Tenofovir Alafenamide for Chronic Hepatitis B Patients with Advanced Fibrosis and Partial Virologic Responses to Oral Nucleos(T)Ide Analogues- Interim Report

( Ming-lung Yu ),( Ming-lun Yeh ),( Chi-yi Chen ),( Pin-nan Cheng ),( Ming-jong Bair ),( Jyh-jou Chen ),( Ching-chu Lo ),( Chi-ming Tai ),( Ching-yang Tsai ),( Kuo-chih Tseng ),( Chien-hung Chen ),( C 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

Aims: Insufficient data regarding the treatment strategy for partial response to nucleot(s)ide analogue (NUC) raised the aim of investigating tenofovir alafenamide (TAF) switching for chronic hepatitis B (CHB) patients with advanced fibrosis and partial response to other NUCs. Methods: CHB patients with advanced fibrosis (stage 3 or 4) and under NUC (except TAF) therapy with detectable hepatitis B virus (HBV) DNA for >52 weeks are enrolled to TAF 25 mg/day for 96 weeks. The objectives are viral suppression, alanine aminotransferase (ALT) normalization and safety. Results: From Feb. 2019, 34 patients, including 21 (61.8%) with entecavir, 10 (29.4%) TDF and 3 (8.8%) lamivudine or adefovir, were enrolled (15 [44.1%] male, median 53 years). The fibroscan demonstrated a mean of 10.5 kPa (7 [20.6%] cirrhotic). Sixteen (47.1%) patients were HBV e antigen positive, seven (20.6%) had YMDD mutation. The median HBV DNA level declined from 68.5 IU/mL at enrollment to 27.0 IU/mL at 4^th week, and undetectable at 12^th, 24^th, 36^th week, respectively, after TAF switching, with undetectable HBV DNA in 14/34 (41.2%), 17/33 (51.5%), 15/25 (60.0%), and 9/15 (60.0%) patients and rate of ALT normalization (≤40 U/L) of 85.3%, 85.3%, 84.8%, 92.0%, and 80.0%, respectively, after TAF switching. (figure 1) Two patients experienced transient virological breakthrough and another one developed at the final time follow up. Serum creatinine and eGFR levels were stable after TAF switching (figure 1). Two patients early terminated including one at 12^th week due to personal reason, and another one accidently died at 20^th week due to acute heart attack. Others suffered only mild degrees of adverse events which were considered unrelated to treatment. Conclusions: The preliminary results demonstrated the TAF switching is effective and safe in viral suppression for CHB patients with advanced fibrosis and partial virologic responses to other NUCs.

Sofosbuvir/Ledipasvir in the Treatment of Chronic Hepatitis C - A Subgroup Analysis from A Nationwide Real-World HCV Registry Program (TACR) in Taiwan

( Ming-Lung Yu ),( Chi-Yi Chen ),( Kuo-Chih Tseng ),( Ching-Chu Lo ),( Pin-Nan Cheng ),( Cheng-Yuan Peng ),( Ming-Jong Bair ),( Chih-Lang Lin ),( Chi-Ming Tai ),( Chi-Chieh Yang ),( Chih-Wen Lin ),( C 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

Aims: TASL HCV Registry (TACR) is a nationwide registry program organized and supervised by Taiwan Association for the Study of the Liver (TASL), which aims to setup the database and biobank of patients with chronic hepatitis C (CHC) in Taiwan. The present study aimed to evaluate the treatment outcome of sofosbuvir (SOF)/ledipasvir (LDV) in Taiwanese CHC patients in TACR. Methods: By May 2020, 19 tertiary hospitals, 23 community hospitals and one primary care clinic join the TACR program. The baseline characteristics, prior liver and non-liver related medical history, DAA regimens, laboratory results, treatment course and outcome were recorded. The primary objective was sustained virological response, defined as undetectable HCV RNA 3 months after end-of-treatment (SVR12). Results: A total of 4742 SOF/LDV+ ribavirin treated CHC patients with available SVR12 data from 39 sites were enrolled in the current analysis. The mean age was 61.3 years, and female accounted for 54.8% of the population. The dominant viral genotypes were GT1b (52.6%) and GT2 (35.6%). 1354 (28.6%) patients had liver cirrhosis, including 156 (3.3%) with liver decompensation, 552 (11.6%) had preexisting hepatocellular carcinoma (HCC) before DAAs treatment and 413 (8.7%) had hepatitis B virus dual infections. The overall SVR12 rate was 98.5%, with 98.5%, 98.2%, 99.7% and 98.6% in treatment- naïve non-cirrhotics, treatment-naïve cirrhotics, treatment- experienced non-cirrhotics and treatment-experienced cirrhotics patients, respectively. While patients were stratified by HCV genotype, the SVR12 was 98.5%, 98.4% and 98.5% among those with GT1, GT2 and GT6 infection, respectively. The strongest factor independent associated with treatment failure was DAA adherence < 60% (odds ratio [OR]/95% confidence intervals [CI]: 125.4/25.7-612.4, P<0.0001), followed by active HCC (OR/CI: 6.20/2.57-14.97, P<0.0001), HIV co-infection (OR/CI: 3.01/1.14-7.92, P=0.026), and male gender (OR/ CI: 1.85/1.09-3.13, P=0.023). The eGFR decreased significantly at the end of treatment (EOT) (89.3 ml/min/1.73㎡ vs. 93.2 ml/min/1.73㎡, P< 0.001) and remained stable 3 months after EOT (89.3 ml/min/1.73㎡). However, the decreased eGFR was observed only in patients whose baseline eGFR > 90 ml/ min/1.73㎡. Instead, patients with chronic kidney diseases whose pretreatment eGFR < 60 ml/min/1.73㎡ had improved eGFR after SOF/LDV. Conclusions: SOF/LDV is highly effective in treating CHC patients in real-world setting of Taiwan. The satisfactory result could be explicitly generalized to patients with different viral genotypes and liver disease severities.

