The tyrosine kinase inhibitor nintedanib activates SHP-1 and induces apoptosis in triple-negative breast cancer cells

Chun-Yu Liu,Tzu-Ting Huang,Pei-Yi Chu,Chun-Teng Huang,Chia-Han Lee,Wan-Lun Wang,Ka-Yi Lau,Wen-Chun Tsai,Tzu-I Chao,Jung-Chen Su,Ming-Huang Chen,Chung-Wai Shiau,Ling-Ming Tseng,Kuen-Feng Chen 생화학분자생물학회 2017 Experimental and molecular medicine Vol.49 No.-

Triple-negative breast cancer (TNBC) remains difficult to treat and urgently needs new therapeutic options. Nintedanib, a multikinase inhibitor, has exhibited efficacy in early clinical trials for HER2-negative breast cancer. In this study, we examined a new molecular mechanism of nintedanib in TNBC. The results demonstrated that nintedanib enhanced TNBC cell apoptosis, which was accompanied by a reduction of p-STAT3 and its downstream proteins. STAT3 overexpression suppressed nintedanib-mediated apoptosis and further increased the activity of purified SHP-1 protein. Moreover, treatment with either a specific inhibitor of SHP-1 or SHP-1-targeted siRNA reduced the apoptotic effects of nintedanib, which validates the role of SHP-1 in nintedanib-mediated apoptosis. Furthermore, nintedanib-induced apoptosis was attenuated in TNBC cells expressing SHP-1 mutants with constantly open conformations, suggesting that the autoinhibitory mechanism of SHP-1 attenuated the effects of nintedanib. Importantly, nintedanib significantly inhibited tumor growth via the SHP-1/p-STAT3 pathway. Clinically, SHP-1 levels were downregulated, whereas p-STAT3 was upregulated in tumor tissues, and SHP-1 transcripts were associated with improved disease-free survival in TNBC patients. Our findings revealed that nintedanib induces TNBC apoptosis by acting as a SHP-1 agonist, suggesting that targeting STAT3 by enhancing SHP-1 expression could be a viable therapeutic strategy against TNBC.

A Saliency Detection Method Based on Global Contrast

Chun-yan Yu,Wei-shi Zhang,Chun-li Wang 보안공학연구지원센터 2015 International Journal of Signal Processing, Image Vol.8 No.7

To highlight the saliency object clearly from the foreground, we propose a saliency detection method based on global contrast with cluster. Due to the fact that background pixels usually have similar patches, we use cluster analysis to merge the background regions. By using mean shift filter, the background pixels with similar color level are clustered and the saliency calculation can be decreased a lot. In the method, we use the contrast of color feature with all the other pixels to compute the saliency map. A weight coefficient is utilized to improve the detection accuracy in global contrast differences evaluation. The results of extensive experiments on public dataset show that our method perform well and can highlight the salient object clearly against the other five state-of-the-art methods. Besides, we demonstrate that the applications in image segmentation and fusion with our saliency map can get satisfactory results.

Evaluation of Ride Comfort for Active Suspension System Based on Selftuning Fuzzy Sliding Mode Control

Chun-Yu Hsiao,Yu-Hsien Wang 제어·로봇·시스템학회 2022 International Journal of Control, Automation, and Vol.20 No.4

This paper describes the application of a self-tuning fuzzy sliding mode controller (STFSMC) to design the control signal of an electro-hydraulic actuator under standard road excitation based on ISO 8608. The proposed damper was designed to achieve effective vibration isolation with an actuator force. The proposed damper was incorporated into a quarter-car system through experiments for the subsequent dynamic analysis of the suspension system. A single-input single-output (SISO) fuzzy inference was strategically used to regulate the slope of a sliding surface. In addition, the fuzzy control methodology was applied to achieve self-tuning online output of the scale factor of the fuzzy sliding mode controller. The comfortable riding time and ride comfort level were also evaluated based on ISO 2631-1. Experimental results revealed that the proposed controller demonstrated evident improvements in vehicle vibration suppression and the ride quality in comparison with passive and fuzzy logic controller control systems.

Post-Acute Care as a Key Component in a Healthcare System for Older Adults

Yu-Chun Wang,Ming-Yueh Chou,Chih-Kuang Liang,Li-Ning Peng,Liang-Kung Chen,Ching-Hui Loh 대한노인병학회 2019 Annals of geriatric medicine and research Vol.23 No.2

Older adults often experience functional decline following acute medical care. This func-tional decline may lead to permanent disability, which will increase the burden on the medical and long-term care systems, families, and society as a whole. Post-acute care aims to promote the functional recovery of older adults, prevent unnecessary hospital readmission, and avoid premature admission to a long-term care facility. Research has shown that post-acute care is a cost-effective service model, with both the hospital-at-home and community hospital post-acute care models being highly effective. This paper describes the post-acute care models of the United States and the United Kingdom and uses the example of Taiwan’s highly effective post-acute care system to explain the bene-fits and importance of post-acute care. In the face of rapid demographic aging and smaller household size, a post-acute care system can lower medical costs and improve the health of older adults after hospitalization.

