195 results on '"Pei-Jung Lu"'
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2. The activation of <scp> EP300 </scp> by <scp>F11R</scp> leads to <scp>EMT</scp> and acts as a prognostic factor in triple‐negative breast cancers
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Chien‐Hsiu Li, Chih‐Yeu Fang, Ming‐Hsien Chan, Pei‐Jung Lu, Luo‐Ping Ger, Jan‐Show Chu, Yu‐Chan Chang, Chi‐Long Chen, and Michael Hsiao
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Pathology and Forensic Medicine - Published
- 2023
3. Supplementary Figure 1 from Carboxyl-Terminal Modulator Protein Positively Regulates Akt Phosphorylation and Acts as an Oncogenic Driver in Breast Cancer
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Pei-Jung Lu, Michael Hsiao, Yu-Hao Zeng, Kuen-Haur Lee, Yi-Hua Jan, Yu-Chia Chen, Hong-Tai Chang, Yu-Cheng Lee, Tai-I Hsu, Jiun-Chin Chen, Luo-Ping Ger, Wen-Chi Liao, and Yu-Peng Liu
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PDF file, 75K, Overexpression of CTMP enhances PI3K-mediated Akt phosphorylation.
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- 2023
4. Supplementary Materials and Methods from Carboxyl-Terminal Modulator Protein Positively Regulates Akt Phosphorylation and Acts as an Oncogenic Driver in Breast Cancer
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Pei-Jung Lu, Michael Hsiao, Yu-Hao Zeng, Kuen-Haur Lee, Yi-Hua Jan, Yu-Chia Chen, Hong-Tai Chang, Yu-Cheng Lee, Tai-I Hsu, Jiun-Chin Chen, Luo-Ping Ger, Wen-Chi Liao, and Yu-Peng Liu
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PDF file, 146K.
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- 2023
5. Supplementary Figure 3 from Carboxyl-Terminal Modulator Protein Positively Regulates Akt Phosphorylation and Acts as an Oncogenic Driver in Breast Cancer
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Pei-Jung Lu, Michael Hsiao, Yu-Hao Zeng, Kuen-Haur Lee, Yi-Hua Jan, Yu-Chia Chen, Hong-Tai Chang, Yu-Cheng Lee, Tai-I Hsu, Jiun-Chin Chen, Luo-Ping Ger, Wen-Chi Liao, and Yu-Peng Liu
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PDF file, 187K, The N-terminal domain, 1-64 a.a., of CTMP is required, but not sufficient, to induce Akt phosphorylation, colony formation and cell proliferation.
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- 2023
6. Supplementary Table 2 from Carboxyl-Terminal Modulator Protein Positively Regulates Akt Phosphorylation and Acts as an Oncogenic Driver in Breast Cancer
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Pei-Jung Lu, Michael Hsiao, Yu-Hao Zeng, Kuen-Haur Lee, Yi-Hua Jan, Yu-Chia Chen, Hong-Tai Chang, Yu-Cheng Lee, Tai-I Hsu, Jiun-Chin Chen, Luo-Ping Ger, Wen-Chi Liao, and Yu-Peng Liu
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PDF file, 63K, Association of CTMP expression with prognosis of patients with different cancer type in 4 cohorts from Prognoscan database.
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- 2023
7. Supplementary Figure 2 from Cisplatin Selects for Multidrug-Resistant CD133+ Cells in Lung Adenocarcinoma by Activating Notch Signaling
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Michael Hsiao, Pei-Jung Lu, Chia-Ning Shen, Jean Lu, Ya-Wen Hsiao, Chien-Hsin Lee, Tsung-Ching Lai, Yu-Cheng Lee, Alexander T.H. Wu, Chi-Tai Yeh, Ming-Shyan Huang, Chih-Jen Yang, and Yu-Peng Liu
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PDF file - 287K, Cisplatin-induced enrichment of CD133+ cells
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- 2023
8. Supplementary Figure 3 from Cisplatin Selects for Multidrug-Resistant CD133+ Cells in Lung Adenocarcinoma by Activating Notch Signaling
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Michael Hsiao, Pei-Jung Lu, Chia-Ning Shen, Jean Lu, Ya-Wen Hsiao, Chien-Hsin Lee, Tsung-Ching Lai, Yu-Cheng Lee, Alexander T.H. Wu, Chi-Tai Yeh, Ming-Shyan Huang, Chih-Jen Yang, and Yu-Peng Liu
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PDF file - 289K, Carboplatin induced DNA damage and CD133+ cell enrichment
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- 2023
9. Supplementary Figure 6 from Cisplatin Selects for Multidrug-Resistant CD133+ Cells in Lung Adenocarcinoma by Activating Notch Signaling
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Michael Hsiao, Pei-Jung Lu, Chia-Ning Shen, Jean Lu, Ya-Wen Hsiao, Chien-Hsin Lee, Tsung-Ching Lai, Yu-Cheng Lee, Alexander T.H. Wu, Chi-Tai Yeh, Ming-Shyan Huang, Chih-Jen Yang, and Yu-Peng Liu
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PDF file - 342K, Inhibition of cisplatin-induced enrichment of CD133+ cells by Notch1 knockdown
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- 2023
10. Supplementary Figure 2 from Carboxyl-Terminal Modulator Protein Positively Regulates Akt Phosphorylation and Acts as an Oncogenic Driver in Breast Cancer
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Pei-Jung Lu, Michael Hsiao, Yu-Hao Zeng, Kuen-Haur Lee, Yi-Hua Jan, Yu-Chia Chen, Hong-Tai Chang, Yu-Cheng Lee, Tai-I Hsu, Jiun-Chin Chen, Luo-Ping Ger, Wen-Chi Liao, and Yu-Peng Liu
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PDF file, 70K, PI3K inibitor blocked serum-induced Akt phosphorylation.
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- 2023
11. Supplementary Figure 5 from Cisplatin Selects for Multidrug-Resistant CD133+ Cells in Lung Adenocarcinoma by Activating Notch Signaling
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Michael Hsiao, Pei-Jung Lu, Chia-Ning Shen, Jean Lu, Ya-Wen Hsiao, Chien-Hsin Lee, Tsung-Ching Lai, Yu-Cheng Lee, Alexander T.H. Wu, Chi-Tai Yeh, Ming-Shyan Huang, Chih-Jen Yang, and Yu-Peng Liu
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PDF file - 255K, The role of ABC transporters in cisplatin-induced multi-drug resistance to paclitaxol in H460 and H661 cell lines
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- 2023
12. Supplementary Methods from Cisplatin Selects for Multidrug-Resistant CD133+ Cells in Lung Adenocarcinoma by Activating Notch Signaling
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Michael Hsiao, Pei-Jung Lu, Chia-Ning Shen, Jean Lu, Ya-Wen Hsiao, Chien-Hsin Lee, Tsung-Ching Lai, Yu-Cheng Lee, Alexander T.H. Wu, Chi-Tai Yeh, Ming-Shyan Huang, Chih-Jen Yang, and Yu-Peng Liu
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PDF file - 143K
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- 2023
13. Supplementary Figure 1 from Cisplatin Selects for Multidrug-Resistant CD133+ Cells in Lung Adenocarcinoma by Activating Notch Signaling
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Michael Hsiao, Pei-Jung Lu, Chia-Ning Shen, Jean Lu, Ya-Wen Hsiao, Chien-Hsin Lee, Tsung-Ching Lai, Yu-Cheng Lee, Alexander T.H. Wu, Chi-Tai Yeh, Ming-Shyan Huang, Chih-Jen Yang, and Yu-Peng Liu
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PDF file - 2.1MB, Cell differentiation and migration of GFP+ cells isolated from H460 cell line
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- 2023
14. Supplementary Figure 4 from Carboxyl-Terminal Modulator Protein Positively Regulates Akt Phosphorylation and Acts as an Oncogenic Driver in Breast Cancer
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Pei-Jung Lu, Michael Hsiao, Yu-Hao Zeng, Kuen-Haur Lee, Yi-Hua Jan, Yu-Chia Chen, Hong-Tai Chang, Yu-Cheng Lee, Tai-I Hsu, Jiun-Chin Chen, Luo-Ping Ger, Wen-Chi Liao, and Yu-Peng Liu
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PDF file, 114K, CTMP mRNA expression data adapted from GEO public available microarray database, GSE3744.
