63 results on '"Ming Teh Chen"'
Search Results
2. Characterizing deep brain biosignals: The advances and applications of implantable MEMS-based devices
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Hsin-Yu Wu, Kao-Jung Chang, Ximiao Wen, Aliaksandr A. Yarmishyn, He-Jhen Dai, Kai-Hsiang Chan, Hsiao Yu-Jer, Ming-Teh Chen, Yueh Chien, Hsin-I Ma, Wensyang Hsu, Meng-Shiue Lee, and Shih-Hwa Chiou
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MEMS technology ,Brain biosignals ,Neural electrical signals ,Intracranial pressure ,Optogenetics ,Materials of engineering and construction. Mechanics of materials ,TA401-492 - Abstract
The brain is the center of the nervous system controlling other organs. The brain is characterized by extreme complexity of its structure and delicate texture, which makes it difficult to investigate by invasive methods. The advances in semiconductor manufacturing technology led to the development of implantable microelectromechanical system (MEMS)-based devices that can be implanted into the brain with reduced risk of damage to the brain tissue due to their small size and low stiffness. Such devices are now widely applied in the clinic and brain research for understanding brain functions, diagnosing brain-related diseases, and pursuing innovative therapies. Inevitably, these invasive devices cause damage to the brain tissue, such as wounds, inflammation, and scars, eventually leading to dysfunction of the device. Therefore, it is vital to find an optimal design solution for such devices taking into consideration such parameters as size, stiffness and biocompatibility. In this review, we focus on three main brain applications of such devices: detection of electrical signals, intracranial pressure (ICP), and optogenetics. We summarize the current application scope of such MEMS-based devices in brain research and clinical application, and compare them based on their mechanical and biological properties. The understanding of the device design, methods of application, and current development can support neuroscientists and neurologists to make revolutionary discoveries in the brain research field. more...
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- 2022
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Catalog
3. Musashi-1 promotes cancer stem cell properties of glioblastoma cells via upregulation of YTHDF1
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Aliaksandr A. Yarmishyn, Yi-Ping Yang, Kai-Hsi Lu, Yi-Chen Chen, Yueh Chien, Shih-Jie Chou, Ping-Hsing Tsai, Hsin-I. Ma, Chian-Shiu Chien, Ming-Teh Chen, and Mong-Lien Wang
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YTHDF1 ,Musashi-1 ,Glioblastoma ,Cancer progression ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 ,Cytology ,QH573-671 - Abstract
Abstract Background Glioblastoma (GBM) is the most lethal brain tumor characterized by high morbidity and limited treatment options. Tumor malignancy is usually associated with the epigenetic marks, which coordinate gene expression to ascertain relevant phenotypes. One of such marks is m6A modification of RNA, whose functional effects are dependent on the YTH family m6A reader proteins. Methods and results In this study, we investigated the expression of five YTH family proteins in different GBM microarray datasets from the Oncomine database, and identified YTHDF1 as the most highly overexpressed member of this family in GBM. By performing the knockdown of YTHDF1 in a GBM cell line, we found that it positively regulates proliferation, chemoresistance and cancer stem cell-like properties. Musashi-1 (MSI1) is a postranscriptional gene expression regulator associated with high oncogenicity in GBM. By knocking down and overexpressing MSI1, we found that it positively regulates YTHDF1 expression. The inhibitory effects imposed on the processes of proliferation and migration by YTHDF1 knockdown were shown to be partially rescued by concomitant overexpression of MSI1. MSI1 and YTHDF1 were shown to be positively correlated in clinical glioma samples, and their concomitant upregulation was associated with decreased survival of glioma patients. We identified the direct regulation of YTHDF1 by MSI1. Conclusions Given the fact that both proteins are master regulators of gene expression, and both of them are unfavorable factors in GBM, we suggest that in any future studies aimed to uncover the prognostic value and therapy potential, these two proteins should be considered together. more...
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- 2020
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4. Entering a new era of molecular classification of brain tumors: An update of 2021 World Health Organization classification in adult gliomas
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Ching-Ying Wang, Shih-Chieh Lin, Ming-Teh Chen, and Yi-Yen Lee
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Surgery - Published
- 2023
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5. Oncogenic circRNA C190 Promotes Non–Small Cell Lung Cancer via Modulation of the EGFR/ERK Pathway
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Yuh Min Chen, Jerry Chieh-Yu Chen, Chian Shiu Chien, Yueh Chien, Teh Ia Huo, Afeez Adekunle Ishola, Shih Hwa Chiou, Po-Kuei Hsu, Aliaksandr A. Yarmishyn, Mong Lien Wang, Ping-Hsing Tsai, Ming-Teh Chen, Yuan-Tzu Lan, Yung-Hung Luo, Yi-Ping Yang, Hsin-I Ma, and Kung-Hao Liang more...
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Male ,MAPK/ERK pathway ,Cancer Research ,Lung Neoplasms ,Cell ,Mice, Nude ,Mice ,Cyclin-dependent kinase ,Carcinoma, Non-Small-Cell Lung ,medicine ,Animals ,Humans ,Gene knockdown ,Cyclin-dependent kinase 1 ,biology ,Chemistry ,Kinase ,Oncogenes ,RNA, Circular ,Cell cycle ,ErbB Receptors ,Disease Models, Animal ,medicine.anatomical_structure ,Oncology ,Cancer research ,biology.protein ,Cyclin-dependent kinase 6 - Abstract
Lung cancers are the leading cause of cancer-related mortality worldwide, and the majority of lung cancers are non–small cell lung carcinoma (NSCLC). Overexpressed or activated EGFR has been associated with a poor prognosis in NSCLC. We previously identified a circular noncoding RNA, hsa_circ_0000190 (C190), as a negative prognostic biomarker of lung cancer. Here, we attempted to dissect the mechanistic function of C190 and test the potential of C190 as a therapeutic target in NSCLC. C190 was upregulated in both NSCLC clinical samples and cell lines. Activation of the EGFR pathway increased C190 expression through a MAPK/ERK-dependent mechanism. Transient and stable overexpression of C190 induced ERK1/2 phosphorylation, proliferation, and migration in vitro and xenograft tumor growth in vivo. RNA sequencing and Expression2Kinases (X2K) analysis indicated that kinases associated with cell-cycle and global translation are involved in C190-activated networks, including CDKs and p70S6K, which were further validated by immunoblotting. CRISPR/Cas13a-mediated knockdown of C190 decreased proliferation and migration of NSCLC cells in vitro and suppressed tumor growth in vivo. TargetScan and CircInteractome databases predicted that C190 targets CDKs by sponging miR-142-5p. Analysis of clinical lung cancer samples showed that C190, CDK1, and CDK6 expressions were significantly higher in advanced-stage lung cancer than in early-stage lung cancer. In summary, C190 is directly involved in EGFR–MAPK–ERK signaling and may serve as a potential therapeutic target for the treatment of NSCLC. Significance: The circRNA C190 is identified as a mediator of multiple pro-oncogenic signaling pathways in lung cancer and can be targeted to suppress tumor progression. more...
