Platelet-Derived Growth Factor Receptor-α Subunit Targeting Suppresses Metastasis in Advanced Thyroid Cancer In Vitro and In Vivo

( Ching-ling Lin ),( Ming-lin Tsai ),( Yu-hsin Chen ),( Wei-ni Liu ),( Chun-yu Lin ),( Kai-wen Hsu ),( Chien-yu Huang ),( Yu-jia Chang ),( Po-li Wei ),( Shu-huey Chen ),( Li-chi Huang ),( Chia-hwa Lee 한국응용약물학회 2021 Biomolecules & Therapeutics(구 응용약물학회지) Vol.29 No.5

Thyroid cancer is the most common endocrine malignancy. Patients with well-differentiated thyroid cancers, such as papillary and follicular cancers, have a favorable prognosis. However, poorly differentiated thyroid cancers, such as medullary, squamous and anaplastic advanced thyroid cancers, are very aggressive and insensitive to radioiodine treatment. Thus, novel therapies that attenuate metastasis are urgently needed. We found that both PDGFC and PDGFRA are predominantly expressed in thyroid cancers and that the survival rate is significantly lower in patients with high PDGFRA expression. This finding indicates the important role of PDGF/PDGFR signaling in thyroid cancer development. Next, we established a SW579 squamous thyroid cancer cell line with 95.6% PDGFRA gene insertion and deletions (indels) through CRISPR/Cas9. Protein and invasion analysis showed a dramatic loss in EMT marker expression and metastatic ability. Furthermore, xenograft tumors derived from PDGFRA geneedited SW579 cells exhibited a minor decrease in tumor growth. However, distant lung metastasis was completely abolished upon PDGFRA gene editing, implying that PDGFRA could be an effective target to inhibit distant metastasis in advanced thyroid cancers. To translate this finding to the clinic, we used the most relevant multikinase inhibitor, imatinib, to inhibit PDGFRA signaling. The results showed that imatinib significantly suppressed cell growth, induced cell cycle arrest and cell death in SW579 cells. Our developed noninvasive apoptosis detection sensor (NIADS) indicated that imatinib induced cell apoptosis through caspase-3 activation. In conclusion, we believe that developing a specific and selective targeted therapy for PDGFRA would effectively suppress PDGFRA-mediated cancer aggressiveness in advanced thyroid cancers.

Three P5CS genes including a novel one from Lilium regale play distinct roles in osmotic, drought and salt stress tolerance

Chi Wei,Qi Cui,Xi-Qing Zhang,Yu-Qian Zhao,Gui-Xia Jia 한국식물학회 2016 Journal of Plant Biology Vol.59 No.5

Proline accumulations in abiotically stressed plants is generally considered to benefit their stress tolerance. The Δ1-Pyrroline-5-carboxylate synthetase (P5CS) gene family, which encodes the rate-limiting enzyme in proline biosynthesis pathway, usually contains two duplicated genes in most plants. However, three P5CS genes including LrP5CS1, LrP5CS2 as well as a third one, LrP5CS3, were isolated from Lilium regale. LrP5CS3 is highly identical to LrP5CS1 in amino acid sequences, indicating they could come from a paralogous duplication. The phylogenetic tree suggested that the duplication of LrP5CS occurred independently after the divergence of Liliales and commelinoids. The expression of LrP5CS1 was strongly induced in leaves and roots both under drought and salinity, while that of LrP5CS3 was upregulated more moderately. LrP5CS2 stayed almost constitutive under stress. LrP5CS1 exhibited the highest activity after expressed in E. coli. Overexpression of LrP5CS genes conferred enhanced osmotic, drought and salt tolerance on transgenic Arabidopsis without negative effects in unstressed condition. Under salt stress, lines LrP5CS2 accumulated fewer proline than others, and lines LrP5CS1 grew better in root elongation. The roots of lines LrP5CS3 grew better than all others under unstressed condition and osmotic stress. Our study suggests that the three LrP5CS genes play distinct roles respectively in proline accumulation and abiotic stress tolerance.