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- 2023
15. Supplementary Figure 7 from Cisplatin Selects for Multidrug-Resistant CD133+ Cells in Lung Adenocarcinoma by Activating Notch Signaling
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Michael Hsiao, Pei-Jung Lu, Chia-Ning Shen, Jean Lu, Ya-Wen Hsiao, Chien-Hsin Lee, Tsung-Ching Lai, Yu-Cheng Lee, Alexander T.H. Wu, Chi-Tai Yeh, Ming-Shyan Huang, Chih-Jen Yang, and Yu-Peng Liu
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PDF file - 138K, The role of Notch signaling in enrichment of CD133+ cells and multi-drug resistance of H661 cells
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- 2023
16. Two-Way Transpose Multibit 6T SRAM Computing-in-Memory Macro for Inference-Training AI Edge Chips
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Yen-Lin Chung, Ting-Wei Chang, Ren-Shuo Liu, Fu-Chun Chang, Jian-Wei Su, Sih-Han Li, Hongwu Jiang, Shimeng Yu, Ta-Wei Liu, Yung-Ning Tu, Kea-Tiong Tang, Chung-Chuan Lo, Meng-Fan Chang, Shanshi Huang, Yuan Wu, Wei-Hsing Huang, Yen-Chi Chou, Chih-Cheng Hsieh, Pei-Jung Lu, Jing-Hong Wang, Ruhui Liu, Jin-Sheng Ren, Chih-I Wu, Xin Si, and Shyh-Shyuan Sheu
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Process variation ,Edge device ,Computer science ,Computation ,Transpose ,Static random-access memory ,Enhanced Data Rates for GSM Evolution ,Electrical and Electronic Engineering ,Macro ,Computational science ,Efficient energy use - Abstract
Computing-in-memory (CIM) based on SRAM is a promising approach to achieving energy-efficient multiply-and-accumulate (MAC) operations in artificial intelligence (AI) edge devices; however, existing SRAM-CIM chips support only DNN inference. The flow of training data requires that CIM arrays perform convolutional computation using transposed weight matrices. This article presents a two-way transpose (TWT) multiply cell with high resistance to process variation and a novel read scheme that uses input-aware zone prediction of maximum partial MAC values to enhance the signal margin for robust readout. A 28-nm 64-kb TWT CIM macro fabricated using foundry-provided compact 6T-SRAM cells achieved ${T_{AC}}$ of 3.8-21 ns and energy efficiency of 7-61.1 TOPS/W in performing MAC operations using 2-8-b inputs, 4-8-b weights, and 10-20-b outputs.
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- 2022
17. A Local Computing Cell and 6T SRAM-Based Computing-in-Memory Macro With 8-b MAC Operation for Edge AI Chips
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Yung-Ning Tu, William Shih, Jing-Hong Wang, Wei-Chiang Shih, Xin Si, Yajuan He, Yen-Chi Chou, Nan-Chun Lien, Yen-Lin Chung, Meng-Fan Chang, Qiang Li, Jian-Wei Su, Ta-Wei Liu, Ssu-Yen Wu, Pei-Jung Lu, Ren-Shuo Liu, Chih-Cheng Hsieh, Ruhui Liu, Chung-Chuan Lo, Kea-Tiong Tang, and Wei-Hsing Huang
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Process variation ,business.industry ,Computer science ,Sense amplifier ,Header ,Static random-access memory ,Enhanced Data Rates for GSM Evolution ,Electrical and Electronic Engineering ,Macro ,business ,B-MAC ,Computer hardware ,Efficient energy use - Abstract
This article presents a computing-in-memory (CIM) structure aimed at improving the energy efficiency of edge devices running multi-bit multiply-and-accumulate (MAC) operations. The proposed scheme includes a 6T SRAM-based CIM (SRAM-CIM) macro capable of: 1) weight-bitwise MAC (WbwMAC) operations to expand the sensing margin and improve the readout accuracy for high-precision MAC operations; 2) a compact 6T local computing cell to perform multiplication with suppressed sensitivity to process variation; 3) an algorithm-adaptive low MAC-aware readout scheme to improve energy efficiency; 4) a bitline header selection scheme to enlarge signal margin; and 5) a small-offset margin-enhanced sense amplifier for robust read operations against process variation. A fabricated 28-nm 64-kb SRAM-CIM macro achieved access times of 4.1–8.4 ns with energy efficiency of 11.5–68.4 TOPS/W, while performing MAC operations with 4- or 8-b input and weight precision.
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- 2021
18. ICAM2 initiates trans-Blood-CSF barrier migration and stemness properties in leptomeningeal metastasis of triple-negative breast cancer
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Pei-Jung Lu, Jhih-Kai Pan, Wen-Der Lin, Yao-Lung Kuo, Yu-Chia Chen, Zhu-Jun Loh, Forn-Chia Lin, Hui-Chuan Cheng, and Michael Hsiao
- Abstract
Leptomeningeal metastasis (LM) occurs when tumor cells spread to the leptomeningeal space surrounding the brain and the spinal cord, thereby causing poor clinical outcomes. The triple-negative breast cancer (TNBC) has been associated with symptoms of LM and mechanism remained unclear. Through proteomic analysis, we identified high expression of ICAM2 in leptomeningeal metastatic TNBC cells, which promoted the colonization of the spinal cord and resulted in poor survival in vivo. Two-way demonstration indicated that high levels of ICAM2 promoted blood–cerebrospinal fluid barrier (BCB) adhesion, trans-BCB migration, and stemness abilities and determined the specificity of LM in vivo. Furthermore, pulldown and antibody neutralizing assay revealed that ICAM2 determined the specificity of LM through interactions with ICAM1 in the choroid plexus epithelial cells. Therefore, neutralizing ICAM2 can attenuate the progression of LM and prolong survival in vivo. The results suggested that targeting ICAM2 is a potential therapeutic strategy for LM in TNBC.
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- 2022
19. Carboxyl-terminal modulator protein facilitates tumor metastasis in triple-negative breast cancer
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Cheng-Han Lin, Wen-Der Lin, Yun-Chin Huang, Yu-Chia Chen, Zhu-Jun Loh, Luo-Ping Ger, Forn-Chia Lin, Hao-Yi Li, Hui-Chuan Cheng, Kuen-Haur Lee, Michael Hsiao, and Pei-Jung Lu
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Cancer Research ,Molecular Medicine ,Molecular Biology - Abstract
Currently, the survival rate for breast cancer is more than 90%, but once the cancer cells metastasize to distal organs, the survival rate is dramatically reduced, to less than 30%. Triple-negative breast cancer accounts for 15-20% of all breast cancers. Triple-negative breast cancer (TNBC) is associated with poor prognostic and diagnostic outcomes due to the limiting therapeutic strategies, relative to non-TNBC breast cancers. Therefore, the development of targeted therapy for TNBC metastasis remains an urgent issue. In this study, high Carboxyl-terminal modulator protein (CTMP) is significantly associated with recurrence and disease-free survival rate in TNBC patients. Overexpression of CTMP promotes migration and invasion abilities in BT549 cells. Down-regulating of CTMP expression inhibits migration and invasion abilities in MDA-MB-231 cells. In vivo inoculation of high-CTMP cells enhances distant metastasis in mice. The metastasis incidence rate is decreased in mice injected with CTMP-downregulating MDA-MB-231 cells. Gene expression microarray analysis indicates the Akt-dependent pathway is significantly enhanced in CTMP overexpressing cells compared to the parental cells. Blocking Akt activation via Akt inhibitor treatment or co-expression of the dominant-negative form of Akt proteins successfully abolishes the CTMP mediating invasion in TNBC cells. Our findings suggest that CTMP is a potential diagnostic marker for recurrence and poor disease-free survival in TNBC patients. CTMP promotes TNBC metastasis via the Akt-activation-dependent pathway.
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- 2022
20. The activation of EP300 by F11R leads to EMT and acts as a prognostic factor in triple-negative breast cancers
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Chien-Hsiu Li, Chih-Yeu Fang, Ming-Hsien Chan, Chi-Long Chen, Pei-Jung Lu, Luo-Ping Ger, Yu-Chan Chang, and Michael Hsiao
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humanities - Abstract
A role for the JAM family in cancer progression has been demonstrated. Nevertheless, there has been no systematic study of the JAM family in specific cancers through clinical specimens, and the mechanism of the molecule is unclear, particularly in subtypes of breast cancer (BRCA). Based on an extensive analysis of the relative expression of the JAM family in cancer by pan-cancer, we found that the increase of F11R (JAM-A) is the opposite of that of JAM-2, or JAM-3, which is unique to BRCA. BRCA prognoses are related to F11R expression, including survival and recurrence-free survival. It is also noteworthy that F11 has different expression characteristics in subtypes, especially in triple-negative breast cancer (TNBC). Using immunohistochemistry (IHC) analysis as an analytical validation, this study provides consistent results with in-silico. As a result of artificial manipulations of F11R combined with microarray-based analyses, we identified that F11R plays an important role in several aspects of cell motility signaling. An upstream regulators and correlation analysis found that EP300 transcription factors may be involved in TNBC metastasis by modulating RHOA, GSK3B, and TGFBR1 expression through F11R-mediated epithelial-mesenchymal transition (EMT). Accordingly, the findings of this study provide a comprehensive interpretation of the relationship between the clinical value of F11R in BRCA subtype progression and the mechanisms that induce metastasis. These results provide a possible target for the treatment of BRCA.