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- 2022
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6. Data from Oncogenic circRNA C190 Promotes Non–Small Cell Lung Cancer via Modulation of the EGFR/ERK Pathway
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Shih-Hwa Chiou, Mong-Lien Wang, Ming-Teh Chen, Hsin-I. Ma, Teh-Ia Huo, Yuan-Tzu Lan, Kung-Hou Liang, Yuh-Min Chen, Yung-Hung Luo, Po-Kuei Hsu, Jerry Chieh-Yu Chen, Ping-Hsing Tsai, Aliaksandr A. Yarmishyn, Yueh Chien, Yi-Ping Yang, Chian-Shiu Chien, and Afeez Adekunle Ishola more...
- Abstract
Lung cancers are the leading cause of cancer-related mortality worldwide, and the majority of lung cancers are non–small cell lung carcinoma (NSCLC). Overexpressed or activated EGFR has been associated with a poor prognosis in NSCLC. We previously identified a circular noncoding RNA, hsa_circ_0000190 (C190), as a negative prognostic biomarker of lung cancer. Here, we attempted to dissect the mechanistic function of C190 and test the potential of C190 as a therapeutic target in NSCLC. C190 was upregulated in both NSCLC clinical samples and cell lines. Activation of the EGFR pathway increased C190 expression through a MAPK/ERK-dependent mechanism. Transient and stable overexpression of C190 induced ERK1/2 phosphorylation, proliferation, and migration in vitro and xenograft tumor growth in vivo. RNA sequencing and Expression2Kinases (X2K) analysis indicated that kinases associated with cell-cycle and global translation are involved in C190-activated networks, including CDKs and p70S6K, which were further validated by immunoblotting. CRISPR/Cas13a-mediated knockdown of C190 decreased proliferation and migration of NSCLC cells in vitro and suppressed tumor growth in vivo. TargetScan and CircInteractome databases predicted that C190 targets CDKs by sponging miR-142-5p. Analysis of clinical lung cancer samples showed that C190, CDK1, and CDK6 expressions were significantly higher in advanced-stage lung cancer than in early-stage lung cancer. In summary, C190 is directly involved in EGFR–MAPK–ERK signaling and may serve as a potential therapeutic target for the treatment of NSCLC.Significance:The circRNA C190 is identified as a mediator of multiple pro-oncogenic signaling pathways in lung cancer and can be targeted to suppress tumor progression. more...
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- 2023
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7. Supplementary Data from Oncogenic circRNA C190 Promotes Non–Small Cell Lung Cancer via Modulation of the EGFR/ERK Pathway
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Shih-Hwa Chiou, Mong-Lien Wang, Ming-Teh Chen, Hsin-I. Ma, Teh-Ia Huo, Yuan-Tzu Lan, Kung-Hou Liang, Yuh-Min Chen, Yung-Hung Luo, Po-Kuei Hsu, Jerry Chieh-Yu Chen, Ping-Hsing Tsai, Aliaksandr A. Yarmishyn, Yueh Chien, Yi-Ping Yang, Chian-Shiu Chien, and Afeez Adekunle Ishola more...
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List of differentially expressed genes from RNA-seq
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- 2023
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8. Supplementary Information from Oncogenic circRNA C190 Promotes Non–Small Cell Lung Cancer via Modulation of the EGFR/ERK Pathway
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Shih-Hwa Chiou, Mong-Lien Wang, Ming-Teh Chen, Hsin-I. Ma, Teh-Ia Huo, Yuan-Tzu Lan, Kung-Hou Liang, Yuh-Min Chen, Yung-Hung Luo, Po-Kuei Hsu, Jerry Chieh-Yu Chen, Ping-Hsing Tsai, Aliaksandr A. Yarmishyn, Yueh Chien, Yi-Ping Yang, Chian-Shiu Chien, and Afeez Adekunle Ishola more...
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Supplementary materials and methods, supplementary tables, and supplementary figures to support the main manuscript
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- 2023
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9. Overview of the molecular mechanisms of migration and invasion in glioblastoma multiforme
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Ming Teh Chen, Liang Ting Lin, Yi Ping Yang, Yueh Chien, Ju Yu Chen, and Xian Liu
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Brain Neoplasms ,business.industry ,General Medicine ,030204 cardiovascular system & hematology ,Phenotype ,Extracellular matrix ,03 medical and health sciences ,0302 clinical medicine ,Cell Movement ,Transforming Growth Factor beta ,RNA interference ,030220 oncology & carcinogenesis ,microRNA ,Cancer research ,Humans ,Medicine ,Neoplasm Invasiveness ,Epithelial–mesenchymal transition ,Signal transduction ,Stem cell ,Glioblastoma ,business ,Protein kinase B ,Signal Transduction - Abstract
Glioblastoma (GBM) is one of the most devastating cancers, with an approximate median survival of only 16 months. Although some new insights into the fantastic heterogeneity of this kind of brain tumor have been revealed in recent studies, all subclasses of GBM still demonstrate highly aggressive invasion properties to the surrounding parenchyma. This behavior has become the main obstruction to current curative therapies as invasive GBM cells migrate away from these foci after surgical therapies. Therefore, this review aimed to provide a relatively comprehensive study of GBM invasion mechanisms, which contains an intricate network of interactions and signaling pathways with the extracellular matrix (ECM). Among these related molecules, TGF-β, the ECM, Akt, and microRNAs are most significant in terms of cellular procedures related to GBM motility and invasion. Moreover, we also review data indicating that Musashi-1 (MSI1), a neural RNA-binding protein (RBP), regulates GBM motility and invasion, maintains stem cell populations in GBM, and promotes drug-resistant GBM phenotypes by stimulating necessary oncogenic signaling pathways through binding and regulating mRNA stability. Importantly, these necessary oncogenic signaling pathways have a close connection with TGF-β, ECM, and Akt. Thus, it appears promising to find MSI-specific inhibitors or RNA interference-based treatments to prevent the actions of these molecules despite using RBPs, which are known as hard therapeutic targets. In summary, this review aims to provide a better understanding of these signaling pathways to help in developing novel therapeutic approaches with better outcomes in preclinical studies. more...
