300 results on '"Wang, Hui-Chun"'
Search Results
102. Antioxidant and Tyrosinase Inhibitory Constituents from a Desugared Sugar Cane Extract, a Byproduct of Sugar Production
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Chung, Yu-Ming, primary, Wang, Hui-Chun, additional, El-Shazly, Mohamed, additional, Leu, Yann-Lii, additional, Cheng, Ming-Ching, additional, Lee, Chia-Lin, additional, Chang, Fang-Rong, additional, and Wu, Yang-Chang, additional
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- 2011
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103. Using the pER8:GUS Reporter System to Screen for Phytoestrogens from Caesalpinia sappan
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Lai, Wan-Chun, primary, Wang, Hui-Chun, additional, Chen, Guan-Yu, additional, Yang, Juan-Cheng, additional, Korinek, Michal, additional, Hsieh, Chia-Jung, additional, Nozaki, Hiroshi, additional, Hayashi, Ken-Ichiro, additional, Wu, Chih-Chung, additional, Wu, Yang-Chang, additional, and Chang, Fang-Rong, additional
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- 2011
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104. First total synthesis of antrocamphin A and its analogs as anti-inflammatory and anti-platelet aggregation agents
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Lee, Chia-Lin, primary, Huang, Chi-Huan, additional, Wang, Hui-Chun, additional, Chuang, Da-Wei, additional, Wu, Ming-Jung, additional, Wang, Sheng-Yang, additional, Hwang, Tsong-Long, additional, Wu, Chin-Chung, additional, Chen, Yeh-Long, additional, Chang, Fang-Rong, additional, and Wu, Yang-Chang, additional
- Published
- 2011
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105. ChemInform Abstract: Antioxidant Flavone Glycosides from the Root of Pteroxygonum giraldii.
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Li, Bao-Lin, primary, Yang, Zhan-Jun, additional, Jiang, Lin-Ling, additional, Zhang, Xi-Quan, additional, Gu, Hong-Mei, additional, Wang, Hui-Chun, additional, and Tian, Xian-Hua, additional
- Published
- 2009
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106. Encephalitis Depicted by a Combination of C-11 Acetate and F-18 FDG PET/CT
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Wang, Hui-Chun, primary, Zhao, Jun, additional, Zuo, Chuan-Tao, additional, Zhang, Zheng-Wei, additional, Xue, Fang-Ping, additional, Liu, Ping, additional, Hua, Feng-Chun, additional, Tan, Hai-Bo, additional, and Guan, Yi-Hui, additional
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- 2009
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107. Age Dependent Expressiones of Androgen Receptores in Testes and Epididymes of Mandarin Voles(Lasiopodomys mandarinus)
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WANG, Jian-li, primary, WANG, Hui-chun, additional, and TAI, Fa-dao, additional
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- 2009
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108. High-k HfxGdyOz Charge Trapping Layer in Silicon–Oxide–Nitride–Silicon Type Nonvolatile Memory by In situ Radio Frequency Dual-Sputtering Method
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Chou, Pai-Chi, primary, Lai, Chao-Sung, additional, Wang, Jer-Chyi, additional, Wu, Woei-Cherng, additional, Liu, Li-Chi, additional, Fang, Yu-Ching, additional, Hsu, Li, additional, and Wang, Hui-Chun, additional
- Published
- 2009
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109. Chk2-dependent phosphorylation of XRCC1 in the DNA damage response promotes base excision repair
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Chou, Wen-Cheng, primary, Wang, Hui-Chun, additional, Wong, Fen-Hwa, additional, Ding, Shian-ling, additional, Wu, Pei-Ei, additional, Shieh, Sheau-Yann, additional, and Shen, Chen-Yang, additional
- Published
- 2008
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110. Characterizations of HfxMoyNzAlloys as Gate Electrodes for n- and p-Channel Metal Oxide Semiconductor Field Effect Transistors
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Lai, Chao Sung, primary, Peng, Hsing Kan, additional, Huang, Chin Wei, additional, Fan, Kung Ming, additional, Fang, Yu Ching, additional, Hsu, Li, additional, Wang, Hui Chun, additional, Lee, Chung Yuan, additional, and Lin, Shian Jyh, additional
- Published
- 2008
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111. Breast Cancer Risk Is Associated with the Genes Encoding the DNA Double-Strand Break Repair Mre11/Rad50/Nbs1 Complex
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Hsu, Huan-Ming, primary, Wang, Hui-Chun, additional, Chen, Sou-Tong, additional, Hsu, Giu-Cheng, additional, Shen, Chen-Yang, additional, and Yu, Jyh-Cherng, additional
- Published
- 2007
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112. Full Range Work Function Modulation by Nitrogen Incorporation in Hf-Mo Binary Alloys Gate Electrode
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Lai, Chao-Sung, primary, Huang, Chin-Wei, additional, Peng, Hsing-Kan, additional, Chen, Chih-Hsin, additional, Fang, Yu-Ching, additional, Hsu, Li, additional, Wang, Hui-Chun, additional, Lee, Chung-Yuan, additional, and Lin, Shian-Jyh, additional
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- 2007
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113. Novel inorganic pH-insensitive membrane prepared by post N2O plasma treatment on conventional Si3N4/SiO2 stack layer for REFET application
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Wang, Ti-Chuan, primary, Lu, Tseng-Fu, additional, Chin, Chi-Hang, additional, Lue, Cheng-En, additional, Yang, Chia-Ming, additional, Fang, Yu-Ching, additional, Hsu, Li, additional, Wang, Hui-Chun, additional, and Lai, Chao-Sung, additional
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- 2007
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114. Sassarandainol: a new neolignan and anti-inflammatory constituents from the stem of Sassafras randaiense.
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Hou, Ya-Ling, Chang, Hsun-Shuo, Wang, Hui-Chun, Wang, Sheng-Yang, Chen, Tze-Ying, Lin, Chu-Hung, and Chen, Ih-Sheng
- Abstract
A new neolignan, (R)-( − )-sassarandainol (1), together with 10 known compounds (2–11), was isolated from the stem ofSassafras randaiense. The structures were determined by spectroscopic techniques. Among these isolates, γ-tocopherol (5), subamolide B (7) and β-sitosterone (9) exhibited moderate iNOS inhibitory activity on nitrite production induced (%) value of 30.51, 28.68 and 16.96, respectively. [ABSTRACT FROM PUBLISHER]
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- 2015
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115. Analysis of Parameters and Interaction between Parameters in Preparation of Uniform Silicon Dioxide Nanoparticles Using Response Surface Methodology
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Wang, Hui-Chun, primary, Wu, Cheng-Yuan, additional, Chung, Chin-Chun, additional, Lai, Ming-Hong, additional, and Chung, Tsair-Wang, additional
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- 2006
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116. Burkholderia phymatum is a highly effective nitrogen‐fixing symbiont of Mimosa spp. and fixes nitrogen ex planta
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Elliott, Geoffrey N., primary, Chen, Wen‐Ming, additional, Chou, Jui‐Hsing, additional, Wang, Hui‐Chun, additional, Sheu, Shih‐Yi, additional, Perin, Liamara, additional, Reis, Veronica M., additional, Moulin, Lionel, additional, Simon, Marcelo F., additional, Bontemps, Cyril, additional, Sutherland, Joan M., additional, Bessi, Rosana, additional, De Faria, Sergio M., additional, Trinick, Michael J., additional, Prescott, Alan R., additional, Sprent, Janet I., additional, and James, Euan K., additional
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- 2006
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117. Synthesis and Mesogenic Properties of Liquid Crystals Containing Terminal Cyclohexylmethanol, Cyclopentylmethanol, Cyclobutylmethanol and Cyclopropylmethanol Moiety
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Chen, Jo-Nan, primary, Hsu, Fang-Ming, additional, Wang, Hui-Chun, additional, Wu, Chung-Wen, additional, Cheng, Pao-Swu, additional, and Tsai, Wen-Liang, additional
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- 2006
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118. Ataxia Telangiectasia Mutated and Checkpoint Kinase 2 Regulate BRCA1 to Promote the Fidelity of DNA End-Joining
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Wang, Hui-Chun, primary, Chou, Wen-Cheng, additional, Shieh, Sheau-Yann, additional, and Shen, Chen-Yang, additional
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- 2006
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119. Lack of Evidence of Association ofp21WAF1/CIP1Polymorphism with Lung Cancer Susceptibility and Prognosis in Taiwan
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Shih, Chuen-Ming, primary, Lin, Pey-Tzy, additional, Wang, Hui-Chun, additional, Huang, Wei-Chi, additional, and Wang, Yi-Ching, additional
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- 2000
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120. Limonoids from the Seeds of Swietenia macrophyllawith Inhibitory Activity against Dengue Virus 2
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Cheng, Yuan-Bin, Chien, Yi-Ting, Lee, Jin-Ching, Tseng, Chin-Kai, Wang, Hui-Chun, Lo, I-Wen, Wu, Yi-Hung, Wang, Sheng-Yang, Wu, Yang-Chang, and Chang, Fang-Rong
- Abstract
Fractionation of an ethanol-soluble extract of the seeds of Swietenia macrophyllayielded six new limonoids, swielimonoids A–F (1–6), along with 20 known compounds. Compounds 1and 2, mexicanolide-type limonoids, were assigned with an α,β-unsaturated δ-lactone moiety (ring D) and a CC bond between C-8 and C-30. Compounds 3–6could be categorized as highly oxygenated phragmalin-type limonoids. The structures of these new compounds were elucidated through the interpretation of spectroscopic data. The antidengue virus 2 activities of the isolated components from S. macrophyllawere investigated, and of 12 compounds subjected to bioassay, compounds 2and 7–10were found to show inhibitory activity in the range 3.5 to 12.5 μM. Among these, the new limonoid 2exhibited significant antiviral activity (EC50= 7.2 ± 1.33 μM) with a selectivity index (CC50/EC50) value of >27.7.