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- 2022
21. DAH: Domain Adapted Deep Image Hashing
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Pei-Jung Lu, Pao-Yun Ma, Ying-Ying Chang, and Mei-Chen Yeh
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- 2021
22. Therapeutic Targeting of Aldolase A Interactions Inhibits Lung Cancer Metastasis and Prolongs Survival
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Yu Chan Chang, Michael Hsiao, Yi Fang Yang, Yuan Feng Lin, Ming Shyan Huang, Pei Jung Lu, Jean Chiou, Chia Yi Su, Chia-Ning Yang, and Chih Jen Yang
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0301 basic medicine ,Cancer Research ,Lung Neoplasms ,Adenocarcinoma of Lung ,Antineoplastic Agents ,Apoptosis ,Mice, SCID ,medicine.disease_cause ,Metastasis ,Small Molecule Libraries ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Mice, Inbred NOD ,In vivo ,Fructose-Bisphosphate Aldolase ,Tumor Cells, Cultured ,Carcinoma ,medicine ,Animals ,Humans ,Protein Interaction Maps ,Lung cancer ,Cell Proliferation ,Retrospective Studies ,biology ,Cell growth ,business.industry ,Aldolase A ,Cancer ,Prognosis ,medicine.disease ,Xenograft Model Antitumor Assays ,Actins ,Gene Expression Regulation, Neoplastic ,Survival Rate ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,biology.protein ,Cancer research ,Carcinoma, Large Cell ,Female ,Carcinogenesis ,business - Abstract
Cancer metabolic reprogramming promotes tumorigenesis and metastasis; however, the underlying molecular mechanisms are still being uncovered. In this study, we show that the glycolytic enzyme aldolase A (ALDOA) is a key enzyme involved in lung cancer metabolic reprogramming and metastasis. Overexpression of ALDOA increased migration and invasion of lung cancer cell lines in vitro and formation of metastatic lung cancer foci in vivo. ALDOA promoted metastasis independent of its enzymatic activity. Immunoprecipitation and proteomic analyses revealed γ-actin binds to ALDOA; blocking this interaction using specific peptides decreased metastasis both in vitro and in vivo. Screening of clinically available drugs based on the crystal structure of ALDOA identified raltegravir, an antiretroviral agent that targets HIV integrase, as a pharmacologic inhibitor of ALDOA-γ-actin binding that produced antimetastatic and survival benefits in a xenograft model with no significant toxicity. In summary, ALDOA promotes lung cancer metastasis by interacting with γ-actin. Targeting this interaction provides a new therapeutic strategy to treat lung cancer metastasis. Significance: This study demonstrates the role of aldolase A and its interaction with γ-actin in the metastasis of non–small lung cancer and that blocking this interaction could be an effective cancer treatment.
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- 2019
23. 16.3 A 28nm 384kb 6T-SRAM Computation-in-Memory Macro with 8b Precision for AI Edge Chips
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Shyh-Shyuan Sheu, Shih-Chieh Chang, Li-Yang Hung, Kea-Tiong Tang, Meng-Fan Chang, Sih-Han Li, Yen-Lin Chung, Tianlong Pan, Ping-Chun Wu, Yen-Chi Chou, Jin-Sheng Ren, Jian-Wei Su, Ren-Shuo Liu, Pei-Jung Lu, Wei-Chung Lo, Chih-Cheng Hsieh, Chung-Chuan Lo, Ta-Wei Liu, Xin Si, Chih-I Wu, and Ruhui Liu
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Computer science ,business.industry ,Transistor ,law.invention ,Process variation ,Memory management ,law ,System on a chip ,Static random-access memory ,Macro ,business ,Throughput (business) ,Dram ,Computer hardware - Abstract
Recent SRAM-based computation-in-memory (CIM) macros enable mid-to-high precision multiply-and-accumulate (MAC) operations with improved energy efficiency using ultra-small/small capacity (0.4-8KB) memory devices. However, advanced CIM-based edge-AI chips favor multiple mid/large capacity SRAM-CIM macros: with high input (IN) and weight (W) precision to reduce the frequency of data reloads from external DRAM, and to avoid the need for additional SRAM buffers or ultra-large on-chip weight buffers. However, enlarging memory capacity and throughput increases the delay parasitics on WLs and BLs, and the number of parallel computing elements; resulting in longer compute latency (t AC ), lower energy-efficiency (EF), degraded signal margin, and larger fluctuations in power consumption across data-patterns (see Fig. 16.3.1). Recent SRAM-CIM macros tend to not use in-lab SRAM cells, with a logic-based layout, in favor of foundry provided compact-layout 8T [2], 3, [5] or 6T cells with local-computing cells (LCCs) [4], [6] to reduce the cell-array area and facilitate manufacturing. This paper presents a SRAM-CIM structure using (1) a segmented-BL charge-sharing (SBCS) scheme for MAC operations, with low energy consumption and a consistently high signal margin across MAC values (MACV); (2) An new LCC cell, called a source-injection local-multiplication cell (SILMC), to support the SBCS scheme with a consistent signal margin against transistor process variation; and (3) A prioritized-hybrid-ADC (Ph-ADC) to achieve a small area and power overhead for analog readout. A 28nm 384kb SRAM-CIM macro was fabricated using a foundry compact-6T cell with support for MAC operations with 16 accumulations of 8b-inputs and 8b-weights with near-full precision output (20b). This macro achieves a 7.2ns t AC and a 22.75TOPS/W EF for 8b-MAC operations with an FoM (IN-precision × W-precision × output-ratio × output-channel × EF/t AC ) 6× higher than prior work.
- Published
- 2021
24. 15.5 A 28nm 64Kb 6T SRAM Computing-in-Memory Macro with 8b MAC Operation for AI Edge Chips
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Yun-Chen Lo, Yen-Chi Chou, Meng-Fan Chang, Qiang Li, Kea-Tiong Tang, Ruhui Liu, Wei-Chen Wei, Tzu-Hsiang Hsu, Yen-Kai Chen, Ssu-Yen Wu, Zhixiao Zhang, Xin Si, Wei-Chiang Shih, Yajuan He, Chung-Chuan Lo, Syuan-Hao Sie, Jing-Hong Wang, Chih-Cheng Hsieh, Ta-Wei Liu, Yung-Ning Tu, William Shih, Ren-Shuo Liu, Nan-Chun Lien, Jian-Wei Su, Wei-Hsing Huanq, Pei-Jung Lu, and Tai-Hsing Wen
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Process variation ,Physics ,Discrete mathematics ,020208 electrical & electronic engineering ,Sram cell ,Computer Science::Networking and Internet Architecture ,0202 electrical engineering, electronic engineering, information engineering ,Binary number ,02 engineering and technology ,Static random-access memory ,Macro ,020202 computer hardware & architecture - Abstract
Advanced AI edge chips require multibit input (IN), weight (W), and output (OUT) for CNN multiply-and-accumulate (MAC) operations to achieve an inference accuracy that is sufficient for practical applications. Computing-in-memory (CIM) is an attractive approach to improve the energy efficiency $(\mathrm{EF}_{\mathrm{MAC}}]$ of MAC operations under a memory-wall constraint. Previous SRAM-CIM macros demonstrated a binary MAC [4], an in-array 8b W-merging with near-memory computing (NMC) using 6T SRAM cells (limited output precision) [5], a 7b1N-1 bW MAC using a 10T SRAM cell (large area) [3], an 4b1N-5bW MAC with a T8T SRAM cell [1], and 8b1N-1bW NMC with 8T SRAM (long MAC latency $(T_{\mathrm{AC}})$ ) [2]. However, previous works have not achieved high IN/W/OUT precision with fast $\mathrm{T}_{\mathrm{AC}}$ compact-area, high $\mathrm{EF}_{\mathrm{MAC}}$ , and robust readout against process variation, due to (1) small sensing margin in word-wise multiple-bit MAC operations, (2) a tradeoff between read accuracy vs. area overhead under process variation, (3) limited $\mathrm{EF}_{\mathrm{MAC}}$ due to decoupling of software and hardware development.
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- 2020
25. 15.2 A 28nm 64Kb Inference-Training Two-Way Transpose Multibit 6T SRAM Compute-in-Memory Macro for AI Edge Chips
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Heng-Yuan Lee, Jian-Wei Su, Ting-Wei Chang, Chung-Chuan Lo, Shih-Chieh Chang, Shimeng Yu, Hongwu Jiang, Kea-Tiong Tang, Wei-Hsing Huang, Sih-Han Li, Shyh-Shyuan Sheu, Zhixiao Zhang, Ta-Wei Liu, Yung-Ning Tu, Pei-Jung Lu, Meng-Fan Chang, Xin Si, Shanshi Huang, Jing-Hong Wang, Ruhui Liu, Chih-Cheng Hsieh, Yen-Chi Chou, and Ren-Shuo Liu
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Edge device ,Computer science ,business.industry ,020208 electrical & electronic engineering ,020207 software engineering ,Cloud computing ,02 engineering and technology ,Computational science ,Margin (machine learning) ,Transpose ,0202 electrical engineering, electronic engineering, information engineering ,Static random-access memory ,Enhanced Data Rates for GSM Evolution ,Macro ,business - Abstract
Many Al edge devices require local intelligence to achieve fast computing time (t AC ), high energy efficiency (EF), and privacy. The transfer-learning approach is a popular solution for Al edge chips, wherein data used to re-train the Al in the cloud is used to fine-tune (re-train) a few of the neural layers in edge devices. This enables the dynamic incorporation of data from in-situ environments or private information. Computing-in-memory (CIM) is a promising approach to improve EF for Al edge chips, existing CIM schemes support inference [1]–[5] with forward (FWD) propagation; however, they do not support training, requiring both FWD and backward (BWD) propagation, due to differences in weight-access flow for FWD and BWD propagation. As Fig. 15.2.1 shows, efforts to increase the precision of the input (IN), weight (W), and/or output (OUT) tend to degrade r AC and EF for training operations irrespective of scheme: digital FWD and BWD (DF-DB) or CIM-FWD-digital-BWD (CiMF-DB). This work develops a two-way transpose (TWT) SRAM-CIM macro supporting multibit MAC operations for FWD and BWD propagation with fast r AC and high EF within a compact area. The proposed scheme features (1) A TWT multiply cell (TWT-MC) with a high resistance to process variation; and (2) a small-offset gain-enhancement sense amplifier (SOGE-SA) to tolerate a small read margin. A 28nm 64Kb TWT SRAM-CIM macro was fabricated using a foundry-provided compact 6T-SRAM cell for SRAM-CIM devices supporting both inference and training operations for the first time. This macro also demonstrates the fastest t AC (3.8 – 21ns) and highest EF (7 – 61.1TOPS/w) for MAC operations using 2 – 8b inputs, 4 – 8b weights and 12 − 20b outputs.