- Published
- 2021
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10. Musashi-1 promotes cancer stem cell properties of glioblastoma cells via upregulation of YTHDF1
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Yueh Chien, Kai-Hsi Lu, Yi-Ping Yang, Hsin-I Ma, Shih Jie Chou, Yi Chen Chen, Ming-Teh Chen, Chian Shiu Chien, Mong Lien Wang, Ping-Hsing Tsai, and Aliaksandr A. Yarmishyn
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Cancer Research ,Microarray ,Cancer progression ,Biology ,lcsh:RC254-282 ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,Cancer stem cell ,Glioma ,Gene expression ,Genetics ,medicine ,Epigenetics ,lcsh:QH573-671 ,030304 developmental biology ,0303 health sciences ,Gene knockdown ,lcsh:Cytology ,Cancer ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Oncology ,YTHDF1 ,Musashi-1 ,030220 oncology & carcinogenesis ,Cancer research ,Primary Research ,Glioblastoma - Abstract
Background Glioblastoma (GBM) is the most lethal brain tumor characterized by high morbidity and limited treatment options. Tumor malignancy is usually associated with the epigenetic marks, which coordinate gene expression to ascertain relevant phenotypes. One of such marks is m6A modification of RNA, whose functional effects are dependent on the YTH family m6A reader proteins. Methods and results In this study, we investigated the expression of five YTH family proteins in different GBM microarray datasets from the Oncomine database, and identified YTHDF1 as the most highly overexpressed member of this family in GBM. By performing the knockdown of YTHDF1 in a GBM cell line, we found that it positively regulates proliferation, chemoresistance and cancer stem cell-like properties. Musashi-1 (MSI1) is a postranscriptional gene expression regulator associated with high oncogenicity in GBM. By knocking down and overexpressing MSI1, we found that it positively regulates YTHDF1 expression. The inhibitory effects imposed on the processes of proliferation and migration by YTHDF1 knockdown were shown to be partially rescued by concomitant overexpression of MSI1. MSI1 and YTHDF1 were shown to be positively correlated in clinical glioma samples, and their concomitant upregulation was associated with decreased survival of glioma patients. We identified the direct regulation of YTHDF1 by MSI1. Conclusions Given the fact that both proteins are master regulators of gene expression, and both of them are unfavorable factors in GBM, we suggest that in any future studies aimed to uncover the prognostic value and therapy potential, these two proteins should be considered together. more...
- Published
- 2020
11. Musashi-1 promotes stress-induced tumor progression through recruitment of AGO2
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Jia Shen, Jennifer L. Hsu, Hsiao Yun Chen, Mong Lien Wang, Mien Chie Hung, Hsin I. Ma, Yi Ping Yang, Liang Ting Lin, Shih Hwa Chiou, Yi Wei Chen, Chung-Hsuan Chen, Ming Teh Chen, Chung Pin Li, Wen-chang Lin, Wei Chao Chang, Benoit Laurent, Pin I. Huang, and Chih-Hung Hsu more...
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Male ,0301 basic medicine ,Untranslated region ,Immunoprecipitation ,Mice, Nude ,Medicine (miscellaneous) ,Nerve Tissue Proteins ,Chromosomal translocation ,Endogeny ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Cell Line, Tumor ,Neoplasms ,Animals ,Humans ,cancer ,subcellular translocation ,Pharmacology, Toxicology and Pharmaceutics (miscellaneous) ,Mice, Inbred BALB C ,Argonaute 2 ,Chemistry ,Carcinoma ,RNA-Binding Proteins ,Argonaute ,tumor recurrence ,Cytosol ,030104 developmental biology ,Musashi-1 ,Tumor progression ,030220 oncology & carcinogenesis ,Argonaute Proteins ,RNA regulation ,Disease Progression ,Cancer research ,Neoplasm Recurrence, Local ,Cell fractionation ,Research Paper - Abstract
Carcinomatous progression and recurrence are the main therapeutic challenges frequently faced by patients with refractory tumors. However, the underlined molecular mechanism remains obscure. Methods: We found Musashi-1 (MSI1) transported into cytosol under stress condition by confocal microscopy and cell fractionation. Argonaute 2 (AGO2) was then identified as a cytosolic binding partner of MSI1 by Mass Spectrametry, immunoprecipitation, and recombinant protein pull-down assay. We used RNA-IP to determine the MSI1/AGO2 associated regions on downstream target mRNAs. Finally, we overexpressed C-terminus of MSI1 to disrupt endogenous MSI1/AGO2 interaction and confirm it effects on tmor progression. Results: Malignant tumors exhibit elevated level of cytosolic Musashi-1 (MSI1), which translocates into cytosol in response to stress and promote tumor progression. Cytosolic MSI1 forms a complex with AGO2 and stabilize or destabilize its target mRNAs by respectively binding to their 3´ untranslated region or coding domain sequence. Both MSI1 translocation and MSI1/AGO2 binding are essential for promoting tumor progression. Blocking MSI1 shuttling by either chemical inhibition or point mutation attenuates the growth of GBM-xenografts in mice. Importantly, overexpression of the C-terminus of MSI1 disrupts endogenous MSI1/AGO2 interaction and effectively reduces stress-induced tumor progression. Conclusion: Our findings highlight novel molecular functions of MSI1 during stress-induced carcinomatous recurrence, and suggest a new therapeutic strategy for refractory malignancies by targeting MSI1 translocation and its interaction with AGOs. more...
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- 2020
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12. Strategic Decoy Peptides Interfere with MSI1/AGO2 Interaction to Elicit Tumor Suppression Effects
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Yi-Ping Yang, Andy Chi-Lung Lee, Liang-Ting Lin, Yi-Wei Chen, Pin-I Huang, Hsin-I Ma, Yi-Chen Chen, Wen-Liang Lo, Yuan-Tzu Lan, Wen-Liang Fang, Chien-Ying Wang, Yung-Yang Liu, Po-Kuei Hsu, Wen-Chang Lin, Chung-Pin Li, Ming-Teh Chen, Chian-Shiu Chien, and Mong-Lien Wang more...