Impact of Peri-Operative Anemia and Blood Transfusions in Patients with Gastric Cancer Receiving Gastrectomy

Chang, Chih-Chun,Sun, Jen-Tang,Chen, Jing-Yuan,Chen, Yi-Ting,Li, Pei-Yu,Lee, Tai-Chen,Su, Ming-Jang,Wu, Jiann-Ming,Yen, Tzung-Hai,Chu, Fang-Yeh Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.3

Background: Potential disadvantages of blood transfusion during curative gastrectomy for gastric cancer have been reported, and the role of peri-operative transfusions remains to be ascertained. Thus, the aim of our study was to survey its impact in patients with gastric cancer undergoinging gastrectomy. Materials and Methods: Clinical data of patients receiving curative gastrectomy at Far Eastern Memorial Hospital were obtained. Findings for pre-operative anemia states, pre-, peri- and post-operative transfusion of red blood cell (RBC) products as well as post-operative complication events were collected for univariate analysis. Results: A total of 116 patients with gastric cancer received gastrectomy at Far Eastern Memorial Hospital from 2011 to 2014. Both pre-operative and intra- and post-operative transfusion of RBC products were markedly associated with post-operative infectious events (OR: 3.70, 95% CI: 1.43-9.58, P=0.002; OR: 8.20, 95% CI: 3.11-22.62, P<0.001, respectively). In addition, peri- and post-operative RBC transfusion was significantly associated with prolonged hospital stay from admission to discharge (OR: 8.66, 95% CI: 1.73-83.00, P=0.002) and post-operative acute renal failure (OR: 19.69, 95% CI: 2.66-854.56, P<0.001). Also, the overall survival was seemingly decreased by peri-operative RBC transfusion in our gastric cancer cases (P=0.078). Conclusions: Our survey indicated that peri-operative RBC transfusion could increase the risk of infectious events and acute renal failure post curative gastrectomy as well as worsen the overall survival in gastric cancer cases. Hence, unnecessary blood transfusion before, during and after curative gastrectomy should be avoided in patients with gastric cancer.

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.

Quercetin-mediated Cell Cycle Arrest and Apoptosis Involving Activation of a Caspase Cascade through the Mitochondrial Pathway in Human Breast Cancer MCF-7 Cells

Chu-Chung Chou,Jai-Sing Yang,Hsu-Feng Lu,Siu-Wan Ip,Chyi Lo,Chih-Chung Wu,Jing-Pin Lin,Nou-Ying Tang,Jing-Gung Chung,Ming-Jen Chou,Ying-Hock Teng,Dar-Ren Chen 대한약학회 2010 Archives of Pharmacal Research Vol.33 No.8

Dietary polyphenols have been correlated with a reduced risk of developing cancer. Quercetin (a natural polyphenolic compound) induced apoptosis in many human cancer cell lines, including breast cancer MCF-7 cells. However, the involvement of possible signaling pathways and the roles of quercetin in apoptosis are still undefined. The purpose of this study was to investigate the effects of quercetin on the induction of the apoptotic pathway in human breast cancer MCF-7 cells. When MCF-7 cells were treated with quercetin for 24 and 48 h and at various doses (10-175 μM), cell viability decreased significantly in time- and dose-dependent manners. Exposure of MCF-7 cells to 10-175 μM quercetin resulted in an approximate 90.25% decrease in viable cells. To explicate the mechanism underlying the antiproliferative effect of quercetin, cell cycle distribution and apoptosis in MCF-7 cells was investigated after exposure to 150 μM quercetin for 6-48 h. Quercetin caused a remarkable increase in the number of S phase (14.56%to 61.35%) and sub-G1 phase cells (0.1% to 8.32%) in a dose- and time-dependent manner. Quercetin caused S phase arrest by decreasing the protein expression of CDK2, cyclins A and B while increasing the p53 and p57 proteins. Following incubation with quercetin for 48 h, MCF-7 cells showed apoptotic cell death by the decreased levels of Bcl-2 protein and ΔΨ m and increased activations of caspase-6, -8 and -9. Moreover, quercetin increased the AIF protein released from mitochondria to nuclei and the GADD153 protein translocation from endoplasmic reticulum to the nuclei. These data suggested that quercetin may induce apoptosis by direct activation of the caspase cascade through the mitochondrial pathway in MCF-7 cells.

