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.

Photo-induced antifouling polyvinylidene fluoride ultrafiltration membrane driven by weak visible light

Ting Wang,Ling-li Jiang,Lu-lu Huang,Li-guang Wu,Chun-juan Li,Jing Cai 한국공업화학회 2020 Journal of Industrial and Engineering Chemistry Vol.89 No.-

To enhance the performance of ultrafiltration membranes, a polyvinylidenefluoride (PVDF) blendingmembrane with photo-induced antifouling performance was fabricated. La3+- and Yb3+-doped titaniumdioxide-reduced graphene oxide (TiO2-RGO) composites were initially prepared by adsorption-phasesynthesis coupled with solvothermal reduction. The doped TiO2-RGO composites were then blendedwith the PVDF materials. The results showed that adding well-distributed, doped, and hydrophilic TiO2-RGO improved the pore structures and surface polarity of the blending membranes, thus improving theirpermeation and antifouling performance. After addition of doped TiO2-RGO with photocatalytic activity,the antifouling performance of the resulting blending membranes increased under weak visible-lightirradiation. The agglomerated doped TiO2-RGO in the polymeric matrix reduced the hydrophilicity andporosity of the resulting membranes, thereby decreasing their water permeability and antifoulingperformance. Solvothermal reduction through ethylene glycol also improved the photocatalytic activityof Yb-doped TiO2-RGO and enhanced the affinity between doped TiO2-RGO and PVDF. These two effectssimultaneously increased the water permeability and photo-induced antifouling performance of theblending membranes. Theflux recovery rate of the blending membranes containing Yb-doped TiO2-RGOtreated by ethylene glycol exceeded 69% after illumination. In particular, theflux recovery rate ofmembranes reached about 96% after illumination coupling with washing.

Examine the moderating role of mobile technology anxiety in mobile learning: a modified model of goal-directed behavior

Huang, Rui-Ting,Jabor, Mohd Khata,Tang, Tzy-Wen,Chang, Sheng-Chun 서울대학교 교육연구소 2022 Asia Pacific Education Review Vol.23 No.1

Although there are numerous mobile learning studies, limited efforts have been devoted to investigating the moderating role of mobile technology anxiety on mobile learning outcome. Accordingly, the primary purpose of this study is not only to examine the key elements that could influence desire to take mobile learning and mobile learning continuance intention, but also to explore the moderating impact of mobile technology anxiety on mobile learning outcome. 676 college students participated in this study, and the partial least squares structural equation modeling (PLS-SEM) analysis was performed to analyze the data. The study findings have demonstrated that desire to take mobile learning, attitude toward mobile learning, and perceived usefulness are positively linked to mobile learning continuance intention. Second, it has been found that attitude, positive anticipated emotion, negative anticipated emotion, and subjective norm play a key role in determining better desire to take mobile learning, whereas perceived behavioral control has no impact on desire to take mobile learning. Additionally, it has been shown that perceived usefulness, and personal learning initiative are two critical antecedents of attitude toward mobile learning. Finally, the study findings have shown that mobile technology anxiety would moderate the relationship between attitude toward mobile learning and mobile learning continuance intention.

Thalidomide Combined with Chemotherapy in Treating Patients with Advanced Colorectal Cancer

Huang, Xin-En,Yan, Xiao-Chun,Wang, Lin,Ji, Zhu-Qing,Li, Li,Liu, Meng-Yan,Qian, Ting,Shen, Hui-Ling,Gu, Han-Gang,Liu, Yong,Gu, Ming,Deng, Li-Chun Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.17

