Quantitative phosphoproteomic analysis identifies the potential therapeutic target EphA2 for overcoming sorafenib resistance in hepatocellular carcinoma cells

Chih-Ta Chen,Li-Zhu Liao,Ching-Hui Lu,Yung-Hsuan Huang,Yu-Kie Lin,Jung-Hsin Lin,Lu-Ping Chow 생화학분자생물학회 2020 Experimental and molecular medicine Vol.52 No.-

Limited therapeutic options are available for advanced-stage hepatocellular carcinoma owing to its poor diagnosis. Drug resistance to sorafenib, the only available targeted agent, is commonly reported. The comprehensive elucidation of the mechanisms underlying sorafenib resistance may thus aid in the development of more efficacious therapeutic agents. To clarify the signaling changes contributing to resistance, we applied quantitative phosphoproteomics to analyze the differential phosphorylation changes between parental and sorafenib-resistant HuH-7 cells. Consequently, an average of ~1500 differential phosphoproteins were identified and quantified, among which 533 were significantly upregulated in resistant cells. Further bioinformatic integration via functional categorization annotation, pathway enrichment and interaction linkage analysis led to the discovery of alterations in pathways associated with cell adhesion and motility, cell survival and cell growth and the identification of a novel target, EphA2, in resistant HuH-7R cells. In vitro functional analysis indicated that the suppression of EphA2 function impairs cell proliferation and motility and, most importantly, overcomes sorafenib resistance. The attenuation of sorafenib resistance may be achieved prior to its development through the modulation of EphA2 and the subsequent inhibition of Akt activity. Binding analyses and in silico modeling revealed a ligand mimic lead compound, prazosin, that could abate the ligand-independent oncogenic activity of EphA2. Finally, data obtained from in vivo animal models verified that the simultaneous inhibition of EphA2 with sorafenib treatment can effectively overcome sorafenib resistance and extend the projected survival of resistant tumor-bearing mice. Thus our findings regarding the targeting of EphA2 may provide an effective approach for overcoming sorafenib resistance and may contribute to the management of advanced hepatocellular carcinoma.

Laser Interference Lithography and Nanoimprint Techniques for Lower Reflection Transparent Conducting Oxide Hybrid Films

Ta-Hsin Chou,Kuei-Yuan Cheng,Chih-Chieh Su,Tien-Li Chang,Chih-Wei Hsieh,Jen-Hui Tsai 한국정밀공학회 2010 International Journal of Precision Engineering and Vol.11 No.4

The transparent conducting oxide (TCO) film is a significant component in flat panel display industry, applied for flexible display, e-paper, and touch panel. The TCO materials have high refractive index, so the phenomenon of high reflectance is the major issue and needs solved in present and future market. In this study, the structure and process of new lower reflection TCO hybrid film is introduced. The laser interference lithography and UV nanoimprint are combined for fabrication of sub-wavelength structures on PET film, then the tin-doped indium oxide (ITO) deposited on structures. Finally, the best result of this hybrid film is reflectance reduced to 3.3% at wavelength 550nm, just 13% of the original film, and the resistance of ITO layer is 1.05x10-3 Ω-cm. This result is useful for the TCO film applied in low reflection demand products in the future.

Sealed-bid Auction Schemes using Threshold Cryptosystem

Wei-Chen Wu,Horng-Twu Liaw,Chih-Ta Yen 보안공학연구지원센터(IJUNESST) 2013 International Journal of u- and e- Service, Scienc Vol.6 No.1

Taiwanese Female Vegetarians Have Lower Lipoprotein-Associated Phospholipase A2 Compared with Omnivores

Chih-Wei Chen,Chin-Lon Lin,Chih-Ta Lin,Ying-Lung Lin,Tin-Kwang Lin 연세대학교의과대학 2011 Yonsei medical journal Vol.52 No.1