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- 2014
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121. Efficacy of conventional whole-body ¹⁸F-FDG PET/CT in the incidental findings of parotid masses.
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Wang HC, Zuo CT, Hua FC, Huang ZM, Tan HB, Zhao J, Guan YH, Wang, Hui-Chun, Zuo, Chuan-Tao, Hua, Feng-Chun, Huang, Zhe-Min, Tan, Hai-Bo, Zhao, Jun, and Guan, Yi-Hui
- Abstract
Objective: The objective of this study was to evaluate the incidence of incidental parotid masses with conventional whole-body ¹⁸F-deoxyglucose (FDG) PET/CT and assess the ability of PET/CT to characterize these unexpected parotid lesions.Methods: Fifty eight incidental findings of parotid masses with routine FDG PET/CT whole-body scan were reviewed in this retrospective analysis, which were selected from the patients without any known or suspected parotid disease in our PET center, from June 2005 to May 2009. 51 cases were operated or underwent a biopsy after a short-term PET/CT study; the remaining 7 cases had a follow-up. Parotid mass that showed both noncontrast CT (irregular shape and blurry border) and PET malignant features (high FDG uptake, SUV(max) > 3.0) was considered as positive for malignancy. Correlation of FDG PET/CT with histology or follow-up outcome was performed.Results: Fifty eight unexpected findings of parotid masses accounted for 0.3% of the total cases in 4 years, including 11 (19.0%) malignant tumors and 47 (81.0%) benign lesions. 13 lesions manifested single nodule with malignant CT features and intense FDG activity, of which 6 were proved to be malignant; thus, sensitivity and positive predictive values were 54.5% (6 of 11) and 46.2% (6 of 13), respectively. 45 lesions showed either single nodule with benign CT features, or a low FDG uptake (SUV(max) ≤ 3.0), of which 40 were true negatives; therefore, specificity and negative predictive values were 85.1% (40 of 47) and 88.9% (40 of 45), respectively. All parotid masses except 9 benign and 1 malignant showed a high FDG uptake. Compared with SUV only, combined interpretation of PET and CT results displayed a lower sensitivity (90.9-54.5%), but a higher specificity (19.1-85.1%) and a higher overall accuracy.Conclusions: Whole-body FDG-PET/CT at the time of surveying the entire body condition is helpful for detecting the asymptomatic parotid masses. Combined noncontrast CT is an essential evidence for improving the diagnostic accuracy of FDG-PET/CT for parotid masses. [ABSTRACT FROM AUTHOR]- Published
- 2010
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122. Efficacy of conventional whole-body F-FDG PET/CT in the incidental findings of parotid masses.
- Author
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Wang, Hui-Chun, Zuo, Chuan-Tao, Hua, Feng-Chun, Huang, Zhe-Min, Tan, Hai-Bo, Zhao, Jun, and Guan, Yi-Hui
- Abstract
Objective: The objective of this study was to evaluate the incidence of incidental parotid masses with conventional whole-body F-deoxyglucose (FDG) PET/CT and assess the ability of PET/CT to characterize these unexpected parotid lesions. Methods: Fifty eight incidental findings of parotid masses with routine FDG PET/CT whole-body scan were reviewed in this retrospective analysis, which were selected from the patients without any known or suspected parotid disease in our PET center, from June 2005 to May 2009. 51 cases were operated or underwent a biopsy after a short-term PET/CT study; the remaining 7 cases had a follow-up. Parotid mass that showed both noncontrast CT (irregular shape and blurry border) and PET malignant features (high FDG uptake, SUV > 3.0) was considered as positive for malignancy. Correlation of FDG PET/CT with histology or follow-up outcome was performed. Results: Fifty eight unexpected findings of parotid masses accounted for 0.3% of the total cases in 4 years, including 11 (19.0%) malignant tumors and 47 (81.0%) benign lesions. 13 lesions manifested single nodule with malignant CT features and intense FDG activity, of which 6 were proved to be malignant; thus, sensitivity and positive predictive values were 54.5% (6 of 11) and 46.2% (6 of 13), respectively. 45 lesions showed either single nodule with benign CT features, or a low FDG uptake (SUV ≤ 3.0), of which 40 were true negatives; therefore, specificity and negative predictive values were 85.1% (40 of 47) and 88.9% (40 of 45), respectively. All parotid masses except 9 benign and 1 malignant showed a high FDG uptake. Compared with SUV only, combined interpretation of PET and CT results displayed a lower sensitivity (90.9-54.5%), but a higher specificity (19.1-85.1%) and a higher overall accuracy. Conclusions: Whole-body FDG-PET/CT at the time of surveying the entire body condition is helpful for detecting the asymptomatic parotid masses. Combined noncontrast CT is an essential evidence for improving the diagnostic accuracy of FDG-PET/CT for parotid masses. [ABSTRACT FROM AUTHOR]
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- 2010
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123. Lack of Evidence of Association of p21 WAF1/CIP1 Polymorphism with Lung Cancer Susceptibility and Prognosis in Taiwan.
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Shih, Chuen-Ming, Lin, Pey-Tzy, Wang, Hui-Chun, Huang, Wei-Chi, and Wang, Yi-Ching
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- 2000
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124. Touch interface for markless AR based on Kinect
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Wang, Yulin, Jiang, Xudong, Yang, Ming, Zhang, David, Yi, Xie, Hsieh, Ching-Tang, Kuo, Tai-Ku, Wang, Hui-Chun, Wu, Yeh-Kuang, and Chang, Liung-Chun
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- 2014
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125. RETRACTED: Inosine‐specific cleavage of RNA for microarray analysis of RNA A‐to‐I editing targets
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Huang, Hurng‐Wern, Chang, Hsueh‐Wei, Wang, Hui‐Chun, Lu, Chiu‐Jin, Chen, Shaio‐Wen, Yi, Szu‐Cheng, Wang, Hay‐Yan, Cho, Chung‐Lung, Wu, Cheng‐Hsuan, Yang, Jyuer‐Ger, and Tseng, Chao‐Neng
- Abstract
This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor. It has come to our attention that there is substantial duplication of some figures between this Kaohsiung Journal of Medical Science article and an earlier paper by the same authors, Chao‐Neng Tseng et al, A method to identify RNA A‐to‐I editing targets using I‐specific cleavage and exon array analysis, Molecular and Cellular Probes, Vol 27, 38‐45 (2013), https://doi.org/10.1016/j.mcp.2012.08.008. One of the conditions of submission of a paper for publication is that authors declare explicitly that their work is original and has not appeared in a publication elsewhere. Re‐use of any data should be appropriately cited. As such this article represents a severe abuse of the scientific publishing system. The scientific community takes a very strong view on this matter and apologies are offered to readers of the journal that this was not detected during the submission process.
