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.

Dielectric properties of Mg0.95Ni0.05TiO3 ceramic modified by Nd0.5Na0.5TiO3 at microwave frequencies

Chun-Hsu Shen,Cheng-Liang Huang,Chuan-Feng Shih,Chih-Ming Huang 한국물리학회 2009 Current Applied Physics Vol.9 No.5

The effect of Nd0.5Na0.5TiO3 addition on the microwave dielectric properties of Mg0.95Ni0.05TiO3 ceramics was investigated. The Nd0.5Na0.5TiO3 content plays a significant role in improving the dielectric properties. Microwave dielectric measurements show an increase in the dielectric constant (εr) and temperature coefficient of the resonant frequency (τf) and a decrease in the quality factor (Q × f value) with increasing Nd0.5Na0.5TiO3 content. By properly adjusting the Nd0.5Na0.5TiO3 content, a zero τf value can also be obtained, which make Mg0.95Ni0.05TiO3 a promising material in wireless systems. At 1300 ℃, the 0.81Mg0.95Ni0.05TiO3–0.19Nd0.5Na0.5TiO3 ceramics possess excellent microwave dielectric properties: a dielectric constant (εr) of 25.61, a Q × f value of 69,100 GHz, and a τf value of -6 ppm/℃. The effect of Nd0.5Na0.5TiO3 addition on the microwave dielectric properties of Mg0.95Ni0.05TiO3 ceramics was investigated. The Nd0.5Na0.5TiO3 content plays a significant role in improving the dielectric properties. Microwave dielectric measurements show an increase in the dielectric constant (εr) and temperature coefficient of the resonant frequency (τf) and a decrease in the quality factor (Q × f value) with increasing Nd0.5Na0.5TiO3 content. By properly adjusting the Nd0.5Na0.5TiO3 content, a zero τf value can also be obtained, which make Mg0.95Ni0.05TiO3 a promising material in wireless systems. At 1300 ℃, the 0.81Mg0.95Ni0.05TiO3–0.19Nd0.5Na0.5TiO3 ceramics possess excellent microwave dielectric properties: a dielectric constant (εr) of 25.61, a Q × f value of 69,100 GHz, and a τf value of -6 ppm/℃.

Induction of Apoptosis by a Combination of Paclitaxel and Carboplatin in the Presence of Hyperthermia

Huang, Tao,Gong, Wei-Hua,Li, Xiu-Cheng,Zou, Chun-Ping,Jiang, Guang-Jian,Li, Xu-Hui,Feng, Dian-Peng Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.1

Purpose: To study enhancing effects of paclitaxel in the thermochemotherapy of osteosarcoma cell lines and related mechanisms. Materials and Methods: Paclitaxel and carboplatin were used alone or jointly on OS732 cell lines in the presence of hyperthermia. Inhibition of proliferation was measured by MTT assay and cellular changes were assessed with inverted phase contrast and fluorescence microscopy. Apoptosis was analyzed with flow cytometry (FCM) and Fas expression by immunocytochemistry. Results: At $43^{\circ}C$, one hour after the application of 10ug/ml paclitaxel and $5{\mu}g/ml$ carboplatin on OS732 cells jointly, the survival rate was 15.8% which was significantly lower than with $10{\mu}g/ml$ paclitaxel (45.8%) and $5{\mu}g/ml$ carboplatin (47.7%) respectively (P<0.01). Moreover, changes of morphology and apoptotic rates indicated that the apoptosis-inducing effect of combined application was also much enhanced, as evident also regarding Fas expression. Conclusion: Paclitaxel is conducive to thermochemotherapy of osteosarcoma cell lines, possibly accomplished by up-regulation of Fas expression with induction of apoptosis.

