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.

Treatment outcomes of patients with stage II pure endometrioid-type endometrial cancer: a Taiwanese Gynecologic Oncology Group (TGOG-2006) retrospective cohort study

Hung-Chun Fu,Jen-Ruei Chen,Min-Yu Chen,Keng-Fu Hsu,Wen-Fang Cheng,An Jen Chiang,Yu-Min Ke,Yu-Chieh Chen,Yin-Yi Chang,Chia-Yen Huang,Chieh-Yi Kang,Yuan-Yee Kan,Sheng-Mou Hsiao,Ming-Shyen Yen 대한부인종양학회 2018 Journal of Gynecologic Oncology Vol.29 No.5

Objective: Choice of hysterectomy and adjuvant treatment for International Federation of Gynecology and Obstetrics (FIGO) 2009 stage II endometrioid endometrial cancer (EEC) is still controversial. Aims of this study were to evaluate survival benefits and adverse effects of different hysterectomies with or without adjuvant radiotherapy (RT), and to identify prognostic factors. Methods: The patients at 14 member hospitals of the Taiwanese Gynecologic Oncology Group from 1992 to 2013 were retrospectively investigated. Patients were divided into simple hysterectomy (SH) alone, SH with RT, radical hysterectomy (RH) alone, and RH with RT groups. Endpoints were recurrence-free survival (RFS), overall survival (OS), disease-specific survival (DSS), adverse effects and prognostic factors for survival. Results: Total of 246 patients were enrolled. The 5-year RFS, OS, DSS and recurrence rates for the entire cohort were 89.5%, 94.3%, 96.2% and 10.2%, respectively. Patients receiving RH had more adverse effects including blood loss (p<0.001), recurrent urinary tract infections (p=0.013), and leg lymphedema (p=0.038). Age over 50-year (HR=9.2; 95% confidence interval [CI], 1.2–70.9) and grade 3 histology (HR=7.28; 95% CI, 1.45–36.6) were independent predictors of OS. Grade 3 histology was an independent predictor of RFS (HR=5.13; 95% CI, 1.38–19.1) and DSS (HR=5.97; 95% CI, 1.06–58.7). Patients receiving adjuvant RT had lower locoregional recurrence (p=0.046), but no impact on survival. Conclusion: Different treatment modalities yield similar survival outcomes. Patients receiving SH with RT had lower locoregional recurrent with acceptable morbidity. Age and tumor grading remained significant predictors for survival among patients with FIGO 2009 stage II EEC.

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.

Heart Rate Variability Biofeedback Increased Autonomic Activation and Improved Symptoms of Depression and Insomnia among Patients with Major Depression Disorder

I-Mei Lin,Sheng-Yu Fan,Cheng-Fang Yen,Yi-Chun Yeh,Tze‐Chun Tang,Mei-Feng Huang,Tai-Ling Liu,Peng-Wei Wang,Huang-Chi Lin,Hsin-Yi Tsai,Yu-Che Tsai 대한정신약물학회 2019 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.17 No.2

Objective: Autonomic imbalance is considered a psychopathological mechanism underlying major depressive disorder (MDD). Heart rate variability (HRV) is an index for autonomic activation. Poor sleep quality is common among patients with MDD. HRV biofeedback (BF) has been used for regulating autonomic balance among patients with physical illness and mental disorders. The purpose of present study was to examine the effects of HRV-BF on depressive symptoms, sleep quality, pre-sleep arousal, and HRV indices, in patients with MDD and insomnia. Methods: In this case-controlled study, patients with MDD and Pittsburgh Sleep Quality Index (PSQI) score higher than 6 were recruited. The HRV-BF group received weekly 60-minute protocol for 6 weeks, and the control group who have matched the age and sex received medical care only. All participants were assessed on Beck Depression Inventory-II, Back Anxiety Inventory, PSQI, and Pre-Sleep Arousal Scale. Breathing rates and electrocardiography were also performed under resting state at pre-testing, and post-testing conditions and for the HRV-BF group, also at 1-month follow-up. Results: In the HRV-BF group, symptoms of depression and anxiety, sleep quality, and pre-sleep arousal were significantly improved, and increased HRV indices, compared with the control group. Moreover, in the HRV-BF group, significantly improved symptoms of depression and anxiety, decreased breathing rates, and increased HRV indices were detected at post-testing and at 1-month follow-up, compared with pre-testing values. Conclusion: This study confirmed that HRV-BF is a useful psychosocial intervention for improving autonomic balance, baroreflex, and symptoms of depression and insomnia in MDD patients.