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- 2013
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126. Lucidone Suppresses Hepatitis C Virus Replication by Nrf2-Mediated Heme Oxygenase-1 Induction
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Chen, Wei-Chun, Wang, Sheng-Yang, Chiu, Chien-Chih, Tseng, Chin-Kai, Lin, Chun-Kuang, Wang, Hui-Chun, and Lee, Jin-Ching
- Abstract
ABSTRACTUpon screening of plant-derived natural products against hepatitis C virus (HCV) in the replicon system, we demonstrate that lucidone, a phytocompound, isolated from the fruits of Lindera erythrocarpaMakino, significantly suppressed HCV RNA levels with 50% effective concentrations of 15 ± 0.5 μM and 20 ± 1.1 μM in HCV replicon and JFH-1 infectious assays, respectively. There was no significant cytotoxicity observed at high concentrations, with a 50% cytotoxic concentration of 620 ± 5 μM. In addition, lucidone significantly induced heme oxygenase-1 (HO-1) production and led to the increase of its product biliverdin for inducing antiviral interferon response and inhibiting HCV NS3/4A protease activity. Conversely, the anti-HCV activity of lucidone was abrogated by blocking HO-1 activity or silencing gene expression of HO-1 or NF-E2-related factor 2 (Nrf2) in the presence of lucidone, indicating that the anti-HCV action of lucidone was due to the stimulation of Nrf-2-mediated HO-1 expression. Moreover, the combination of lucidone and alpha interferon, the protease inhibitor telaprevir, the NS5A inhibitor BMS-790052, or the NS5B polymerase inhibitor PSI-7977, synergistically suppressed HCV RNA replication. These findings suggest that lucidone could be a potential lead or supplement for the development of new anti-HCV agent in the future.
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- 2012
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127. Lack of Evidence of Association of p21WAF1/CIP1Polymorphism with Lung Cancer Susceptibility and Prognosis in Taiwan
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Shih, Chuen‐Ming, Lin, Pey‐Tzy, Wang, Hui‐Chun, Huang, Wei‐Chi, and Wang, Yi‐Ching
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An association between the Arg allele of the p21WAF1/CIP1codon 31 polymorphism and lung cancer has been reported. However, the genotype distribution of the p21codon 31 polymorphism, as well as the association of this polymorphism with lung cancer risk and prognosis, remain undefined in the Taiwanese population. Therefore, we investigated the genotype distribution of the p21codon 31 polymorphism in 155 lung cancer patients and 189 non‐cancer controls. The genotype frequencies in the Taiwanese non‐cancer controls were 0.51 (Ser) and 0.49 (Arg). χ2analysis indicated significant differences in Taiwanese genotype distribution of p21from those reported for Swedes (P=0.001), Caucasians (P=0.001), Indians (P=0.001), and African‐Americans (P=0.001). However, our data did not demonstrate an association of the Arg allele of the p21polymorphism with lung cancer risk in Taiwan. Lung cancer patients with Ser/Arg and Arg/Arg genotypes were at a nonsignificant 1.15‐fold increased risk of lung cancer when compared to individuals with the Ser/Ser genotype (95%CI, 0.70–1.86). In addition, although p21is a downstream target of p53, we found no significant correlation of the p21polymorphism with the p53polymorphism and p53gene mutation in lung cancer patients. We further investigated the association of the p21polymorphism with prognosis in 154 lung cancer patients. Patients with the Ser/Ser genotype tended to have a poorer prognosis than those with the Ser/Arg and Arg/Arg genotypes (P=0.097, by the log rank test). Our data suggest that the p21codon 31 polymorphism may not play a significant role in cancer susceptibility and the prognosis of lung cancer patients in Taiwan.
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- 2000
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128. Characterizations of HfxMoyNz Alloys as Gate Electrodes for n- and p-Channel Metal Oxide Semiconductor Field Effect Transistors.
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Lai, Chao Sung, Peng, Hsing Kan, Huang, Chin Wei, Fan, Kung Ming, Fang, Yu Ching, Hsu, Li, Wang, Hui Chun, Lee, Chung Yuan, and Lin, Shian Jyh
- Abstract
In this article, the work functions (Φ
m ) of hafnium–molybdenum (Hfx Moy ) alloys were modified using nitrogen in dc reactive cosputtering for the first time. The Hfx Moy Nz alloys show low resistivity and excellent thermal stability up to 900 °C. In addition, the work functions (Φm ) of the Hfx Moy Nz alloys were tuned from the conduction band (4.17 eV) to the valence band (5.16 eV) by increasing the nitrogen flow ratio. From the X-ray diffraction (XRD) data, the MoN(200) peak can be observed for samples with a nitrogen ratio higher than 6%, which was responsible for the work function (Φm ) increase in the Hfx Moy Nz alloys. [ABSTRACT FROM AUTHOR]- Published
- 2008
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129. Anti-proliferation Effect on Human Breast Cancer Cells viaInhibition of pRb Phosphorylation by Taiwanin E Isolated from Eleutherococcus trifoliatus
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Wang, Hui-Chun, Tseng, Yen-Hsueh, Wu, Hui-Rong, Chu, Fang-Hua, Kuo, Yueh-Hsiung, and Wang, Sheng-Yang
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Eleutherococcus trifoliatushas been used as a folk medicine since ancient times, especially as refreshing qi medicines. In our current study, taiwanin E, which possesses strong cytotoxicity, was isolated from the branches of E. trifoliatusby using a bioactivity guided fractionation procedure. Taiwanin E presented a potent anti-proliferation activity on the growth of a human breast adenocarcinoma cell line (MCF-7), with an IC50value for cytotoxicity of 1.47 μM. Cell cycle analysis revealed that the proportion of cells in the G0/G1phase increased in a dose-dependent manner (from 79.4% to 90.2%) after 48 h exposure to taiwanin E at a dosage range from 0.5 to 4μM. After treatment with taiwanin E, phosphorylation of retinoblastoma protein (pRb) in MCF-7 cells was inhibited, accompanied by a decrease in the levels of cyclin D1, cyclin D3and cyclin-dependent kinase 4 (cdk4) and cdk6; in addition, there was an increase in the expression of cyclin-dependent kinase inhibitors p21WAF-1/Cip1and p27Kip1. The results suggest that taiwanin E inhibits cell cycle progression of MCF-7 at the G0/G1transition.
- Published
- 2014
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130. The effectiveness of Fuzi in combination with routine heart failure treatment on chronic heart failure patients.