- Published
- 2020
26. Phosphatidylinositol-4-phosphate 5-kinase type 1α attenuates Aβ production by promoting non-amyloidogenic processing of amyloid precursor protein
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Wen-Ming Hsu, Yi-Shuian Huang, Ju Yun Chou, Po Fan Wu, Hsinyu Lee, Noopur Bhore, Pei Yi Wu, Yen Lurk Lee, Pei Jung Lu, Yun Wen Chen, and Yung-Feng Liao
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0301 basic medicine ,Phosphatidylinositol 4,5-Diphosphate ,Phosphatidylinositol 4-phosphate ,Endosome ,Proteolysis ,Cell ,Peptide ,Biochemistry ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Alzheimer Disease ,Genetics ,medicine ,Amyloid precursor protein ,Animals ,Humans ,Molecular Biology ,chemistry.chemical_classification ,Amyloid beta-Peptides ,medicine.diagnostic_test ,biology ,Kinase ,Cell biology ,Rats ,Phosphotransferases (Alcohol Group Acceptor) ,030104 developmental biology ,medicine.anatomical_structure ,HEK293 Cells ,chemistry ,Cell culture ,biology.protein ,030217 neurology & neurosurgery ,Biotechnology - Abstract
Alzheimer's disease (AD) is characterized by a chronic decline in cognitive function and is pathologically typified by cerebral deposition of amyloid-β peptide (Aβ). The production of Aβ is mediated by sequential proteolysis of amyloid precursor protein (APP) by β- and γ-secretases, and has been implicated as the essential determinant of AD pathology. Previous studies have demonstrated that the level of phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] in the membrane may potentially modulate Aβ production. Given that PI(4,5)P2 is produced by type 1 phosphatidylinositol-4-phosphate 5-kinases (PIP5Ks), we sought to determine whether the level of PIP5K type Iα (PIP5K1A) can affect production of Aβ by modulating the lipid composition of the membrane. Using a HEK-derived cell line that constitutively expresses yellow fluorescent protein-tagged APP (APP-YFP), we demonstrated that overexpression of PIP5K1A results in significant enhancement of non-amyloidogenic APP processing and a concomitant suppression of the amyloidogenic pathway, leading to a marked decrease in secreted Aβ. Consistently, cells overexpressing PIP5K1A exhibited a significant redistribution of APP-YFP from endosomal compartments to the cell surface. Our findings suggest that PIP5K1A may play a critical role in governing Aβ production by modulating membrane distribution of APP, and as such, the pathway may be a valuable therapeutic target for AD.
- Published
- 2020
27. Additional file 1 of Epigenetic silencing of AATK in acinar to ductal metaplasia in murine model of pancreatic cancer
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Ding, Li-Yun, Ya-Chin Hou, I-Ying Kuo, Hsu, Ting-Yi, Tsung-Ching Tsai, Hsiu-Wei Chang, Hsu, Wei-Yu, Chih-Chieh Tsao, Chung-Chen Tian, Po-Shun Wang, Hao-Chen Wang, Chung-Ta Lee, Yi-Ching Wang, Sheng-Hsiang Lin, Hughes, Michael W., Woei-Jer Chuang, Pei-Jung Lu, Yan-Shen Shan, and Huang, Po-Hsien
- Abstract
Additional file 1: Figure S1. The TCGA cohort patients formed clusters of: (1) benign (n=36), (2) early development and differentiation (n=86), (3) transition (n=36), and (4) QM-PDA (n=20) based on differential gene expression patterns.
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- 2020
- Full Text
- View/download PDF
28. Additional file 6 of Epigenetic silencing of AATK in acinar to ductal metaplasia in murine model of pancreatic cancer
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Ding, Li-Yun, Ya-Chin Hou, I-Ying Kuo, Hsu, Ting-Yi, Tsung-Ching Tsai, Hsiu-Wei Chang, Hsu, Wei-Yu, Chih-Chieh Tsao, Chung-Chen Tian, Po-Shun Wang, Hao-Chen Wang, Chung-Ta Lee, Yi-Ching Wang, Sheng-Hsiang Lin, Hughes, Michael W., Woei-Jer Chuang, Pei-Jung Lu, Yan-Shen Shan, and Huang, Po-Hsien
- Abstract
Additional file 6: Table S1. Survival analysis of VAV1 targeted the cell cycle pathway gene network and cytokeratin 6B expression in a combined analysis of 1207 pancreatic cancer samples from 10 studies included in the cBioPortal [61, 62].
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- 2020
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29. Additional file 7 of Epigenetic silencing of AATK in acinar to ductal metaplasia in murine model of pancreatic cancer
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Ding, Li-Yun, Ya-Chin Hou, I-Ying Kuo, Hsu, Ting-Yi, Tsung-Ching Tsai, Hsiu-Wei Chang, Hsu, Wei-Yu, Chih-Chieh Tsao, Chung-Chen Tian, Po-Shun Wang, Hao-Chen Wang, Chung-Ta Lee, Yi-Ching Wang, Sheng-Hsiang Lin, Hughes, Michael W., Woei-Jer Chuang, Pei-Jung Lu, Yan-Shen Shan, and Huang, Po-Hsien
- Abstract
Additional file 7: Table S2. Details of reagents and materials. #, not available; *, in the TSA IHC Kit a higher dilution factor was chosen for optimized signal to background ratio.
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- 2020
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30. Additional file 2 of Epigenetic silencing of AATK in acinar to ductal metaplasia in murine model of pancreatic cancer
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Ding, Li-Yun, Ya-Chin Hou, I-Ying Kuo, Hsu, Ting-Yi, Tsung-Ching Tsai, Hsiu-Wei Chang, Hsu, Wei-Yu, Chih-Chieh Tsao, Chung-Chen Tian, Po-Shun Wang, Hao-Chen Wang, Chung-Ta Lee, Yi-Ching Wang, Sheng-Hsiang Lin, Hughes, Michael W., Woei-Jer Chuang, Pei-Jung Lu, Yan-Shen Shan, and Huang, Po-Hsien
- Abstract
Additional file 2: Figure S2. Collection of AATK expression in ADM in KC mice. Insert, higher magnification of Fig. 7a, region 1.
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- 2020
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31. Additional file 3 of Epigenetic silencing of AATK in acinar to ductal metaplasia in murine model of pancreatic cancer
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Ding, Li-Yun, Ya-Chin Hou, I-Ying Kuo, Hsu, Ting-Yi, Tsung-Ching Tsai, Hsiu-Wei Chang, Hsu, Wei-Yu, Chih-Chieh Tsao, Chung-Chen Tian, Po-Shun Wang, Hao-Chen Wang, Chung-Ta Lee, Yi-Ching Wang, Sheng-Hsiang Lin, Hughes, Michael W., Woei-Jer Chuang, Pei-Jung Lu, Yan-Shen Shan, and Huang, Po-Hsien
- Abstract
Additional file 3: Figure S3. miR-338-3p in situ hybridization in adjacent normal and tumoral sections of pancreatic cancer. U6 snRNA expression was used as positive control.
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- 2020
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32. Additional file 4 of Epigenetic silencing of AATK in acinar to ductal metaplasia in murine model of pancreatic cancer
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Ding, Li-Yun, Ya-Chin Hou, I-Ying Kuo, Hsu, Ting-Yi, Tsung-Ching Tsai, Hsiu-Wei Chang, Hsu, Wei-Yu, Chih-Chieh Tsao, Chung-Chen Tian, Po-Shun Wang, Hao-Chen Wang, Chung-Ta Lee, Yi-Ching Wang, Sheng-Hsiang Lin, Hughes, Michael W., Woei-Jer Chuang, Pei-Jung Lu, Yan-Shen Shan, and Huang, Po-Hsien
- Abstract
Additional file 4: Figure S4. The individual features of human pancreatic cancer and adjacent normal tissue sections.
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- 2020
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33. TGFβ promotes mesenchymal phenotype of pancreatic cancer cells, in part, through epigenetic activation of VAV1
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Po-Chen Chu, Yan Shen Shan, L. Y. Ding, Chang Shi Chen, Chung Ta Lee, C. C. Tsao, Po Hsien Huang, B. H. Chen, W. Y. Hsu, and Pei Jung Lu
- Subjects
DNA (Cytosine-5-)-Methyltransferase 1 ,0301 basic medicine ,Cancer Research ,Tumour heterogeneity ,Antineoplastic Agents ,Mice, Transgenic ,Adenocarcinoma ,Biology ,Epigenesis, Genetic ,Metastasis ,Mice ,03 medical and health sciences ,Transforming Growth Factor beta ,Cell Line, Tumor ,Pancreatic cancer ,Genetics ,medicine ,Animals ,Humans ,DNA (Cytosine-5-)-Methyltransferases ,Epigenetics ,Promoter Regions, Genetic ,Proto-Oncogene Proteins c-vav ,Molecular Biology ,Smad4 Protein ,Regulation of gene expression ,medicine.disease ,Gene Expression Regulation, Neoplastic ,Pancreatic Neoplasms ,030104 developmental biology ,Benzamides ,DNA methylation ,Cancer cell ,Disease Progression ,Cancer research ,Pyrazoles ,Transforming growth factor - Abstract
The highly homeostasis-resistant nature of cancer cells leads to their escape from treatment and to liver metastasis, which in turn makes pancreatic ductal adenocarcinoma (PDAC) difficult to treat, especially the squamous/epithelial-to-mesenchymal transition (EMT)-like subtype. As the molecular mechanisms underlying tumour heterogeneity remain elusive, we investigated whether epigenetic regulation might explain inter-individual differences in the progression of specific subtypes. DNA methylation profiling performed on cancer tissues prior to chemo/radiotherapy identified one hypermethylated CpG site (CpG6882469) in the VAV1 gene body that was correlated with demethylation of two promoter CpGs (CpG6772370/CpG6772811) in both PDAC and peripheral blood. Transforming growth factor β treatment induced gene-body hypermethylation, dissociation of DNMT1 from the promoter, and VAV1 expression via SMAD4 and mutant KrasG12D. Pharmacological inhibition of TGFβ-VAV1 signalling decreased the squamous/EMT-like cancer cells, promoted nuclear VAV1 localization, and enhanced the efficacy of gemcitabine in prolonging the survival of KPfl/flC mice. Together, the three VAV1 CpGs serve as biomarkers for prognosis and early detection, and the TGFβ-VAV1 axis represents a therapeutic target.
