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.

Effect of the Circle-Grid Electrodes on Concentrated GaAs Solar Cell Efficiency

Chen-Chen Chung,Binh Tinh Tran,Ming-Hung Han,Kung-Liang Lin,Hung-Wei Yu,Yen-Teng Ho,Chun-Yen Chang,Edward Yi Chang 대한금속·재료학회 2014 ELECTRONIC MATERIALS LETTERS Vol.10 No.5

In this study, we investigate the effect of the shading factor of the front grid pattern on concentrated solar cell efficiency, taking the trade-off between the series resistance of the electrodes and the amount of incident light into consideration. We examine the thermal effect with regard to five different circle-grid electrode patterns of the front contact. The front contacts with different grid patterns affect the characteristics of light-concentratedtype GaAs single-junction solar cells. The device parameters analyzed include the open-circuit voltage (Voc), short-circuit current (Isc), fill factor (FF) and conversion efficiency (η). The results of our study show that for a concentration ratio greater than 60x with AM1.5G, the device with a shading factor of 7.1% has the best cell efficiency of 27.05%, due to the smaller current crowding at the center spot. The results indicate that the conversion efficiency of solar cells can be improved by establishing a compromise between the shading effect and the series resistance effect.

Application of Auriculotherapy for Post-Burn Scar Syndrome in Young Adults with Major Burns

Cha-Chun Chen,San-Pei Chen,Shu-Yu Lyu,Chung-Hua Hsu 사단법인약침학회 2021 Journal of Acupuncture & Meridian Studies Vol.14 No.4

Background: A burn scar is a type of hypertrophic scar that can cause significant clinical symptoms, discomfort, and post-burn scar (PBS) syndrome in up to 77% of patients with burn injuries. Medication and rehabilitation are rarely effective at managing patient discomfort, and both laser and surgical interventions are postponed until the scar stabilizes and discomfort is tolerable. Objectives: The present study was conducted to investigate the effectiveness of auricular acupuncture among burn victims from the Formosa Color Dust Explosion in Taiwan. Methods: We enrolled 31 victims of the 2016 Formosa Color Dust Explosion who met the study inclusion criteria. The intervention involved placement of magnetic beads over the auricular Shenmen and Subcortex acupoints on one ear. Patients performed selfmassage five times per day, and both magnet beads were removed between the fifth and seventh days during the sessions. Several evaluation tools were used to assess clinical symptoms: the visual analogue scale for pain assessment, Burn Man Itch Scale for perceived patient itchiness, 5-D Pruritus Scale for sleep quality, and heart rate variability (HRV) for effects on the autonomic nervous system. Results: The clinical symptoms were significantly decreased following the intervention, but the effect did not endure. The normal-to-normal heart rate interval, heart rate analysis abnormalities, and very low frequency heart rate were significantly decreased among patients with abnormal HRV (SD < 40) following treatment. Conclusion: Stimulation of the auricular Shenmen and Subcortex acupoints may effectively reduce pain, itchiness, and sleep disturbances among patients with PBS syndrome.

Swelling and hydraulic characteristics of two grade bentonites under varying conditions for low-level radioactive waste repository design

Chih-Chung Chung,Guo-Liang Ren,I-Ting Chen,Che-Ju, Cuo,Hao-Chun Chang Korean Nuclear Society 2024 Nuclear Engineering and Technology Vol.56 No.4

Bentonite is a recommended material for the multiple barriers in the final disposal of low-level radioactive waste (LLW) to prevent groundwater intrusion and nuclear species migration. However, after drying-wetting cycling during the repository construction stage and ion exchange with the concrete barrier in the long-term repository, the bentonite mechanical behaviors, including swelling capacity and hydraulic conductivity, would be further influenced by the groundwater intrusion, resulting in radioactive leakage. To comprehensively examine the factors on the mechanical characteristics of bentonite, this study presented scenarios involving MX-80 and KV-1 bentonites subjected to drying-wetting cycling and accelerated ion migration. The experiments subsequently measured free swelling, swelling pressure, and hydraulic conductivity of bentonites with intrusions of seawater, high pH, and low pH solutions. The results indicated that the solutions caused a reduction in swelling volume and pressure, and an increase in hydraulic conductivity. Specifically, the swelling capability of bentonite with drying-wetting cycling in the seawater decreased significantly by 60%, while hydraulic conductivity increased by more than three times. Therefore, the study suggested minimizing drying-wetting cycling and preventing seawater intrusion, ensuring a long service life of the multiple barriers in the LLW repository.

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.

Leukocyte invasion of the brain after peripheral trauma in zebrafish (Danio rerio)

Chen Xiang-Ke,Kwan Joseph Shiu-Kwong,Wong Gordon Tin-Chun,Yi Zhen-Ni,Ma Alvin Chun-Hang,Chang Raymond Chuen-Chung 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-

Despite well-known systemic immune reactions in peripheral trauma, little is known about their roles in posttraumatic neurological disorders, such as anxiety, sickness, and cognitive impairment. Leukocyte invasion of the brain, a common denominator of systemic inflammation, is involved in neurological disorders that occur in peripheral inflammatory diseases, whereas the influences of peripheral leukocytes on the brain after peripheral trauma remain largely unclear. In this study, we found that leukocytes, largely macrophages, transiently invaded the brain of zebrafish larvae after peripheral trauma through vasculature-independent migration, which was a part of the systemic inflammation and was mediated by interleukin-1b (il1b). Notably, myeloid cells in the brain that consist of microglia and invading macrophages were implicated in posttraumatic anxiety-like behaviors, such as hyperactivity (restlessness) and thigmotaxis (avoidance), while a reduction in systemic inflammation or myeloid cells can rescue these behaviors. In addition, invading leukocytes together with microglia were found to be responsible for the clearance of apoptotic cells in the brain; however, they also removed the nonapoptotic cells, which suggested that phagocytes have dual roles in the brain after peripheral trauma. More importantly, a category of conserved proteins between zebrafish and humans or rodents that has been featured in systemic inflammation and neurological disorders was determined in the zebrafish brain after peripheral trauma, which supported that zebrafish is a translational model of posttraumatic neurological disorders. These findings depicted leukocyte invasion of the brain during systemic inflammation after peripheral trauma and its influences on the brain through il1b-dependent mechanisms.