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Tai, Chi-Jung, El-Shazly, Mohamed, Yang, Yi-Hsin, Tsai, Yi-Hong, Csupor, Dezső, Hohmann, Judit, Wu, Yang-Chang, Tseng, Tzyy-Guey, Chang, Fang-Rong, and Wang, Hui-Chun
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DRUG efficacy , *HERBAL medicine , *CLINICAL trials , *CONFIDENCE intervals , *RISK assessment , *DOSE-effect relationship in pharmacology , *HEART failure , *CHINESE medicine , *LONGITUDINAL method , *PROPORTIONAL hazards models , *THERAPEUTICS - Abstract
Fuzi, Aconiti Lateralis Radix Praeparata, is widely used in Traditional Chinese Medicine (TCM) for the treatment of acute heart failure (HF) for 2000 years. However, the clinical evidence of Fuzi in the treatment of chronic HF is limited, especially when used in combination with Western medications. This population-based propensity score (PS)-matched cohort study aimed to evaluate the effectiveness of Fuzi on the chronic HF. From 4753 chronic HF patients who had used TCM herbal medicine, we performed 1:1 PS matching and selected target patients with (n = 921) and without (n = 921) Fuzi use for further analysis. The primary outcomes were all-cause mortality and composite cardiovascular (CV) outcomes. Hazard ratio (HR) was calculated by Cox proportional hazard regression and the competing risk analysis. The dose-response relationship and the association between the initiation of TCM herbal medicine and the primary outcomes were evaluated by restricted cubic spline (RCS) functions. There was no difference in all-cause mortality (HR, 0.99; 95% confidence interval [CI], 0.76–1.27) and composite CV outcomes (HR, 0.96; 95% CI, 0.84–1.11) between the Fuzi user and non-user groups. For CV safety issue, the result showed that Fuzi use was not associated with a higher risk of cardiac arrhythmias (HR, 1.03; 95% CI, 0.83–1.29). The dose-response relationship showed that Fuzi cumulative dose (≥150g) was associated with lower composite CV risk (HR, 0.76; 95% CI, 0.59–0.99). In addition, the RCS model showed that late initiation (≥2.5 years) of TCM herbal drugs in chronic HF patients had a higher risk of all-cause mortality (HR, 1.81; 95%CI, 1.07–3.08). This study is the first real-world evidence to demonstrate the effect of Fuzi combined with routine HF treatment. Importantly, the result indicated that long-term Fuzi use had a significant benefit in preventing cardiovascular events. The late initiation of TCM herbal drugs was associated with a higher risk of all-cause mortality. Further clinical trials are needed to support or undermine the assumption of using Fuzi and current Western medications to treat chronic HF. [Display omitted] • Fuzi use (cumulative dose >150 g) had benefit in preventing cardiovascular events. • Fuzi use was not associated with a higher risk of cardiac arrhythmias. • Late initiation of TCM herbal drugs was associated with increased all-cause mortality. [ABSTRACT FROM AUTHOR]
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- 2022
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131. 3,5,2′,4′-Tetramethoxystilbene, a fully methylated resveratrol analog, prevents platelet aggregation and thrombus formation by targeting the protease-activated receptor 4 pathway.
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Chiang, Yi-Chun, Wu, Yu-Shan, Kang, Ya-Fei, Wang, Hui-Chun, Tsai, Meng-Chun, and Wu, Chin-Chung
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PROTEASE-activated receptors , *THROMBIN receptors , *RESVERATROL , *BLOOD platelet aggregation , *THROMBOSIS , *BLOOD coagulation , *STRUCTURE-activity relationships , *BLOOD coagulation factors - Abstract
Thrombin is a potent platelet activator and a key mediator of blood coagulation, thereby playing a crucial role in cardiovascular disease. Recently, protease-activated receptor 4 (PAR4), one of thrombin receptors in human platelets, is emerging as a promising target for antiplatelet therapy. 3,5,2′,4′-Tetramethoxystilbene (TMS), a resveratrol analog, have demonstrated promising effects on preventing atherosclerosis and hypertension, whereas its antiplatelet effect has never been investigated. Herein we show that TMS at concentrations of a few micromolar selectively inhibits PAR4-mediated human platelet aggregation, ATP secretion, integrin αIIbβ3 activation, and signaling pathways. In a whole-blood model of arterial flow, TMS also significantly reduced in vitro thrombus formation. Analysis of the structure-activity relationships of TMS and a panel of stilbene analogs reveal that full methylation of hydroxy groups of the stilbenes is the critical structural determinant for the anti-PAR4 activity. Our results suggest that fully methylated resveratrol analogs with anti-PAR4 activity are potential candidates for development of novel antiplatelet agents. [Display omitted] • The resveratrol derivative, TMS, shows selective inhibition of PAR4-mediated human platelet aggregation. • TMS reduced in vitro thrombus formation under whole blood flow conditions. • Methylation of the hydroxy groups of the resveratrol derivatives is critical for the anti-PAR4 activity. [ABSTRACT FROM AUTHOR]
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- 2022
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132. A method to identify RNA A-to-I editing targets using I-specific cleavage and exon array analysis
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Tseng, Chao-Neng, Chang, Hsueh-Wei, Stocker, Joel, Wang, Hui-Chun, Lu, Chiu-Chin, Wu, Cheng-Hsuan, Yang, Jyuer-Ger, Cho, Chung-Lung, and Huang, Hurng-Wern
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EXONS (Genetics) , *DNA microarrays , *RNA editing , *GENETIC disorders , *KNOCKOUT mice , *HEMATOPOIESIS - Abstract
Abstract: RNA A-to-I editing is the most common single-base editing in the animal kingdom. Dysregulations of RNA A-to-I editing are associated with developmental defects in mouse and human diseases. Mouse knockout models deficient in ADAR activities show lethal phenotypes associated with defects in nervous system, failure of hematopoiesis and reduced tolerance to stress. While several methods of identifying RNA A-to-I editing sites are currently available, most of the critical editing targets responsible for the important biological functions of ADARs remain unknown. Here we report a method to systematically analyze RNA A-to-I editing targets by combining I-specific cleavage and exon array analysis. Our results show that I-specific cleavage on editing sites causes more than twofold signal reductions in edited exons of known targets such as Gria2, Htr2c, Gabra3 and Cyfip2 in mice. This method provides an experimental approach for genome-wide analysis of RNA A-to-I editing targets with exon-level resolution. We believe this method will help expedite inquiry into the roles of RNA A-to-I editing in various biological processes and diseases. [Copyright &y& Elsevier]
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- 2013
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133. Preparation of Dearomatized p-Coumaric Acid Derivatives as DNA Damage Response Inhibitors with Potent In Vitro Antitumor Effect.
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Fási L, Gonda T, Tóth N, Vass M, Gyovai A, Nagy V, Ocsovszki I, Zupkó I, Kúsz N, Nové M, Spengler G, Berkecz R, Wang HC, Chang FR, and Hunyadi A
- Subjects
- Humans, Structure-Activity Relationship, Molecular Structure, Propionates chemistry, Propionates pharmacology, Propionates chemical synthesis, Dose-Response Relationship, Drug, Cell Line, Tumor, Antineoplastic Agents pharmacology, Antineoplastic Agents chemistry, Antineoplastic Agents chemical synthesis, DNA Damage drug effects, Coumaric Acids chemistry, Coumaric Acids pharmacology, Coumaric Acids chemical synthesis, Drug Screening Assays, Antitumor, Cell Proliferation drug effects
- Abstract
Our research group previously identified graviquinone (1) as a promising antitumor metabolite that is formed in situ when the antioxidant methyl caffeate scavenges free radicals. Furthermore, it exerted a DNA damaging effect on cancer cells and a DNA protective effect on normal keratinocytes. To expand and explore chemical space around qraviquinone, in the current work we synthesized 9 new alkyl-substituted derivatives and tested their in vitro antitumor potential. All new compounds bypassed ABCB1-mediated multidrug resistance and showed highly different cell line specificity compared with 1. All compounds were more potent in MDA-MB-231 than on MCF-7 cells. The n-butyl-substituted derivatives 2 and 8 modulated the cell cycle and inhibited the ATR-mediated phosphorylation of checkpoint kinase-1 in MCF-7 cells. As a significant expansion of our previous findings, our results highlight the potential antitumor value of alkyl-substituted graviquinone derivatives., (© 2024 The Author(s). ChemMedChem published by Wiley-VCH GmbH.)
- Published
- 2024
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134. Simulation of climate change effect on the global distribution of Rosa multiflora .