An unusual cause of pneumonia: Strongyloides stercoralis infection

( Chun-jing Lu ),( Jin-yan Zhang ),( Wei-feng Huang ) 대한내과학회 2023 The Korean Journal of Internal Medicine Vol.38 No.5

The Influence of Construction Scheme of Asymmetric Three-Cabin Utility Tunnelling on the Surface Settlement Behaviour

Zuo Chun Li,Gui He Wang,Jun Wei Hao,Yao Zhou,Xiao Yang Wang,Heng Xuan,Feng Huang 대한토목학회 2021 KSCE JOURNAL OF CIVIL ENGINEERING Vol.25 No.9

The asymmetric three-cabin structure is one of the favourite choices in urban utility tunnel engineering, as it can provide a higher space utilization and clearer classification for pipelines. However, few work has been done on utility tunnel in such special cross-section during undercutting construction until now. Besides, as the loose soil layers such as sand and silt are often encountered during the utility tunnelling, its influence on surface settlement become one of the main concerns. This study focuses on the influence of the construction scheme on the surface settlement details for an asymmetric three-cabin utility tunnel. A 3D finite element method (FEM) model was established including both the stratum and a utility tunnel based on the Beijing Daxing International Airport (BDIA) Expressway Urban Utility Tunnel project. With this model, the behaviour of the surface settlement with the undercutting construction of the utility tunnel was investigated, and the causes and values of surface settlement in five construction stages were analyzed. By changing the construction spacing and sequence of mid and side cabins, the surface settlement and structural deformation were compared. The numerical results demonstrated a strong correlation between the cross-section shape and surface settlement characteristics. And the symmetry line of the surface settlement trough was offset by 1 m to the side with the larger cross-section. The second (excavation of upper bench in mid-cabin) and fourth (excavation of upper bench in side-cabin) stages caused the largest surface settlement, which were 41.9% and 18.07% of the total settlement, respectively. In addition, after optimizing the field tunnelling scheme, the surface settlement was reduced by 31.9% using the side-tunnel first construction sequence. The proposed numerical model is able to predict the settlement characteristics in each construction stage, which is important and provides a basis for further studies on the surface settlement mechanism and optimal design of the asymmetric three-cabin utility tunnelling scheme.

藍전果忍冬科技生産示範園的建立與硏究

안봉운 ( Feng Yun An ),현영남 ( Yong Nan Xuan ),안영희 ( Young Hee Ahn ),김미란 ( Mei Lan Jin ),요점춘 ( Zhan Chun Yao ),양금화 ( Jin Hua Liang ),주청선 ( Qing Xian Zhou ),렴성철 ( Cheng Zhe Lian ),황빙군 ( Bing Jun Huang ),소보군 한국녹지환경디자인학회 2008 녹지환경학회지 Vol.4 No.2

Lonicera caerulea L. var. edulis Turcz et Herd. with great nutrient and commercial edible value, is a kind of wild berry resource in regions of Changbai Moutains, China. Systematic cultivation technology for its large-scale production is developed and formation of cultivated land with area of 150 hectares is established. With high-yield technology, the production yield can be increased by twice. Systematic cultivation technology and establishment of technology demonstration garden lay the foundation for construction of production base and large-scale production of Lonicera caerulea L. var. edulis Turcz et Herd.

Twelve Weeks of Ledipasvir/Sofosbuvir for Patients with Chronic Hepatitis C Genotype 2 Infection: Integrated Analysis of Three Clinical Studies

( Chung-feng Huang ),( Yasuhiro Asahina ),( Chun-jen Liu ),( Edward Gane ),( Yoshito Itoh ),( Norifumi Kawada ),( Yoshiyuki Ueno ),( Jin Youn ),( Chen-yu Wang ),( Joe Llewellyn ),( Anu Osinusi ),( Jen 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: HCV genotype (GT) 2 is the second most common genotype in several Asian countries including Taiwan and Korea. Treatment options for GT2 remain limited in these countries. The once-daily fixed-dose combination of ledipasvir/sofosbuvir (LDV/SOF) was evaluated for the treatment of GT 2, in patients with or without compensated cirrhosis, in three phase 2 and 3 studies. Methods: This was a retrospective analysis of subjects treated with LDV/SOF for 12 weeks in the GS-US-337-1655 (Taiwan), GS-US-337-1903 (Japan) and GS-US-1468 (New Zealand) studies. Subjects analyzed in this integrated analysis were either mono-infected with HCV GT2, or co-infected with HCV GT2 and HBV. The data was pooled and safety and efficacy were analyzed. Results: Overall 200 subjects were treated and analyzed; 88% of subjects were Asian, 46% male, 31% had prior treatment failure, 15% were cirrhotic, 25% were IL28B non-CC, 34% were 65 years or older and 22% (n=43) were co-infected with HBV. The overall SVR rate was 97% (194/200), and was 93% (27/29) among patients with cirrhosis and 97% (59/61) in patients who had failed previous therapy. Of the 197 patients with available testing; NS5A resistance-associated substitutions (RASs) were present in 86% (169/197) at baseline. SVR12 rate was 98% (165/169) in patients with baseline NS5A RASs compared with 100% (28/28) in patients without NS5A RASs. No new RASs emerged in patients with virologic failure. Treatment with LDV/SOF for 12 weeks was well tolerated. Overall the most common adverse events AEs were headache and nasopharyngitis. Few subjects experienced serious AEs, none of which were assessed as treatment related. One patient discontinued treatment due to AE. Conclusions: Treatment with LDV/SOF for 12 weeks is highly effective and well tolerated in patients with GT2 HCV infection, including patients who are treatment experienced and/or have compensated cirrhosis, baseline NS5A RASs and with HBV/HCV coinfection.