Effect of Moving Structure on the Spatial Accuracy and Compensation of the Coordinate Measuring Machine

Tzu-Chi Chan,Yu Ping Hong,Jia-Hong Yu 한국정밀공학회 2021 International Journal of Precision Engineering and Vol.22 No.9

The coordinate measuring machine (CMM) is one of the most widely used precision measurement machines in the machinery industry. In this study, the analysis and compensation of structural deformation in spatial coordinates effectively depicts the improvement of the spatial accuracy of the motion of a three-dimensional measuring machine in a measurement area. In addition to accuracy, it is also projected that the measurement can be carried out more efficiently. Therefore, the measurement speed of the CMM and dynamic characteristics of the structure are becoming increasingly important. Consequently, the measuring machine has better dynamic characteristics and meets high precision requirements. During measurement, the geometric errors generated by the machine are mainly because of its moving structure in the spatial position. In this study, the CMM is driven by aerostatic bearings; the boundary conditions and parameter settings of each component are established to obtain analysis results that are highly consistent with the actual machine characteristics. The finite element method is used as an analysis tool, including static deformation, modal, spectrum, and transient analyses. Because of the structural deformation and spatial geometric errors caused by the moving structure of the measuring machine, the relative deformation errors can be evaluated through the analysis of the spatial position error compensation to improve the measurement accuracy of the machine.

Enhanced Curdlan Production in Agrobacterium sp. ATCC 31749 by Addition of Low-polyphosphates

Lijun Yu,Jianrong Wu,Jia Liu,Xiaobei Zhan,Zhiyong Zheng,Chi Chung Lin 한국생물공학회 2011 Biotechnology and Bioprocess Engineering Vol.16 No.1

A large amount of adenosine triphosphate with high energy phosphate bonds is required for uridine triphosphate regeneration during curdlan biosynthesis by Agrobacterium sp. ATCC 31749. To supply high energy for curdlan synthesis, three low-polyphosphates (Na_4P_2O_7,Na_5P_3O_10, and (NaPO_3)_6) with higher energy phosphate bonds were employed to substitute for KH_2PO_4-K_2HPO_4in fermentation medium. Two genes encoding the polyphosphate metabolizing enzymes, polyphosphate kinase and exopolyphosphatase, were amplified and showed 95%homology to those in Agrobacterium sp. C58 by sequence analysis. The curdlan yields were enhanced by 23 and 134% when phosphate concentrations 0.024 mol/L of Na_5P_3O_10 and 0.048 mol/L of (NaPO_3)_6 respectively, were added in the medium. The maximum curdlan yield of 30 ±1.02 g/L was obtained with the addition of 0.048 mol/L of (NaPO_3)_6 with 5 g/L CaCO_3 in the medium. When CaCO_3 was removed from the culture and the three lowpolyphosphates were added, the pH and biomass yield dropped remarkably and little or no curdlan was produced. The culture containing 0.048 mol/L of (NaPO_3)_6 was mixed with KH_2PO_4-K_2HPO_4 and CaCO_3 in the medium,but showed no effect on curdlan production. However,curdlan yield was improved by 49 ~ 60% when CaCO_3was removed from the medium and KH_2PO_4-K_2HPO_4acted as a buffer. It appears that the positive effect of (NaPO_3)_6 on curdlan production required the buffering capacity of CaCO_3 and the absence of KH_2PO_4-K_2HPO_4competing as a phosphate supplier.

Comedications and potential drug-drug interactions with direct-acting antivirals in hepatitis C patients on hemodialysis

( Po-yao Hsu ),( Yu-ju Wei ),( Jia-jung Lee ),( Sheng-wen Niu ),( Jiun-chi Huang ),( Cheng-ting Hsu ),( Tyng-yuan Jang ),( Ming-lun Yeh ),( Ching-i Huang ),( Po-cheng Liang ),( Yi-hung Lin ),( Ming-ye 대한간학회 2021 Clinical and Molecular Hepatology(대한간학회지) Vol.27 No.1

