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.

Systematic Review on Epstein-Barr Virus (EBV) DNA in Diagnosis of Nasopharyngeal Carcinoma in Asian Populations

Han, Bao-Lin,Xu, Xiang-Ying,Zhang, Chun-Zhi,Wu, Jian-Juan,Han, Chun-Feng,Wang, Hui,Wang, Xuan,Wang, Guang-Shun,Yang, Shu-Juan,Xie, Yao Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.6

Objective: To conduct a meta-analysis to investigate the value of EBV DNA in diagnosis of nasopharyngeal cancer (NPC) in Asian populations, and provide important evidence for screening. Methods: Prospective or respective case-control or cohort studies regarding the detection role of EBV DNA for NPC were included in our study. We conducted a comprehensive literature search in PubMed, EMBASE, and the Chinese Biomedical Database (CBM database between January 1980 and March 2012. Results: A total of 18 studies with 1492 NPC cases and 2641 health controls were included. Almost of the included studies were conducted in China, and only one other conducted in Thailand. The overall results demonstrated that the pooled sensitivity, specificity, positive likelihood (+LR) and negative likelihood (-LR) were 0.73 (0.71-0.75), 0.89 (0.88-0.90), 8.84 (5.65-13.84) and 0.19(0.11-0.32), respectively. The overall EBV DNA detection showed the largest area of 0.932 under the summary receiver operator curve (SROC). The accuracy of detection by plasma for NPC (0.86) was higher than in serum (0.81), with largest areas under the SROC of 0.97 and 0.91, respectively. Conclusion: Our results demonstrated the EBV DNA detection in plasma or serum has high sensitivity and specificity in diagnosis of NPC, especially in Chinese populations with a high risk of cancer.

Research on Contamination-Resistant SiO2 Optical Thin Films in a Vacuum Environment

Wang Sheng-zhao,Nan Chun-juan,Qiao Jian-liang,Guo Xin-feng 한국물리학회 2020 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.77 No.1

The Contamination resistance of SiO2 optical films prepared by using sol-gel method was investigated and improved in this research. FDTS (1H, 1H, 2H, 2H-perfluorodecyltrichlorosilane) was used to modify SiO2 thin films. Fourier Transform Infrared Spectrometer (FT-IR) and X-ray photoelectron spectroscopy (XPS) were used to evaluate the components on surface of the SiO2 thin films. The optical properties and hydrophobicity were also measured. The results show that the SiO2 thin film modification with FDTS causes -OH groups to be replaced by organic groups containing fluorine. The transmittance peak of SiO2 thin film changes, and the surface contact angle of water droplets on the SiO2 film increases from 35° to 107° after surface modification with FTDS. After the SiO2 thin films had been put in a vacuum environment for 24 hours, the peak transmittance of the modified SiO2 film under the same conditions is reduced to 0.14%, which is less than 3.17% of the unmodified film. The peak transmittance of the modified SiO2 thin films is also improved.

Characterization and Electrical Conductivity of Carbon-Coated Metallic (Ni, Cu, Sn) Nanocapsules

Wang, Dong Xing,Shah, Asif,Zhou, Lei,Zhang, Xue Feng,Liu, Chun Jing,Huang, Hao,Dong, Xing Long Korean Society of Microscopy 2015 Applied microscopy Vol.45 No.4

Carbon-coated Ni, Cu and Sn nanocapsules were investigated by means of X-ray diffraction (XRD), transmission electron microscopy (TEM) and a four-point probe device. All of these nanocapsules were prepared by an arc-discharge method, in which the bulk metals were evaporated under methane ($CH_4$) atmosphere. Three pure metals (Ni, Cu, Sn) were typically diverse in formation of the carbon encapsulated nanoparticles and their different mechanisms were investigated. It was indicated that a thick carbon layers formed on the surface of Ni(C) nanocapsules, whereas a thin shell of carbon with 1~2 layers covered on Cu(C) nanocapsules, and the Sn(C) nanocapsules was, in fact, a longger multi-walled carbon nanotubes partially-filled with metal Sn. As one typical magnetic/dielectric nanocomposite particles, Ni(C) nanocapsules and its counterpart of oxide-coated Ni(O) nanocapsules were compared in the electrically conductive behaviors for further applications as the electromagnetic materials.