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Yang ST, Wang HC, Jing WK, Wang QG, Yan HJ, Qiu XQ, and Jian HY
- Subjects
- China, Computer Simulation, Plant Dispersal, Rosa growth & development, Climate Change, Introduced Species, Ecosystem
- Abstract
Rosa multiflora , originated from East Asia, is one of the original ancestors of modern roses. It is also an important genetic resource and rootstock for rose cultivation. Due to its high resistance and vigorous growth, R. multiflora has become an invasive species in some introduction sites, such as North America. To explore the correlation between the suitable habitat of R. multiflora and climate change, we predicted its potential geographic distribution with an optimized MaxEnt model based on 1246 distribution records and nine bioclimatic variables. The results showed that the mean temperature of the coldest quarter, minimum temperature of the coldest month, precipitation of the warmest quarter, and isothermality were significant bioclimatic variables affecting the potential geographic distribution of R. multiflora. Under current climate conditions, R. multiflora naturally distributed in the plains and hilly areas to the east and south of the Loess Plateau. The distribution pattern in the mid-holocene was similar to its current distribution, but the highly suitable distribution area was in the south of North China Plain, the Sichuan Basin, and parts of the Middle-Lower Yangtze Plain. During the last interglacial, the suitable areas generally contrac-ted southward, while the highly suitable areas significantly expanded and mainly located in the Sichuan Basin, the Middle-Lower Yangtze Plains, the Yunnan-Guizhou Plateau, and the Southeast Hills. Beyond its natural distribution in East Asia, R. multiflora had been introduced and spread to most parts of Europe and the central and eastern United States. The distribution area of R. multiflora would expand under three warming scenarios of different shared socioeconomic pathways (SSP1-2.6, SSP2-4.5, and SSP5-8.5) during 2041-2060 and 2081-2100. Its average distribution center (centroid) would shift towards higher latitude, indicating that the distribution of R. multiflora was closely related to climate change and that global warming might lead to an expansion of its distribution area. These results would improve our understanding of the ecological adaptability of R. multiflora , facilitate the predicting of its future distribution, and provide a theoretical basis for monitoring and early warning measures following its introduction.
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- 2024
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135. Synthesis of bioactive evodiamine and rutaecarpine analogues under ball milling conditions.
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Hu HC, Yu SY, Tsai YH, Hsieh PW, Wang HC, Chen YN, Chuang YT, Lee MY, Chang HW, Hu HC, Wu YC, Chang FR, Szatmári I, and Fülöp F
- Subjects
- Quinazolines chemistry, Indole Alkaloids, Quinazolinones
- Abstract
Mechanochemical reactions achieved by processes such as milling and grinding are promising alternatives to traditional solution-based chemistry. This approach not only eliminates the need for large amounts of solvents, thereby reducing waste generation, but also finds applications in chemical and materials synthesis. The focus of this study is on the synthesis of quinazolinone derivatives by ball milling, in particular evodiamine and rutaecarpine analogues. These compounds are of interest due to their diverse bioactivities, including potential anticancer properties. The study examines the reactions carried out under ball milling conditions, emphasizing their efficiency in terms of shorter reaction times and reduced environmental impact compared to conventional methods. The ball milling reaction of evodiamine and rutaecarpine analogues resulted in yields of 63-78% and 22-61%, respectively. In addition, these compounds were tested for their cytotoxic activity, and evodiamine exhibited an IC
50 of 0.75 ± 0.04 μg mL-1 against the Ca9-22 cell line. At its core, this research represents a new means to synthesise these compounds, providing a more environmentally friendly and sustainable alternative to traditional approaches.- Published
- 2024
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136. Indigofera suffruticosa aerial parts extract induce G2/M arrest and ATR/CHK1 pathway in Jurkat cells.
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Tran HL, Lai KH, Chang HS, Chen YS, Wang HC, Yang SS, Chang HW, Hsu CM, Yen CH, and Hsiao HH
- Subjects
- Humans, Jurkat Cells, Annexin A5, Apoptosis, Caffeine, Cell Line, Tumor, G2 Phase Cell Cycle Checkpoints, Plant Components, Aerial, Plant Extracts pharmacology, Ataxia Telangiectasia Mutated Proteins, Indigofera, Leukemia
- Abstract
Background: Indigofera suffruticosa Mill. is used as a folk medicine for treating patients with leukemia, however very little is known regarding the molecular mechanism of its anti-leukemic activity and the chemical profile of the active extract. The present study aimed to reveal the molecular effect of I. suffruticosa aerial parts extract (ISAE) on leukemia cells and its chemical constituents., Methods: Cytotoxicity of ISAE were determined by resazurin viability assay, multitox - Glo multiplex cytotoxicity assay, and Annexin V staining assay. Cell cycle profiles were revealed by propidium iodide staining assay. The effects of ISAE on G2/M arrest signaling and DNA damage were evaluated by Western blot assay and phospho-H2A.X staining assay. The chemical profile of ISAE were determined by tandem mass spectroscopy and molecular networking approach., Results: We showed that the acute lymphoblastic leukemia cell line Jurkat cell was more responsive to ISAE treatment than other leukemia cell lines. In contrast, ISAE did not induce cytotoxic effects in normal fibroblast cells. Cell cycle analysis revealed that ISAE triggered G2/M arrest in Jurkat cells in dose- and time-dependent manners. Elevation of annexin V-stained cells and caspase 3/7 activity suggested ISAE-induced apoptosis. Furthermore, ISAE alone could increase the phosphorylation of CDK1 at Y15 and activate the ATR/CHK1/Wee1/CDC25C signaling pathway. However, the addition of caffeine, a widely used ATR inhibitor to ISAE, reduced the phosphorylation of ATR, CHK1, and CDK1, as well as G2/M arrest in Jurkat cells. Moreover, increased phospho-H2A.X stained cells indicated the involvement of DNA damage in the anti-leukemic effect of ISAE. Finally, qualitative analysis using UPLC-tandem mass spectroscopy and molecular networking revealed that tryptanthrin was the most abundant organoheterocyclic metabolite in ISAE. At equivalent concentrations to ISAE, tryptanthrin induced G2/M arrest of Jurkat cells, which can be prevented by caffeine., Conclusions: ISAE causes G2/M arrest via activating ATR/CHK1/CDK1 pathway and tryptanthrin is one of the active components of ISAE. Our findings provide subtle support to the traditional use of I. suffruitcosa in leukemia management in folk medicine., (© 2024. The Author(s).)
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- 2024
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137. Hybrid molecules of protoflavones and spirooxindole derivatives with selective cytotoxicity against triple-negative breast cancer cells.
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Girst G, Lopes EA, Gonçalves LM, Espadinha M, Kúsz N, Wang HC, Santos MMM, and Hunyadi A
- Abstract
The combination of compounds with complementary bioactivities into hybrid molecules is an emerging concept in drug discovery. In this study, we aimed to synthesize new hybrid compounds based on p53-MDM2/X protein-protein interaction spiropyrazoline oxindole-based inhibitors and ataxia telangiectasia and Rad3-related (ATR) protoflavone-based inhibitors through copper(i) catalysed azide-alkyne cycloaddition. Five new hybrids were prepared along with three representative reference fragments. The compounds were tested against human breast cancer cell lines MCF-7 (hormone-dependent, wild-type p53) and MDA-MB-231 (triple-negative, mutant p53). Most of the new hybrids were more cytotoxic than their reference fragments and several showed 2-4 times selective toxicity against MDA-MB-231 cells. Relevant pharmacological benefit gained from the hybrid coupling was further confirmed by virtual combination index calculations using the Chou method. Compound 13 modulated doxorubicin-induced DNA damage response through inhibiting the ATR-dependent activation of Chk-1, while increasing the activation of Chk-2. Our results suggest that the new hybrids may serve as new leads against triple negative breast cancer., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)
- Published
- 2023
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138. New Verticillene Diterpenoids, Eudesmane Sesquiterpenoids, and Hydroperoxysteroids from the Further Chemical Investigation of a Taiwanese Soft Coral Cespitularia sp.
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Fu CW, Lin YC, Chiou SF, Chen SL, Lin CC, Wang HC, Dai CF, and Sheu JH
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- Animals, Magnetic Resonance Spectroscopy, Molecular Structure, Anthozoa chemistry, Sesquiterpenes, Eudesmane chemistry, Diterpenes chemistry, Sesquiterpenes chemistry
- Abstract
An investigation of the chemical composition of a Formosan soft coral Cespitularia sp. led to the discovery of one new verticillene-type diterpenoid, cespitulactam M ( 1 ); one new eudesmane sesquiterpenoid, cespilamide F ( 2 ); and three new hydroperoxysteroids ( 3 - 5 ) along with twelve known analogous metabolites ( 6 - 17 ). In addition, one new derivative, cespitulactam M-6,2'-diacetate ( 1a ), was prepared from compound 1 . The structures were determined by detailed spectroscopic analyses, particularly HRESIMS and NMR techniques. Moreover, the in vitro cytotoxicity, anti-inflammatory, and antibacterial activity of 1 - 17 and 1a were evaluated.
