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.

Eosinophilia in Pleural Effusions: a Speculative Negative Predictor for Malignancy

Chu, Fang-Yeh,Liou, Ching-Biau,Sun, Jen-Tang,Bei, Chia-Hao,Liou, Tse-Hsuan,Tan, N-Chi,Yu, Yun-Chieh,Chang, Chih-Chun,Yen, Tzung-Hai,Su, Ming-Jang Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.3

Background: Eosinophilic pleural effusion (EPE) is an eosinophil count more than 10% on cytology of pleural samples. Recently, it was reported that malignancy had been the most prevalent cause inducing EPE. Therefore, we conducted an analysis on the prevalence and etiology of EPE and investigated the relationship between EPE and malignancy. Materials and Methods: Data for pleural cell differential count from patients receiving thoracentesis during the period from January 2008 to December 2013 were compared with clinical data and established diagnosis of patients obtained via electronic chart review. Results: A total of 6,801 requests of pleural cytology from 3,942 patients with pleural effusion who had received thoracentesis were available at Far Eastern Memorial Hospital from 2008 to 2013, and of these subjects, 115 (2.9%) were found to have EPE. The most frequent cause of EPE was malignancy (33.0%, n=38), followed by parapneumonic effusions (27.8%, n=32), tuberculosis pleuritis (13.9%, n=16), transudate effusions (12.2%, n=14) and the presence of blood or air in pleural space (10.4%, n=12). Additionally, an inverse relationship of eosinophilia in pleural fluid was identified in patients with malignancy and EPE. The cut-off eosinophil count in pleural fluid was 15% for the most accurate discrimination between malignancy and benign disorders in patients with EPE. At the cut-off level, the sensitivity and specificity were 65.8% and 67.5%, respectively. Conclusions: Pleural fluid eosinophilia was a speculative negative predictor for malignancy, despite the fact that cancers, including lung cancers and metastatic cancers to lung, were the most leading cause of pleural fluid eosinophilia. An inverse correlation was observed between the pleural eosinophil percentage and the likelihood of malignancy in patients with EPE.

Classifying Endemic Fagaceae Species in Taiwan using Leaf Images

( Hao-chun Hsu ),( Cheng-hao Lee ),( Chih-kai Yang ),( Fang-hua Chu ),( Ming-jer Tsai ),( Yan-fu Kuo ) 한국농업기계학회 2018 한국농업기계학회 학술발표논문집 Vol.23 No.1

Fagaceae is one of the plant family which dominate the broad-leaved forests in Taiwan and have considerable value in economy and ecology. Traditionally, plant species identification based on leaf morphologies and is conducted using naked-eye observation. This study is proposed to distinguish the Fagaceae species using image processing and machine learning. In this study, leaf images of 10 Fagaceae species were collected. A serial of traits relevant to leaf morphologies, such as morphological, color, shape, and venation traits, were quantified from the leaf images. A support vector machine classifier was then developed to identify the species using the quantified traits. The proposed approach reached an identification accuracy of 95.8%.

Creatine Kinase (CK)-MB-to-Total-CK Ratio: a Laboratory Indicator for Primary Cancer Screening

Chang, Chih-Chun,Liou, Ching-Biau,Su, Ming-Jang,Lee, Yi-Chen,Liang, Chai-Ting,Ho, Jung-Li,Tsai, Huang-Wen,Yen, Tzung-Hai,Chu, Fang-Yeh Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.15

