Induction of Forkhead Class box O3a and apoptosis by a standardized ginsenoside formulation, KG-135, is potentiated by autophagy blockade in A549 human lung cancer cells

Chih-Jung Yao,Jyh-Ming Chow,Shuang-En Chuang,Chia-Lun Chang,Ming-De Yan,Hsin-Lun Lee,I-Chun Lai,Pei-Chun Lin,Gi-Ming Lai 고려인삼학회 2017 Journal of Ginseng Research Vol.41 No.3

Background: KG-135, a standardized formulation enriched with Rk1, Rg3, and Rg5 ginsenosides, has been shown to inhibit various types of cancer cells; however, the underlying mechanisms are not fully understood. In this study, we explored its effects in A549 human lung cancer cells to investigate the induction of Forkhead Class box O3a (FOXO3a) and autophagy. Methods: Cell viability was determined by sulforhodamine B staining. Apoptosis and cell cycle distribution were analyzed using flow cytometry. The changes of protein levels were determined using Western blot analysis. Autophagy induction was monitored by the formation of acidic vesicular organelles stained with acridine orange. Results: KG-135 effectively arrested the cells in G1 phase with limited apoptosis. Accordingly, a decrease of cyclin-dependent kinase-4, cyclin-dependent kinase-6, cyclin D1, and phospho-retinoblastoma protein, and an increase of p27 and p18 proteins were observed. Intriguingly, KG-135 increased the tumor suppressor FOXO3a and induced the accumulation of autophagy hallmark LC3-II and acidic vesicular organelles without an increase of the upstream marker Beclin-1. Unconventionally, the autophagy adaptor protein p62 (sequestosome 1) was increased rather than decreased. Blockade of autophagy by hydroxychloroquine dramatically potentiated KG-135-induced FOXO3a and its downstream (FasL) ligand accompanied by the cleavage of caspase-8. Meanwhile, the decrease of Bcl-2 and survivin, as well as the cleavage of caspase-9, were also drastically enhanced, resulting in massive apoptosis. Conclusion: Besides arresting the cells in G1 phase, KG-135 increased FOXO3a and induced an unconventional autophagy in A549 cells. Both the KG-135-activated extrinsic FOXO3a/FasL/caspase-8 and intrinsic caspase-9 apoptotic pathways were potentiated by blockade of autophagy. Combination of KG- 135 and autophagy inhibitor may be a novel strategy as an integrative treatment for cancers.

A Hybrid Coordination Approach of In-network Caching for Named Data Networking

Chih Yen Chang,Ming Sang Chang 보안공학연구지원센터 2016 International Journal of Future Generation Communi Vol.9 No.4

In-network caching is an important feature of Information Centric Networking (ICN). All routers in ICN will maintain caching ability, and, for each request, contents are cached at routers along the delivery path. This kind of on-path caching can reduce overall retrieval time. However, the same contents may end up to be cached all over the network causing wastes of caching space and decrease content diversity. Coordinated caching policy decides which contents to be stored at which routers cooperatively for better utilizing cache space. Nevertheless, with limited storage, most of coordinated caching policies use all the caching capacity to store popular contents. It may raise a fairness issue in which unpopular contents can not access caching space and thus lower overall performance. In this paper we propose a hybrid coordinated caching algorithm. By splitting cache space into two parts running different mechanisms respectively, it provides accessibility for both popular and unpopular contents. The evaluation results show that fairness is uplifted while maintaining high hit ratio and minimized latency.

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.

Induction of Forkhead Class box O3a and apoptosis by a standardized ginsenoside formulation, KG-135, is potentiated by autophagy blockade in A549 human lung cancer cells

Yao, Chih-Jung,Chow, Jyh-Ming,Chuang, Shuang-En,Chang, Chia-Lun,Yan, Ming-De,Lee, Hsin-Lun,Lai, I-Chun,Lin, Pei-Chun,Lai, Gi-Ming The Korean Society of Ginseng 2017 Journal of Ginseng Research Vol.41 No.3

Background: KG-135, a standardized formulation enriched with Rk1, Rg3, and Rg5 ginsenosides, has been shown to inhibit various types of cancer cells; however, the underlying mechanisms are not fully understood. In this study, we explored its effects in A549 human lung cancer cells to investigate the induction of Forkhead Class box O3a (FOXO3a) and autophagy. Methods: Cell viability was determined by sulforhodamine B staining. Apoptosis and cell cycle distribution were analyzed using flow cytometry. The changes of protein levels were determined using Western blot analysis. Autophagy induction was monitored by the formation of acidic vesicular organelles stained with acridine orange. Results: KG-135 effectively arrested the cells in G1 phase with limited apoptosis. Accordingly, a decrease of cyclin-dependent kinase-4, cyclin-dependent kinase-6, cyclin D1, and phospho-retinoblastoma protein, and an increase of p27 and p18 proteins were observed. Intriguingly, KG-135 increased the tumor suppressor FOXO3a and induced the accumulation of autophagy hallmark LC3-II and acidic vesicular organelles without an increase of the upstream marker Beclin-1. Unconventionally, the autophagy adaptor protein p62 (sequestosome 1) was increased rather than decreased. Blockade of autophagy by hydroxychloroquine dramatically potentiated KG-135-induced FOXO3a and its downstream (FasL) ligand accompanied by the cleavage of caspase-8. Meanwhile, the decrease of Bcl-2 and survivin, as well as the cleavage of caspase-9, were also drastically enhanced, resulting in massive apoptosis. Conclusion: Besides arresting the cells in G1 phase, KG-135 increased FOXO3a and induced an unconventional autophagy in A549 cells. Both the KG-135-activated extrinsic FOXO3a/FasL/caspase-8 and intrinsic caspase-9 apoptotic pathways were potentiated by blockade of autophagy. Combination of KG-135 and autophagy inhibitor may be a novel strategy as an integrative treatment for cancers.