Platelet-Derived Growth Factor Receptor-α Subunit Targeting Suppresses Metastasis in Advanced Thyroid Cancer In Vitro and In Vivo

( Ching-ling Lin ),( Ming-lin Tsai ),( Yu-hsin Chen ),( Wei-ni Liu ),( Chun-yu Lin ),( Kai-wen Hsu ),( Chien-yu Huang ),( Yu-jia Chang ),( Po-li Wei ),( Shu-huey Chen ),( Li-chi Huang ),( Chia-hwa Lee 한국응용약물학회 2021 Biomolecules & Therapeutics(구 응용약물학회지) Vol.29 No.5

Thyroid cancer is the most common endocrine malignancy. Patients with well-differentiated thyroid cancers, such as papillary and follicular cancers, have a favorable prognosis. However, poorly differentiated thyroid cancers, such as medullary, squamous and anaplastic advanced thyroid cancers, are very aggressive and insensitive to radioiodine treatment. Thus, novel therapies that attenuate metastasis are urgently needed. We found that both PDGFC and PDGFRA are predominantly expressed in thyroid cancers and that the survival rate is significantly lower in patients with high PDGFRA expression. This finding indicates the important role of PDGF/PDGFR signaling in thyroid cancer development. Next, we established a SW579 squamous thyroid cancer cell line with 95.6% PDGFRA gene insertion and deletions (indels) through CRISPR/Cas9. Protein and invasion analysis showed a dramatic loss in EMT marker expression and metastatic ability. Furthermore, xenograft tumors derived from PDGFRA geneedited SW579 cells exhibited a minor decrease in tumor growth. However, distant lung metastasis was completely abolished upon PDGFRA gene editing, implying that PDGFRA could be an effective target to inhibit distant metastasis in advanced thyroid cancers. To translate this finding to the clinic, we used the most relevant multikinase inhibitor, imatinib, to inhibit PDGFRA signaling. The results showed that imatinib significantly suppressed cell growth, induced cell cycle arrest and cell death in SW579 cells. Our developed noninvasive apoptosis detection sensor (NIADS) indicated that imatinib induced cell apoptosis through caspase-3 activation. In conclusion, we believe that developing a specific and selective targeted therapy for PDGFRA would effectively suppress PDGFRA-mediated cancer aggressiveness in advanced thyroid cancers.

On The Security of RFID-based Monitoring Mechanism for Retail Inventory Management

( Yu Yi Chen ),( Jinn Ke Jan ),( Meng Lin Tsai ),( Chun Ching Ku ),( Der Chen Huang ) 한국인터넷정보학회 2012 KSII Transactions on Internet and Information Syst Vol.6 No.2

The aim of this article is to provide a study on the issue of inventory inaccuracy and to show the manner in which RFID technology can improve the inventory management performance. The objective of inventory control is to monitor the stock flow of merchandises in order to understand the operating profit and loss. A proper mechanism of inventory control could be made to help the profitability. As RFID is applied to inventory control, it can improve efficiency, enhance accuracy and achieve security. In this paper, we introduce the evolution of different mechanisms of inventory control with RFID system - counting method, collect-all method, and continuous monitoring method. As for improving the accuracy of inventory check during business hours, continuous monitoring is the solution. We introduce the infrastructure of the RFID inventory management system based on M2M architecture can make the inventory be efficiently monitored with instant warnings.