Purpose: Many studies supported that vegetarians have a lower risk of cardiac diseases and mortality, partly due to better blood pressure and serum cholesterol profiles. However, the inflammatory markers, especially lipoprotein-associated phospholipase A2 (Lp-PLA2), have not been well-studied. This study aimed to compare inflammatory markers and conventional risk factors between vegetarians and omnivores. Materials and Methods: One hundred and seventy-three vegetarians and 190 omnivores were studied. Fasting blood samples were obtained to compare levels of glucose, total cholesterol, triacylglycerol, high density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol, homocysteine, Lp-PLA2 activity, and high-sensitivity C-reactive protein (hs-CRP). Results: Vegetarians had higher serum levels of the following markers: hs-CRP (1.8 ± 3.4 vs. 1.2 1.8 mg/L, respectively; p = 0.05), homocysteine (9.39 ± 3.22 vs. 7.62 ± 2.41 μmol/L, respectively; p < 0.01), and triacylglycerol (96.91 ± 59.56 vs. 84.66 ± 43.24 mg/dL, respectively; p < 0.05). Vegetarians also had lower levels of Lp-PLA2 (18.32 ± 7.19 10-3 μmol/min/mL vs. 20.22 8.13 10-3 μmol/min/mL; p < 0.05), total cholesterol (180.62 ± 36.55 mg/dL vs. 192.73 ± 36.57 mg/dL; p < 0.01), LDL cholesterol (118.15 ± 32.8 vs. 126.41 ± 34.28 mg/dL; p < 0.05), and HDL cholesterol (55.59 ± 13.30 vs. 62.09 ± 14.52 mg/dL, p < 0.01). Multivariate analyses demonstrated that a vegetarian diet increases the chances for high serum hs-CRP and low Lp-PLA2 activity. Conclusion: In addition to lower total cholesterol,LDL-cholesterol, and HDL-cholesterol, Taiwanese female vegetarians have lower serum Lp-PLA2 activity but higher levels of hs-CRP, homocysteine, and triacylglyerol. It might be due to geographic differences of vegetarian diets, and further studies are needed.

Distinct Inflammation Biomarkers in Healthy Individuals and Patients with Schizophrenia: A Reliability Testing of Multiplex Cytokine Immunoassay by Bland-Altman Analysis

Ta-Chuan Yeh,Hsuan-Te Chu,Chia-Kuang Tsai,Hsin-An Chang,Fu-Chi Yang,San-Yuan Huang,Chih-Sung Liang 대한신경정신의학회 2019 PSYCHIATRY INVESTIGATION Vol.16 No.8

Objective Since the inflammatory process has been implicated in the pathophysiology of psychiatric disorder, an important issue emerging is to assess the test-retest reliability of cytokine measurement in healthy individuals and patients with schizophrenia. The objective of the present study was to investigate the test-retest reliability of bead-based multiplex immunoassay technology (BMIT) for cytokine measurement by using a Bland-Altman plot (BAP). Methods Twenty healthy individuals and twenty patients with schizophrenia were enrolled, and a 17-plex cytokine assay was used to measure inflammatory biomarkers at baseline and two weeks later. The test-retest reliability was examined by BAP, 95% limits of agreement (LOA), intraclass correlation coefficient (ICC), and coefficient of repeatability (CoR). Results In the healthy controls, only interleukin (IL)-2, IL-13, IL-10, IL-17, and macrophage inflammatory protein-1β showed excellent ICC. The BAP with 95% LOA determined that 13 cytokines showed acceptable 95% LOA for a 2-week test-retest reliability, and only IL-1β, IL-12 and tumor necrosis factor (TNF)-α had significant test-retest bias. The CoR of cytokines varied significantly, ranging from 1.72 to 218.1. Compared with healthy controls, patients with schizophrenia showed significantly higher levels of IL-5, IL-13, and TNF-α and significantly lower levels of IL-4, IL-12, and interferon-gamma (IFN-γ). Of these six cytokines, IL-12 and TNF-α were considered suboptimal reliability. Conclusion The findings from ICC and CoR implied that the test-retest reliability of BMIT for cytokine measurement were suboptimal. However, the BAP with 95% LOA confirmed that BMIT can reliably distinguish schizophrenia from healthy individuals in cytokine measurement, while significant within-subject variation and between-group overlapping were evident in cytokine expression.