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MSI1 C-terminus ,MSI1/AGO2 disruption ,Cancer Research ,protein–protein interaction ,Oncology ,decoy peptide ,tumor suppression ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Peptide drugs that target protein–protein interactions have attracted mounting research efforts towards clinical developments over the past decades. Increasing reports have indicated that expression of Musashi 1 (MSI1) is tightly correlated to high grade of cancers as well as enrichment of cancer stem cells. Treatment failure in malignant tumors glioblastoma multiform (GBM) had also been correlated to CSC-regulating properties of MSI1. It is thus imperative to develop new therapeutics that could effectively improve current regimens used in clinics. MSI1 and AGO2 are two emerging oncogenic molecules that both contribute to GBM tumorigenesis through mRNA regulation of targets involved in apoptosis and cell cycle. In this study, we designed peptide arrays covering the C-terminus of MSI1 and identified two peptides (Pep#11 and Pep#26) that could specifically interfere with the binding with AGO2. Our Biacore analyses ascertained binding between the identified peptides and AGO2. Recombinant reporter system Gaussian luciferase and fluorescent bioconjugate techniques were employed to determine biological functions and pharmacokinetic characteristics of these two peptides. Our data suggested that Pep#11 and Pep#26 could function as decoy peptides by mimicking the interaction function of MSI1 with its binding partner AGO2 in vitro and in vivo. Further experiments using GMB animal models corroborated the ability of Pep#11 and Pep#26 in disrupting MSI1/AGO2 interaction and consequently anti-tumorigenicity and prolonged survival rates. These striking therapeutic efficacies orchestrated by the synthetic peptides were attributed to the decoy function to C-terminal MSI1, especially in malignant brain tumors and glioblastoma. more...
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- 2022
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13. Nuclear Localization Signal-Enhanced Polyurethane-Short Branch Polyethylenimine-Mediated Delivery of Let-7a Inhibited Cancer Stem-Like Properties by Targeting the 3′-UTR of HMGA2 in Anaplastic Astrocytoma
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Meng-Yin Yang, Ming-Teh Chen, Pin-I Huang, Chien-Ying Wang, Yun-Chin Chang, Yi-Ping Yang, Wen-Liang Lo, Wen-Hsing Sung, Yi-Wen Liao, Yi-Yen Lee, Yuh-Lih Chang, Ling-Ming Tseng, Yi-Wei Chen, and Hsin-I Ma more...
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Medicine - Abstract
Anaplastic astrocytoma (AA) is a grade III glioma that often occurs in middle-aged patients and presents a uniformly poor prognosis. A small subpopulation of cancer stem cells (CSCs) possessing a self-renewing capacity is reported to be responsible for tumor recurrence and therapeutic resistance. An accumulating amount of microRNAs (miRNA) were found aberrantly expressed in human cancers and regulate CSCs. Efforts have been made to couple miRNAs with nonviral gene delivery approaches to target specific genes in cancer cells. However, the efficiency of delivery of miRNAs to AA-derived CSCs is still an applicability hurdle. The present study aimed to investigate the effectiveness and applicability of nonviral vector-mediated delivery of Let-7a with regard to eradication of AA and AA-derived CSC cells. Herein, our miRNA/mRNA microarray and RT-PCR analysis showed that the expression of Let-7a, a tumor-suppressive miRNA, is inversely correlated with the levels of HMGA2 and Sox2 in the AA side population (SP + ) cells. Luciferase reporter assay showed that Let-7a directly targets the 3′-UTRs of HMGA2 in AA-SP + cells. Knockdown of HMGA2 significantly suppressed the protein expression of Sox2 in AA-SP + cells, whereas overexpression of HMGA2 upregulated Sox2 expression in AA-SP - . Nuclear localization signal (NLS) peptides can facilitate nuclear targeting of DNA and are used to improve gene delivery. Using polyurethane-short branch polyethylenimine (PU-PEI) as a therapeutic delivery vehicle, we conjugated NLS with Let-7 and successfully delivered it to AA-SP + cells, resulting in significantly suppressed expression of HMGA2 and Sox2, tumorigenicity, and CSC-like abilities. This treatment facilitated the differentiation of AA-SP + cells into non-SP CSCs. Furthermore, PU-PEI-mediated delivery of NLS-conjugated Let-7a in AA-SP + cells suppressed the expression of drug-resistant and antiapoptotic genes, and increased cell sensitivity to radiation. Finally, the in vivo delivery of PU-PEI-NLS-Let-7a significantly suppressed the tumorigenesis of AA-SP + cells and synergistically improved the survival rate of orthotopically AA-SP + -transplanted immunocompromised mice when combined with radiotherapy. Therefore, PU-PEI-NLS-Let-7a is a potential novel therapeutic approach for AA. more...
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- 2015
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14. MicroRNA142-3p Promotes Tumor-Initiating and Radioresistant Properties in Malignant Pediatric Brain Tumors
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Yi-Yen Lee, Yi-Ping Yang, Ming-Chao Huang, Mong-Lien Wang, Sang-Hue Yen, Pin-I Huang, Yi-Wei Chen, Shih-Hwa Chiou, Yuan-Tzu Lan, Hsin-I Ma, Yang-Hsin Shih, and Ming-Teh Chen M.D., Ph.D.
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Medicine - Abstract
Primary central nervous system (CNS) atypical teratoid/rhabdoid tumor (ATRT) is an extremely malignant pediatric brain tumor observed in infancy and childhood. It has been reported that a subpopulation of CD133 + cells isolated from ATRT tumors present with cancer stem-like and radioresistant properties. However, the exact biomolecular mechanisms of ATRT or CD133-positive ATRT (ATRT-CD133 + ) cells are still unclear. We have previously shown that ATRT-CD133 + cells have pluripotent differentiation ability and the capability of malignant cells to be highly resistant to ionizing radiation (IR). By using microRNA array and quantitative RT-PCR in this study, we showed that expression of miR142-3p was lower in ATRT-CD133 + cells than in ATRT-CD133 - cells. miR142-3p overexpression significantly inhibited the self-renewal and tumorigenicity of ATRT-CD133 + cells. On the contrary, silencing of endogenous miR142-3p dramatically increased the tumor-initiating and stem-like cell capacities in ATRT cells or ATRT-CD133 - cells and further promoted the mesenchymal transitional and radioresistant properties of ATRT cells. Most importantly, therapeutic delivery of miR142-3p in ATRT cells effectively reduced its lethality by blocking tumor growth, repressing invasiveness, increasing radiosensitivity, and prolonging survival time in orthotropic-transplanted immunocompromised mice. These results demonstrate the prospect of developing novel miRNA-based strategies to block the stem-like and radioresistant properties of malignant pediatric brain cancer stem cells. more...