Objective: To assess the safety and effectiveness of thalidomide (produced by CHANGZHOU PHARMACEUTICAL FACTORY CO.LTD) combined with chemotherapy in treating patients with advanced colorectal cancer. Method: A consecutive cohort of pretreated patients with advanced colorectal cancer were treated with thalidomide combined with chemotherapy. And chemotherapy for patients with advanced colorectal cancer were administered according to the condition of patients. Thalidomide was orally administered at a dosage of 50mg/day to 150mg/day before sleeping for at least 14 days. After at least 14 days of treatment, safety and side effects were evaluated. Results: There were 12 female and 3 male patients with advanced cancer recruited into this study, including 9 patients with colon, 6 patients with rectal cancer. The median age of patients was 57(41-82) years. Partial response was observed in 2 patients (2/15), and stable disease in 3 patients(3/15). Incidences of Grade 1 to 2 myelosuppression was observed in 1/15 patients, and Grade 1 to 2 elevation of hepatic enzyme was recorded in 1/15 patients. Adverse effects on the gastrointestinal tract were documented in 1/15 patients, and were Grade 1. No Grade 3-4 toxicities were diagnosed. No treatment related death was found. Conclusions: Thalidomide combined with chemotherapy was safe and mildly effective in treating patients with advanced colorectal cancer. However, further study should be conducted to clarify the effectiveness of this combination.

Fabrication of PVDF-blended ultrafiltration membranes incorporated by chiral mesoporous silica for enantioseparation

Ting Wang,Xiao-xing Huang,Li-guang Wu,Chun-juan Li,Dong-feng Zhu 한국공업화학회 2022 Journal of Industrial and Engineering Chemistry Vol.109 No.-

Novel poly(vinylidene fluoride) (PVDF) ultrafiltration membranes blending with chiral mesoporous SiO2materials were constructed to improve the anti-fouling and separation performance of PVDF-blendedmembranes. The formation of asymmetric mesoporous structure of chiral mesoporous SiO2 caused theirlarge hydrophilic surface and significant chiral features, which enhanced the hydrophilicity and polarityof the resulting PVDF membranes blended with chiral mesoporous SiO2. So, the PVDF-blended membranescontaining chiral mesoporous SiO2 had a high permeation performance and anti-fouling property. After blending with chiral mesoporous SiO2, the maximum flux of membranes exceeded 500 Lm2h1and was 6.5-fold higher than that of neat PVDF. Due to the stereo-specific interaction between enantiomersand chiral recognition sites introduced by chiral mesoporous SiO2 in the membranes, allPVDF-blended membranes had evident enantioseparation performance for DL-racemic tryptophan. TheC-SiO2-20/PVDF-blended membranes had the highest enantioseparation performance under the sameaddition content and the maximum enantiomeric excess (e.e.%) was more than 20 %. Given the strongstereo-specific interaction and hydrogen bonding between d-tryptophan and b-cyclodextrin (b-CD), theaddition of more b-CD would introduce more chiral recognition sites into the membranes, therebyenhancing the enantioseparation performance of the membranes for d-tryptophan. The maximum e.e. % of C-SiO2-20/b-CD/PVDF-blended membranes for the tryptophan enantiomer reached 55%.

Risk of Hepatitis B Virus (HBV) Reactivation in HBsAg-Negative, Anti-HBc-Negative Patients Receiving Rituximab for Autoimmune Diseases in HBV Endemic Areas

Lan Ting-Yuan,Lin Yen-Chun,Tseng Tai-Chung,Yang Hung-Chih,Kao Jui-Hung,Cheng Chiao-Feng,Lee Tai-Ju,Huang Shang-Chin,Lu Cheng-Hsun,Li Ko-Jen,Hsieh Song-Chou 거트앤리버 소화기연관학회협의회 2023 Gut and Liver Vol.17 No.2