- Published
- 2023
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139. Severinia buxifolia-isolated acridones inhibit lung cancer invasion and decrease HIFα protein synthesis involving 5'UTR-mediated translation inhibition.
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Chen PW, Huang SK, Chou WC, Chang FR, Cheng YB, and Wang HC
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- Humans, Cell Line, Tumor, 5' Untranslated Regions, Cell Hypoxia, Hypoxia-Inducible Factor 1, alpha Subunit genetics, Hypoxia-Inducible Factor 1, alpha Subunit metabolism, Hypoxia, Lung Neoplasms pathology
- Abstract
Background: Lung cancer is one of the most common cancers worldwide and is by far the leading cause of cancer death attributed to its rapid metastasis and poor prognosis. Given that hypoxia-inducible factors (HIFs) are associated with cancer metastasis, discovering agents to inhibit HIF-mediated invasive cancer is highly desired., Purpose: This study aimed to investigate the natural acridone compounds isolated from Severinia buxifolia for the potential to delay hypoxia-induced lung cancer invasiveness by HIF inhibition., Methods: Using a hypoxia-responsive element (HRE) luciferase reporter, cell migration and invasion assays, real-time PCR, Western blot, and DNA recombinant clones, compound effect on HIF activity, cancer metastasis, HIF-1α mRNA transcription, HIFs protein stability, and HIF-1α translation were observed under hypoxia conditions., Results: Atalaphyllidine (Sbs-A) and atalaphyllinine (Sbs-B) were found to show the most potent effects on HIF transcriptional activity and HIF-1α protein expression in NSCLC cell line A549, although Sbs-A and Sbs-B might not attribute decreasing HIF-1α mRNA expression to potent inhibition of HIF activity. HIF-1α protein stability was not affected by Sbs-A; also, prolyl hydroxylase and proteasome inhibitors could not reverse the inhibitory effect from compounds. Furthermore, 3 - 10 μM low concentrations of Sbs-A inhibited HIF target gene expression, gelatin zymography activity, and A549 cancer invasion. Ultimately, Sbs-A inhibited HIF-1α 5'UTR-mediated translation independent of oxygen concentration, underlying the mechanism of compounds inhibiting HIF-1α protein expression., Conclusion: Our study proposed Severinia buxifolia-isolated acridone compounds inhibited 5'-mRNA HIFA-mediated translation and provided evidence supporting the ability of acridone compounds in targeting HIFα for delayed lung cancer metastasis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier GmbH. All rights reserved.)
- Published
- 2023
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140. Golden berry 4β-hydroxywithanolide E prevents tumor necrosis factor α-induced procoagulant activity with enhanced cytotoxicity against human lung cancer cells.
- Author
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Hsieh KY, Tsai JY, Lin YH, Chang FR, Wang HC, and Wu CC
- Subjects
- A549 Cells drug effects, Apoptosis drug effects, Caspases metabolism, Cell Line, Tumor, Humans, Microscopy, Fluorescence, Real-Time Polymerase Chain Reaction, Tumor Necrosis Factor-alpha pharmacology, Antineoplastic Agents pharmacology, Blood Coagulation drug effects, Carcinoma, Non-Small-Cell Lung drug therapy, Lung Neoplasms drug therapy, Physalis chemistry, Tumor Necrosis Factor-alpha antagonists & inhibitors, Withanolides pharmacology
- Abstract
Inflammation in the tumor microenvironment is positively correlated with cancer progression and metastasis as well as the risk of thromboembolism in lung cancer patients. Here we show, in human non-small cell lung cancer (NSCLC) cell lines, the master inflammatory cytokine tumor necrosis factor (TNF-α) induced tissue factor expression and procoagulant activity, and these effects were potently inhibited by 4β-hydroxywithanolide E (4HW), a natural compound isolated from Physalis peruviana. Furthermore, combination of 4HW and TNF-α caused synergistic cytotoxicity against NSCLC cells by inducing caspase-dependent apoptosis. The underlying mechanism by which 4HW reverses the procoagulant effect of TNF-α but enhances its cytotoxic effect appears to be due to inhibition of NF-κB, which is a key switch for both inflammation-induced coagulation and cell survival. Our results suggest that 4HW may have a potential application for treating inflammation-derived cancer progression and cancer-associated hypercoagulable state.
- Published
- 2021
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141. Bioactive Triterpenoids from the Leaves and Twigs of Lithocarpus litseifolius and L. corneus.
- Author
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Cheng YB, Liu FJ, Wang CH, Hwang TL, Tsai YF, Yen CH, Wang HC, Tseng YH, Chien CT, Chen YA, Chang FR, and Wu YC
- Subjects
- Anti-HIV Agents pharmacology, Anti-Inflammatory Agents pharmacology, Cell Line, Cell Survival drug effects, HIV drug effects, Humans, Magnetic Resonance Spectroscopy, Mass Spectrometry, Neutrophils drug effects, Plant Extracts isolation & purification, Terpenes isolation & purification, Fagaceae chemistry, Plant Extracts pharmacology, Plant Leaves chemistry, Plant Stems chemistry, Terpenes pharmacology
- Abstract
Phytochemical investigation of the leaves and twigs of Lithocarpus litseifolius and Lithocarpus corneus resulted in the isolation of four new triterpenoids (1: -4: ), three triterpenoids (5: -7: ) isolated from a natural source for the first time, and six known compounds (8: -13: ). In addition, four known triterpenoids (14: -17: ) were isolated from L. corneus . Compound 1: is a 3,4- seco -lupane-type triterpenoid, and compounds 2: -4: are lupane-type triterpenoids in different oxidation states. The structures of all isolated compounds were identified by spectroscopic methods, especially NMR and mass spectrometry data. The absolute configuration of 2: and 3: was confirmed by X-ray single crystallographic analysis. The anti-inflammatory activities of 1: -17: and anti-HIV activities of 2: -17: were evaluated. Among them, 3- epi -betulinic acid (8: ) showed a strong anti-HIV activity comparable to abacavir, a drug used for treating HIV/AIDS. 3,4- seco -4(23),20(29)-lupadiene-3,28-dioic acid (5: ) exhibited potent inhibition of superoxide-anion generation with 86.9 ± 2.8% inhibition at 1 µM., Competing Interests: Conflict of Interest: There is no conflict of interest., (Georg Thieme Verlag KG Stuttgart · New York.)
- Published
- 2018
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142. 18 F-FDG PET/CT delayed images with forced diuresis for revaluating abdominopelvic malignancies.
- Author
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Wang HC, Wang ZM, Wang YB, Chen XH, and Cui LL
- Subjects
- Adult, Aged, Aged, 80 and over, Colorectal Neoplasms pathology, Female, Fluorodeoxyglucose F18, Humans, Male, Middle Aged, Positron Emission Tomography Computed Tomography, Radiopharmaceuticals, Retrospective Studies, Urogenital Neoplasms pathology, Colorectal Neoplasms diagnostic imaging, Diuretics administration & dosage, Furosemide administration & dosage, Urogenital Neoplasms diagnostic imaging
- Abstract
Purpose: The aim of this retrospective study was to evaluate the role of delayed images after forced diuresis coupled with oral hydration in abdominopelvic
18 F-FDG PET/CT., Materials and Methods: Forty-six patients consisting of 17 urological diseases, 9 gynecological tumors, 18 colorectal malignancies, and 2 cancers of unknown primary site were retrospectively analyzed. All patients who presented with indeterminate or equivocal abdominopelvic foci on standard18 F-FDG PET/CT underwent a delayed abdominopelvic imaging after administration of 20 mg furosemide intravenously and extra water intake of 500 mL. PET/CT images before and after furosemide were compared with each other and their findings correlated with pathology or clinical follow-up (>6 months)., Results: On initial PET/CT, the glucose metabolism characters of lesions were disguised by radioactive urine, or some undetermined18 F-FDG accumulating foci near the urinary tract appeared. While postdiuretic PET/CT demonstrated an excellent urinary tracer washout, and hypermetabolic lesions could be clearly detected and precisely localized in all cases. On the other hand, the suspected active foci caused by potential stagnation of excreted18 F-FDG in urinary tract were eliminated. The sensitivity, specificity, and accuracy were 94.4% (34/36), 8/10, 91.3% (42/46), respectively. Furthermore, the additional lesions with surrounding invasion or locoregional metastasis were discovered in 8 of 46 (17.4%) patients only by the delayed images, including 2 gynecological and 6 rectal malignancies., Conclusion: Detection of abdominopelvic malignancies can be improved using delayed18 F-FDG PET/CT images after a diuretic and oral hydration.- Published
- 2017
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143. Lower antioxidative capacity of multidrug-resistant cancer cells confers collateral sensitivity to protoflavone derivatives.