Background/Aims: Direct-acting antivirals (DAAs) have been approved for hepatitis C virus (HCV) treatment in patients with end-stage renal disease (ESRD) on hemodialysis. Nevertheless, the complicated comedications and their potential drug-drug interactions (DDIs) with DAAs might limit clinical practice in this special population. Methods: The number, class, and characteristics of comedications and their potential DDIs with five DAA regimens were analyzed among HCV-viremic patients from 23 hemodialysis centers in Taiwan. Results: Of 2,015 hemodialysis patients screened in 2019, 169 patients seropositive for HCV RNA were enrolled (mean age, 65.6 years; median duration of hemodialysis, 5.8 years). All patients received at least one comedication (median number, 6; mean class number, 3.4). The most common comedication classes were ESRD-associated medications (94.1%), cardiovascular drugs (69.8%) and antidiabetic drugs (43.2%). ESRD-associated medications were excluded from DDI analysis. Sofosbuvir/velpatasvir/voxilaprevir had the highest frequency of potential contraindicated DDIs (red, 5.6%), followed by glecaprevir/pibrentasvir (4.0%), sofosbuvir/ledipasvir (1.3%), sofosbuvir/velpatasvir (1.3%), and elbasvir/grazoprevir (0.3%). For potentially significant DDIs (orange, requiring close monitoring or dose adjustments), sofosbuvir/velpatasvir/voxilaprevir had the highest frequency (19.9%), followed by sofosbuvir/ledipasvir (18.2%), glecaprevir/pibrentasvir (12.6%), sofosbuvir/velpatasvir (12.6%), and elbasvir/grazoprevir (7.3%). Overall, lipid-lowering agents were the most common comedication class with red-category DDIs to all DAA regimens (n=62), followed by cardiovascular agents (n=15), and central nervous system agents (n=10). Conclusions: HCV-viremic patients on hemodialysis had a very high prevalence of comedications with a broad spectrum, which had varied DDIs with currently available DAA regimens. Elbasvir/grazoprevir had the fewest potential DDIs, and sofosbuvir/velpatasvir/voxilaprevir had the most potential DDIs. (Clin Mol Hepatol 2021;27:186-196)

ONYX-II: Efficacy of Ombitasvir/Paritaprevir/Ritonavir + Dasabuvir + Ribavirin in HCV Genotype 1b-Infected Patients with Compensated Cirrhosis from South Korea and Taiwan

( Seung Woon Paik ),( Chi-jen Chu ),( Yan Luo ),( Kwang-hyub Han ),( Jia-horng Kao ),( Jeong Heo ),( Cheng-yuan Peng ),( Yoon Jun Kim ),( Ting-tsung Chang ),( Young-suk Lim ),( Ming Lung Yu ),( Linda 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1

Background: Chronic hepatitis C virus (HCV) infection is associated with development of complications including hepatocellular carcinoma, liver failure and cirrhosis. Patients with cirrhosis are historically more difficult to cure. In southeastern Asia, the most prevalent HCV genotype (GT) is GT1b. In western populations, the 3 direct-acting antiviral (3-DAA) regimen of ombitasvir (OBV), ritonavir-boosted paritaprevir (PTV/r; identified by AbbVie and Enanta) and dasabuvir (DSV) ± ribavirin (RBV) demonstrated sustained virologic response (SVR) at post-treatment week 12 (SVR12) rates of 99% in patients with GT1b infection and compensated cirrhosis regardless of prior treatment experience. The regimen, however, has not been investigated in southeastern Asian populations. The ONYX-II study is evaluating the efficacy and safety of this regimen in Asian patients with HCV GT1b infection and compensated cirrhosis. Methods: Treatment-naive and interferon-based therapy-experienced patients with HCV GT1b-infection and compensated cirrhosis were enrolled in South Korea, Taiwan, and China, and received 12 weeks of OBV/PTV/r (25 mg/150 mg/100 mg once daily) and DSV (250 mg twice daily) with RBV (weight-based). Patients will be followed for 48 weeks after the last dose of study drugs. The primary objectives are to compare the SVR12 rate to the known SVR rate of telaprevir + peg-interferon (IFN) + RBV therapy, and to assess the safety of OBV/PTV/r + DSV + RBV. Results: Twenty-one and 20 subjects were enrolled in South Korea and Taiwan, respectively. Of South Korean patients, 52% were male and 71% were treatment-experienced; of Taiwanese patients, 45% were male and 65% were treatment-experienced. Safety data and SVR at post-treatment week 4 (SVR4) will be available for presentation. Conclusions: The ONYX-II study evaluates the 3-DAA regimen of OBV/PTV/r + DSV with RBV for Asian patients with compensated cirrhosis and HCV GT1b infection. Resultant data may provide evidence for treatment guidelines for HCV GT1b in this population.