Background: For the determination of creatine kinase (CK)-MB, the immunoinhibition method is utilized most commonly. However, the estimated CK-MB activity may be influenced by the presence of CK isoenzymes in some conditions like cancer. Thus, a CK-MB-to-total-CK ratio more than 1.0 could be found in such a situation. The study aimed to explore the relationship of cancer to high CK-MB-to-total-CK ratio. Materials and Methods: From January 2011 to December 2014, laboratory data on all CK-MB and total CK test requests were extracted at Far Eastern Memorial Hospital (88,415 requests). Patients with a CK-MB-to-total-CK ratio more than 1.0 were registered in this study. Clinical data including tumor location, tumor TNM stage and metastatic status were also collected. Results: A total of 846 patients were identified with a CK-MB-to-total-CK ratio more than 1.0. Of these, 339 (40.1%) were diagnosed with malignancies. The mean CK-MB-to-total-CK ratio was significantly higher in malignancy than in non-malignancy ($1.35{\pm}0.28$ vs $1.25{\pm}0.23$, p<0.001) groups. The most frequent malignancy with a CK-MB-to-total-CK ratio more than 1.0 was colorectal cancer ($1.42{\pm}0.28$, 16.5%, n=56), followed by lung cancer ($1.38{\pm}0.24$, 15.9%, n=54) and hepatocellular carcinoma (14.5%, n=49). Higher CK-MB-to-total-CK ratios in hematological malignancies ($1.44{\pm}0.41$)were also noted. Additionally, the CK-MB-to-total-CK ratio was markedly higher in advanced stage malignancy than in early stage ($1.37{\pm}0.26$ vs. $1.29{\pm}0.31$, p=0.014) and significantly higher in liver metastasis than in non-liver metastasis ($1.48{\pm}0.30$ vs. $1.30{\pm}0.21$, p<0.001). Conclusions: The CK-MB-to-total-CK ratio is an easily available indicator and could be clinically utilized as a primary screening tool for cancer. Higher ratio of CK-MB-to-total-CK was specifically associated with certain malignancies, like colorectal cancer, lung cancer and hepatocellular carcinoma, as well as some cancer-associated status factors such as advanced stage and liver metastasis.

Impact of Peri-Operative Anemia and Blood Transfusions in Patients with Gastric Cancer Receiving Gastrectomy

Chang, Chih-Chun,Sun, Jen-Tang,Chen, Jing-Yuan,Chen, Yi-Ting,Li, Pei-Yu,Lee, Tai-Chen,Su, Ming-Jang,Wu, Jiann-Ming,Yen, Tzung-Hai,Chu, Fang-Yeh Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.3

Background: Potential disadvantages of blood transfusion during curative gastrectomy for gastric cancer have been reported, and the role of peri-operative transfusions remains to be ascertained. Thus, the aim of our study was to survey its impact in patients with gastric cancer undergoinging gastrectomy. Materials and Methods: Clinical data of patients receiving curative gastrectomy at Far Eastern Memorial Hospital were obtained. Findings for pre-operative anemia states, pre-, peri- and post-operative transfusion of red blood cell (RBC) products as well as post-operative complication events were collected for univariate analysis. Results: A total of 116 patients with gastric cancer received gastrectomy at Far Eastern Memorial Hospital from 2011 to 2014. Both pre-operative and intra- and post-operative transfusion of RBC products were markedly associated with post-operative infectious events (OR: 3.70, 95% CI: 1.43-9.58, P=0.002; OR: 8.20, 95% CI: 3.11-22.62, P<0.001, respectively). In addition, peri- and post-operative RBC transfusion was significantly associated with prolonged hospital stay from admission to discharge (OR: 8.66, 95% CI: 1.73-83.00, P=0.002) and post-operative acute renal failure (OR: 19.69, 95% CI: 2.66-854.56, P<0.001). Also, the overall survival was seemingly decreased by peri-operative RBC transfusion in our gastric cancer cases (P=0.078). Conclusions: Our survey indicated that peri-operative RBC transfusion could increase the risk of infectious events and acute renal failure post curative gastrectomy as well as worsen the overall survival in gastric cancer cases. Hence, unnecessary blood transfusion before, during and after curative gastrectomy should be avoided in patients with gastric cancer.

The Immunotyping Distribution of Serum Monoclonal Paraprotein and Environmental Impact on Multiple Myeloma (MM) and Monoclonal Gammopathy of Uncertain Significance (MGUS) in Taiwan: A Medical Center-Based Experience

Chang, Chih-Chun,Su, Ming-Jang,Lee, Shu-Jene,Tsai, Yu-Hui,Kuo, Lin-Yin,Lin, I-Hsin,Huang, Hui-Ling,Yen, Tzung-Hai,Chu, Fang-Yeh Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.1