Microstructure and Mechanical Properties of Polyurethane/nylon/montmorillonite Nanocomposite

Chun, Byoung-Chul,Cho, Tae-Keun,Chong, Mi-Hwa,Chung, Yong-Chan,Martin, David,Chen, Jihua,Park, Jong-Shin The Korean Fiber Society 2007 Fibers and polymers Vol.8 No.1

Nanocomposite of polyurethane(PU), Nylon66(nylon), and montmorillonite(MMT) was prepared by a twin screw extruder, and the dispersion of MMT and the mechanical properties of the nanocomposite were analyzed. Dimethyl hydrogenated tallow 2-ethylhexyl ammonium modified Cloisite 25A(C25A) and methyl tallow bis-2-hydroxyethyl ammonium modified Cloisite 30B(C30B) were used as MMT. XRD and TEM analysis indicated that the continuous melt mixing by a twin screw extruder was effective in MMT dispersion. C30B having hydroxyl group on its surface has better dispersion than C25A in the PU/nylon matrix. Maximum stress and strain at break were the maximum at 1 wt% MMT regardless of matrix composition, and decreased at higher MMT content. Best MMT dispersion was also observed at 1 wt% MMT for the entire matrix composition. Aggregation of MMT occurred at MMT content higher than 1 wt%. Nylon addition also induced the aggregation of MMT because of the high polarity of nylon surface. Dispersion of MMT was very important in improving the mechanical properties of PU/nylon nanocomposite.

Mechanical properties of polyurethane/montmorillonite nanocomposite prepared by melt mixing

Chun, Byoung Chul,Cho, Tae Keun,Chong, Mi Hwa,Chung, Yong-Chan,Chen, Jihua,Martin, David,Cieslinski, Robert C. Wiley Subscription Services, Inc., A Wiley Company 2007 Journal of applied polymer science Vol.106 No.1

<P>Nanocomposites from polyurethane (PU) and montmorillonite (MMT) were prepared under melt-mixing condition, by a twin screw extruder along with a compatibilizer to enhance dispersion of MMT. MMT used in this study was Cloisite 25A (modified with dimethyl hydrogenated tallow 2-ethylhexyl ammonium) or Cloisite 30B (modified with methyl tallow bis-2-hydroxyethyl ammonium). Maleic anhydride grafted polypropylene (MAPP) was used as the compatibilizer. XRD and TEM analysis demonstrated that melt mixing by a twin-screw extruder was effective in dispersing MMT through the PU matrix. The PU/Cloisite 30B composite exhibited better interlayer separation than the PU/Cloiste 25A composite. Nanoparticle dispersion was the best at 1 wt % of MMT and improved with compatibilizer content for both composites. Properties of the composites such as complex viscosity and storage modulus were higher than that of a pure PU matrix and increased with the increase in MMT content, but decreased with the increase in compatibilizer content. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007</P>

Apache REEF: Retainable Evaluator Execution Framework

Chun, B.-G.,Condie, T.,Chen, Y.,Cho, B.,Chung, A.,Curino, C.,Douglas, C.,Interlandi, M.,Jeon, B.,Jeong, J. S. ACM ASSOCIATION FOR COMPUTING MACHINERY 2017 ACM transactions on computer systems Vol.35 No.2

Evaluation of Antiobesity Activity of Soybean Meal Products Fermented by Lactobacillus plantarum FPS 2520 and Bacillus subtilis N1 in Rats Fed with High-Fat Diet

Chung-Hsiung Huang,Chun-Lung Chen,Shun-Hsien Chang,Guo-Jane Tsai 한국식품영양과학회 2020 Journal of medicinal food Vol.23 No.6

Single strain or mixed strains of Lactobacillus plantarum FPS 2520 and Bacillus subtilis N1 were used to ferment soybean meal (SBM), and the antiobesity activity of the fermented SBM product was investigated in rats fed with high-fat diet (HFD). After fermentation, free amino nitrogen, total peptide, and isoflavone contents were markedly raised, and genistein and daidzein were the major isoflavones in the fermented SBM. After fed with HFD for 10 weeks, obese Sprague-Dawley rats were orally treated with various fermented products for 6 weeks. The body weight gains, as well as weights of abdominal fat and epididymis fat, of rats fed with fermented SBM products were significantly downregulated. The treatment with the mixed-strains fermented SBM product significantly decreased plasma levels of triglyceride (TG), total cholesterol (TC), and low-density lipoprotein-cholesterol, but increased the level of high-density lipoprotein-cholesterol. Moreover, the levels of TG, TC, fatty acid synthase, and acetyl-CoA carboxylase (ACC) in liver were diminished, and the activities of hormone-sensitive lipase and lipoprotein lipase in adipose tissue were augmented. Taken together, these data demonstrated the antiobesity activity of fermented SBM products, among which the product fermented by the mixed strains being the most effective one. Therefore, these fermented SBM products are potential to be developed as functional foods or additives for treatment of obesity and prevention against obesity-induced complications.