The economic burden of hip fractures in Asia

Ta-Wei Tai,Yu-Hsuan Lin,Chao-Jui Chang,Chih-Hsing Wu 대한골다공증학회 2021 Osteoporosis and Sarcopenia Vol.7 No.2

Reduction of Musical Residual Noise Using Hybrid-Mean Filter

Ching-Ta Lu,Kun-Fu Tseng,Chih-Tsung Chen 보안공학연구지원센터(IJSIP) 2013 International Journal of Signal Processing, Image Vol.6 No.4

Significant down-regulation of growth hormone receptor expression revealed as a new unfavorable prognostic factor in hepatitis C virus-related hepatocellular carcinoma

( Ching-chih Lin ),( Ta-wei Liu ),( Ming-lun Yeh ),( Yi-shan Tsai ),( Pei-chien Tsai ),( Chung-feng Huang ),( Jee-fu Huang ),( Wan-long Chuang ),( Chia-yen Dai ),( Ming-lung Yu ) 대한간학회 2021 Clinical and Molecular Hepatology(대한간학회지) Vol.27 No.2

Background/Aims: Growth hormone (GH) is the main regulator of somatic growth, metabolism, and gender dimorphism in the liver. GH receptor (GHR) signaling in cancer is derived from a large body of evidence, although the GHR signaling pathway involved in the prognosis of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV)-related HCC, remains unclear. We aimed to explore the expression of GHR and analyze its association with clinicopathologic features and prognosis of patients with chronic hepatitis C and HCC. Methods: The expression of GHR mRNA was investigated by quantitative real-time polymerase chain reaction in paired tumors and adjacent non-tumorous (ANT) liver tissues of 200 patients with chronic hepatitis C and HCC. Western blotting and immunofluorescence assays using the HCV-infected Huh7.5.1 cell model was performed. Results: GHR mRNA was significantly lower in HCV-HCC tissues than in corresponding ANT liver tissues. GHR mRNA and protein levels also decreased in the HCV-infected Huh7.5.1 cell model. Notably, lower GHR expression was associated with age of >60 years (P=0.0111) and worse clinicopathologic characteristics, including alpha-fetoprotein >100 ng/mL (P=0.0403), cirrhosis (P=0.0075), vascular invasion (P=0.0052), pathological stage II-IV (P=0.0002), and albumin ≤4.0 g/dL (P=0.0055), which were linked with poor prognosis of HCC. Most importantly, the high incidence of recurrence and poor survival rates in patients with a low ratio of tumor/ANT GHR (≤0.1) were observed, indicating that low expression levels of GHR had great risk for development of HCC in patients with chronic hepatitis C. Conclusions: Our study demonstrates a significant down-regulation of GHR expression as a new unfavorable independent prognostic factor in patients with chronic hepatitis C and HCC. (Clin Mol Hepatol 2021;27:313-328)

Optimization of Tool Path Planning in 5-Axis Flank Milling of Ruled Surfaces with Improved PSO

Hsin-Ta Hsieh,Chih-Hsing Chu 한국정밀공학회 2012 International Journal of Precision Engineering and Vol. No.

Previous studies have shown that machining error in 5-axis flank milling can be systematically reduced by optimization of tool path planning. However, the solution quality of the optimization methods adopted by those studies was not satisfactory,due to the constraint that the cutter must contact the boundary curves of the ruled surface to be machined. This work proposes an improved tool path planning method based on Particle Swarm Optimization (PSO) algorithms without this constraint. The method enlarges the feasible region in the optimization by allowing cutter location to deviate the boundary curves along the normal, tangent, and bi-normal directions. Design of experiment techniques are applied to determine better parameter setting in the PSO. A new objective function is formulated as the weighted sum of the errors induced by overcut and undercut. We can choose to minimize the total machining error, the overcut, or the undercut by properly adjusting the weight value. Compared to previous methods, the improved path planning method produces smaller machining error and offers better planning flexibility.

Proposed Digital Control Scheme for Improved Current Share of Multiphase DC/DC Converters

Jen-Ta Su,Chih-Wen Liu 전력전자학회 2011 ICPE(ISPE)논문집 Vol.2011 No.5

In this paper, a novel control scheme is proposed to improve the current share for multiphase DC/DC converters. The proposed control scheme is based upon gain scheduling method to automatically tune the parameters such as on resistance of power MOSFET or board impedance between each phase for optimization in current balance. The purpose of this paper is proposed a digitally control method to implement the voltage mode control with current sense by inductor series resistance and combined with gain scheduling method. The proposed scheme is verified on 12V input with 1 V output, 40 A 2-phases interleaved DC/DC buck converter and the simulation and experimental results are presented to demonstrate the theoretical analysis.