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.

Transaxillary Capsulorrhaphy with Reimplantation to Correct Bottoming-Out Deformity in Breast Mycobacterial Periprosthetic Infection: A Case Report with Literature Review

Huang Tsung-Chun,Lee Jian-Jr,Yang Kuo-Hui,Chou Chia-Huei,Chang Yu-Chen 대한성형외과학회 2023 Archives of Plastic Surgery Vol.50 No.6

Augmentation mammoplasty is one of the most popular cosmetic surgeries, but there is a high reoperation rate (29.7%) commonly due to capsular contracture, implant malpositioning, infection, and unsatisfactory size. Although infection only accounts for 2% of cases, its management is very challenging, especially with nontuberculous mycobacteria (NTM) infection. Breast prosthetic NTM infection is a rare but is a disastrous condition with an incidence of approximately 0.013%. Immediate salvage reimplantation is usually not suggested, and most studies recommend a gap of 3 to 6 months after combination antibiotics therapy before reimplantation. However, delayed reimplantation often leads to great psychological stress and struggle between the doctor and patient. We present the case report of successful reimplantation in treating prosthetic NTM infections in a 28-year-old female. We discuss a novel technique “transaxillary capsulorrhaphy” to correct the bottoming-out deformity. One year after the combination of antibiotics and surgery, the follow-up computed tomography scan showed complete remission of NTM without recurrence. We discuss the surgical technique in detail. The 1-year follow-up assessment (photos and dynamic video) revealed good cosmesis and reliable correction using the new technique. This report is the first formal description and discussion of one-stage reimplantation following NTM infections. Transaxillary capsulorrhaphy allows for a successful salvage operation when an implant is displaced. This approach provides highly favorable result in eastern women undergoing revision augmentation mammoplasty. This study reflects level of evidence V, considering opinions of respected authorities based on clinical experience, descriptive studies, or reports of expert committees.

The Performance Improvement of an Enhanced CPU Scheduler Using Improved D_EDF Scheduling Algorithm

Chia-Ying Tseng,Po-Chun Huang 보안공학연구지원센터 2013 International Journal of Hybrid Information Techno Vol.6 No.5

Delay of Surgery for Spinal Metastasis due to the COVID-19 Outbreak Affected Patient Outcomes

Chia-Jung Hsieh,Chun-Yu Wu,Yen-Heng Lin,Yu-Cheng Huang,Wen-Chi Yang,Tom Wei-Wu Chen,Wei-Li Ma,Wei-Hsin Lin,Feng-Ming Hsu,Furen Xiao,Shih-Hung Yang,Dar-Ming Lai,Chang-Mu Chen,Shin-Yi Chao,Fon-Yih Tsuan 대한척추신경외과학회 2023 Neurospine Vol.20 No.4

Objective: The present study is to analyze the effects of the coronavirus disease 2019 (COVID 2019) outbreak and the subsequent lockdown on the outcomes of spinal metastasis patients. Methods: The study was a retrospective analysis of data from a prospective cohort study. All patients underwent surgical intervention for spinal metastases between January 2019 and December 2021 and had at least 3 months of postoperative follow-up. The primary outcome was overall mortality during the 4 different stages (pre-COVID-19 era, COVID-19 pandemic except in Taiwan, national lockdown, lifting of the lockdown). The secondary outcomes were the oncological severity scores, medical/surgical accessibility, and patient functional outcome during the 4 periods as well as survival/mortality. Results: A total of 233 patients were included. The overall mortality rate was 41.20%. During the Taiwan lockdown, more patients received palliative surgery than other surgical methods, and no total en bloc spondylectomy was performed. The time from surgeon visit to operation was approximately doubled after the COVID-19 outbreak in Taiwan (75.97, 86.63, 168.79, and 166.91 hours in the 4 periods, respectively). The estimated survival probability was highest after the national lockdown was lifted and lowest during the lockdown. In the multivariate analysis, increased risk of mortality was observed with delay of surgery, with emergency surgery having a higher risk with delays above 33 hours, urgent surgery (below 59 and above 111 hours), and elective surgery (above 332 hours). Conclusion: The COVID-19 pandemic and related policies have altered daily clinical practice and negatively impacted the survival of patients with spinal metastases.