Structural Maintenance of Chromosomes 4 is a Predictor of Survival and a Novel Therapeutic Target in Colorectal Cancer

Feng, Xiao-Dong,Song, Qi,Li, Chuan-Wei,Chen, Jian,Tang, Hua-Mei,Peng, Zhi-Hai,Wang, Xue-Chun Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.21

Background: Structural maintenance of chromosomes 4 (SMC-4) is a chromosomal ATPase which plays an important role in regulate chromosome assembly and segregation. However, the role of SMC-4 in the incidence of malignancies, especially colorectal cancer is still poorly understood. Materials and Methods: We here used quantitative PCR and Western blot analysis to examine SMC-4 mRNA and protein levels in primary colorectal cancer and paired normal colonic mucosa. SMC-4 clinicopathological significance was assessed by immunohistochemical staining in a tissue microarray (TMA) in which 118 cases of primary colorectal cancer were paired with noncancerous tissue. The biological function of SMC-4 knockdown was measured by CCK8 and plate colony formation assays. Fluorescence detection has been used to detect cell cycling and apoptosis. Results: SMC-4 expression was significantly higher in colorectal cancer and associated with T stage, N stage, AJCC stage and differentiation. Knockdown of SMC-4 expression significantly suppressed the proliferation of cancer cells and degraded its malignant degree. Conclusions: Our clinical and experimental data suggest that SMC-4 may contribute to the progression of colorectal carcinogenesis. Our study provides a new therapeutic target for colorectal cancer treatment.

Dynamic Analysis of Excavator Working Linkage System

Chun Qi Zheng,Guo Zhong Zhang,Bang Feng Wang 대한기계학회 1997 Asia-Pacific Vibration Conference Vol.1 No.1

High Survivin and Low Zinc Finger of the Cerebellum 1 Expression Indicates Poor Prognosis in Triple-negative Breast Carcinoma

Chun-Tao Shi,Jun Ma,Qi-Feng Shi,Ye Zhang,Hao-Nan Wang 한국유방암학회 2019 Journal of breast cancer Vol.22 No.2

Purpose: Triple-negative breast carcinoma (TNBC) is accompanied with high risk of metastasis and recurrence. The present study aimed to explore the clinicopathological and prognostic roles of putative tumor-related genes in patients with TNBC. Methods: Thirty pairs of frozen-thawed tumors were used to select reliable indicators via real-time quantitative polymerase chain reaction (RT-qPCR). Then, 150 pathology specimens were used to evaluate the expression of proteins in TNBC through immunohistochemistry. In addition, Kaplan-Meier curves and Cox regression analysis were also performed to analyze the overall survival and disease-free survival. Results: RT-qPCR results indicated that among all the proteins analyzed using fresh-frozen TNBC samples, the expression levels of only Survivin and zinc finger of the cerebellum 1 (ZIC1) were obviously different from those in the corresponding normal tissues. Survivin and ZIC1 expression had opposite effects on the clinicopathological diagnosis and prognostic assessment in TNBC patients. Further, there was a negative correlation between Survivin and ZIC1 expression. In addition, the “Survivin-positive ZIC1-negative group” was associated with histologic grade, lymph node metastasis, and TNM staging (p < 0.001) and this was also an independent factor for evaluating the prognosis of TNBC in patients. Conclusion: In summary, the expression levels of Survivin and ZIC1 in TNBC are different from those in normal tissues and are negatively correlated mutually. The combined detection of Survivin and ZIC1 expression levels could allow better comprehensive diagnosis and prognostic evaluation for TNBC patients.