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- 2014
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15. Deregulated MicroRNAs Identified in Isolated Glioblastoma Stem Cells: An Overview
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Pei-Ming Chua, Hsin-I Ma, Li-Hsin Chen, Ming-Teh Chen, Pin-I Huang, Shinn-Zong Lin M.D., Ph.D., and Shih-Hwa Chiou M.D., Ph.D.
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Medicine - Abstract
Glioblastoma multiforme (GBM), the most common and aggressive primary brain tumor, is extremely resistant to current treatment paradigms and has a high rate of tumor recurrence. Recent progress in the field of tumor-initiating cells suggests that GBM stem cells (GBMSCs) may be responsible for tumor progression, resistance to treatment, and tumor relapse. Therefore, understanding the biologically significant pathways involved in modulating GBMSC-specific characteristics offers great promise for development of novel therapeutics, which may improve therapeutic efficacy and overcome present drug resistance. In addition, targeting deregulated microRNA (miRNA) has arisen as a new therapeutic strategy in treating malignant gliomas. In GBMSCs, miRNAs regulate a wide variety of tumorigenic processes including cellular proliferation, stemness maintenance, migration/invasion, apoptosis, and tumorigenicity. Nevertheless, the latest progress with GBMSCs and subsequent miRNA profiling is limited by the identification and isolation of GBMSCs. In this review, we thus summarize current markers and known features for isolation as well as the aberrant miRNAs that have been identified in GBM and GBMSCs. more...
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- 2013
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16. Plasma Level of Circular RNA hsa_circ_0000190 Correlates with Tumor Progression and Poor Treatment Response in Advanced Lung Cancers
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Chao Yu Liu, Shih Hwa Chiou, Tzu-Wei Lin, Yuh Min Chen, Chian Shiu Chien, Yung Hung Luo, Yueh Chien, Aliaksandr A. Yarmishyn, Yi Ping Yang, Tsai Wang Huang, Afeez Adekunle Ishola, Mong Lien Wang, Kang Yun Lee, Wen Chien Huang, Ming Teh Chen, Cheng Chang Chang, and Ping Hsing Tsai more...
- Subjects
0301 basic medicine ,Cancer Research ,programmed death-ligand 1 ,medicine.medical_treatment ,lcsh:RC254-282 ,Article ,Metastasis ,droplet digital PCR ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,microRNA ,medicine ,Liquid biopsy ,Lung cancer ,liquid biopsy ,business.industry ,circular RNA ,Immunotherapy ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,lung cancer ,030104 developmental biology ,Oncology ,Tumor progression ,030220 oncology & carcinogenesis ,Cancer research ,Adenocarcinoma ,business - Abstract
Lung cancer (LC) causes the majority of cancer-related deaths. Circular RNAs (circRNAs) were reported to play roles in cancers by targeting pro- and anti-oncogenic miRNAs. However, the mechanisms of circRNAs in LC progression and their prognostic value of treatment response remain unclear. By using next generation sequencing (NGS) of LC cell lines&rsquo, transcriptomes, we identified highly overexpressed hsa_circ_0000190 and hsa_circ_000164 as potential biomarkers. By using the highly sensitive RT-ddPCR method, these circRNAs were shown to be secreted by cell lines and were detected in human blood. Clinical validation by RT-ddPCR was carried out on 272 (231 LC patients and 41 controls) blood samples. Higher hsa_circ_0000190 levels were associated with larger tumor size (p <, 0.0001), worse histological type of adenocarcinoma (p = 0.0028), later stage (p <, 0.0001), more distant metastatic organs (p = 0.0039), extrathoracic metastasis (p = 0.0004), and poor survival (p = 0.047) and prognosis. Using liquid biopsy-based RT-ddPCR, we discovered the correlation between increased hsa_circ_0000190 plasma level (p <, 0.0001) and higher programmed death-ligand 1 (PD-L1) level in tumor (p = 0.0283). Notably, long-term follow-up of the immunotherapy treated cases showed that upregulated plasma hsa_circ_0000190 level correlated with poor response to systemic therapy and immunotherapy (p = 0.0002, 0.0058, respectively). Secretory circRNAs are detectable in blood by LB-based RT-ddPCR and may serve as blood-based biomarkers to monitor disease progression and treatment efficacy. more...
- Published
- 2020
17. Hippocampal desynchronization of functional connectivity prior to the onset of status epilepticus in pilocarpine-treated rats.
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Chi-Han Wang, Chou P Hung, Ming-Teh Chen, Yang-Hsin Shih, and Yung-Yang Lin
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Medicine ,Science - Abstract
Status epilepticus (SE), a pro-epileptogenic brain insult in rodent models of temporal lobe epilepsy, is successfully induced by pilocarpine in some, but not all, rats. This study aimed to identify characteristic alterations within the hippocampal neural network prior to the onset of SE. Sixteen microwire electrodes were implanted into the left hippocampus of male Sprague-Dawley rats. After a 7-day recovery period, animal behavior, hippocampal neuronal ensemble activities, and local field potentials (LFP) were recorded before and after an intra-peritoneal injection of pilocarpine (350 mg/kg). The single-neuron firing, population neuronal correlation, and coincident firing between neurons were compared between SE (n = 9) and nonSE rats (n = 12). A significant decrease in the strength of functional connectivity prior to the onset of SE, as measured by changes in coincident spike timing between pairs of hippocampal neurons, was exclusively found in SE rats. However, single-neuron firing and LFP profiles did not show a significant difference between SE and nonSE rats. These results suggest that desynchronization in the functional circuitry of the hippocampus, likely associated with a change in synaptic strength, may serve as an electrophysiological marker prior to SE in pilocarpine-treated rats. more...