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- 2016
34. High-CLDN4 ESCC cells harbor stem-like properties and indicate for poor concurrent chemoradiation therapy response in esophageal squamous cell carcinoma
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Yi Ching Wang, Wei Lun Chang, Bor Shyang Sheu, Cheng-Han Lin, Forn Chia Lin, Pei Jung Lu, Pei Fung Kuo, Yu Peng Liu, Hao Yi Li, Wan Chun Hung, Michael Hsiao, Hui Chuan Cheng, Marcus J. Calkins, Yun Chin Yao, and Wen Ching Wang
- Subjects
cancer stem-like cells ,concurrent chemoradiation therapy ,business.industry ,thiamine tetrahydrofurfuryl disulfide (TTFD) ,Concurrent chemoradiation ,Esophageal cancer ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,lcsh:RC254-282 ,Esophageal squamous cell carcinoma ,digestive system diseases ,esophageal squamous cell carcinoma ,Therapy response ,Oncology ,Cancer stem cell ,Cancer research ,Medicine ,Biomarker (medicine) ,biomarker ,CLDN4 ,CCRT ,business ,neoplasms ,Original Research - Abstract
Background: Esophageal squamous cell carcinoma (ESCC) is the major type of esophageal cancer in Asia and demonstrates poor survival rates following a therapeutic regimen. Methods: Cancer stem cells (CSCs) are responsible for tumor initiation, progression, and treatment failure in cancers. Therefore, identification and characterization of CSCs may help to improve clinical outcomes for ESCC patients. Tumor sphere formation assay are performed to isolate cancer stem-like ESCC cells. QRT-PCR, tumor initiation, metastasis, CCRT treatment are used to evaluate ESCC cells’ stemness properties in vitro and in vivo. Results: The authors’ data demonstrates that cancer stem-like ESCC cells harbored stemness characteristics including self-renewal, differentiation, and transdifferentiation, and possess tumor initiation, metastasis, and treatment inefficiency properties. For the identification of useful biomarkers of cancer stem-like ESCC cells, the authors further identified that CLDN4 was upregulated in cancer stem-like ESCC cells when compared with bulk cancer cells. High-CLDN4 cells harbored stemness and cisplatin/concurrent chemoradiation therapy (CCRT) resistance properties and a high level of CLDN4 was correlated with poor prognosis and poor CCRT response in ESCC patients. Importantly, thiamine tetrahydrofurfuryl disulfide (TTFD) decreased CLDN4 and attenuated stemness in ESCC cells, and TTFD combined with CCRT improved CCRT response in vivo. Conclusions: CLDN4 was suggested as prognostic and a CCRT response indicator for ESCC patients. TTFD combined with CCRT has potential to improve ESCC patient’s clinical outcomes in the future.
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- 2019
35. Supplemental_Data_7_20190530-R1 – Supplemental material for High-CLDN4 ESCC cells harbor stem-like properties and indicate for poor concurrent chemoradiation therapy response in esophageal squamous cell carcinoma
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Cheng-Han Lin, Hao-Yi Li, Liu, Yu-Peng, Pei-Fung Kuo, Wen-Ching Wang, Forn-Chia Lin, Chang, Wei-Lun, Bor-Shyang Sheu, Yi-Ching Wang, Hung, Wan-Chun, Hui-Chuan Cheng, Yun-Chin Yao, Calkins, Marcus J., Hsiao, Michael, and Pei-Jung Lu
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110203 Respiratory Diseases ,FOS: Clinical medicine ,111702 Aged Health Care ,FOS: Health sciences ,111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified ,111299 Oncology and Carcinogenesis not elsewhere classified - Abstract
Supplemental material, Supplemental_Data_7_20190530-R1 for High-CLDN4 ESCC cells harbor stem-like properties and indicate for poor concurrent chemoradiation therapy response in esophageal squamous cell carcinoma by Cheng-Han Lin, Hao-Yi Li, Yu-Peng Liu, Pei-Fung Kuo, Wen-Ching Wang, Forn-Chia Lin, Wei-Lun Chang, Bor-Shyang Sheu, Yi-Ching Wang, Wan-Chun Hung, Hui-Chuan Cheng, Yun-Chin Yao, Marcus J. Calkins, Michael Hsiao and Pei-Jung Lu in Therapeutic Advances in Medical Oncology
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- 2019
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36. A six-CpG panel with DNA methylation biomarkers predicting treatment response of chemoradiation in esophageal squamous cell carcinoma
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Wu Wei Lai, Chien-Yu Lin, I-Ying Kuo, Wei Lun Chang, Bor Shyang Sheu, Yi Ching Wang, and Pei Jung Lu
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Male ,0301 basic medicine ,Oncology ,medicine.medical_specialty ,Esophageal Neoplasms ,Kaplan-Meier Estimate ,Disease-Free Survival ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Intensive care ,Internal medicine ,Biomarkers, Tumor ,medicine ,Humans ,Framingham Risk Score ,Receiver operating characteristic ,business.industry ,Gastroenterology ,Chemoradiotherapy ,Methylation ,DNA Methylation ,Middle Aged ,Prognosis ,Treatment Outcome ,030104 developmental biology ,CpG site ,030220 oncology & carcinogenesis ,DNA methylation ,Cohort ,Carcinoma, Squamous Cell ,CpG Islands ,Female ,Esophageal Squamous Cell Carcinoma ,business - Abstract
Prognosis of esophageal squamous cell carcinoma (ESCC) patients remains poor, and the chemoradiotherapy (CRT) applied to ESCC patients often failed. Therefore, development of biomarkers to predict CRT response is immensely important for choosing the best treatment strategy of an individual patient. The methylation array and pyrosequencing methylation assay were performed in pre-treatment endoscopic biopsies to identify probes with differential CpG methylation levels between good and poor CRT responders in a cohort of 12 ESCC patients. Receiver operating characteristic curves and multivariate logistic regressions were conducted to build the risk score equation of selected CpG probes in another cohort of 91 ESCC patients to predict CRT response. Kaplan–Meier analysis was used to estimate progression-free survival or time-to-progression of patients predicted with good and poor CRT responses. Nine differentially methylated CpG probes were identified to be associated with CRT response. A risk score equation comprising six CpG probes located in IFNGR2, KCNK4, NOTCH4, NPY, PAX6, and SOX17 genes were built. The risk score was derived from the sum of each probe multiplied by its corresponding coefficient. Such a risk score has a good prediction performance in discriminating poor CRT responders from good responders (AUC: 0.930). Moreover, poor CRT responders predicted by risk score significantly had poorer prognosis in terms of shorter progression-free survival and time-to-progression (p = 0.004–0.008). We established a proof-of-concept CRT response prediction panel consisting of six-CpG methylation biomarkers in identifying ESCC patients who are at high risk of CRT failure and need intensive care.
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- 2016
37. Paricalcitol Attenuates Cardiac Fibrosis and Expression of Endothelial Cell Transition Markers in Isoproterenol-Induced Cardiomyopathic Rats
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Michael Hsiao, Pei Jung Lu, Wen Hsien Lu, Jau Cheng Liou, Gwo Ching Sun, Chun Peng Liu, Pei Wen Cheng, Ching-Jiunn Tseng, and Chi Cheng Lai
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Male ,0301 basic medicine ,Paricalcitol ,medicine.medical_specialty ,Epithelial-Mesenchymal Transition ,Cardiac fibrosis ,Cardiomyopathy ,030204 cardiovascular system & hematology ,Critical Care and Intensive Care Medicine ,Rats, Inbred WKY ,Calcitriol receptor ,03 medical and health sciences ,0302 clinical medicine ,Fibrosis ,Internal medicine ,medicine ,Vitamin D and neurology ,Animals ,business.industry ,Isoproterenol ,Endothelial Cells ,medicine.disease ,Actins ,Rats ,Platelet Endothelial Cell Adhesion Molecule-1 ,Endothelial stem cell ,Disease Models, Animal ,030104 developmental biology ,Endocrinology ,Ergocalciferols ,Cardiomyopathies ,business ,medicine.drug ,Kidney disease - Abstract
Acute cardiomyopathy is a health problem worldwide. Few studies have shown an association between acute cardiomyopathy and low vitamin D status. Paricalcitol, a vitamin D receptor activator, clinically benefits patients with advanced kidney disease. The effect of paricalcitol supplement on cardiac remodeling in cardiomyopathic rats is unknown. This experimental study investigated the effect of paricalcitol in rats with cardiomyopathy induced by isoproterenol.Prospective, randomized, controlled experimental study.Hospital-affiliated animal research institution.Eight-week-old male Wistar-Kyoto rats.Male Wistar-Kyoto rats were first injected intraperitoneally with isoproterenol to create a rat model of acute cardiomyopathy. Then paricalcitol was administered intraperitoneally to isoproterenol-injected rats at a dosage of 200 ng three times a week for 3 weeks. Relevant cardiomyopathy-related variables were measured regularly in three groups of rats, controls, isoproterenol, and isoproterenol plus paricalcitol. Rat hearts were obtained for evaluation of cardiac fibrosis using Masson trichrome staining and commercially available software, and evaluation of cell transition using immunofluorescence staining analysis.Isoproterenol infusions generated significant cardiac fibrosis (p0.001). Subsequent paricalcitol treatment attenuated the isoproterenol-induced cardiac fibrosis (p = 0.006). Fluorescence showed colocalization of endothelial and fibroblast cell markers (cluster differentiation 31 and α-smooth muscle actin, respectively) in the isoproterenol-treated hearts. Paricalcitol injections attenuated the isoproterenol-induced fluorescence intensity of two cell markers (p0.01).Paricalcitol injections may ameliorate isoproterenol-induced cardiac fibrosis possibly through regulating cell transition.