Background/Aims: Rituximab is known to be associated with high hepatitis B virus (HBV) reactivation rate in patients with resolved HBV infection and hematologic malignancy. However, data regarding HBV reactivation (HBVr) in rheumatic patients receiving rituximab is limited. To assess the HBVr rate in hepatitis B surface antigen (HBsAg)-negative patients receiving rituximab for autoimmune diseases in a large real-world cohort. Methods: From March 2006 to December 2019, 900 patients with negative HBsAg receiving at least one cycle of rituximab for autoimmune diseases in a tertiary medical center in Taiwan were retrospectively reviewed. Clinical outcome and factors associated with HBVr were analyzed. Results: After a median follow-up period of 3.3 years, 21 patients developed HBVr, among whom 17 patients were positive for hepatitis B core antibody (anti-HBc) and four were negative. Thirteen patients had clinical hepatitis flare, while eight patients had HBsAg seroreversion without hepatitis. Old age, anti-HBc positivity, undetectable serum hepatitis B surface antibody level at rituximab initiation and a higher average rituximab dose were associated with a higher HBVr rate. There was no significant difference in the HBVr risk between rheumatoid arthritis and other autoimmune diseases. Among anti-HBc-negative patients, subjects without HBV vaccination at birth had an increased risk of HBVr (4/368, 1.1%) compared with those who received vaccination (0/126, 0%). Conclusions: In HBV endemic areas where occult HBV is prevalent, anti-HBc-negative patients, may still be at risk for HBVr after rituximab exposure. HBVr may still be considered in HBsAgnegative patients developing abnormal liver function after rituximab exposure, even in patients with negative anti-HBc.

A Proteomic Analysis of Leaf Responses to Enhanced Ultraviolet-B Radiation in Two Rice (Oryza sativa L.) Cultivars Differing in UV Sensitivity

Xing-Chun Wu,Chang-Xun Fang,Jin-Yang Chen,Qing-Shui Wang,Ting Chen,Wen-Xiong Lin,Zhong-Liang Huang 한국식물학회 2011 Journal of Plant Biology Vol.54 No.4

To determine the proteomic response to UV irradiation, two cultivars, i.e., Lemont (UV tolerant) and Dular (UV sensitive), were exposed to natural and enhanced ultraviolet-B (UV-B) irradiation for 1, 7, and 14 days, and two-dimensional gel electrophoresis in combination with mass spectrometry (MS) and bioinformatics were used to compare the different proteomic responses in the leaves of the two cultivars. Thirty-nine proteins were up- or downregulated following the UV-B treatments. Among them, 30 increased or decreased more than 1.5-fold in abundance. They were further tested by using matrix-assisted laser desorption/ionization time of flight MS and performed a database search. Twentyfour proteins were thus identified. These identified proteins were mostly upregulated in Lemont, whereas only 14 of them upregulated in Dular. Nine proteins involved in glycometabolism and fatty acid metabolisms, signal transduction, and protein synthesis and folding in Dular were not changed. These results suggest that there was a complex regulative mechanism on the proteomes in rice leaves upon UV-B exposure.

Creatine Kinase (CK)-MB-to-Total-CK Ratio: a Laboratory Indicator for Primary Cancer Screening

Chang, Chih-Chun,Liou, Ching-Biau,Su, Ming-Jang,Lee, Yi-Chen,Liang, Chai-Ting,Ho, Jung-Li,Tsai, Huang-Wen,Yen, Tzung-Hai,Chu, Fang-Yeh Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.15

Background: For the determination of creatine kinase (CK)-MB, the immunoinhibition method is utilized most commonly. However, the estimated CK-MB activity may be influenced by the presence of CK isoenzymes in some conditions like cancer. Thus, a CK-MB-to-total-CK ratio more than 1.0 could be found in such a situation. The study aimed to explore the relationship of cancer to high CK-MB-to-total-CK ratio. Materials and Methods: From January 2011 to December 2014, laboratory data on all CK-MB and total CK test requests were extracted at Far Eastern Memorial Hospital (88,415 requests). Patients with a CK-MB-to-total-CK ratio more than 1.0 were registered in this study. Clinical data including tumor location, tumor TNM stage and metastatic status were also collected. Results: A total of 846 patients were identified with a CK-MB-to-total-CK ratio more than 1.0. Of these, 339 (40.1%) were diagnosed with malignancies. The mean CK-MB-to-total-CK ratio was significantly higher in malignancy than in non-malignancy ($1.35{\pm}0.28$ vs $1.25{\pm}0.23$, p<0.001) groups. The most frequent malignancy with a CK-MB-to-total-CK ratio more than 1.0 was colorectal cancer ($1.42{\pm}0.28$, 16.5%, n=56), followed by lung cancer ($1.38{\pm}0.24$, 15.9%, n=54) and hepatocellular carcinoma (14.5%, n=49). Higher CK-MB-to-total-CK ratios in hematological malignancies ($1.44{\pm}0.41$)were also noted. Additionally, the CK-MB-to-total-CK ratio was markedly higher in advanced stage malignancy than in early stage ($1.37{\pm}0.26$ vs. $1.29{\pm}0.31$, p=0.014) and significantly higher in liver metastasis than in non-liver metastasis ($1.48{\pm}0.30$ vs. $1.30{\pm}0.21$, p<0.001). Conclusions: The CK-MB-to-total-CK ratio is an easily available indicator and could be clinically utilized as a primary screening tool for cancer. Higher ratio of CK-MB-to-total-CK was specifically associated with certain malignancies, like colorectal cancer, lung cancer and hepatocellular carcinoma, as well as some cancer-associated status factors such as advanced stage and liver metastasis.