Possible Applications for Fascial Anatomy and Fasciaology in Traditional Chinese Medicine

Yu Bai,소광섭,Byung-Cheon Lee,Yong Huang,Chun-lei Wang,Jun Wang,Jin-peng Wu,Jing-xing Dai,Janos Palhalmi,Ou Sha,David Tai Wai Yew,Lin Yuan 사단법인약침학회 2010 Journal of Acupuncture & Meridian Studies Vol.3 No.2

Research using medical imaging instruments such as computed tomography and magnetic resonance imaging has led to the proposal that the fascial network distributed over the human body is the anatomical basis for the acupoints and meridians of traditional Chinese medicine. Therefore, we put forward a new theory of anatomy called fascial anatomy. In fascial anatomy, a human body is divided into two major systems. One is the supporting-storing system of unspecialized connective tissues. The other is a functional system. An undifferentiated non-specific connective tissue network, with the participation of the nervous and the immune systems, constitutes the supporting-storing system of the human body. The various differentiated functional cells in the body that are supported and surrounded by the supporting-storing system constitute the functional system. The discipline that studies the supporting-storing system and the mutual relationship between this system and the functional system in a living human body is called fasciaology. The establishment of fascial anatomy and fasciaology opens a new research field in anatomy; consequently, fasciaology will play a significant role in biological medicine and traditional Chinese medical research, as well as future clinical practice.

Estimation of channel MSE for ATSC 3.0 receiver and its applications

Yu-Sun Liu,Chun-Hung Huang,Shingchern D. You 한국통신학회 2022 ICT Express Vol.8 No.2

In this paper, we propose a method to estimate the mean square error (MSE) of the estimated channel for ATSC (Advanced Television Systems Committee) 3.0 systems. When combining the channel MSE and noise variance, we can better estimate the a priori LLR (log likelihood ratio) for the sum–product algorithm. The experimental results show that doing so yields better BER (bit error rate) performance in the 0 dB echo channel. The improvement in the 2-D channel estimation is about 0.2 dB. In the 1-D estimation case, the proposed approach is essential to decode codewords.

Fabrication and Study of Novel Piezoresistive Polymer Composites Sensor for 3D Printing Applications

( Yu-yen Chen ),( Cheng-chun Huang ),( Ching-yuan Su ),( Yao-chuan Tsai ) 한국농업기계학회 2018 한국농업기계학회 학술발표논문집 Vol.23 No.1

With the technology development, the technique of 3D printing has gradually matured. The characteristic of 3D printing is that it can print the product directly without another complex process. If the 3D printing could be applied to manufacturing sensor elements, it could be quicker and cheaper for the sensor element fabrication and the sensor forms will be applicable. Piezoresistive effect is a common sensor sensing principle which is through the deformation of the material to cause the resistance changes. In this study, a piezoresistive polymer composites material was developed, which can be manufactured by the photo-curable 3D printing. The different amount of the conductive carbon black (CB) nanoparticles was employed and added into photo-curable resin for obtaining the conductive percolation threshold of the polymer composites and measuring the piezoresistivity of the polymer composites. The conductive percolation threshold is around 1.0~1.5wt%, and the gauge factor of 1.5wt% is 9~17. The gauge factor was found which would decrease with the increasing strains. This study can be applied on fabricating the piezoresistive pressure and tactile sensors which can be used to the agricultural, industrial and various industries.

Repairing Facial Soft Tissue Defects by Swelling Anesthesia after Tumor Resection with Narrow Pedicle Flaps

Huang, Chun-Hui,Qian, Han-Gen,Zhao, Xiao-Yu,Shen, Guo-Liang,Lin, Wei,Qi, Qiang Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.15

Aims: To investigate the role of swelling anesthesia in repairing facial soft tissue defects after tumor resection and temporal superficial artery frontal branch of narrow pedicle flap. Materials and Methods: From January 2008 to June 2008, 16 patients from Department of Ophthalmology with eye or eyelid tumors after eyeball removal of eye and part resection of surrounding soft tissue, undergoing postoperative swelling anesthesia with superficial temporal artery flap repair to prevent facial soft tissue defect formation and bone exposure, were recruited. Results: In all 16 patients facial soft tissue defect repair had good effects, with limited bleeding, and short operation times. Seven days after surgery, all flaps were in good repair. On postoperative follow-up after 3 months, flaps showed a similar appearance as with facial tissue. Conclusions: Swelling anesthesia for superficial temporoparietal artery frontal branch of narrow pedicle flap to repair soft tissue defect after facial tumor resection is feasible, and is linked with good analgesic effects, high postoperative survival of skin flaps, and good cosmetic effects.