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.

Key Application Technologies of High Efficiency Power Quality Control Systems

Liu, Ding-Guo,Shuai, Zhi-Kang,Tu, Chun-Ming,Cheng, Ying,Luo, An The Korean Institute of Power Electronics 2013 JOURNAL OF POWER ELECTRONICS Vol.13 No.3

Large capacity reactive power compensation and harmonic control in the low-voltage grid of an enterprise, are important technical means to improve power quality and reduce power loss. In this paper, the principle of an efficient power quality controller is analyzed. Then, key application technologies of the HPQC which would influence the performances of the HPQC are studied. Based on an analysis of the harmonic shunt problem, a frequency dividing control strategy of the HPQC continuous subsystem is proposed. A parameter design method of the HPQC discrete subsystem and its installation method are also proposed to ensure the system compensation effect. HPQC systems have been designed for a copper foil plant. The effectiveness of this paper has been verified by the simulation and application results.

Corona generated Radio Interference of the 750 kV AC Bundle Conductors in Sandy and Dusty Weather Condition in the High Altitude Area

Liu, Yun-Peng,Zhu, Lei,Lv, Fang-Cheng,Wan, Bao-Quan,Pei, Chun-Ming The Korean Institute of Electrical Engineers 2014 Journal of Electrical Engineering & Technology Vol.9 No.5

Sandy and dusty weather condition often occurs in the high altitude areas of China, which may greatly influence the corona generated radio interference (RI) characteristics of the bundle conductors of 750 kV AC power transmission lines. Corona generated RI of the conductors of the 750 kV AC power transmission lines used in practice is measured by EMI receiver with a coupling circuit and a coupling capacitor connected between the high voltage side and the earth side in fine and sandy and dusty condition. The measuring frequency is 0.5 MHz, and the quasi-peak detection is used. RI excitation function is calculated based on the corona RI current measured by the EMI receiver. Corona generated RI characteristics were analyzed from sand concentration and sand particle size. The test result shows that the corona generated RI excitation function is influenced by the sandy and dusty condition. Corona discharge of the conductors is more serious in sandy and dusty condition with an ultraviolet (UV) detector. Corona generated RI excitation function increases with the increase of sand concentration and also increases with the increase of particle size.

Lack of Assocation of Glutathione S-transferase T1 Gene Null and Susceptibility to Lung Cancer in China: a Meta-analysis

Liu, Hong-Zhou,Peng, Jie,Zheng, Fang,Wang, Chun-Hong,Han, Ming-Jun Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.12

Background: Variation in metabolic genes is regarded as an important factor in processes leading to cancer. However, the effect of GSTT1 null genotype is divergent in the form of lung cancer. Methods: Studies were conducted at different research databases from 1990 to 2013 and the total odds ratio (OR) and 95% confidence interval (CI) were calculated for lung cancer. Review Manager 5.2 and STATE 12 are employed. Results: Total OR value is calculated from 17 articles with 2,118 cases and 2,915 controls. We discovered no significant increase in lung cancer risk among subjects carrying GSTT1 null genotype [OR = 1.15; 95% CI 0.97-1.36] in this meta-analysis. Conclusion: The GSTT1 deletion polymorphism does not have a significant effect on the susceptibility to lung cancer overall in China.

Characteristics of registered studies for Coronavirus disease 2019 (COVID-19): a systematic review

Ming Yang,Ya-xi Shang,Zi-yu Tian,Min Xiong,Chun-li Lu,Jiang Yue,Zhang Yao,Zhang Ying-ying,Jin Xin-yan,Jin Qiu-bai,Zhang Ying-ying,Willcox Merlin L.,Liu Jian-ping 한국한의학연구원 2020 Integrative Medicine Research Vol.9 No.3

Background: The World Health Organization characterized the Coronavirus disease 2019 (COVID-19) as a pandemic on March 11th. Many clinical trials on COVID-19 have been registered, and we aim to review the study characteristics and provide guidance for future trials to avoid duplicated effort. Methods: Studies on COVID-19 registered before March 3rd, 2020 on eight registry platforms worldwide were searched and the data of design, participants, interventions, and outcomes were extracted and analyzed. Results: Three hundred and ninety-three studies were identified and 380 (96.7%) were from mainland China, while 3 in Japan, 3 in France, 2 in the US, and 3 were international collaborative studies. Two hundred and sixty-six (67.7%) aimed at therapeutic effect, others were for prevention, diagnosis, prognosis, etc. Two hundred and two studies (51.4%) were randomized controlled trials. Two third of therapeutic studies tested Western medicines including antiviral drugs (17.7%), stem cell and cord blood therapy (10.2%), chloroquine and derivatives (8.3%), 16 (6.0%) on Chinese medicines, and 73 (27.4%) on integrated therapy of Western and Chinese medicines. Thirty-one studies among 266 therapeutic studies (11.7%) used mortality as primary outcome, while the most designed secondary outcomes were symptoms and signs (47.0%). Half of the studies (45.5%) had not started recruiting till March 3rd. Conclusion: Inappropriate outcome setting, delayed recruitment and insufficient numbers of new cases in China implied many studies may fail to complete. Strategies and protocols of the studies with robust and rapid data sharing are warranted for emergency public health events, helping the timely evidence-based decision-making.