An Emission-Aware Day-Ahead Power Scheduling System for Internet of Energy

( Chenn-jung Huang ),( Kai-wen Hu ),( An-feng Liu ),( Liang-chun Chen ),( Chih-ting Chen ) 한국인터넷정보학회 2019 KSII Transactions on Internet and Information Syst Vol.13 No.10

As a subset of the Internet of Things, the Internet of Energy (IoE) is expected to tackle the problems faced by the current smart grid framework. Notably, the conventional day-ahead power scheduling of the smart grid should be redesigned in the IoE architecture to take into consideration the intermittence of scattered renewable generations, large amounts of power consumption data, and the uncertainty of the arrival time of electric vehicles (EVs). Accordingly, a day-ahead power scheduling system for the future IoE is proposed in this research to maximize the usage of distributed renewables and reduce carbon emission caused by the traditional power generation. Meanwhile, flexible charging mechanism of EVs is employed to provide preferred charging options for moving EVs and flatten the load profile simultaneously. The simulation results revealed that the proposed power scheduling mechanism not only achieves emission reduction and balances power load and supply effectively, but also fits each individual EV user’s preference.

Anti-Angiogenic Activity of Gecko Aqueous Extracts and its Macromolecular Components in CAM and HUVE-12 Cells

Tang, Zhen,Huang, Shu-Qiong,Liu, Jian-Ting,Jiang, Gui-Xiang,Wang, Chun-Mei Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.5

Gecko is a kind of traditional Chinese medicine with remarkable antineoplastic activity. However, undefined mechanisms and ambiguity regarding active ingredients limit new drug development from gecko. This study was conducted to assess anti-angiogenic properties of the aqueous extracts of fresh gecko (AG) or macromolecular components separated from AG (M-AG). An enzyme-linked immunosorbent assay (ELISA) approach was applied to detect the vascular endothelial growth factor (VEGF) secretion of the tumor cells treated with AG or M-AG. The effect of AG or M-AG on vascular endothelial cell proliferation and migratory ability was analyzed by tetrazolium dye colorimetric method, transwell and wound-healing assays. Chick embryo chorioallantoic membrane (CAM) assays were used to ensure the anti-angiogenic activity of M-AG in vivo. The results showed that AG or M-AG inhibited the VEGF secretion of tumor cells, the relative inhibition rates of AG and M-AG being 27.2% and 53.2% respectively at a concentration of $20{\mu}L/mL$. AG and M-AG inhibited the vascular endothelial (VE) cell proliferation with IC50 values of $11.5{\pm}0.5{\mu}L/mL$ and $12.9{\pm}0.4{\mu}L/mL$ respectively. The VE cell migration potential was inhibited significantly (p<0.01) by the AG (${\geq}24{\mu}L/mL$) or M-AG (${\geq}12\mu}L/mL$) treatment. In vivo, neovascularization of CAM treated with M-AG was inhibited significantly (p<0.05) at a concentration of ${\geq}0.4{\mu}L/mL$. This study provided evidence that anti-angiogenesis is one of the anti-tumor mechanisms of AG and M-AG, with the latter as a promising active component.