Background: Whether ambient exposure to environmental pollutants leads to hematopoietic malignancies such as multiple myeloma (MM) remains to be ascertained. Therefore, we aimed to investigate the immunotyping distribution of serum monoclonal paraprotein and the environmental influence on MM and monoclonal gammopathy of uncertain significance (MGUS) in the Taiwanese population. Materials and Methods: Serum protein electrophoresis with immunosubtraction by the capillary zone electrophoresis method was performed as primary screening for MM and MGUS. Clinical, pathological, and residence data of patients were also obtained. Results: From August, 2013 to June, 2015, a total of 327 patients underwent serum protein electrophoresis with immunosubtraction. Among these, 281 demonstrated no remarkable findings or non-malignant oligoclonal gammopathy, 23 were detected to have MGUS, 18 were identified as MM, and a further 5 were found as other malignancies. The most frequent immunotyping distribution of serum monoclonal paraprotein was IgG kappa (54.3%, n=25), followed by IgA lambda (15.2%, n=7) and IgG lambda (10.9%, n=5) in subjects with gammopathy. Additionally, it was shown that the elderly (OR: 4.61, 95% CI: 1.88-11.30, P<0.01) and males (OR: 2.04, 95% CI: 1.04-4.02, P=0.04) had significantly higher risk of developing MM and MGUS. There was no obvious impact of environmental factors on the health risk of MM and MGUS evolution (OR: 0.77, 95% CI: 0.40-1.50, P=0.49). Conclusions: The most frequent immunotyping distribution of serum monoclonal paraprotein included IgG kappa, IgA lambda and IgG lambda in MM and MGUS in the Taiwanese population. The elderly and male subjects are at significantly higher risk of MM and MGUS development, but there was no obvious impact of environmental factors on risk.

Clinical Significance of Smudge Cells in Peripheral Blood Smears in Hematological Malignancies and Other Diseases

Chang, Chih-Chun,Sun, Jen-Tang,Liou, Tse-Hsuan,Kuo, Chin-Fu,Bei, Chia-Hao,Lin, Sheng-Jun,Tsai, Wei-Ting,Tan, N-Chi,Liou, Ching-Biau,Su, Ming-Jang,Yen, Tzung-Hai,Chu, Fang-Yeh Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.4

Background: It is reported that the percentage of smudge cells in the blood smear could be a prognostic indicator in chronic lymphocytic leukemia. However, the clinical significance of smudge cells in other hematological malignancies, solid tumors or non-malignant diseases is less clear. Hence, this study was conducted to survey the clinical significance of smudge cells in hematological cancers and other disorders. Materials and Methods: From January to November, 2015, the clinical data of patients who received blood examination with differential counts for clinical purpose and were found to have smudge cells in the peripheral blood film in Far Eastern Memorial Hospital were selected. The percentage of smudge cells and patient outcomes were evaluated for further univariate and survival analyses. Results: A total of 102 patients with smudge cells in their blood smears were included. Smudge cells were frequently presented in out-of-hospital cardiac arrest (OHCA; n=30), infections (n=23), hematological cancers (n=23) and solid cancers (n=10). There was no relationship between the percentage of smudge cells and the patient mortality in all diseases (OR: 1.08, 95% CI: 0.47-2.48, P=1.000) as well as the OHCA group (OR: 1.91, 95% CI: 0.38-9.60, P=0.694). It was observed that in patients with all cancers with the percentage of smudge cells less than 50% had a lower mortality rate in comparison with those who had the percentage of smudge cells of 50% or more (OR: 22.29, 95% CI: 2.38-208.80, P<0.001). Additionally, it was seemingly that patients with smudge cells of 50% or more had a lower survival rate than those with smudge cells less than 50% in all cancers with follow-up at 2-month intervals, but without statistical significance (P=0.064). Conclusions: Our survey indicated that in all cancers, those who had higher percentage of smudge cells were prone to have poor outcomes when compared with the subjects with lower percentage of smudge cells. This finding was quite different from the results of previous studies in which the race-ethnicity of most study populations was non-Asian; hence, further investigations are required. Besides, there was no apparent association of the percentage of smudge cells with patient outcomes in all diseases, including OHCA.

Proactive Consultation by a Clinical Pathologist Prevents Diagnostic Delay in Hematological Malignancies

Chang, Chih-Chun,Su, Ming-Jang,Ho, Jung-Li,Sun, Jen-Tang,Tsai, Huang-Wen,Tang, Hui-Fei,Chu, Fang-Yeh Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.3