Korean-Chinese Person Name Translation for Cross Language Information Retrieval

( Yu Chun Wang ),( Yi Hsun Lee ),( Chu Cheng Lin ) 한국언어정보학회 2007 학술대회 논문집 Vol.2007 No.-

Named entity translation plays an important role in many applications, such as information retrieval and machine translation. In this paper, we focus on translating person names, the most common type of name entity in Korean-Chinese cross language information retrieval (KCIR). Unlike other languages, Chinese uses characters (ideographs), which makes person name translation difficult because one syllable may map to several Chinese characters. We propose an effective hybrid person name translation method to improve the performance of KCIR. First, we use Wikipedia as a translation tool based on the inter-language links between the Korean edition and the Chinese or English editions. Second, we adopt the Naver people search engine to find the query name``s Chinese or English translation. Third, we extract Korean-English transliteration pairs from Google snippets, and then search for the English-Chinese transliteration in the database of Taiwan``s Central News Agency or in Google. The performance of KCIR using our method is over five times better than that of a dictionary-based system. The mean average precision is 0.3490 and the average recall is 0.7534. The method can deal with Chinese, Japanese, Korean, as well as non-CJK person name translation from Korean to Chinese. Hence, it substantially improves the performance of KCIR.

Effects of Oxygen Content on the Simultaneous Microbial Removal of SO2 and NOx in Biotrickling Towers

Xing Chun Wang,Xiao Yi Bi,Pei Shi Sun,Jin Quan Chen,Ping Zou,Xiao Ming Ma,Jing Zhang,Hai Yu Wang,Xiao Yi Xu 한국생물공학회 2015 Biotechnology and Bioprocess Engineering Vol.20 No.5

This study uses microbial methods to research the influence of oxygen (O2) content on the removal efficiency of sulfur dioxide (SO2) and nitrogen oxides (NOx) in a tandem twin-towers desulfurization and denitrification process system. Oxygen can play a significant role in biotrickling towers. Other important factors had already been optimized prior to the study, including inlet concentration, gas flow rate, and temperature. SO2 and NOx were prepared by a chemical method. A gas flow meter was used to regulate nitrogen (N2) that had been stored in steel cylinders. In this way, the O2 content was adjusted in the biotrickling towers by controlling the N2 flow rate. Five gradients of O2 content were selected for investigation, namely 4, 8, 12, 16, and 20%. Results indicated that the SO2 removal efficiency from mixed gas (SO2 and NOx) can reach 100%, from all of the five O2 gradients, in biotrickling towers. In a tandem twin-towers desulfurization and denitrification process system, the NOx removal efficiency and the inlet concentration of nitrogen dioxide (NO2) gradually increased as the O2 content increased. Specifically, the average removal efficiency of NOx increased from 49.28 to 80.85% as the O2 content changed from 4 to 20%. The oxygen levels influenced the removal of NOx but the SO2 removal efficiency in mixed gas was always stable.

First-Principles Study of the Influence of Zirconium on the Diffusion of Uranium Defects in Uranium Dioxide

Huan Wang,Yu Zou,Zhong Zhang,Kai-Yuan Wang,Huan An,Chang-Yong Zhan,Jun Wang,Jian-Chun Wu 한국물리학회 2019 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.74 No.8

The migration properties of uranium vacancies and interstitials in zirconium-doped uranium dioxide are studied by using density functional theory (DFT) and the climbing-image nudge elastic band (CI-NEB) method. The strong correlations among uranium $5f$ electrons were described by using a spherically averaged Hubbard parameter. In the model, the zirconium atoms are introduced by replacing the uranium atoms at the nearest and the next nearest neighbor sites along the diffusion path of uranium defects. The doping with zirconium obviously reduces the migration barriers for defects in uranium dioxide. The effect of doping with zirconium on the diffusion of uranium defects decreases with increasing distance between the zirconium dopant and the uranium defects. Further, we investigated the lattice distortion and the electron transfer associated with the migration of uranium defects, and we analyzed the physical origin of the reduction in the migration barriers caused by zirconium doping.