Management of Hyperacute Stroke during the Coronavirus Disease of 2019 Pandemic: The Modified Code Stroke in a Medical Center in Taiwan

Po-Yu Lin,Yu-Ming Chang,Chih-Yuan Huang,Chih-Hao Lin,Ming-Tsung Chuang,Po-Lin Chen,Pi-Shan Sung,Chih-Hung Chen 대한뇌졸중학회 2020 Journal of stroke Vol.22 No.2

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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.

Dendrite Evolution of Delta (δ) Ferrite and Precipitation Behavior of Sigma (σ) Phase during Multipass Dissimilar Stainless Steels Welding

Chih-Chun Hsieh,Xiaofei Guo,Chia-Ming Chang,Weite Wu 대한금속·재료학회 2010 METALS AND MATERIALS International Vol.16 No.3

The purpose of this study is to discuss the development of dendrite δ-ferrite and the precipitation behavior of σ phase in the overlapping heat-affected zones, or the fusion zones, during the multipass dissimilar stainless steels welding process. The color metallographic and color separation techniques were used to clearly identify the δ, σ, and γ phases. The experimental results indicated that the grain refinement was very obvious in the second and third pass fusion zones (304-1 and 304-2) when the welding pass was increased from 1 to 3. This refining phenomenon was attributed to the higher cooling rate and the degree of supercooling. The δ phase precipitated in the secondary and the tertiary dendrite arms of the δ-ferrite and it was able to grow on the dendrite arms along the [111] crystallographic in a 45o angle. The σ phase was also able to form stably after the phase decomposition of δ-ferrite into globular and lacy morphologies.

Influence of Residential Environment and Lifestyle on Multiple Primary Malignancies in Taiwan

Chang, Chih-Chun,Chung, Yi-Hua,Liou, Ching-Biau,Lee, Yi-Chen,Weng, Wei-Ling,Yu, Yun-Chieh,Yen, Tzung-Hai,Wu, Jiann-Ming Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.8

Background: Multiple primary malignancies (MPM) have become increasingly prevalent worldwide. This investigation was aimed at establishing the clinicopathological characteristics of MPM patients and evaluating the impact of the living environment on MPM in the Taiwanese population. Materials and Methods: From January 2009 to December 2013, a total of 8,268 cancer patients were identified in our institutional center. Of these, 125 were diagnosed as MPM and thus enrolled. Data for clinicopathological features and treatment approaches for these MPM patients living in urban or suburb zone were obtained. Findings for the air pollution status in Taiwan were also collected. Results: The most common cancer match of MPM was esophageal cancer with hypopharyngeal cancer (12.8%), followed by colorectal cancer with gastric cancer (6.4%) and colorectal cancer with breast cancer (5.6%). The air quality was significantly worse in the urban than in the suburban zone and there was a remarkably higher portion of MPM patients in the urban zone suffering from grade III and IV post-chemotherapeutic neutropenia (30.8% vs 15.1%, P=0.036). Conclusions: The tumor frequency and site distribution should be taken into the clinical evaluation because there is a relatively high risk of developing MPM. This study also highlighted the potential influence of environmental factors on post-chemotherapeutic neutropenia for patients with MPM.

Precipitation Behavior of σ Phase in Fusion Zone of Dissimilar Stainless Steel Welds during Multi-Pass GTAW Process

( Chih Chun Hsieh ),( Tao Chih Chang ),( Dong Yih Lin ),( Ming Che Chen ),( Wei Te Wu ) 대한금속재료학회 ( 구 대한금속학회 ) 2007 METALS AND MATERIALS International Vol.13 No.5

The purpose of this study is to investigate the precipitation characteristics of σ phase in the fusion zone of stainless steel welds at various welding passes during a tungsten arc welding (GTAW) process. The morphology, quantity, and chemical composition of the δ-ferrite and σ phase were analyzed using optical microscopy (OM), a ferritscope (FS), a X-ray diffractometer (XRD), scanning electron microscopy (SEM), an electron probe micro-analyzer (EPMA), and a wavelength dispersive spectrometer (WDS), respectively. Massive δ-ferrite was observed in the fusion zone of the first pass welds during welding of dissimilar stainless steels. The σ phase precipitated at the inner δ-ferrite particles and decreased δ-ferrite content during the third pass welding. The σ and δ phases can be stabilized by Si element, which promoted the phase transformation of δ→σ + γ2 in the fusion zone of the third pass welds. It was found that the σ phase was a Fe-Cr-Si intermetallic compound found in the fusion zone of the third pass welds during multi-pass welding.

The Effect of Strangulation and Girdling on Root Growth and Fruit Quality of ‘Haak Yip’ Litchi

Ming-Chih Chen,Tsu-Liang Chang,Iou-Zen Chen 한국원예학회 2008 한국원예학회 기타간행물 Vol.- No.-