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- 2016
38. MiR-193a-5p/ERBB2 act as concurrent chemoradiation therapy response indicator of esophageal squamous cell carcinoma
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Cheng-Han Lin, Yun Chin Yao, Chen Hsun Tsai, Michael Hsiao, Pei Jung Lu, Jui Lin Liang, Yu Cheng Lee, Wei Lun Chang, Bor Shyang Sheu, Ching Tung Yeh, Hao Yi Li, Wan Chun Hung, Tai I. Hsu, Wu Wei Lai, Yi Ching Wang, Marcus J. Calkins, and Forn Chia Lin
- Subjects
0301 basic medicine ,Oncology ,Esophageal Neoplasms ,Carcinogenesis ,Receptor, ErbB-2 ,Mice, SCID ,Esophageal squamous cell carcinoma ,Mice ,0302 clinical medicine ,Mice, Inbred NOD ,Risk Factors ,Trastuzumab ,miR-193a-5p ,CCRT ,ERBB2 ,3' Untranslated Regions ,indicator ,Chemoradiotherapy ,Concurrent chemoradiation ,Esophageal cancer ,Prognosis ,University hospital ,esophageal squamous cell carcinoma ,Gene Expression Regulation, Neoplastic ,030220 oncology & carcinogenesis ,Carcinoma, Squamous Cell ,Research Paper ,medicine.drug ,medicine.medical_specialty ,Down-Regulation ,03 medical and health sciences ,Mir 193a 3p ,Cell Line, Tumor ,Internal medicine ,medicine ,Animals ,Humans ,neoplasms ,business.industry ,medicine.disease ,Surgery ,MicroRNAs ,030104 developmental biology ,Therapy response ,Case-Control Studies ,Neoplasm Recurrence, Local ,business - Abstract
// Cheng-Han Lin 1, 9, * , Chen-Hsun Tsai 2, * , Ching-Tung Yeh 1 , Jui-Lin Liang 1, 3 , Wan-Chun Hung 1 , Forn-Chia Lin 4 , Wei-Lun Chang 1, 5 , Hao-Yi Li 1 , Yun-Chin Yao 6 , Tai-I Hsu 2 , Yu-Cheng Lee 2 , Yi-Ching Wang 7 , Bor-Shyang Sheu 1, 5 , Wu-Wei Lai 8 , Marcus J. Calkins 1 , Michael Hsiao 9 , Pei-Jung Lu 1, 2 1 Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan 2 Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan 3 Department of General Surgery, Chi-Mei Medical Center, Liouying, Tainan 736, Taiwan 4 Department of Radiation Oncology, National Cheng Kung University Hospital, Tainan 704, Taiwan 5 Department of Internal Medicine, National Cheng Kung University Hospital, Tainan 704, Taiwan 6 Clinical Medicine Research Center, National Cheng Kung University Hospital, Tainan 704, Taiwan 7 Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan 8 Department of Surgery Medicine, National Cheng Kung University Hospital, Tainan 704, Taiwan 9 Genomics Research Center, Academia Sinica, Taipei 115, Taiwan * These authors contributed equally to this work Correspondence to: Michael Hsiao, email: mhsiao@gate.sinica.edu.tw Pei-Jung Lu, email: pjlu2190@mail.ncku.edu.tw Keywords: miR-193a-5p, ERBB2, CCRT, esophageal squamous cell carcinoma, indicator Received: October 16, 2015 Accepted: March 31, 2016 Published: May 18, 2016 ABSTRACT Concurrent chemoradiation therapy (CCRT) is the predominant treatment in esophageal cancer, however resistance to therapy and tumor recurrence are exceedingly common. Elevated ERBB2/Her2 may be at least partially responsible for both the high rates of recurrence and resistance to CCRT. This receptor tyrosine kinase is upregulated in 10–20% of esophageal squamous cell carcinoma (ESCC) tissues, and amplification of ERBB2 has been correlated with poor prognosis in esophageal cancer. Tissues from 131 ESCC patients, along with cell and animal models of the disease were used to probe the underlying mechanisms by which ERBB2 upregulation occurs and causes negative outcomes in ESCC. We found that overexpression of ERBB2 inhibited radiosensitivity in vitro . Furthermore, miR-193a-5p reduced ERBB2 expression by directly targeting the 3’UTR. Increased miR-193a-5p enhanced radiosensitivity and inhibited tumorigenesis in vitro and in vivo . Additionally, low miR-193a-5p expression correlated with poor prognosis in ESCC patients, and ESCC patients with good CCRT response exhibited higher miR-193a-5p expression. Our data suggest that patients with high miR-193a-5p will likely benefit from CCRT treatment alone, however a combination of CCRT with Herceptin may be beneficial for patients with low miR-193a-5p expression.
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- 2016
39. Serine/theonine kinase 4 is a potential biomarker for assessment of β‐catenin‐mediated colon cancer prognosis
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Pei-Jung Lu, Tai-I Hsu, and Micheal Hsiao
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Colorectal cancer ,Kinase ,business.industry ,medicine.disease ,Biochemistry ,Serine ,Potential biomarkers ,Catenin ,Genetics ,Cancer research ,medicine ,business ,Molecular Biology ,Biotechnology - Published
- 2020
40. Wnt Signaling Regulates Blood Pressure by Downregulating a GSK-3β–Mediated Pathway to Enhance Insulin Signaling in the Central Nervous System
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Michael Hsiao, Tung Chen Yeh, Gwo Ching Sun, Pei Jung Lu, Pei Wen Cheng, Ching-Jiunn Tseng, Ying Ying Chen, Hsin Hung Chen, Bo Rong Chen, and Wen Han Cheng
- Subjects
medicine.medical_specialty ,Insulin Receptor Substrate Proteins ,Endocrinology, Diabetes and Metabolism ,Wnt signaling pathway ,LRP6 ,Biology ,IRS1 ,Insulin receptor ,Endocrinology ,Internal medicine ,Internal Medicine ,medicine ,biology.protein ,Phosphorylation ,Signal transduction ,Protein kinase B - Abstract
Aberrant Wnt signaling appears to play an important role in the onset of diabetes. Moreover, the insulin signaling pathway is defective in the nucleus tractus solitarii (NTS) of spontaneously hypertensive rats (SHRs) and fructose-fed rats. Nevertheless, the relationships between Wnt signaling and the insulin pathway and the related modulation of blood pressure (BP) in the central nervous system have yet to be established. The aim of this study was to investigate the potential signaling pathways involved in Wnt-mediated BP regulation in the NTS. Pretreatment with the LDL receptor–related protein (LRP) antagonist Dickkopf-1 (DKK1) significantly attenuated the Wnt3a-induced depressor effect and nitric oxide production. Additionally, the inhibition of LRP6 activity using DKK1 significantly abolished Wnt3a-induced glycogen synthase kinase 3β (GSK-3β)S9, extracellular signal–regulated kinases 1/2T202/Y204, ribosomal protein S6 kinaseT359/S363, and AktS473 phosphorylation; and increased insulin receptor substrate 1 (IRS1)S332 phosphorylation. GSK-3β was also found to bind directly to IRS1 and to induce the phosphorylation of IRS1 at serine 332 in the NTS. By contrast, administration of the GSK-3β inhibitor TWS119 into the brain decreased the BP of hypertensive rats by enhancing IRS1 activity. Taken together, these results suggest that the GSK-3β-IRS1 pathway may play a significant role in Wnt-mediated central BP regulation.
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- 2015
41. GPCR dimerization in brainstem nuclei contributes to the development of hypertension
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Mei Chi Hsu, Tung Chen Yeh, Bo Rung Chen, Ching-Jiunn Tseng, Wen Han Cheng, Michael Hsiao, Pei Wen Cheng, Pei Jung Lu, Gwo Ching Sun, and Wen Yu Ho
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Pharmacology ,Enkephalin ,business.industry ,Solitary nucleus ,respiratory system ,In vitro ,Cell biology ,medicine.anatomical_structure ,nervous system ,Opioid ,medicine ,Brainstem ,Receptor ,business ,Neuroscience ,Nucleus ,hormones, hormone substitutes, and hormone antagonists ,circulatory and respiratory physiology ,medicine.drug ,G protein-coupled receptor - Abstract
Background and Purpose μ-Opioid receptors, pro-opiomelanocortin and pro-enkephalin are highly expressed in the nucleus tractus solitarii (NTS) and μ receptor agonists given to the NTS dose-dependently increased BP. However, the molecular mechanisms of this process remain unclear. In vitro, μ receptors heterodimerize with α2A-adrenoceptors. We hypothesized that α2A-adrenoceptor agonists would lose their depressor effects when their receptors heterodimerize in the NTS with μ receptors.