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- 2012
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18. MicroRNA-142-3p is involved in regulation of MGMT expression in glioblastoma cells
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Pin I. Huang, Yi Yen Lee, Shih Hwa Chiou, Mong Lien Wang, Chun Fu Lin, Yi Ping Yang, Hsiao Yun Chen, Yi Wei Chen, Aliaksandr A. Yarmishyn, Ming Teh Chen, and Hsin I. Ma
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0301 basic medicine ,Untranslated region ,Carmustine ,Programmed cell death ,Temozolomide ,business.industry ,Transfection ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Oncology ,030220 oncology & carcinogenesis ,Gene expression ,microRNA ,DNA Repair Protein ,Cancer research ,medicine ,business ,medicine.drug - Abstract
Background Glioblastoma multiforme (GBM) is the most malignant brain tumor, and there is no effective treatment strategy. Patients with GBM have a median overall survival of only 14.6 months. Current treatment consists of safe and maximal surgical excision, followed by concurrent chemoradiotherapy and maintenance chemotherapy. There are several obstacles that hinder the effectiveness of this aggressive treatment. Temozolomide (TMZ) is an oral alkylating drug that acts through alkylating the O6 position of guanine in DNA that leads to cell death. However, the expression and enzymatic activity of the DNA repair protein MGMT limits the therapeutic benefit from treatment with TMZ. MGMT reduces the efficacy of alkylating drugs by removing the methyl or alkyl group from damaged O6-methylguanine. Expression levels of MGMT play an important role in the outcome of GBM patients. miRNAs are a group of small regulatory RNAs that control target gene expression by binding to mRNAs. miR-142-3p has been found to be an important factor in the development and maintenance of the oncogenic state. Results In this study, we sought to investigate whether miR-142-3p can regulate MGMT gene expression in GBM cells. Here, we show that miR-142-3p downregulates MGMT expression through binding to the 3'-UTR of MGMT mRNA, thus affecting protein translation. Responsiveness to TMZ was significantly enhanced after transfection with miR-142-3p. Overexpression of miR-142-3p also sensitized GBM cells to alkylating drugs. Conclusion Above all, our findings demonstrate that miR-142-3p plays a critical role in regulating MGMT expression, has great potential for future clinical applications, and acts as a new diagnostic marker for this intractable disease. more...
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- 2018
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19. Multiple myeloma with cavernous sinus involvement
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Kai-Yuan Chen, Sanford P.C. Hsu, Ming-Teh Chen, and Yang-Hsin Shih
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Medicine (General) ,R5-920 - Published
- 2013
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20. Tumor Mesenchymal Stromal Cells Regulate Cell Migration of Atypical Teratoid Rhabdoid Tumor through Exosome-Mediated miR155/SMARCA4 Pathway
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Aliaksandr A. Yarmishyn, Yi Yen Lee, Yueh Chien, Phan Nguyen Nhi Nguyen, Ming Teh Chen, Chien Ying Wang, Mong Lien Wang, Chien Min Lin, Hsin I. Ma, Yi Wei Chen, Pin I. Huang, Yi Ping Yang, Yung Yang Liu, Wen Liang Lo, and Wen Jin Ho more...
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0301 basic medicine ,Cancer Research ,Cell type ,Cell ,tumor-associated mesenchymal stem cells ,Exosome ,lcsh:RC254-282 ,Article ,Flow cytometry ,03 medical and health sciences ,0302 clinical medicine ,SMARCA4 ,medicine ,exosome ,Tumor microenvironment ,miR155 ,medicine.diagnostic_test ,Chemistry ,Mesenchymal stem cell ,atypical teratoid/rhabdoid tumor ,Cell migration ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Microvesicles ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Cancer research - Abstract
Atypical teratoid/rhabdoid tumor (ATRT) is a rare pediatric brain tumor with extremely high aggressiveness and poor prognosis. The tumor microenvironment is regulated by a complex interaction among distinct cell types, yet the crosstalk between tumor-associated mesenchymal stem cells (tMSCs) and naï, ve ATRT cells are unclear. In this study, we sought to identify the secretory factor(s) that is responsible for the tMSC-mediated regulation of ATRT migration. Comparing with ATRT cell alone, co-culture of tMSCs or addition of its conditioned medium (tMSC-CM) promoted the migration of ATRT, and this effect could be abrogated by exosome release inhibitor GW4869. The exosomes in tMSC-CM were detected by transmission electron microscope and flow cytometry. ATRT naï, ve cell-derived conditioned media (ATRT-CM) also enhanced the exosome secretion from tMSCs, indicating the interplay between ATRT cells and tMSCs. Microarray analysis revealed that, compared with that in bone marrow-derived MSCs, microRNA155 is the most upregulated microRNA in the tMSC-CM. Tracing the PK67-labeled exosomes secreted from tMSCs confirmed their incorporation into naï, ve ATRT cells. After entering ATRT cells, miR155 promoted ATRT cell migration by directly targeting SMARCA4. Knockdown of SMARCA4 mimicked the miR155-driven ATRT cell migration, whereas SMARCA4 overexpression or the delivery of exosomes with miR155 knockdown suppressed the migration. Furthermore, abrogation of exosome release with GW4869 reduced the tumorigenesis of the xenograft containing naï, ve ATRT cells and tMSCs in immunocompromised recipients. In conclusion, our data have demonstrated that tMSCs secreted miR155-enriched exosomes, and the exosome incorporation and miR155 delivery further promoted migration in ATRT cells via a SMARCA4-dependent mechanism. more...
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- 2019
21. Musashi-1 Regulates MIF1-Mediated M2 Macrophage Polarization in Promoting Glioblastoma Progression
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Yueh Chien, Wen-chang Lin, Aliaksandr A. Yarmishyn, Wen Liang Lo, Andy Chi-Lung Lee, Hsin-I Ma, Yi-Wei Chen, Pin I. Huang, Mong Lien Wang, Yi-Ping Yang, Man-Sheung Chan, Ming-Teh Chen, and Chian Shiu Chien more...