Background: Diagnostic difficulties in hematological malignancies may lead to unacceptably prolonged help-seeking to diagnostic interval as well as increased complications and poor outcomes. Proactive consultation by a clinical pathologist (PCCP) may help clinical diagnosis and therapeutic strategy. Hence, the aim of this investigation was to evaluate the effect of PCCP on the help-seeking to diagnostic interval in hematological cancer cases. Materials and Methods: From January to November, 2015, abnormal results of hematological laboratory testing with added laboratory comment were selectively screened out, and patients with such abnormalities in hematological laboratory testing and accompanied laboratory comment with PCCP were enrolled. Results: A total of 125 aberrant results of hematological laboratory testing were given with accompanied laboratory comments with PCCP and 40.8% (n=51) of these patient-oriented comments had an effect on clinical diagnosis and therapeutic strategy. Twelve of the subjects belonged to newly diagnosed hematological malignancies with the assistance of PCCP, and the help-seeking to diagnostic interval was also shortened from 42 days to 26 days in chronic lymphoid leukemia (CLL), from 83 days to 11 days in multiple myeloma (MM), and from 128 days to 15 days in myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN). During the monitoring interval, neither complication events nor deaths were reported in the study group. Conclusions: It was seemingly that PCCP prevented diagnostic delay in hematological malignancies via shortening the help-seeking to diagnostic interval, particularly in CLL, MM and MDS/MPN cases. PCCP can be considered to play an essential role in prompt establishment of diagnosis in hematological malignancies for those who newly present.

The effect of urban redevelopment on retail shopping property values: a case study in Hong Kong

Wadu Mesthrige Jayantha,Chu Chun Ming 서울시립대학교 도시과학연구원 2015 도시과학국제저널 Vol.19 No.3

Purpose – Redevelopment, an essential aspect of the urban regeneration process, brings positive externalities to neighbourhoods. This study evaluates the effect of the improvements of neighbourhoods, brought about by redevelopment, on nearby ground-floor retail shopping property values. This study uses a hedonic price model to determine whether there is a relationship between redevelopment work and nearby shopping property values and the influence of neighbourhood improvements on the price of shopping properties if there is such relationship. The analysis is based on three large-scale redevelopment projects, each having a commercial space ranging from 30,000 to 50,000 sq.ft. The results show that an improved neighbourhood environment brings significant value enhancement to nearby shopping properties. Potential tenants are willing to pay a sale rental price premium ranging from 13% to 34% on shops located near redeveloped areas. The results also reveal that potential shop tenants are willing to pay a premium of 0.1% more on a shop with a cockloft. These findings imply that a neighbourhood environment that has been improved through well-planned redevelopment projects adds value to nearby properties. This study contributes an indication of the amount a tenant or buyer would be willing to pay on shops near redeveloped areas and can be used as a reference for users, developers and investors.

Methodological Study on the Evaluation of Face Mask Use Scale among Public Adult: Cross-Language and Psychometric Testing

Lam, Simon Ching,Chong, Andy Chun Yin,Chung, Jessie Yuk Seng,Lam, Ming Yee,Chan, Lai Man,Shum, Cho Yee,Wong, Eliza Yi Ni,Mok, Yat Man,Lam, Ming Tat,Chan, Man Man,Tong, Ka Ying,Chu, Oi Lee,Siu, Fong Ki 한국성인간호학회 2020 성인간호학회지 Vol.32 No.1

Purpose: This study aimed to establish the translation adequacy and examine the psychometric properties of FaceMask Use Scale (FMUS). Methods: This methodological study employed a cross-sectional design with repeatedmeasures. Phase 1 examined the equivalence and relevance of English and Chinese versions of FMUS. Phase2 examined the internal consistency, stability and construct validity. Different sample batches (213 universitystudents and 971 general public) were used appropriately for psychometric testing. The 2-phase data were collectedbetween January and April 2017. Results: In Phase 1, the semantic equivalence and relevance (item- and scale-levelcontent-validity-index=100%) was satisfactory. Furthermore, from 133 paired test-retest responses, the quadraticweighted kappa (.53~.73, p<.001) and Intraclass Correlation Coefficient (ICC=.81) between the English andChinese version of FMUS were satisfactory. In Phase 2, FMUS demonstrated satisfactory internal consistency(Cronbach’s ⍺=.80~.81; corrected item-total correlation coefficients=.46~.67) and two-week test-retest stability(ICC=.84). The known-groups method (t=3.08, p<.001), exploratory (71.10% of total variance in two-factor model)and confirmatory factory analysis (x2/df=4.02, Root Mean Square Residual=.03, Root Mean Square Error ofApproximation=.06, Goodness of Fit Index=.99, Comparative Fit Index=.99) were all satisfactory for establishingthe construct validity. Conclusion: The FMUS has an equivalence Chinese and English versions, satisfactoryreliability and validity for measuring the practice of face mask use. This poses clinical and research implications forthose community health nurses who works on respiratory protection. Further research should be conducted on the‘negligent practice’ of FMU.