Health Care Utilization and Expenditures of Patients with Diabetes Comorbid with Depression Disorder: A National Population-Based Cohort Study

Chun-Jen Huang,Hui-Min Hsieh,Herng-Chia Chiu,Peng-Wei Wang,Mei-Hsuan Lee,Chih-Yi Li,Ching-Hua Lin 대한신경정신의학회 2017 PSYCHIATRY INVESTIGATION Vol.14 No.6

Objective: The study investigated to compare health care utilization and expenditures between diabetic patients with and without depression in Taiwan. Methods: Health care utilization and expenditure among diabetic patients with and without depression disorder during 2000 and 2004 were examined using Taiwan’s population-based National Health Insurance claims database. Health care utilization included outpatient visits and the use of inpatient services, and health expenditures were outpatient, inpatient, and total medical expenditures. Moreover, general estimation equation models were used for analyzing the factors associated with outpatient visits and expenditures. Multiple logistic regression analysis was applied for identifying the factors associated with hospitalization. Results: The average annual outpatient visits and annual total medical expenditures in the study period were 44.23–52.20; NT$87,496–133,077 and 30.75–32.92; NT$64,411–80,955 for diabetic patients with and without depression. After adjustment for covariates, our results revealed that gender and complication were associated with out-patient visits. Moreover, the time factor was associated with the total medical expenditure, and residential urbanization and complication factors were associated with hospitalization. Conclusion: Health care utilization and expenditures for diabetic patients with depression were significantly higher than those without depression. Sex, complications, time, and urbanization are the factors associated with health care utilization and expenditures.

Comparative global immune-related gene profiling of somatic cells, human pluripotent stem cells and their derivatives: implication for human lymphocyte proliferation

Chia-Eng Wu,Chen-Wei Yu,Kai-Wei Chang,Wen-Hsi Chou,Chen-Yu Lu,Elisa Ghelfi,Fang-Chun Wu,Pey-Shynan Jan,Mei-Chi Huang,Patrick Allard,Shau-Ping Lin,Hong-Nerng Ho,Hsin-Fu Chen 생화학분자생물학회 2017 Experimental and molecular medicine Vol.49 No.-

Human pluripotent stem cells (hPSCs), including embryonic stem cells (ESCs) and induced PSCs (iPSCs), represent potentially unlimited cell sources for clinical applications. Previous studies have suggested that hPSCs may benefit from immune privilege and limited immunogenicity, as reflected by the reduced expression of major histocompatibility complex class-related molecules. Here we investigated the global immune-related gene expression profiles of human ESCs, hiPSCs and somatic cells and identified candidate immune-related genes that may alter their immunogenicity. The expression levels of global immune-related genes were determined by comparing undifferentiated and differentiated stem cells and three types of human somatic cells: dermal papilla cells, ovarian granulosa cells and foreskin fibroblast cells. We identified the differentially expressed genes CD24, GATA3, PROM1, THBS2, LY96, IFIT3, CXCR4, IL1R1, FGFR3, IDO1 and KDR, which overlapped with selected immune-related gene lists. In further analyses, mammalian target of rapamycin complex (mTOR) signaling was investigated in the differentiated stem cells following treatment with rapamycin and lentiviral transduction with specific short-hairpin RNAs. We found that the inhibition of mTOR signal pathways significantly downregulated the immunogenicity of differentiated stem cells. We also tested the immune responses induced in differentiated stem cells by mixed lymphocyte reactions. We found that CD24- and GATA3-deficient differentiated stem cells including neural lineage cells had limited abilities to activate human lymphocytes. By analyzing the transcriptome signature of immune-related genes, we observed a tendency of the hPSCs to differentiate toward an immune cell phenotype. Taken together, these data identify candidate immune-related genes that might constitute valuable targets for clinical applications.

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.

