Increase of Phosphatase and Tensin Homolog by Silymarin to Inhibit Human Pharynx Squamous Cancer

Chin-Hui Su,Li-Jen Chen,Jyh Fei Liao,Juei-Tang Cheng 한국식품영양과학회 2013 Journal of medicinal food Vol.16 No.9

Silymarin is an active principle from the seeds of the milk thistle plant and is widely used as a hepatoprotective gent due to its antioxidant-like activity. In the present study, we evaluated the potential efficacy of silymarin against oral cancer and investigated its possible mechanism of action. Cell viability assay and western blotting analyses were used to identify silymarin-induced apoptotic cell death in human pharynx squamous cell carcinoma (FaDu) cells. The short interfering RNA (siRNA) is used to confirm the role of phosphatase and tensin homolog (PTEN) in silymarin-induced apoptosis. Treatment of FaDu cells with silymarin resulted in a significant decrease in cell viability (up to 70%). Silymarin inhibited the phosphorylation of Akt (over 10-fold) with an increase in expression of PTEN (five to sixfold). Consequently, the level of Bcl-2 expression was decreased five to sixfold and caspase 3 activated to induce apoptosis. Treatment with siRNA specific to PTEN gene diminished the action of silymarin. The results suggest that silymarin inhibits the Akt signaling pathway by increasing PTEN expression in FaDu cells and directly affects Bcl-2 family members. Also, we demonstrated the inhibitory activity of silymarin for oral cancer is related to cell survival. These mechanisms may in part explain the actions of silymarin and provide a rationale for the development of silymarin as an anticancer agent.

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.

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.

Clinical Features of Patients with Esophageal and Second Primary Cancers

Tsai, Huang-Wen,Chang, Chih-Chun,Sun, Jen-Tang,Liou, Ching-Biau,Lin, Hsiu-Chen,Lin, I-Hsin,Yu, Yun-Chieh,Weng, Wei-Ling,Leong, Ka-I,Yen, Tzung-Hai,Wu, Jiann-Ming Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.22

Background: The prevalence of esophageal cancer (EC) with second primary cancers (SPC) is increasing worldwide. This study was aimed to understand the clinical features of EC patients with SPC in the Taiwanese population. Materials and Methods: Clinical and laboratory data for 180 EC patients with or without SPC were collected between January 2009 and December 2013. Information on treatment approaches, location of SPCs and ABO blood type were also collected and stratified. Results: The most common SPC in EC patients was hypopharyngeal cancer, followed by laryngeal cancer and hepatocellular carcinoma in our study. Malignancies of colon, prostate and lung were also found. There was a significant higher portion of blood type A in the EC patients with SPC compared with those without (42.4% vs 19.5%, P=0.006). Conclusions: The frequency and SPC site distribution and blood type A should be considered in clinical evaluation of EC patients with a high risk of developing SPC in the Taiwanese population.

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.

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.

Comparison of trauma systems in Asian countries: a cross-sectional study

정영희,위대한,신상도,히데하루 다나카,Goh E. Shaun,Wen-Chu Chiang,Jen-Tang Sun,Li-Min Hsu,켄타로 카지노,Sabariah Faizah Jamaluddin,아키오 키무라,James F. Holmes,송경준,노영선,홍기정,문성우,박주옥,김민정 대한응급의학회 2019 Clinical and Experimental Emergency Medicine Vol.6 No.4

Objective This study aimed to compare the demographic characteristics and trauma service structures and processes of hospitals in 15 countries across the Asia Pacific, and to provide baseline data for the integrated trauma database: the Pan-Asian Trauma Outcomes Study (PATOS). Methods Medical directors and emergency physicians at PATOS-participating hospitals in countries across the Asia Pacific were surveyed through a standardized questionnaire. General information, trauma care system data, and trauma emergency department (ED) outcomes at each hospital were collected by email and analyzed using descriptive statistics. Results Survey data from 35 hospitals across 15 countries were collected from archived data between June 2014 and July 2015. Designated trauma centers were identified as the highest hospital level for trauma patients in 70% of surveyed countries. Half of the hospitals surveyed had special teams for trauma care, and almost all prepared activation protocol documents for these teams. Most hospitals offered specialized trauma education programs, and 72.7% of hospitals had a hospital-based trauma registry. The total number of trauma patients visiting the ED across 25 of the hospitals was 300,376. The overall survival-to-discharge rate was 97.2%; however, it varied greatly between 85.1% and 99.7%. The difference between survival-to-discharge rates of moderate and severe injury groups was highest in Taiwan (41.8%) and lowest in Thailand (18.6%). Conclusion Trauma care systems and ED outcomes vary widely among surveyed hospitals and countries. This information is useful to build further detailed, systematic platforms for trauma surveillance and evidence-based trauma care policies.

ASTROD I, Test of Relativity, Solar-System Measurement and G-Wave Detection

Wei-Tou Ni,Albrecht Rudiger,Etienne Samain,Stephan Schiller,Diana Shaul,Sachie Shiomi,Timothy Sumner,Chien-Jen Tang,Jinhe Tao,Pierre Touboul,Haitao Wang,Andreas Wicht,Ji Wu,Xue-Jun Wu,Yaoheng Xiong,Ch 한국물리학회 2004 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.45 No.1

ASTROD-I is a mission concept under study to realize the general concept of ASTROD (Astrodynamical Space Test of Relativity using Optical Devices). This mission concept has one spacecraft carrying a payload of a telescope, ve lasers, and a clock together with ground stations (ODSN: Optical Deep Space Network) to test the optical scheme of interferometric and pulse ranging and yet give important scientic results. The scientic goals include a better measurement of the relativistic parameters, a better sensitivity in using optical Doppler tracking method for detecting gravitational waves, and measurement of many solar system parameters more precisely. The weight of this spacecraft is estimated to be about 300-350 kg with a payload of about 100-120 kg. The spacecraft is to be launched with initial period about 290 days and to pass by Venus twice to receive gravity-assistance for achieving shorter periods. With good orbit design, after about 370 days from launch, the spacecraft will arrive at the other side of the Sun for the determination of relativistic parameters.