Manufacture and antibacterial characteristics of Eucommia ulmoides leaves vinegar

Chun-Feng Jia,Wang-Ning Yu,Bo-Lin Zhang 한국식품과학회 2020 Food Science and Biotechnology Vol.29 No.5

In this work, the fermentation conditions and theantibacterial characteristics of Eucommia ulmoides leavesvinegar (EV) were studied. By single factor orthogonaltest, it was found that under optimal fermentation conditions(bran addition 10%, sugar addition 8%, leaven addition0.3% and acetic acid bacteria solution 12%), the aceticacid content and CA content of EV were 45.5 ± 2.8 mg/mL and 0.98 ± 0.08 mg/mL, respectively. Then, by thedisc diffusion method, it was concluded that the antibacterialeffect of EV was significantly higher than that ofEucommia ulmoides leaves enzymatic hydrolysate andZhenjiang aromatic vinegar (P\0.05). An investigationinto action mode of EV against Bacillus subtilis indicatedthat, under the combined action of CA and acetic acid, EVexerted its antibacterial effect by damaging bacterial cellwall and cell membrane, increasing the cell permeabilitywhich resulted in the structural lesions and release of cellcomponents, thus led to cell death.

A comparison of volatile fractions obtained from Lonicera macranthoides via different extraction processes: ultrasound, microwave, Soxhlet extraction, hydrodistillation, and cold maceration

Chun Wu,Feng Wang,Jiang Liu,Yuanfeng Zou,Xingfu Chen 한국한의학연구원 2015 Integrative Medicine Research Vol.4 No.3

Background: Hydrodistillation has been traditionally used to extract volatile fraction in traditional Chinese medicine. However, with the development of Soxhlet extraction (SE), microwave (MW), ultrasound (US), and cold maceration (CM), hydrodistillation (HD) is being replaced to meet some practical requirements. In this study, we investigated the effect of the five methods on the volatile fraction extract of Lonicera macranthoides. Methods: Volatile fraction from the flower buds of Lonicera macranthoides was obtained by using different extraction methods, HD, SE, MW, US, and CM. The compositions of volatile fraction were analyzed by gas chromatography–mass spectrometric and further compared among extraction methods. Results: Extracts obtained by the five methods reveal the qualitative and quantitative diversity in their compositions, especially for the low-content compositions. According to the results, SE shows the great value in the research where the high molecular-mass compound is of primary interest, and MW offers a way for the isolation of specific compound like octadecadienoic acid and hexadecanoic acid. HD, US, and CM have the advantage over SE and MW for the integrity of the constituents, whereas the phenomenon of compound degradation seems not so serious in solvent extraction methods such as US or CM as HD. Additionally, US and CM show superiority over time or material saving and diversity of the constituent. Conclusion: HD is still the best choice for the pure volatile fraction without organic solvent pollution. However, when it comes to some specifically actual demands, it can be replaced by the four methods for the volatile fraction extraction process, especially for production of certain compound groups.

Operational modal analysis of Canton Tower by a fast frequency domain Bayesian method

Feng-Liang Zhang,Yan-Chun Ni,Yan-Chun Ni,You-Wu Wang 국제구조공학회 2016 Smart Structures and Systems, An International Jou Vol.17 No.2

The Canton Tower is a high-rise slender structure with a height of 610 m. A structural health monitoring system has been instrumented on the structure, by which data is continuously monitored. This paper presents an investigation on the identified modal properties of the Canton Tower using ambient vibration data collected during a whole day (24 hours). A recently developed Fast Bayesian FFT method is utilized for operational modal analysis on the basis of the measured acceleration data. The approach views modal identification as an inference problem where probability is used as a measure for the relative plausibility of outcomes given a model of the structure and measured data. Focusing on the first several modes, the modal properties of this supertall slender structure are identified on non-overlapping time windows during the whole day under normal wind speed. With the identified modal parameters and the associated posterior uncertainty, the distribution of the modal parameters in the future is predicted and assessed. By defining the modal root-mean-square value in terms of the power spectral density of modal force identified, the identified natural frequencies and damping ratios versus the vibration amplitude are investigated with the associated posterior uncertainty considered. Meanwhile, the correlations between modal parameters and temperature, modal parameters and wind speed are studied. For comparison purpose, the frequency domain decomposition (FDD) method is also utilized to identify the modal parameters. The identified results obtained by the Bayesian method, the FDD method and a finite element model are compared and discussed.