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0301 basic medicine ,Cancer Research ,Population ,Biology ,medicine.disease_cause ,lcsh:RC254-282 ,Article ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,Glioma ,medicine ,M2 macrophages ,Progenitor cell ,education ,macrophage inhibitory factor ,Tumor microenvironment ,education.field_of_study ,glioblastoma progression ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,M2 Macrophage ,medicine.disease ,030104 developmental biology ,Musashi-1 ,Oncology ,Tumor progression ,030220 oncology & carcinogenesis ,Cancer research ,ISO-1 ,Carcinogenesis - Abstract
Simple Summary Glioblastoma (GBM) is the most lethal type of brain cancer. It is well known that the malignancy of cancers is dependent not only on the oncogenic properties of the tumor cells, but also on the composition of the tumor microenvironment, which includes macrophages of the immune system. The prevalence of M2 type macrophages usually promotes tumor progression as opposed to tumor-suppressing function of M1 type macrophages. In our previous studies, we identified Musashi-1 (MSI1) RNA-binding protein as a principal oncogenic factor in GBM. In this study, in a pursuit of finding secreted factors that may alter tumor microenvironment in GBM, we identified MIF1 cytokine to be positively regulated by MSI1. Moreover, we found that MSI1-mediated MIF1 secretion promotes differentiation of macrophages into pro-oncogenic M2 phenotype. The oncogenic role of MSI1/MIF1/M2 macrophage regulatory axis was also confirmed in GBM mouse models, which makes it a promising target for novel drug discovery. Abstract Glioblastoma (GBM) is the most malignant brain tumor which is characterized by high proliferation and migration capacity. The poor survival rate has been attributed to limitations of the current standard therapies. The search for novel biological targets that can effectively hamper tumor progression remains extremely challenging. Previous studies indicated that tumor-associated macrophages (TAMs) are the abundant elements in the tumor microenvironment that are closely implicated in glioma progression and tumor pathogenesis. M2 type TAMs are immunosuppressive and promote GBM proliferation. RNA-binding protein Musashi-1 (MSI1) has recently been identified as a marker of neural stem/progenitor cells, and its high expression has been shown to correlate with the growth of GBM. Nevertheless, the relationship between MSI1 and TAMs in GBM is still unknown. Thus, in our present study, we aimed to investigate the molecular interplay between MSI1 and TAMs in contributing to GBM tumorigenesis. Our data revealed that the secretion of macrophage inhibitory factor 1 (MIF1) is significantly upregulated by MSI1 overexpression in vitro. Importantly, M2 surface markers of THP-1-derived macrophages were induced by recombinant MIF1 and reduced by using MIF1 inhibitor (S,R)-3-(4-hHydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid (ISO-1). Furthermore, GBM tumor model data suggested that the tumor growth, MIF1 expression and M2 macrophage population were significantly downregulated when MSI1 expression was silenced in vivo. Collectively, our findings identified a novel role of MSI1 in the secretion of MIF1 and the consequent polarization of macrophages into the M2 phenotype in promoting GBM tumor progression. more...
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- 2021
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22. Musashi-1 regulates AKT-derived IL-6 autocrinal/paracrinal malignancy and chemoresistance in glioblastoma
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Tzu Chien Chen, Shih Hwa Chiou, Chi Chang Tsai, Wei Hsiu Liu, Yi Ping Yang, Pin I. Huang, Liang Ting Lin, Yi Wei Chen, Ming Long Tsai, Yuh Lih Chang, Wen Liang Lo, Yi Yen Lee, Shu Hsien Lee, Hsiao Yun Chen, Ming Teh Chen, and Mong Lien Wang more...
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Male ,0301 basic medicine ,Oncology ,Gerontology ,medicine.medical_treatment ,Apoptosis ,Mice ,0302 clinical medicine ,RNA, Small Interfering ,Mice, Inbred BALB C ,biology ,Brain Neoplasms ,RNA-Binding Proteins ,chemoresistance ,humanities ,Cytokine ,030220 oncology & carcinogenesis ,Signal Transduction ,Research Paper ,medicine.medical_specialty ,Cell Survival ,Mice, Nude ,Nerve Tissue Proteins ,Malignancy ,GBM ,03 medical and health sciences ,Cell Line, Tumor ,Internal medicine ,medicine ,Animals ,Humans ,Progenitor cell ,Interleukin 6 ,Protein kinase B ,Inflammation ,IL-6 ,Interleukin-6 ,business.industry ,Computational Biology ,Cancer ,medicine.disease ,030104 developmental biology ,Musashi-1 ,Drug Resistance, Neoplasm ,biology.protein ,Cytokine secretion ,Neoplasm Recurrence, Local ,Glioblastoma ,business ,Proto-Oncogene Proteins c-akt ,Neoplasm Transplantation - Abstract
// Hsiao-Yun Chen 1 , Liang-Ting Lin 2, * , Mong-Lien Wang 2, * , Shu-Hsien Lee 2, * , Ming-Long Tsai 1 , Chi-Chang Tsai 2 , Wei-Hsiu Liu 4 , Tzu-Chien Chen 5 , Yi-Ping Yang 1, 4 , Yi-Yen Lee 1, 8 , Yuh-Lih Chang 2, 5 , Pin-I Huang 1, 6 , Yi-Wei Chen 1, 6 , Wen-Liang Lo 1, 7 , Shih-Hwa Chiou 1, 2, 3, 5 , Ming-Teh Chen 1, 3,8 1 Institute of Clinical Medicine, National Yang-Ming University, Taipei Veterans General Hospital, Taipei, Taiwan 2 Institute of Pharmacology, National Yang-Ming University, Taipei Veterans General Hospital, Taipei, Taiwan 3 School of Medicine, National Yang-Ming University, Taipei Veterans General Hospital, Taipei, Taiwan 4 Graduate Institute of Medical Sciences, National Defense Medical Center, Department of Neurological Surgery, Taipei Veterans General Hospital, Taipei, Taiwan 5 Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan 6 Cancer Center, Taipei Veterans General Hospital, Taipei, Taiwan 7 Division of Oral and Maxillofacial Surgery, Department of Stomatology, Taipei Veterans General Hospital, Taipei, Taiwan 8 Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan * These authors have contributed equally to this work Correspondence to: Shih-Hwa Chiou, email: shchiou@vghtpe.gov.tw Ming-Teh Chen, email: mtchen@vghtpe.gov.tw Keywords: Musashi-1, apoptosis, IL-6, chemoresistance, GBM Received: October 14, 2015 Accepted: May 11, 2016 Published: June 7, 2016 ABSTRACT Glioblastoma multiform (GBM) is one of the most lethal human malignant brain tumors with high risks of recurrence and poor treatment outcomes. The RNA-binding protein Musashi-1 (MSI1) is a marker of neural stem/progenitor cells. Recent study showed that high expression level of MSI1 positively correlates with advanced grade of GBM, where MSI1 increases the growth of GBM. Herein, we explore the roles of MSI1 as well as the underlying mechanisms in the regulation of drug resistance and tumorigenesis of GBM cells. Our results demonstrated that overexpression of MSI1 effectively protected GBM cells from drug-induced apoptosis through down-regulating pro-apoptotic genes; whereas inhibition of AKT withdrew the MSI1-induced anti-apoptosis and cell survival. We further showed that MSI1 robustly promoted the secretion of the pro-inflammatory cytokine IL-6, which was governed by AKT activity. Autonomously, the secreted IL-6 enhanced AKT activity in an autocrine/paracrine manner, forming a positive feedback regulatory loop with the MSI1-AKT pathway. Our results conclusively demonstrated a novel drug resistance mechanism in GBM cells that MSI1 inhibits drug-induced apoptosis through AKT/IL6 regulatory circuit. MSI1 regulates both cellular signaling and tumor-microenvironmental cytokine secretion to create an intra- and intercellular niche for GBM to survive from chemo-drug attack. more...