- Author
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Stanković T, Dankó B, Martins A, Dragoj M, Stojković S, Isaković A, Wang HC, Wu YC, Hunyadi A, and Pešić M
- Subjects
- ATP Binding Cassette Transporter, Subfamily B, Member 1 metabolism, Animals, Cell Line, Tumor, Drug Resistance, Multiple, Flavones chemistry, Humans, Molecular Structure, Rats, Reactive Oxygen Species metabolism, Structure-Activity Relationship, Antioxidants metabolism, Flavones pharmacology, Neoplasms drug therapy, Neoplasms metabolism
- Abstract
Purpose: Multidrug resistance (MDR) may develop due to a series of adaptive responses under a new stress conditions, such as chemotherapy. Novel strategies are urgently needed to fight MDR in cancer, and chemotherapeutics that are selective for MDR cancer cells offer a promising approach. Certain protoflavones were previously found to have potential in this regard., Methods: Cytotoxicity of six protoflavones was assessed in different P-glycoprotein overexpressing MDR cancer cell lines and in their non-MDR counterparts. The impacts of compound 5, 6-methylprotoflavone previously published and a new derivative, 6-bromoprotoflavone (compound 6), on the cell cycle distribution were evaluated, and 6 was also studied for its potential to regulate the intracellular antioxidative capacity., Results: Protoflavones showed a significant cytotoxicity against all cancer cell lines and selectivity toward MDR cancer cells adapted to conventional chemotherapeutics. Inverse sensitivity versus MDR selectivity pattern was observed. Treatment with H₂O₂ showed that MDR cancer cells are more vulnerable to oxidative stress. Compounds 5 and 6 significantly decreased the portion of MDR cells in the G1 phase. The levels of reactive oxygen and nitrogen species (ROS/RNS) between MDR and non-MDR cells significantly differed upon exposure to 6, accompanied by changes in the glutathione (GSH) levels and in the expression of manganese superoxide dismutase (MnSOD), glutathione-S-transferase π (GST π) and hypoxia-inducible factor-1α (HIF-1α)., Conclusions: Our results suggest that MDR cancer cells can be more vulnerable to the pro-oxidative activity of protoflavones due to an impaired antioxidative defense that might arise during the adaptation processes provoked by chemotherapy.
- Published
- 2015
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144. (-)-Liriopein B Suppresses Breast Cancer Progression via Inhibition of Multiple Kinases.
- Author
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Wang HC, Chang FR, Huang TJ, Kuo CY, Tsai YC, and Wu CC
- Subjects
- Antineoplastic Agents, Phytogenic chemistry, Antineoplastic Agents, Phytogenic isolation & purification, Breast metabolism, Breast pathology, Breast Neoplasms metabolism, Breast Neoplasms pathology, Cell Line, Tumor, Cell Proliferation drug effects, ErbB Receptors metabolism, Female, Humans, Liriope Plant chemistry, MAP Kinase Signaling System drug effects, Plant Proteins chemistry, Plant Proteins isolation & purification, Protein Kinase Inhibitors chemistry, Protein Kinase Inhibitors isolation & purification, Antineoplastic Agents, Phytogenic pharmacology, Breast drug effects, Breast Neoplasms drug therapy, Phosphatidylinositol 3-Kinases metabolism, Plant Proteins pharmacology, Protein Kinase Inhibitors pharmacology, Proto-Oncogene Proteins c-akt metabolism, Signal Transduction drug effects
- Abstract
Numerous breast cancer patients who achieve an initial response to HER-targeted therapy rapidly develop resistance within one year, leading to treatment failure. Observations from clinical samples indicate that such resistance correlates with an increase in Src, EGFR, and PI3K/Akt activities and a decrease in PTEN activity. Furthermore, Akt survival signaling activation is also found in tumors treated by toxic chemotherapeutic agents. Because cotreatment with a PI3K inhibitor is a promising strategy to delay acquired resistance by preventing secondary gene activation, we therefore investigated the effects of a newly identified compound, (-)-Liriopein B (LB), on PI3K/Akt signaling activity in breast cancer cells. Our results showed that nontoxic doses of LB are able to inhibit AKT activation in both luminal-like MCF-7 and basal-like MDA-MB-231 breast cancer cells. Low doses of LB also inhibited cell migration, invasion, and cancer-stem cell sphere formation. Suppression of EGF-induced EGFR and ERK1/2 activation by LB might contribute in part to retardation of cancer progression. Furthermore, LB increases sensitivity of MDA-MB-231 cells to gefitinib in vitro, suggesting that EGFR may not be the only target of LB. Finally, a small scale in vitro kinase assay screen demonstrated that LB has a potent inhibitory effect on multiple kinases, including PI3K, Src, EGFR, Tie2, lck, lyn, RTK5, FGFR1, Abl, and Flt. In conclusion, this study demonstrates for the first time that the compound LB improves tumor therapeutic efficacy and suggests LB as a promising candidate for studying new leads in the development of kinase inhibitors.
- Published
- 2015
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145. Biological evaluation of secondary metabolites from the roots of Myrica adenophora.
- Author
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Ting YC, Ko HH, Wang HC, Peng CF, Chang HS, Hsieh PC, and Chen IS
- Subjects
- Antioxidants chemistry, Biphenyl Compounds chemistry, Flavonoids chemistry, Free Radical Scavengers chemistry, Glycosides chemistry, Molecular Structure, Picrates chemistry, Proanthocyanidins chemistry, Diarylheptanoids chemistry, Myrica chemistry, Plant Roots chemistry
- Abstract
Bioassay-guided fractionation of the roots of Myrica adenophora led to isolation of 24 known compounds and hitherto unknown compounds, including three A-type proanthocyanidins [adenodimerins A-C], two esters of sucrose [myricadenins A and B ], and the phenolic glycoside 6'-O-galloyl orbicularin. Spectroscopic analyses were used to determine their structures. Adenodimerin A, myricananin C, and myricetin showed strong 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activities, with SC50 values of 7.9, 16.3, and 15.9 μM, respectively. Adenodimerin A, myricanone, myricananin C, (-)-myricanol, myricanol 11-O-β-D-glucopyranoside, and myricetin showed stronger 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS) radical scavenging activities than the positive control, with SC50 values of 7.5, 19.6, 12.0, 22.3, 19.6, and 15.6 μM, respectively. 5-Deoxymyricanone, porson, 12-hydroxymyricanone (-)-myricanol, and (+)-galeon exhibited anti-tubercular activity against Mycobacterium tuberculosis H37Rv in vitro and MICs values of 25.8, 40.0, 35.8, 30.0, and 15.0 μg/mL, respectively. Myricadenin A, myricanone, myricananin C, and (-)-myricanol exhibited anti-inflammatory activities in the iNOS assay with EC50 values of 18.1, 1.00, 13.0, and 7.5 μM, respectively., (Copyright © 2014 Elsevier Ltd. All rights reserved.)
- Published
- 2014
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146. Inosine-specific cleavage of RNA for microarray analysis of RNA A-to-I editing targets.
- Author
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Huang HW, Chang HW, Wang HC, Lu CJ, Chen SW, Yi SC, Wang HY, Cho CL, Wu CH, Yang JG, and Tseng CN
- Subjects
- Adenosine Deaminase chemistry, Animals, Brain Chemistry, Mice, Mice, Inbred ICR, Microarray Analysis, Inosine chemistry, RNA Cleavage, RNA Editing
- Abstract
Dysregulations of RNA A-to-I editing are associated with developmental defects in mouse and human diseases. Although several methods of identifying RNA A-to-I editing sites are currently available, most of the critical editing targets responsible for the important biological functions of adenosine deaminases that act on RNA (ADARs) remain unknown. Here we report a modified I-specific cleavage method that improves the quality of the RNA product. Preliminary microarray comparison of RNAs subjected to I-specific cleavage or mock digestion reported 165 genes that showed more than 0.2-fold reductions due to the cleavage. Six of the 165 genes were randomly selected for further verification, and three were verified to be targets of I-specific cleavage. This method may provide an alternative method of identifying novel RNA A-to-I editing sites using a microarray and facilitate the inquiry into the roles of RNA A-to-I editing in various biological processes., (Copyright © 2012. Published by Elsevier B.V.)