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- 2015
42. Fructose induced neurogenic hypertension mediated by overactivation of p38 MAPK to impair insulin signaling transduction caused central insulin resistance
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Chi Cheng Lai, Hsin Hung Chen, Ching-Jiunn Tseng, Pei Wen Cheng, Yu Te Lin, Tung Chen Yeh, Gwo Ching Sun, Michael Hsiao, Wen Yu Ho, Pei Jung Lu, and Chun Peng Liu
- Subjects
0301 basic medicine ,Blood Glucose ,Male ,medicine.medical_treatment ,Blood Pressure ,Type 2 diabetes ,Nitric Oxide Synthase Type I ,Biochemistry ,Rats, Inbred WKY ,p38 Mitogen-Activated Protein Kinases ,Antioxidants ,chemistry.chemical_compound ,Superoxides ,Rats, Inbred SHR ,Insulin ,Phosphorylation ,Neurogenic hypertension ,Hypertension ,Lipoproteins, HDL ,Signal Transduction ,medicine.medical_specialty ,Fructose ,Biology ,Nitric Oxide ,Nitric oxide ,Diabetes Mellitus, Experimental ,Cyclic N-Oxides ,03 medical and health sciences ,Insulin resistance ,Physiology (medical) ,Internal medicine ,medicine ,Solitary Nucleus ,Animals ,Triglycerides ,medicine.disease ,IRS1 ,Rats ,Insulin receptor ,030104 developmental biology ,Endocrinology ,chemistry ,Gene Expression Regulation ,biology.protein ,Insulin Receptor Substrate Proteins ,Spin Labels ,Insulin Resistance ,Proto-Oncogene Proteins c-akt - Abstract
Type 2 diabetes are at a high risk of complications related to hypertension, and reports have indicated that insulin levels may be associated with blood pressure (BP). Fructose intake has recently been reported to promote insulin resistance and superoxide formation. The aim of this study is to investigate whether fructose intake can enhance superoxide generation and impair insulin signaling in the NTS and subsequently elevate BP in rats with fructose-induced hypertension. Treatment with fructose for 4 weeks increased the BP, serum fasting insulin, glucose, homeostatic model assessment-insulin resistance, and triglyceride levels and reduced the serum direct high-density lipoprotein level in the fructose group. The Tempol treatment recovered the fructose-induced decrease in nitric oxide production in the NTS. Immunoblotting and immunofluorescence analyses further showed that fructose increased the p38- and fructose-induced phosphorylation of insulin receptor substrate 1 (IRS1S307) and suppressed AktS473 and neuronal nitric oxide synthase phosphorylation. Similarly, fructose was able to impair insulin sensitivity and increase insulin levels in the NTS. Fructose intake also increased the production of superoxide in the NTS. The results of this study suggest that fructose might induce central insulin resistance and elevate BP by enhancing superoxide production and activating p38 phosphorylation in the NTS.
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- 2017
43. Additional file 1: Figure S1. of miR-105/93-3p promotes chemoresistance and circulating miR-105/93-3p acts as a diagnostic biomarker for triple negative breast cancer
- Author
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Hao-Yi Li, Jui-Lin Liang, Yao-Lung Kuo, Hao-Hsien Lee, Calkins, Marcus, Hong-Tai Chang, Forn-Chia Lin, Yu-Chia Chen, Tai-I Hsu, Hsiao, Michael, Ger, Luo-Ping, and Pei-Jung Lu
- Abstract
Association between identified miRNAs and overall survival in TNBC and non-TNBC patients. A Identification of dysregulated miRNAs in TNBC compared with non-TNBC using Student t test. B Elevated expression of miR-301b, miR-181a-3p, miR-105, and miR-93 were individually associated with poor overall survival in 1095 non-triple negative breast cancer patients by Kaplan-Meier analysis. The correlation between indicated miRNAs and overall survival in (C) 204 TNBC patients and (D) 1095 non-TNBC patients was analyzed by Kaplan-Meier analysis. E Indicated miRNAs expression levels were examined in the independent cohort (GSE40267, N = 173), which contained 94 TNBC, 79 non-TNBC. Figure S2 miR-105 and miR-93-3p promote cellular migration but not proliferation. The effect of ectopic overexpression or silencing of indicated miRNAs on cell proliferation as determined by (A) colony-forming assay and (B) MTT assay. C The effect of ectopic overexpression or silencing of indicated miRNAs on cell migration ability as measured by the Boyden chamber transwell migration assay. D The miRNA-overexpressing HCC70 cells and miRNA silenced-BT-549 cells were seeded into matrigel-coated transwells to evaluate cell invasion in vitro. Figure S3 miR-105 and miR-93-3p confer cisplatin resistance. Cisplatin was administered with the indicated dose to cells with (A) ectopic overexpression or (B) silencing of indicated miRNAs prior to determining cell viability by the MTT assay. C Co-transfection with miR-105 and miR-93-3p antagomiRs in HCC1937 followed by measurement of the cisplatin response by MTT assay. D miR-105/93-3p co-silenced-BT-549 cells were seeded at 10,000 cells/ml into an ultra-low attachment plate for 10 days to evaluate mammosphere formation, as an indicator of stemness. Relative efficiency of mammosphere formation was measured in control and miR-105/93-3p-knockdown BT-549 cells. Figure S4 miR-105 and miR-93-3p activate Wnt/β-catenin signaling. A Bioinformatic analysis to identify potential miR-105 and miR-93-3p target genes. B The miR-105 and miR-93-3p associated mRNA profiling, paired with miRNA microarrays from the same patients were analyzed by IPA. C Ectopic overexpression of miR-105 or miR-93-3p and subsequent determination of β-catenin activity by the TOP/FOP reporter assay. D Immunoblotting was performed to measure levels of the indicated proteins in miR-105 or miR-93-3p manipulated TNBC cells. Figure S5 miR-93-3p/105 target to SFRP1 and decrease SFRP1 expression level. A Bioinformatic prediction of target genes for miR-105/93-3p involved in Wnt/b-catenin signaling. B IPA was performed to identify potential upstream regulators of Wnt/β-catenin that are modulated in TNBC with high expression of miR-105 or miR-93-3p. C RNA hybrid was performed to examine the binding energy between miR-105 or miR-93-3p with 3′-UTR of SFRP1. D Ectopic overexpression or silencing of indicated miRNAs followed by determination of SFRP1 protein levels by immunoblotting. Figure S6 miR-93-3p/105 can serve as biomarker for early TNBC patients and inversely correlated with SFRP1 in TNBC but not in non-TNBC patients. A The SFRP1 levels were determined in 12 non-TNBC N-T paired tissues by immunoblotting. B The contingency plot showed the distribution of SFRP1 in the indicated circulating miRNA levels. C Overall survival of 249 TNBC patients and 93 TNBC patients with chemotherapy, those were obtained from Kaplan-Meier plotter website were stratified with SFRP1 by Kaplan-Meier analysis. D Combination of circulating miR-93-3p/105 to evaluate the predictive power for stage I/II (N = 46) or stage III/IV (N = 21) stage of TNBC by ROC curve. (PDF 29884 kb)
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- 2017
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44. Additional file 2: Table S1. of miR-105/93-3p promotes chemoresistance and circulating miR-105/93-3p acts as a diagnostic biomarker for triple negative breast cancer
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Hao-Yi Li, Jui-Lin Liang, Yao-Lung Kuo, Hao-Hsien Lee, Calkins, Marcus, Hong-Tai Chang, Forn-Chia Lin, Yu-Chia Chen, Tai-I Hsu, Hsiao, Michael, Ger, Luo-Ping, and Pei-Jung Lu
- Abstract
Dysregulated miRNAs in TNBC patients. (DOCX 13 kb)
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- 2017
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45. Additional file 1: Figure S1. of miR-105/93-3p promotes chemoresistance and circulating miR-105/93-3p acts as a diagnostic biomarker for triple negative breast cancer
- Author
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Hao-Yi Li, Jui-Lin Liang, Yao-Lung Kuo, Hao-Hsien Lee, Calkins, Marcus, Hong-Tai Chang, Forn-Chia Lin, Yu-Chia Chen, Tai-I Hsu, Hsiao, Michael, Ger, Luo-Ping, and Pei-Jung Lu
- Abstract
