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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.
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.
Jer-Chyi Wang,Chin-Hsiang Liao,Chih-Ting Lin,Ruey-Dar Chang,Li-Chun Chang,Chih-I Wu,Jung-Hung Chang 한국물리학회 2015 Current Applied Physics Vol.15 No.4
Carrier injection and charge loss characteristics of nonvolatile memories with chemically-synthesized (CS) and vacuum-deposited (VD) gold nanoparticles (Au-NPs) have been investigated. Compared to CS counterparts, the memories with VD Au-NPs exhibit a higher dot density of 3.77 × 1011 cm-2, leading to a larger memory window. Further, the energy from valence-band edge to vacuum level (EVB_vac) of tunneling oxide for the samples with CS and VD Au-NPs is found to be 9.04 and 9.85 eV respectively. The small EVB_vac value of the memories with CS Au-NPs is resulted from the formation of a thin chemical oxide (SiOx) on thermally-grown SiO2 tunneling layer during the chemically synthesized process, contributing to a slow erasing behavior. Besides, the programming of the memories with VD Au-NPs is saturated at high gate bias, which has been well-explained by the electrons induced potential coupling between Au-NPs. Superior data retention property and high temperature dependence of charge loss are observed for the memories with CS Au-NPs, which can be ascribed to the thick tunneling oxide layer by the additional SiOx film.
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.
Interpreting the 750 GeV diphoton resonance using photon jets in hidden-valley-like models
Chang, Jung,Cheung, Kingman,Lu, Chih-Ting American Physical Society 2016 Physical review. D Vol.93 No.7
<P>Motivated by the diphoton resonance recently reported by the ATLAS and CMS collaborations at root s = 13 TeV, we interpret the resonance as a scalar boson X(750) in hidden-valley-like models. The scalar boson X can mix with the standard model Higgs boson and thus can be produced via gluon fusion. It then decays into a pair of very light hidden particles Y of O(1 GeV), each of which in turn decays to a pair of collimated pi(0)'s, and these two pi(0)'s decay into photons which then form photon jets. A photon jet (gamma jet) is a special feature that consists of a cluster of collinear photons from the decay of a fast moving light particle [O(1 GeV)]. Because these photons inside the photon jet are so collimated that it cannot be distinguished from a single photon, in the final state of the decay of X(750) a pair of photon jets looks like a pair of single photons, which the experimentalists observed and reconstructed the 750 GeV diphoton resonance. Prospects for LHC Run-2 about other new and testable features are also discussed.</P>