- Published
- 2013
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147. Active Constituents from Liriope platyphylla Root against Cancer Growth In Vitro.
- Author
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Wang HC, Wu CC, Cheng TS, Kuo CY, Tsai YC, Chiang SY, Wong TS, Wu YC, and Chang FR
- Abstract
Liriope spicata is a well-known herb in traditional Chinese medicine, and its root has been clinically demonstrated to be effective in the treatment of metabolic and neural disorders. The constituents isolated from Liriope have also recently been shown to possess anticancer activity, although the mechanism of which remains largely unknown. Here, we illustrate the anticancer activity of LPRP-9, one of the active fractions we fractionated from the Liriope platyphylla root part (LPRP) extract. Treatment with LPRP-9 significantly inhibited proliferation of cancer cell lines MCF-7 and Huh-7 and down-regulated the phosphorylation of AKT. LPRP-9 also activates the stress-activated MPAK, JNK, p38 pathways, the p53 cell-cycle checkpoint pathway, and a series of caspase cascades while downregulating expression of antiapoptotic factors Bcl-2, Bcl-XL, and survivin. Such activities strongly suggest a role for LPRP-9 in apoptosis and autophagy. We further purified and identified the compound (-)-Liriopein B from LPRP-9, which is capable of inhibiting AKT phosphorylation at low concentration. The overall result highlights the anticancer property of LPRP-9, suggests its mechanism for inhibition of proliferation and promotion of cell death for cancer cells via regulation of multitarget pathways, and denotes the importance of purifying components of fraction LPRP-9 to aid cancer therapy.
- Published
- 2013
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148. First total synthesis of antrocamphin A and its analogs as anti-inflammatory and anti-platelet aggregation agents.
- Author
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Lee CL, Huang CH, Wang HC, Chuang DW, Wu MJ, Wang SY, Hwang TL, Wu CC, Chen YL, Chang FR, and Wu YC
- Subjects
- Alkynes pharmacology, Anisoles pharmacology, Anti-Inflammatory Agents pharmacology, Anticoagulants pharmacology, Humans, Molecular Structure, Neutrophils drug effects, Structure-Activity Relationship, Alkynes chemical synthesis, Anisoles chemical synthesis, Anti-Inflammatory Agents chemical synthesis, Anticoagulants chemical synthesis
- Abstract
Naturally occurring antrocamphin A (1) is a potent anti-inflammatory compound from the edible fungus Antrodia camphorata (Taiwanofungus camphoratus), whose wild fruiting body is used as a valuable folk medicine in Taiwan. This study is the first total synthesis of antrocamphin A (1) and its analogs. Their inhibition ability on NO release, superoxide anion generation, elastase release and platelet aggregation are reported herein.
- Published
- 2011
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149. Risk of estrogen receptor-positive and -negative breast cancer and single-nucleotide polymorphism 2q35-rs13387042.
- Author
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Milne RL, Benítez J, Nevanlinna H, Heikkinen T, Aittomäki K, Blomqvist C, Arias JI, Zamora MP, Burwinkel B, Bartram CR, Meindl A, Schmutzler RK, Cox A, Brock I, Elliott G, Reed MW, Southey MC, Smith L, Spurdle AB, Hopper JL, Couch FJ, Olson JE, Wang X, Fredericksen Z, Schürmann P, Bremer M, Hillemanns P, Dörk T, Devilee P, van Asperen CJ, Tollenaar RA, Seynaeve C, Hall P, Czene K, Liu J, Li Y, Ahmed S, Dunning AM, Maranian M, Pharoah PD, Chenevix-Trench G, Beesley J, Bogdanova NV, Antonenkova NN, Zalutsky IV, Anton-Culver H, Ziogas A, Brauch H, Justenhoven C, Ko YD, Haas S, Fasching PA, Strick R, Ekici AB, Beckmann MW, Giles GG, Severi G, Baglietto L, English DR, Fletcher O, Johnson N, dos Santos Silva I, Peto J, Turnbull C, Hines S, Renwick A, Rahman N, Nordestgaard BG, Bojesen SE, Flyger H, Kang D, Yoo KY, Noh DY, Mannermaa A, Kataja V, Kosma VM, García-Closas M, Chanock S, Lissowska J, Brinton LA, Chang-Claude J, Wang-Gohrke S, Shen CY, Wang HC, Yu JC, Chen ST, Bermisheva M, Nikolaeva T, Khusnutdinova E, Humphreys MK, Morrison J, Platte R, and Easton DF
- Subjects
- Adult, Aged, Asian People genetics, Breast Neoplasms pathology, Carcinoma, Ductal, Breast chemistry, Carcinoma, Ductal, Breast genetics, Carcinoma, Intraductal, Noninfiltrating chemistry, Carcinoma, Intraductal, Noninfiltrating genetics, Case-Control Studies, Confidence Intervals, Confounding Factors, Epidemiologic, Female, Gene Frequency, Genetic Predisposition to Disease, Genotype, Humans, Linkage Disequilibrium, Middle Aged, Odds Ratio, Receptors, Progesterone genetics, Biomarkers, Tumor analysis, Breast Neoplasms chemistry, Breast Neoplasms genetics, Neoplasms, Hormone-Dependent chemistry, Neoplasms, Hormone-Dependent genetics, Polymorphism, Single Nucleotide, Receptors, Estrogen analysis, White People genetics
- Abstract
Background: A recent genome-wide association study identified single-nucleotide polymorphism (SNP) 2q35-rs13387042 as a marker of susceptibility to estrogen receptor (ER)-positive breast cancer. We attempted to confirm this association using the Breast Cancer Association Consortium., Methods: 2q35-rs13387042 SNP was genotyped for 31 510 women with invasive breast cancer, 1101 women with ductal carcinoma in situ, and 35 969 female control subjects from 25 studies. Odds ratios (ORs) were estimated by logistic regression, adjusted for study. Heterogeneity in odds ratios by each of age, ethnicity, and study was assessed by fitting interaction terms. Heterogeneity by each of invasiveness, family history, bilaterality, and hormone receptor status was assessed by subclassifying case patients and applying polytomous logistic regression. All statistical tests were two-sided., Results: We found strong evidence of association between rs13387042 and breast cancer in white women of European origin (per-allele OR = 1.12, 95% confidence interval [CI] = 1.09 to 1.15; P(trend) = 1.0 x 10(-19)). The odds ratio was lower than that previously reported (P = .02) and did not vary by age or ethnicity (all P > or = .2). However, it was higher when the analysis was restricted to case patients who were selected for a strong family history (P = .02). An association was observed for both ER-positive (OR = 1.14, 95% CI = 1.10 to 1.17; P = 10(-15)) and ER-negative disease (OR = 1.10, 95% CI = 1.04 to 1.15; P = .0003) and both progesterone receptor (PR)-positive (OR = 1.15, 95% CI = 1.11 to 1.19; P = 5 x 10(-14)) and PR-negative disease (OR = 1.10, 95% CI = 1.06 to 1.15; P = .00002)., Conclusion: The rs13387042 is associated with both ER-positive and ER-negative breast cancer in European women.
- Published
- 2009
- Full Text
- View/download PDF
150. Research on receptors related to acupuncture analgesia and positron emission tomography radioligands: a review.
- Author
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Wang HC, Zuo CT, and Guan YH
- Subjects
- Animals, Humans, Receptors, Dopamine physiology, Acupuncture Analgesia, Positron-Emission Tomography methods, Receptors, GABA physiology, Receptors, Opioid physiology, Receptors, Serotonin physiology
- Published
- 2009
- Full Text
- View/download PDF
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