher comapred to the HG group (P < 0.05). Rates of apoptosis were also significantly lower than that of the HG group. Moreover, lycopene blocked phosphorylation of p38 MAPK in EPCs (P < 0.05). To confirm the causal relationship between MAPK inhibition and the protective effects of lycopene against HG-induced cellular injury, we treated cells with SB203580, a phosphorylation inhibitor. The inhibitor significantly inhibited HG-induced EPC injury. CONCLUSIONS: Lycopene promotes proliferation, migration, adhesion, and in vitro vasculogenesis capacity as well as reduces apoptosis of EPCs. Further, the underlying molecular mechanism of the protective effects of lycopene against HG-induced EPC injury may involve the p38 MAPK signal transduction pathway. Specifically, lycopene was shown to inhibit HG-induced EPC injury by inhibiting p38 MAPKs.

Validating a Repeat Visit Model to Historical Temple by Structural Equation Modeling

( Ya Fen Lee ),( Yun Yao Chi ) 한국문화관광학회 2009 문화관광연구 Vol.11 No.2

This paper is attempted to model the tourists` repeat visit inclination for historical temple according to itself critical properties and religious motivation. The numbers of 450 questionnaires were investigated in sites of Tainan Grand Matus (TGM) temple and Taintan temple in Tainan, Taiwan. Using the data, the hypothesized paths were test with a structural equation modeling (SEM) approach by the LISREL procedure. The construct and indicators of the SEM were measured by 18 items embodying religious motivation, satisfaction, and revisit inclination. Total satisfaction contained three indicators: (1) activity; (2) culture; and (3) landscape. The results show that the proposed SEMs of TGM temple and Taintan temple are accepted as the best models.

Enhanced Whole-cell Biodehydrogenation of 11β-hydroxyl Medroxyprogesterone in a Biphasic System Containing Ionic Liquid

Jun-Yao He,Pu Wang,Yu-Fen Yang,Song-Lin Xie 한국생물공학회 2011 Biotechnology and Bioprocess Engineering Vol.16 No.5

A hydrophilic ionic liquid, 1-butyl-3-methylimidazolium (L)-lactate ([bmim][lactate]), was successfully employed as a co-solvent to improve the biodehydrogenation of steroid 11β-hydroxyl medroxyprogesterone (HMP)to pregna-1,4-diene-6α-methyl-3,20-dione-11β,17α-dihydroxy (PDMDD) in an aqueous-organic biphasic system using Arthrobacter simplex UR106 cells. First, a suitable biphasic system was constituted, composed of toluene and Tris-HCl buffer (0.05 mol/L, pH 7.6) at a 0.4 (V_(org)/V_(aq))volumetric phase ratio. Investigation of biodehydrogenation with the addition of [bmim][lactate] to the aqueous phase was then performed. The results demonstrate that biodehydrogenation is more efficient in a biphasic system containing 2% [bmim][lactate] as a co-solvent compared to an aqueous-toluene two-phase system. Higher bioconversion (83.2% versus 56.4%) was observed after 16 h at a substrate concentration of 80 mg HMP in 8 mL of toluene.

A comprehensive analysis and comparison between vacuum and electric oven drying methods on Chinese saffron (Crocus sativus L.)

Chong Yao,Xiao-Dong Qian,Gui-Fen Zhou,Shu-Wei Zhang,Li-Qin Li,Qiaosheng Guo 한국식품과학회 2019 Food Science and Biotechnology Vol.28 No.2

The red stigmas of saffron are one of the mostexpensive spices in the world and serve as a traditionalChinese medicine. More saffron has been cultivated inChina, and different drying technologies have been studied. However, a comprehensive and comparative analysis ofdifferent drying approaches has not been well studied. Inthis study, we compared electric oven and vacuum ovendrying approaches on saffron. We found saffron was driedquicker under high vacuum drying mode with high temperatureand the quicker drying rate provided, the moreopen microstructural interstices on the saffron surface. Both methods were best fit to Midilli and Kucuk model. Besides, the coloring, aroma and bitterness strength afterdrying showed the similar results. In sum, our data suggestedthe optimal drying temperature was 100 C for20 min for two evaluated methods, however consideringthe machine cost, the electric oven drying would be the firstchoice.