Effects of co-ion initial concentration ratio on removal of Pb2+ from aqueous solution by modified sugarcane bagasse

Jing Zhu,Jun-xia Yu,Jia-dong Chen,Jie-sen Zhang,Jia-qi Tang,Yuan-lai Xu,Yue-fei Zhang,Ru-an Chi 한국화학공학회 2017 Korean Journal of Chemical Engineering Vol.34 No.6

A modified sugarcane bagasse (SCB) fixed bed column was used to remove Pb2+ from aqueous solution. To determine the optimal condition for Pb2+ separation, Ca2+ was chosen as the model interfering ion, and effects of Ca2+ and Pb2+ initial concentration ratio (C0 Ca : C0 Pb) on the adsorption of Pb2+ were investigated. Results showed that adsorption amount ratio of Ca2+ and Pb2+ (qe Ca : qe Pb) had a good linear relationship with C0 Ca : C0 Pb. Mass ratio of Pb2+ absorbed on the modified SCB was higher than 95% at C0 Ca : C0 Pb<1.95, illustrating that Pb2+ could be selectively removed from aqueous solution. To verify that, simulated waste water containing co-ions of K+, Na+, Cd2+ and Ca2+ was treated, and results showed that the equilibrium amount of Pb2+, K+, Na+, Cd2+ and Ca2+ adsorbed was 134.14, 0.083, 0.058, 1.28, and 1.28mg g−1, respectively, demonstrating that the modified SCB could be used to remove Pb2+ from aqueous solution in the investigated range.

Strategies to Reduce the Arteriovenous Access Obstruction in Hemodialysis Patients

Kai-Ling Yang,Chai-Chi Huang,Ying-Fang Zhang,Shin-Yng Chang,Yu-Jia Zhang,Ya-Fang Ho,Huey-Liang Kuo 한국간호과학회 2019 한국간호과학회 학술대회 Vol.2019 No.10

Laboratory Measurement of Mechanical and Hydraulic Apertures of Smooth Aluminum Joints under Different Confining Stresses

( Xuan-xinh Nguyen ),( Jia-jyun Dong ),( Chi-wen Yu ),( Tan-minh Le ) 대한지질공학회 2019 대한지질공학회 학술발표회논문집 Vol.2019 No.2

Fluid flow through rock mass is a critical issue for rock engineering practice and geoscience from shallow to great depth. Among others, the stress-dependent aperture of single fracture is a key for predicting the hydro-mechanical coupling effect of rock mass. To understand the reducing flow rate along a smooth joint with a reduction of aperture, laboratory measurements of mechanical/hydraulic apertures of sawed, polished aluminum samples via YOKO 2 system under a confining stress up to 120 MPa were conducted. The closure of smooth aluminum joints (reduction of mechanical aperture, E) under different normal stress was characterized based on the volume reduction measurements. The hydraulic aperture (e) was determined based on measured flow rate and a cubic law. The hysteresis of the mechanical/hydraulic aperture was observed. However, the permanent aperture closure decreases significantly after the first loading/unloading cycle. The stress dependency of apertures fit the hyperbolic function and semi-logarithmic closure law well. Based on the measurements, we found the ratio of mechanical aperture to hydraulic aperture (E/e) decreased with decreasing hydraulic aperture, which the existing model cannot predict the observed trend. The results of this study provide an important base line for depicting the relation between mechanical aperture and hydraulic aperture, which is widely used to predict the hydraulic aperture from mechanical aperture.

Acquired Localized Hypertrichosis Induced by Internal Fixation and Plaster Cast Application

Hui-Jun Ma,Yang Yang,Hui-Yong Ma,Chi-Yu Jia,Ting-Hui Li 대한피부과학회 2013 Annals of Dermatology Vol.25 No.3

Hypertrichosis refers to increased vellus hair growth and is independent to androgen excess. The acquired localized hypertrichosis (ALH) is one of the typical hypertrichosis,which mainly results from chronic irritation, inflammation,friction, and occlusion by plaster of Paris. Here, we report a young boy who had ALH on his right hand following a closed fracture with internal fixation and plaster cast application. The case is unusual because the hairy area is limited to the operative region of internal fixation. We suggest that the local vascular changes and skin inflammation induced by internal fixation and plaster cast application may be associated with ALH.