Enhancement of Aggregation-Induced Emission in Dye-Encapsulating Polymeric Micelles for Bioimaging

Wu, Wen-Chung,Chen, Ching-Yi,Tian, Yanqing,Jang, Sei-Hum,Hong, Yuning,Liu, Yang,Hu, Rongrong,Tang, Ben Zhong,Lee, Yi-Ting,Chen, Chin-Ti,Chen, Wen-Chang,Jen, Alex K.-Y. WILEY-VCH Verlag 2010 Advanced Functional Materials Vol.20 No.9

<P>Three amphiphilic block copolymers are employed to form polymeric micelles and function as nanocarriers to disperse hydrophobic aggregation-induced emission (AIE) dyes, 1,1,2,3,4,5-hexaphenylsilole (HPS) and/or bis(4-(N-(1-naphthyl) phenylamino)-phenyl)fumaronitrile (NPAFN), into aqueous solution for biological studies. Compared to their virtually non-emissive properties in organic solutions, the fluorescence intensity of these AIE dyes has increased significantly due to the spatial confinement that restricts intramolecular rotation of these dyes and their better compatibility in the hydrophobic core of polymeric micelles. The effect of the chemical structure of micelle cores on the photophysical properties of AIE dyes are investigated, and the fluorescence resonance energy transfer (FRET) from the green-emitting donor (HPS) to the red-emitting acceptor (NPAFN) is explored by co-encapsulating this FRET pair in the same micelle core. The highest fluorescence quantum yield (∼62%) could be achieved by encapsulating HPS aggregates in the micelles. Efficient energy transfer (>99%) and high amplification of emission (as high as 8 times) from the NPAFN acceptor could also be achieved by spatially confining the HPS/NPAFN FRET pair in the hydrophobic core of polymeric micelles. These micelles could be successfully internalized into the RAW 264.7 cells to demonstrate high-quality fluorescent images and cell viability due to improved quantum yield and reduced cytotoxicity.</P> <B>Graphic Abstract</B> <P>Highly efficient fluorescence probes are achieved through the encapsulation of aggregation-induced emission molecules, 1,1,2,3,4,5-hexaphenylsilole (HPS) and/or bis(4-(N-(1-naphthyl) phenylamino)-phenyl)fumaronitrile (NPAFN) in the core of polymeric micelles. Bright fluorescence cell images are shown with tunable colors of green directly from HPS aggregates and red through efficient fluorescence resonance energy transfer (FRET) from HPS aggregates to NPAFN aggregates. <img src='wiley_img_2010/1616301X-2010-20-9-ADFM200902043-content.gif' alt='wiley_img_2010/1616301X-2010-20-9-ADFM200902043-content'> </P>

Quercetin-mediated Cell Cycle Arrest and Apoptosis Involving Activation of a Caspase Cascade through the Mitochondrial Pathway in Human Breast Cancer MCF-7 Cells

Chu-Chung Chou,Jai-Sing Yang,Hsu-Feng Lu,Siu-Wan Ip,Chyi Lo,Chih-Chung Wu,Jing-Pin Lin,Nou-Ying Tang,Jing-Gung Chung,Ming-Jen Chou,Ying-Hock Teng,Dar-Ren Chen 대한약학회 2010 Archives of Pharmacal Research Vol.33 No.8

Dietary polyphenols have been correlated with a reduced risk of developing cancer. Quercetin (a natural polyphenolic compound) induced apoptosis in many human cancer cell lines, including breast cancer MCF-7 cells. However, the involvement of possible signaling pathways and the roles of quercetin in apoptosis are still undefined. The purpose of this study was to investigate the effects of quercetin on the induction of the apoptotic pathway in human breast cancer MCF-7 cells. When MCF-7 cells were treated with quercetin for 24 and 48 h and at various doses (10-175 μM), cell viability decreased significantly in time- and dose-dependent manners. Exposure of MCF-7 cells to 10-175 μM quercetin resulted in an approximate 90.25% decrease in viable cells. To explicate the mechanism underlying the antiproliferative effect of quercetin, cell cycle distribution and apoptosis in MCF-7 cells was investigated after exposure to 150 μM quercetin for 6-48 h. Quercetin caused a remarkable increase in the number of S phase (14.56%to 61.35%) and sub-G1 phase cells (0.1% to 8.32%) in a dose- and time-dependent manner. Quercetin caused S phase arrest by decreasing the protein expression of CDK2, cyclins A and B while increasing the p53 and p57 proteins. Following incubation with quercetin for 48 h, MCF-7 cells showed apoptotic cell death by the decreased levels of Bcl-2 protein and ΔΨ m and increased activations of caspase-6, -8 and -9. Moreover, quercetin increased the AIF protein released from mitochondria to nuclei and the GADD153 protein translocation from endoplasmic reticulum to the nuclei. These data suggested that quercetin may induce apoptosis by direct activation of the caspase cascade through the mitochondrial pathway in MCF-7 cells.