Schistosomiasis Combined with Colorectal Carcinoma Diagnosed Based on Endoscopic Findings and Clinicopathological Characteristics: A Report on 32 Cases

Liu, Wei,Zeng, Hong-Ze,Wang, Qi-Ming,Yi, Hang,Mou, Yi,Wu, Chun-Cheng,Hu, Bing,Tang, Cheng-Wei Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.8

Aims and Background: To improve understanding of the relationship between schistosome-related enteropathy and colorectal carcinoma with particular focus on endoscopic findings and clinicopathological characteristics of colonic schistosomiasis. Materials and Methods: All cases of intestinal schistosomiasis diagnosed at West China Hospital, Chengdu, China, between October 2006 and October 2012 were included in this study. A total of 179 cases of colonic schistosomiasis diagnosed through colonoscopy and pathological examinations were collected for analysis and the demographics, symptoms, endoscopic findings and clinicopathological characteristics were retrospectively evaluated. Results: Of the 179 colonic schistosomiasis patients, 32 combined with colorectal cancer (CRC) were found, between the ages of 44 and 85 years (24 males, 75%). These 32 lesions were classified as 12 endophytic/ulcerative (37.5%), 10 exophytic/fungating (31.2%), 4 annular (12.5%), 3 giant polypus (9.4%), and 3 IIc (superficial depressed type) (9.4%). The segments of rectum and sigmoid colon were involved in 19 patients (59.4%) and 6 patients (18.8%), respectively. The histopathologic types were classified as follows: 30 welldifferentiated adenocarcinomas, one mucinous adenocarcinoma and one poorly differentiated adenocarcinoma. The pathological findings suggest colorectal malignancy with deposited schistosome ova. Conclusions: Chronic schistosomal infestation has a probable etiological role in promoting genesis of colorectal neoplasms.

Compound HRAS/PIK3CA Mutations in Chinese Patients with Alveolar Rhabdomyosarcomas

Liu, Chun-Xia,Li, Xiao-Ying,Li, Cheng-Fang,Chen, Yun-Zhao,Cui, Xiao-Bin,Hu, Jian-Ming,Li, Feng Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.4

The rhabdomyosarcoma (RMS) is the most common type of soft tissue tumor in children and adolescents; yet only a few screens for oncogenic mutations have been conducted for RMS. To identify novel mutations and potential therapeutic targets, we conducted a high-throughput Sequenom mass spectrometry-based analysis of 238 known mutations in 19 oncogenes in 17 primary formalin-fixed paraffin-embedded RMS tissue samples and two RMS cell lines. Mutations were detected in 31.6% (6 of 19) of the RMS specimens. Specifically, mutations in the NRAS gene were found in 27.3% (3 of 11) of embryonal RMS cases, while mutations in NRAS, HRAS, and PIK3CA genes were identified in 37.5% (3 of 8) of alveolar RMS (ARMS) cases; moreover, PIK3CA mutations were found in 25% (2 of 8) of ARMS specimens. The results demonstrate that tumor profiling in archival tissue samples is a useful tool for identifying diagnostic markers and potential therapeutic targets and suggests that these HRAS/ PIK3CA mutations play a critical role in the genesis of RMS.

Glutathione S-transferase M1 Null Genotype and Hepatocellular Carcinoma Susceptibility in China and India: Evidence from an Updated Meta-analysis

Liu, Hong-Zhou,Peng, Jie,Peng, Chun-Yan,Yan, Ming,Zheng, Fang Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.12

Background: Glutathione S-transferase M1 (GSTM1) have been reported to be associated with hepatocellular carcinoma. However, the effect of the GSTMl null genotype was divergent in the literature and we therefore performed the present meta-analysis to explore the relationship in detail. Materials and Metbods: Reported studies were searched from 1990 to March 1, 2014 in PubMed and Wanfang Med Online. The total odds oatio (OR) and 95% CI were calculated and analyzed by Review Manager 5.1 and STATE 12. Results: Total OR was calculated from 26 articles with 3,769 cases and 5,517 controls and the association proved significant (OR [95%CI]=1.50 [1.25, 1.80], P<0.05) in the Chinese population. However, there was no significant association between hepatocellular carcinoma risk among subjects carrying the GSTM1 null genotype (OR [95%CI]=1.20 [0.88-1.64], P=0.24) in subgroups of publication in English and in Indian populations (OR [95%CI]=1.80 [0.80-4.20], P=0.15). Conclusions: The GSTM1 deletion polymorphism might not have a significant effect on the susceptibility of hepatocellular carcinoma overall.