Association between identified miRNAs and overall survival in TNBC and non-TNBC patients. A Identification of dysregulated miRNAs in TNBC compared with non-TNBC using Student t test. B Elevated expression of miR-301b, miR-181a-3p, miR-105, and miR-93 were individually associated with poor overall survival in 1095 non-triple negative breast cancer patients by Kaplan-Meier analysis. The correlation between indicated miRNAs and overall survival in (C) 204 TNBC patients and (D) 1095 non-TNBC patients was analyzed by Kaplan-Meier analysis. E Indicated miRNAs expression levels were examined in the independent cohort (GSE40267, N = 173), which contained 94 TNBC, 79 non-TNBC. Figure S2 miR-105 and miR-93-3p promote cellular migration but not proliferation. The effect of ectopic overexpression or silencing of indicated miRNAs on cell proliferation as determined by (A) colony-forming assay and (B) MTT assay. C The effect of ectopic overexpression or silencing of indicated miRNAs on cell migration ability as measured by the Boyden chamber transwell migration assay. D The miRNA-overexpressing HCC70 cells and miRNA silenced-BT-549 cells were seeded into matrigel-coated transwells to evaluate cell invasion in vitro. Figure S3 miR-105 and miR-93-3p confer cisplatin resistance. Cisplatin was administered with the indicated dose to cells with (A) ectopic overexpression or (B) silencing of indicated miRNAs prior to determining cell viability by the MTT assay. C Co-transfection with miR-105 and miR-93-3p antagomiRs in HCC1937 followed by measurement of the cisplatin response by MTT assay. D miR-105/93-3p co-silenced-BT-549 cells were seeded at 10,000 cells/ml into an ultra-low attachment plate for 10 days to evaluate mammosphere formation, as an indicator of stemness. Relative efficiency of mammosphere formation was measured in control and miR-105/93-3p-knockdown BT-549 cells. Figure S4 miR-105 and miR-93-3p activate Wnt/β-catenin signaling. A Bioinformatic analysis to identify potential miR-105 and miR-93-3p target genes. B The miR-105 and miR-93-3p associated mRNA profiling, paired with miRNA microarrays from the same patients were analyzed by IPA. C Ectopic overexpression of miR-105 or miR-93-3p and subsequent determination of β-catenin activity by the TOP/FOP reporter assay. D Immunoblotting was performed to measure levels of the indicated proteins in miR-105 or miR-93-3p manipulated TNBC cells. Figure S5 miR-93-3p/105 target to SFRP1 and decrease SFRP1 expression level. A Bioinformatic prediction of target genes for miR-105/93-3p involved in Wnt/b-catenin signaling. B IPA was performed to identify potential upstream regulators of Wnt/β-catenin that are modulated in TNBC with high expression of miR-105 or miR-93-3p. C RNA hybrid was performed to examine the binding energy between miR-105 or miR-93-3p with 3′-UTR of SFRP1. D Ectopic overexpression or silencing of indicated miRNAs followed by determination of SFRP1 protein levels by immunoblotting. Figure S6 miR-93-3p/105 can serve as biomarker for early TNBC patients and inversely correlated with SFRP1 in TNBC but not in non-TNBC patients. A The SFRP1 levels were determined in 12 non-TNBC N-T paired tissues by immunoblotting. B The contingency plot showed the distribution of SFRP1 in the indicated circulating miRNA levels. C Overall survival of 249 TNBC patients and 93 TNBC patients with chemotherapy, those were obtained from Kaplan-Meier plotter website were stratified with SFRP1 by Kaplan-Meier analysis. D Combination of circulating miR-93-3p/105 to evaluate the predictive power for stage I/II (N = 46) or stage III/IV (N = 21) stage of TNBC by ROC curve. (PDF 29884 kb)
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- 2017
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46. Additional file 2: Table S1. of miR-105/93-3p promotes chemoresistance and circulating miR-105/93-3p acts as a diagnostic biomarker for triple negative breast cancer
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Hao-Yi Li, Jui-Lin Liang, Yao-Lung Kuo, Hao-Hsien Lee, Calkins, Marcus, Hong-Tai Chang, Forn-Chia Lin, Yu-Chia Chen, Tai-I Hsu, Hsiao, Michael, Ger, Luo-Ping, and Pei-Jung Lu
- Abstract
Dysregulated miRNAs in TNBC patients. (DOCX 13 kb)
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- 2017
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47. Additional file 3: Table S2. of miR-105/93-3p promotes chemoresistance and circulating miR-105/93-3p acts as a diagnostic biomarker for triple negative breast cancer
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Hao-Yi Li, Jui-Lin Liang, Yao-Lung Kuo, Hao-Hsien Lee, Calkins, Marcus, Hong-Tai Chang, Forn-Chia Lin, Yu-Chia Chen, Tai-I Hsu, Hsiao, Michael, Ger, Luo-Ping, and Pei-Jung Lu
- Abstract
Univariate and multivariate analysis of clinical features and four oncomiRs associated with overall survival. (DOCX 12 kb)
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- 2017
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48. Additional file 3: Table S2. of miR-105/93-3p promotes chemoresistance and circulating miR-105/93-3p acts as a diagnostic biomarker for triple negative breast cancer
- Author
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Hao-Yi Li, Jui-Lin Liang, Yao-Lung Kuo, Hao-Hsien Lee, Calkins, Marcus, Hong-Tai Chang, Forn-Chia Lin, Yu-Chia Chen, Tai-I Hsu, Hsiao, Michael, Ger, Luo-Ping, and Pei-Jung Lu
- Abstract
Univariate and multivariate analysis of clinical features and four oncomiRs associated with overall survival. (DOCX 12 kb)
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- 2017
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49. MicroRNA-296-5p (miR-296-5p) functions as a tumor suppressor in prostate cancer by directly targeting Pin1
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Pei Jung Lu, Jing Hong Guo, Chen Hsun Tsai, Chi Long Chen, Yu Chieh Lee, Kuen Haur Lee, Tai I. Hsu, Forn Chia Lin, Jen Tai Lin, Yu Cheng Lee, and Michael Hsiao
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PCA3 ,Untranslated region ,Male ,Molecular Sequence Data ,Down-Regulation ,Biology ,Prostate cancer ,Pin1 ,Downregulation and upregulation ,Cell Line, Tumor ,microRNA ,medicine ,Humans ,RNA, Messenger ,3' Untranslated Regions ,Molecular Biology ,Cell Proliferation ,miR-296-5p ,Gene knockdown ,Base Sequence ,Cell growth ,Prostatic Neoplasms ,Cell Biology ,Peptidylprolyl Isomerase ,medicine.disease ,Up-Regulation ,Gene Expression Regulation, Neoplastic ,NIMA-Interacting Peptidylprolyl Isomerase ,MicroRNAs ,Gene Knockdown Techniques ,Cancer research ,PIN1 - Abstract
Upregulation of Pin1 was shown to advance the functioning of several oncogenic pathways. It was recently shown that Pin1 is potentially an excellent prognostic marker and can also serve as a novel therapeutic target for prostate cancer. However, the molecular mechanism of Pin1 overexpression in prostate cancer is still unclear. In the present study, we showed that the mRNA expression levels of Pin1 were not correlated with Pin1 protein levels in prostate cell lines which indicated that Pin1 may be regulated at the post-transcriptional level. A key player in post-transcriptional regulation is represented by microRNAs (miRNAs) that negatively regulate expressions of protein-coding genes at the post-transcriptional level. A bioinformatics analysis revealed that miR-296-5p has a conserved binding site in the Pin1 3′-untranslated region (UTR). A luciferase reporter assay demonstrated that the seed region of miR-296-5p directly interacts with the 3′-UTR of Pin1 mRNA. Moreover, miR-296-5p expression was found to be inversely correlated with Pin1 expression in prostate cancer cell lines and prostate cancer tissues. Furthermore, restoration of miR-296-5p or the knockdown of Pin1 had the same effect on the inhibition of the ability of cell proliferation and anchorage-independent growth of prostate cancer cell lines. Our results support miR-296-5p playing a tumor-suppressive role by targeting Pin1 and implicate potential effects of miR-296-5p on the prognosis and clinical application to prostate cancer therapy.
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- 2014
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50. Resveratrol decreases fructose-induced oxidative stress, mediated by NADPH oxidase via an AMPK-dependent mechanism
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Gwo Ching Sun, Wen Yu Ho, Ching-Jiunn Tseng, Pei Jung Lu, Michael Hsiao, Wen Hsien Lu, Bo Zone Chen, Tung Chen Yeh, Pei Wen Cheng, Yu Ting Su, and Wen Han Cheng
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Pharmacology ,chemistry.chemical_classification ,medicine.medical_specialty ,Reactive oxygen species ,NADPH oxidase ,biology ,SOD2 ,AMPK ,Resveratrol ,medicine.disease_cause ,Superoxide dismutase ,chemistry.chemical_compound ,Endocrinology ,AMP-activated protein kinase ,chemistry ,Internal medicine ,medicine ,biology.protein ,Oxidative stress - Abstract
Background and Purpose Oxidative stress is an important pathogenic factor in the development of hypertension. Resveratrol, the main antioxidant in red wine, improves NO bioavailability and prevents cardiovascular disease. The aim of this study was to examine whether resveratrol decreases the generation of reactive oxygen species (ROS), thereby reducing BP in rats with fructose-induced hypertension. Experimental Approach Rats were fed 10% fructose with or without resveratrol (10 mg·kg−1·day−1) for 1 week or for 4 weeks with resveratrol treatment beginning at week 2; systolic BP (SBP) was measured by tail-cuff method. Endogenous in vivo O2− production in the nucleus tractus solitarii (NTS) was determined with dihydroethidium. Real-time PCR and immunoblotting analyses were used to quantify RNA and protein expression levels. Key Results In fructose-fed rats, ROS levels in the NTS were higher, whereas the NO level was significantly decreased. Also, RNA and protein levels of NADPH oxidase subunits (p67, p22-phox) were elevated, superoxide dismutase 2 (SOD2) reduced and AMP-activated PK (AMPK) T172 phosphorylation levels in the NTS were lower in fructose-fed rats. Treatment with the AMPK activator resveratrol decreased levels of NADPH oxidase subunits and ROS, and increased NO and SOD2 levels in the NTS of fructose-fed rats. Administration of resveratrol, in combination with fructose at week 0 and later at week 2, significantly reduced the SBP of fructose-fed rats. Conclusions and Implications Collectively, resveratrol decreased BP through the phosphorylation of AMPK, Akt and neuronal NOS in fructose-fed rats. These novel findings suggest that resveratrol may be a potential pharmacological candidate for the treatment of hypertension.
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- 2014
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