A Study on the Perception and Preference of the Wuxing Image Integrated into the Lucky Charm

TSAI I-CHEN,Chen, Chun-Chih,Chia-Hui Huang 한국일러스트레이션학회 2021 일러스트레이션 포럼 Vol.22 No.66

Lucky charms are mainly derived from people's wish to bring good luck or get rid of misfortune through the power of faith. Confronted by obstacles and disappointments, modern people would turn to traditional cultural beliefs to help them get over difficulties. Consumers in Taiwan are showing growing interests in lucky charms, while manufacturers are working hard to develop various types of lucky charms to meet the diverse needs of consumers. In recent years, most of the lucky charms are based on tangible or intangible images from religions, geomantic omen, folklore, etc. Also, in response to consumers' aesthetic needs, more aesthetic elements are incorporated into the design. Besides fundamental elements of religion, geomantic omen, folklore and other beliefs, manufacturers also need to understand consumers' perception and preferences to better meet their needs. The study aimed to explore the perception and preference of consumers for Wuxing lucky charms, and analyze consumers’ preferences of the geomantic omen images. This paper collected data through literature review and questionnaire survey of 79 people based on their identity and preference to identify important factors that influence consumers' preference so as to facilitate the design of lucky charms. The study analyzed the respondents' preferences of typical Wuxing lucky charms through the questionnaire survey, and found consumers prefer traditional, refined and delicate design. Also, they like products that could bring them good luck, revealing consumers' preference for geomantic omen image. This study will help manufacturers determine the focus of design, and provide references in this regard. From the study, we found that products with explicit colors can arouse more resonance from consumers. Therefore, it is suggested that when designing the Wuxing products, we can increase the use of Wuxing colors to highlight its characteristics and charms, and better meet the needs of consumers.

Using Kano Model to Explore the Charm of Painting Art Works in the Meaning of Life and Death

Kuo, Chin-Chin,Chen, Chun-Chih,Chia-Hui Huang 한국일러스트레이션학회 2022 일러스트레이션 포럼 Vol.23 No.70

The study of life and death is a learning topic. When we face to the life and death issue, it relates to our own lives. Most people are happy with life, but are full of fear of death. This research uses life and death as an example to explore "the creation of the meaning of life and death in composite media." It is hoped that through the extension of the meaning and images of life and death, the themes and elements of painting creation can be integrated to provide the exploration and thinking direction of the meaning of life. This research hopes to extend the meaning and imagery of life and death and incorporate the creative themes and elements of mixed media, so as to provide a direction for the exploration and thinking of the meaning of life. Applying the Miryoku Engineering Evaluation Grid Method to clarify the relationship between the meaning of life and death, style and perceptual imagery, and through the artistic creation of mixed media, summarize the preferences of mixed media creation works that affect the expression of birth and death images. Using the Evaluation Grid Method, 7 people with high involvement in the creation of mixed media and the imagery of life and death were conducted in-depth interviews on the charm and feelings of the meaning of life and death. By summarizing the attractiveness factors of choosing between life and death, the conclusion can be used as a basis for the development of future painting creation after subsequent verification and research on the purpose of life, the meaning of life, the value of survival, and the true meaning of death.

Echocardiographic parameters and indices in 23 healthy Maltese dogs

Chih-Hung Tsai,Chao-Chun Huang,Chia Chi Ho,Marta Claretti 대한수의학회 2021 Journal of Veterinary Science Vol.22 No.5

Background: Echocardiography is a primary tool used by veterinarians to evaluate heart diseases. In recent years, various studies have targeted standard echocardiographic values for different breeds. Reference data are currently lacking in Maltese dogs and it is important to fill this gap as this breed is predisposed to myxomatous mitral valve disease, which is a volume overload disease. Objectives: To establish the normal echocardiographic parameters for Maltese dogs. Methods: In total, 23 healthy Maltese dogs were involved in this study. Blood pressure measurements, thoracic radiography, and complete transthoracic echocardiography were performed. The effects of body weight, age and sex were evaluated, and the correlations between weight and linear and volumetric dimensions were calculated by regression analysis. Results: The mean vertebral heart size was 9.1 ± 0.4. Aside from the ejection fraction, fractional shortening, and the left atrial to aorta root ratio, all the other echocardiographic parameters were significantly correlated with weight. Conclusion: This study describes normal echocardiographic parameters that may be useful in the echocardiographic evaluation of Maltese dogs.