Efficacy and Safety of 12 Weeks of Daclatasvir, Asunaprevir Plus Ribavirin for the Treatment of HCV Genotype 1b Infection without Baseline NS5A Resistance-Associated Variants (DARING)-Interim Report

( Ming-lung Yu ),( Chao-hung Hung ),( Yi-hsiang Huang ),( Cheng-yuan Peng ),( Chun-yen Lin ),( Pin-nan Cheng ),( Rong-nan Chien ),( Shih-jer Hsu ),( Chen-hua Liu ),( Jee-fu Huang ),( Chung-feng Huang 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: The current study aims to elucidate the treatment efficacy (defined as undetectable HCV RNA throughout 12 weeks of post-treatment follow-up, SVR12) and safety DCV/ASV plus ribavirin for 12 weeks in HCV-1b patients without NS5A RAS. Methods: This is a single-arm, open-label phase 2 study. Seventy directly acting antivirals (DAA)-naïve HCV-1b patients without L31/Y93 RAS are planned to receive daclatasvir (60 mg/ day) and asunaprevir (100 mg twice daily) plus weight-based ribavirin (1000-1200 mg/day) for 12 weeks. After treatment they were followed up for 12 weeks. Results: As of 31 Oct 2017, 58 eligible patients are allocated to treatment, with a mean age of 59.3 years and female predominance (67.2%, 39/58). The mean HCV RNA was 5.87+0.77 log10 IU/mL; 23 patients (39.7 %) had significant hepatic fibrosis (>F2). In the modified intention-to-treat analysis, the rate of undetectable HCV at week 1, week 2, week 4, week 8 and endof- treatment was 25 % (14/56), 84.8 % (39/46), 100 % (46/46), 100 % (38/38) and 100 % (27/27), respectively. Undetectable HCV RNA were observed in all of the patients with HCV RNA assessable 4 weeks (SVR4, 18/18) and 12 weeks (SVR12, 12/12) post treatment. None of the 18 patients who completed the 12-week treatment experienced relapse during post-treatment follow-up. The most common adverse event was fatigue (78.3 %), followed by pruritus (65.2 %) and dizziness (52.2 %), of which were considered as ribavirin related. None of the participating subjects withdrew treatment or follow-up throughout the trial peroid. Three serious adverse events were reported which included urosepsis, appendicitis and left ureteral stone. All were unrelated to the investigating drugs. Conclusions: 12 weeks of DCV/ASV plus ribavirin was highly effective and safe in HCV-1b patients without NS5A RAS in the interim analysis. The satisfactory results would be anticipated in the full patient set.

Influence of Pinewood Nematode, Bursaphelenchus xylophilus, on the Growth of Endoparasitic Fungus Esteya vermicola

Chun Yan Wang(왕춘연),Chung Ha Lee(이청하),Mi Ra Lee(이미라),Beom Sik Yun(윤범식),Lei Liu(유뢰),Zhen Wang(왕젠),Zhe Ming Fang(방철명),Dong Liang Zhang(장동량),Zheng Li(이정),Chang Keun Sung(성창근) 한국생명과학회 2010 생명과학회지 Vol.20 No.5

본 논문은 선충 포식성 곰팡이에 대한 선충의 영향을 조사한 연구로, 소나무 기생곰팡이인 E. vermicola에 미치는 소나무 선충의 영향을 체계적으로 분석하였다. 선충 대사물과 선충 균질액 모두 E. vermicola의 성장을 빠르게 촉진하였으나, 선충 대사물이 선충 균질액보다 약간 높은 효과를 보였다. 또한 소나무 선충이 생성하는 휘발성 물질이 E. vermicola 성장에 미치는 영향을 분석하는 새로운 실험방법을 개발하였다. 본 연구결과에 따르면, 선충의 휘발성 물질은 E. vermicola에 아무런 영향을 끼치지 않는다는 재현성 있는 결과를 도출하였다. 본 연구는 소나무 선충의 생물학적인 조절인자로서 E. vermicola을 적용할 수 있는 정보를 제공할 수 있을 것이다. The influence of nematodes on nematophagous fungi has seldom been investigated. In the present study, the influence of pinewood nematode on its endoparasitic fungus, Esteya vermicola, was investigated systemically. Although both nematodal metabolite and nematodal homogenate could stimulate and speed up the growth of E. vermicola, the impact of nematodal metabolite was slightly higher than that of nematodal homogenate. In addition, a method was developed to investigate the influence of volatiles, discharged by pinewood nematodes in their metabolic process, on the growth of E. vermicola. Reproductive results were given and confirmed that nematodal volatiles have no influence on the cell growth of E. vermicola. This study may provide information for the application of E. vermicola as biological control agent of pinewood nematode.