Proteomic Analysis of the Aging-related Proteins in Human Normal Colon Epithelial Tissue

( Ming Li ),( Zhi Qiang Xiao ),( Zhu Chu Chen ),( Jian Ling Li ),( Cui Li ),( Peng Fei Zhang ),( Mao Yu Li ) 생화학분자생물학회 2007 BMB Reports Vol.40 No.1

Review on Kinematics Calibration Technology of Serial Robots

Chen-Gang,Li-Tong,Chu-Ming,Jia-Qing Xuan,Sun-Han Xu 한국정밀공학회 2014 International Journal of Precision Engineering and Vol. No.

Robot kinematics calibration is of great significance for improving robot absolute pose accuracy, which can be divided into modelbasedand non-parametric kinematics calibration. For model-based kinematics calibration, kinematics calibration modeling, posemeasurement of end-effector, kinematics parameters calibration and error compensation are systematically analyzed. And with theincreasing demand for autonomy, the autonomous kinematics calibration is introduced. On the other hand, research status of nonparametrickinematics calibration is elaborated, the advantages and disadvantage of which are discussed respectively. On the basis,comprehensive and organized description and summarization of the three kinds of calibrations are given. Overall, aiming at robotkinematics calibration, existing achievements are summarized, a typical calibration process is carried out and calibration precautionsare detailed, then calibration results of various methods are compared and analyzed. Finally, existing problems in kinematicscalibration are analyzed and development prospects are presented.

Real-World Effectiveness and Safety of SOF/LDV for Pa-tients with Chronic Hepatitis C in Taiwan

( Ching-chu Lo ),( Pin-nan Cheng ),( Chi-yi Chen ),( Chung-feng Huang ),( Hsing-tao Kuo ),( Kuo-chih Tseng ),( Yi-hsiang Huang ),( Chi-ming Tai ),( Cheng-yuan Peng ),( Ming-jong Bair ),( Chien-hung Ch 대한간학회 2021 춘·추계 학술대회 (KASL) Vol.2021 No.1

Proteomic Analysis of the Aging-related Proteins in Human Normal Colon Epithelial Tissue

Li, Ming,Xiao, Zhi-Qiang,Chen, Zhu-Chu,Li, Jian-Ling,Li, Cui,Zhang, Peng-Fei,Li, Mao-Yu Korean Society for Biochemistry and Molecular Biol 2007 Journal of biochemistry and molecular biology Vol.40 No.1

In order to screen the aging related proteins in human normal colon epithelia, the comparative proteomics analysis was applied to get the two-dimensional electrophoresis (2-DE) profiles with high resolution and reproducibility from normal colon epithelial tissues of young and aged people. Differential proteins between the colon epithelia of two age groups were found with PDQuest software. The thirty five differential protein-spots were identified by peptide mass fingerprint (PMF) based on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) and database searching. Among them there are sixteen proteins which are significantly up-regulated in the colonic mucosal epithelia of young people group, which include ATP synthase beta chain, electron transfer flavoprotein alpha-subunit, catalase, glutathione peroxidase 1, annexin A2 and heat shock cognate 71 kDa protein, etc.; There are nineteen proteins which are significantly up-regulated in the colonic mucosal epithelia of aged people group, which include far upstream element-binding protein 1, nucleoside diphosphate kinase B, protein disulfide-isomerase precursor and VDAC-2, etc.. The identified differential proteins appear to be involved in metabolism, energy generation, chaperone, antioxidation, signal transduction, protein folding and apoptosis. The data will help to understand the molecular mechanisms of human colon epithelial aging.

Investigation of Planar Optical Waveguide Formed by MeV He+ Ion - Implantation into NaEr(WO₄)₂ Crystal

Feng Chen,Xue-Lin Wang,Ke-Ming Wang,Zhen-Xiang Cheng,Huan-Chu Chen,Ding-Yu Shen 한국진공학회(ASCT) 2002 Journal of Korean Vacuum Science & Technology Vol.6 No.2

NaEr(WO₄)₂ is a new laser material. The planar optical waveguide was formed in NaEr(WO₄)₂ crystal by 2.6 MeV He^+ ion implantation at doses of 1.0-1.5×10^(16) ions/㎤ at room temperature. The effective refractive indices of the dark modes were measured using the prism coupling method. Four TE modes and five TM modes were observed in the waveguide. The refractive index profiles were analyzed using the reflectivity calculation method (RCM). The influence of heat treatment at moderate temperature on the refractive index profiles of the waveguide was also investigated. We used the TRIM’98 (Transport of Ions in Matter) code to simulate the damage profile in the NaEr(WO₄)₂ crystal by 2.6 MeV He^+ ion implantation which is helpful for a better understanding of the waveguide formation.