Optimizing the binding activity of the AP2/ERF transcription factor with the GCC box element from Brassica napus by directed evolution

( Xiao Fen Jin ),( Bo Zhu ),( Ri He Peng ),( Hai Hua Jiang ),( Jian Min Chen ),( Jing Zhuang ),( Jian Zhang ),( Quan Hong Yao ),( Ai Sheng Xiong ) 생화학분자생물학회 (구 한국생화학분자생물학회) 2010 BMB Reports Vol.43 No.8

In this study, we cloned the ERF-B3 subfamily transcription factor gene BnaERF-B3-hy15 from Brassica napus L. Huyou15. This 600 bp gene encodes a 199 amino acid classic ethylene responsive factor (ERF), which shown no binding or very weak binding GCC box-binding activity by the yeast one-hybrid assay. We used gene shuffling and the yeast one-hybrid system to obtain three mutated sequences that can bind to the GCC box. Sequence analysis indicated that two residues, Gly156 in the AP2 domain and Phe62 at the N-terminal domain were mutated to arginine and serine, respectively. Changes of Gly156 to arginine and Phe62 to serine increased the GCC- binding activity of BnaERF-B3-hy15 and the alter of Gly156 to arginine changed the AP2-domain structure of BnaERF-B3- hy15. [BMB reports 2010; 43(8): 567-572]

Flower cultivation regimes aff ect apocarotenoid accumulation and gene expression during the development of saff ron stigma

Gui-Fen Zhou,Li-Qin Li,Jiemiao Lu,Jing Li,Chong Yao,Peng Sun,Kaohua Liu,Yan Dong,Luping Qin,Xiao-Dong Qian 한국원예학회 2020 Horticulture, Environment, and Biotechnology Vol.61 No.3

The quality of commercial saff ron largely depends on apocarotenoid levels. Whether they are aff ected by diff erent fl owercultivation regimes remains unknown. In present study, apocarotenoid levels and the expression profi les of 12 genes relatedto apocarotenoid biosynthesis between fi eld- and indoor-cultivated Crocus sativus L. were analyzed during stigma development. Under both cultivation regimes, apocarotenoid accumulation and gene expression showed similar profi les, fi rstsharply increasing and then gradually decreasing with stigma development, which suggested the coordinated function ofgene expression and apocarotenoid accumulation. However, the rate of increase/decrease varied widely between two blossomregimes at diff erent developmental stages. Based on correlation analysis, βCH1 and ZDS seemed to play a more crucial rolein apocarotenoid accumulation under both cultivation regimes. At anthesis, the total apocarotenoid level in saff ron cultivatedin the fi eld was higher than that cultivated indoors. This may be due to lower gene expression levels in the apocarotenoidpathway, especially βCH1 , ZDS , and CCD2 , and higher CCD4a and NCED expression in the competitive pathway in saff roncultivated indoors than that in the fi eld, which indicated higher conversion in apocarotenoid biosynthesis fl ux from crocinsand picrocrocin synthesis to β-ionone and the ABA biosynthetic branch in saff ron cultivated indoors. These results providevaluable information for modifying planting mode to enhance saff ron quality.

OsAREB1, an ABRE-binding protein responding to ABA and glucose, has multiple functions in Arabidopsis

( Xiao Fen Jin ),( Ai Sheng Xiong ),( Ri He Peng ),( Jin Ge Liu ),( Feng Gao ),( Jian Min Chen ),( Quan Hong Yao ) 생화학분자생물학회 2010 BMB Reports Vol.43 No.1

An Investigation on Leisure Needs for Bicycle Lane using Two-Dimensional Quality Model

Ya-Fen Lee,Yun-Yao Chi 세계문화관광학회 2010 Conference Proceedings Vol.11 No.0

This paper aimed at investigating the leisure motivation and bikers needs for bicycle lane. A total of 219 questionnaires from bikers are surveyed, in which 186 questionnaires are valid. The Kano‘s (1984) model is used to obtain key elements of biker‘ needs to bicycle lane. The analysis results show that the major motivation to ride a bicycle is “stimulus-avoidance” and the least motivation is “Social”. The most quality elements of leisure needs belong to one-dimensional elements. And flare equipment at night and lavatory installation have a higher priority of improvement to meet bikers needs.