Multi-walled Carbon Nanotubes/Polypropylene-based Coating Layer on the Composite Metal Filaments: Characteristic Evaluations and Radiation-shielded Fabric

Mei-Feng Lai,Chen-Hung Huang,Ching-Wen Lou,Yu-Chun Chuang,Cyun-Yu Wei,Jia-Horng Lin 한국섬유공학회 2022 Fibers and polymers Vol.23 No.3

In this study, polypropylene (PP) and multi-walled carbon nanotubes (MWCNTs) are used to coat stainless steel(SS) wrapped yarns, the product of which is then fabricated into conductive textiles. Afterwards, the tensile properties,surface resistivity, and electromagnetic shielding effectiveness (EMSE) of conductive textiles are evaluated, therebydetermining the influences of the MWCNTs content. The test results show that using MWCNT can effectively improve themechanical properties of the coated yarns and conductive woven fabrics. In addition, 5 wt % of MWCNT provides the wovenfabrics with a lower surface resistivity and higher EMSE. The influences of the lamination angle and number of laminationlayers on EMSE are investigated, and the maximum EMSE of -49.89 dB occurs when the lamination angle is 0 °/90 °/0 °.

Polypropylene/Carbon Fiber Composite Layered Materials: Electromagnetic Interference Shielding Effect and Mechanical Performance

Mei-Feng Lai,Chen-Hung Huang,Jia-Horng Lin,Yu-Chun Chuang,Ching-Hua Wang,Ching-Wen Lou 한국섬유공학회 2021 Fibers and polymers Vol.22 No.9

In this study, conductive polymer composites and conductive functional fabrics are combined to serve aselectromagnetic shielding planks. Polypropylene (PP), carbon black (CB), and short carbon fibers (SCF) are blended atdifferent ratios to form conductive polymer composites (i.e. PCS series). The mechanical property, electrical property,morphology, and electromagnetic interference shielding effectiveness (EMI SE) of the PCS series are evaluated. The testresults show that with 20 wt% of conductive fillers (i.e. CB and SCF), PCS20 exhibits the optimal tensile strength, flexuralstrength, and electrical property that is 7 order of magnitude higher than that of pure PP plates. Moreover, the EMI SE of thisgroup also reaches -30 dB, which meets level one of civil EMI SE standard. Therefore, PCS20 is used to combine with fourconductive sandwiches. The resulting multilayered functional PCS-sandwich planks are tested in terms of mechanicalproperty, morphology, and EMI SE. The test results show that the planks composed of a pure conductive woven sandwichhave the maximum tensile property and significantly improved impact resistance. All of the multilayered functional plankshave EMI SE that is higher than -50 dB and are qualified for the protection level of standard EMI SE electronic devices.

The Lymphotoxin-α 252 A>G Polymorphism and Breast Cancer: A Meta-analysis

Zhou, Ping,Huang, Wei,Chu, Xing,Du, Liang-Feng,Li, Jian-Ping,Zhang, Chun Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.5

Objective: The aim of this meta-analysis is to evaluate associations between LTA-252 A>G and breast cancer (BC). Methods: Electronic searches of several databases were conducted for all online publications. A total of 7 studies involving 4,625 BC patients and 4,373 controls were identified. Results: This meta-analysis showed no significant association between the LTA-252 A>G polymorphism and BC in overall or Caucasian populations. However, a positive association was found limited to Asian populations. Conclusion: Although there was no significant association found between the LTA-252 A>G polymorphism and BC overall, a positive association was found in Asian populations.