Screening for Metastatic Osteosarcoma Biomarkers with a DNA Microarray

Diao, Chun-Yu,Guo, Hong-Bing,Ouyang, Yu-Rong,Zhang, Han-Cong,Liu, Li-Hong,Bu, Jie,Wang, Zhi-Hua,Xiao, Tao Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.4

Objective: The aim of this study was to screen for possible biomarkers of metastatic osteosarcoma (OS) using a DNA microarray. Methods: We downloaded the gene expression profile GSE49003 from Gene Expression Omnibus database, which included 6 gene chips from metastatic and 6 from non-metastatic OS patients. The R package was used to screen and identify differentially expressed genes (DEGs) between metastatic and non-metastatic OS patients. Then we compared the expression of DEGs in the two groups and sub-grouped into up-regulated and down-regulated, followed by functional enrichment analysis using the DAVID system. Subsequently, we constructed an miRNA-DEG regulatory network with the help of WebGestalt software. Results: A total of 323 DEGs, including 134 up-regulated and 189 down-regulated, were screened out. The up-regulated DEGs were enriched in 14 subcategories and most significantly in cytoskeleton organization, while the down-regulated DEGs were prevalent in 13 subcategories, especially wound healing. In addition, we identified two important miRNAs (miR-202 and miR-9) pivotal for OS metastasis, and their relevant genes, CALD1 and STX1A. Conclusions: MiR-202 and miR-9 are potential key factors affecting the metastasis of OS and CALD1 and STX1A may be possible targets beneficial for the treatment of metastatic OS. However, further experimental studies are needed to confirm our results.

Uterine Intravenous Leiomyomatosis with Intracardiac Extension and Pulmonary Benign Metastases on FDG PET/CT: A Case Report

Hui-Chun Wang,Yu-Bin Wang,Xiao-Hong Chen,Lan-Lan Cui 대한영상의학회 2016 Korean Journal of Radiology Vol.17 No.2

A 48-year-old woman presented with a 50-day history of irregular vaginal bleeding and lower abdominal pain. Ultrasound indicated an extremely large occupying lesion in the pelvic cavity that was highly suggestive of malignancy. Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) was performed to further assess the nature of pelvic abnormality. PET/CT images demonstrated a diffusely lobulated mass ranging from cervix up to the inferior pole of kidneys with mild FDG uptake. Simultaneously, multiple nodules in bilateral lungs and a hypodense lesion in the right ventricle were shown without FDG-avidity. Based on the imaging results, the presumptive diagnosis was uterine intravenous leiomyomatosis with intracardiac extension and pulmonary benign metastases, which was subsequently confirmed by MRI and the lesion biopsy.

Tumor Necrosis Factor-α Gene Polymorphisms and Risk of Oral Cancer: Evidence from a Meta-analysis

Chen, Fang-Chun,Zhang, Fan,Zhang, Zhi-Jiao,Meng, Si-Ying,Wang, Yang,Xiang, Xue-Rong,Wang, Chun,Tang, Yu-Ying Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.12

Numerous studies have been conducted regarding association between TNF-${\alpha}$ and oral cancer risk, but the results remain controversial. The present meta-analysis is performed to acquire a more precise estimation of relationships. Databases of Pubmed, the Cochrane library and the China National Knowledge Internet (CNKI) were retrieved until August 10, 2013. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated with fixed- or random-effect models. The heterogeneity assumption was assessed by I-squared test. Among the eight included case-control studies, all were focused on TNF-${\alpha}$-308G>A and four also concerned the TNF-${\alpha}$-238G>A polymorphism. It was found that oral cancer risk were significant decreased with the TNF-${\alpha}$-308G>A polymorphism in the additive genetic model (GG vs. AA, OR=0.19, 95% CI: [0.04, 1.00], P=0.05, I2=68.9%) and the dominant genetic model (GG+GA vs. AA, OR=0.22, 95% CI: [0.06, 0.82], P=0.03, I2=52.4%); however, no significant association was observed in allele contrast (G vs. A, OR=0.70, 95% CI: [0.23, 2.16], P=0.54, I2=95.9%) and recessive genetic models (GG vs. GA+AA, OR=0.72, 95% CI: [0.33, 1.57], P=0.41, I2=93.1%). For the TNF-${\alpha}$-238G>A polymorphism, significant associations with oral cancer risk were found in the allele contrast (G vs. A, OR=2.75, 95% CI: [1.25, 6.04], P=0.01, I2=0.0%) and recessive genetic models (GG vs. GA+AA, OR=2.23, 95%CI: [1.18, 4.23], P=0.01, I2=0.0%). Conclusively, this meta-analysis indicates that TNF-${\alpha}$ polymorphisms may contribute to the risk of oral cancer. Allele G and the GG+GA genotype of TNF-${\alpha}$-308G>A may decrease the risk of oral cancer, while allele G and the GG genotype of TNF-${\alpha}$-238G>A may cause an increase.