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- 2016
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23. Gamma Knife Radiosurgery for Atypical and Anaplastic Meningiomas
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Kang-Du Liu, Cheng-Ying Shiau, Wan-You Guo, Cheng-Chia Lee, David Hung-Chi Pan, Ming-Teh Chen, Huai-Che Yang, Wei-Hsin Wang, Hsiu-Mei Wu, and Wen-Yuh Chung
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Adult ,Male ,Anaplastic Meningioma ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Gamma knife radiosurgery ,Kaplan-Meier Estimate ,Radiation Dosage ,Radiosurgery ,Disease-Free Survival ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Overall survival ,Humans ,Progression-free survival ,Aged ,Retrospective Studies ,Aged, 80 and over ,Sex Characteristics ,medicine.diagnostic_test ,business.industry ,Magnetic resonance imaging ,Middle Aged ,Survival Analysis ,Surgery ,Radiation therapy ,Treatment Outcome ,030220 oncology & carcinogenesis ,Benign Meningioma ,Female ,Neurology (clinical) ,Meningioma ,business ,030217 neurology & neurosurgery ,Follow-Up Studies - Abstract
Background Atypical and anaplastic meningiomas have much higher recurrence rates after surgical resection compared with benign meningiomas, but the role of adjuvant radiosurgery remains unclear. This study was undertaken to evaluate the outcomes of gamma knife radiosurgery for patients with atypical and anaplastic meningiomas. Methods In this retrospective analysis of a prospectively maintained database, 46 patients with histologically proven atypical or anaplastic meningiomas by current World Health Organization (WHO) criteria underwent postoperative Gamma Knife radiosurgery between 1993 and 2013. The median follow-up period was 32.6 months. The median tumor volume and margin dose were 11.7 mL (range, 2–53 mL) and 13.1 Gy (range, 12.0–16.5 Gy), respectively. Results Local control at 3 and 5 years was 50.6% and 32.1%, respectively. Gender ( P = 0.013) and marginal dose less than or equal to 13Gy ( P = 0.049) were associated with the local control. The 3- and 5-year overall survival for patients with WHO grade II was 97.1% and 88.3%, respectively, compared with 66.7% and 66.7% for patients with WHO grade III meningiomas. Radiation therapy before Gamma Knife radiosurgery (GKRS; P = 0.018) and tumor grade ( P = 0.019) were the factors associated with a worse overall survival rate. Fourteen patients (30.4%) developed adverse radiation effects after GKRS treatment, and all were Radiation Therapy Oncology Group grade I. Conclusions Postoperative GKRS treatment for patients with atypical and anaplastic meningioma is challenging. More aggressive treatment, including of safely maximizing the extent of surgical resection and using a higher margin dose (>13Gy), should be applied to achieve better local control. more...
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- 2016
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24. Can mixed pure hepatocellular carcinoma and germinoma arise together in the brain?
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Shih-Chieh Lin, Yi-Wei Chen, Wan-Yuo Guo, Kai Ping Chang, I-Chun Lai, Tai-Tong Wong, Ming-Teh Chen, Sang-Hue Yen, Donald Ming-Tak Ho, and Lu-Jen Chen
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Pathology ,medicine.medical_specialty ,Liver tumor ,Carcinoma, Hepatocellular ,Adolescent ,medicine.medical_treatment ,pediatric brain tumor ,germinoma ,medicine ,Combined Modality Therapy ,Humans ,Pathological ,radiotherapy ,germ-cell tumor ,Chemotherapy ,Adjuvant radiotherapy ,lcsh:R5-920 ,Germinoma ,business.industry ,Brain Neoplasms ,General Medicine ,hepatocellular carcinoma ,Neoplasms, Germ Cell and Embryonal ,medicine.disease ,Radiation therapy ,Hepatocellular carcinoma ,Female ,business ,lcsh:Medicine (General) - Abstract
Intracranial germ-cell tumors (GCTs) represent 10–15% of all pediatric brain tumors in East Asia. There is a wide histopathological spectrum of intracranial GCTs. Germinomas and nongerminomatous GCTs are the two major classifications. It is difficult to distinguish different subtypes of intracranial GCTs based solely on imaging studies, however, some tumor markers, such as α-fetoprotein or β-human chorionic gonadotropin, are helpful for diagnosis. In this study we present the case of a 13-year-old girl with an intracranial mixed GCT containing a hepatocellular carcinoma and germinoma without a primary liver tumor. Based on this unique pathological diagnosis, a series of treatments were applied, including surgery for gross tumor removal, adjuvant radiotherapy, and chemotherapy. Long-term follow up indicates fair disease control. more...
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- 2015
25. Differentiation of blood T cells: Reprogramming human induced pluripotent stem cells into neuronal cells
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Ping-Hsing Tsai, Yu-Ling Ko, Wen-Chung Yu, Yun Ching Chang, Yi-Yen Lee, Yuh-Lih Chang, Ming-Teh Chen, Chun-Fu Lin, Yu-Hsuan Yang, and Yang Hsin Shih
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electroporation ,nonviral induced pluripotent stem cells ,Adult ,Somatic cell ,T-Lymphocytes ,Induced Pluripotent Stem Cells ,T cells ,Biology ,Neural Stem Cells ,human-induced pluripotent stem cells ,Humans ,Epstein-Barr nuclear antigen-1 ,Induced pluripotent stem cell ,Medicine(all) ,lcsh:R5-920 ,Induced stem cells ,Electroporation ,Cell Differentiation ,General Medicine ,Cellular Reprogramming ,Embryonic stem cell ,Molecular biology ,Cell biology ,Endothelial stem cell ,Stem cell ,lcsh:Medicine (General) ,Reprogramming - Abstract
Background Human induced pluripotent stem cells (iPSCs) morphologically and functionally resemble human embryonic stem cells, which presents the opportunity to use patient-specific somatic cells for disease modeling and drug screening. In order to take one step closer to clinical applications, it is important to generate iPSCs through a less invasive approach and from any accessible tissue, including peripheral blood. Meanwhile, how to differentiate blood cell-derived iPSCs into neuron-like cells is still unclear. Methods We utilized Epstein–Barr nuclear antigen-1-based episomal vectors, a nonviral system that can reprogram somatic cells into iPSCs in both feeder-dependent and feeder-free conditions, to generate iPSCs from T cells via electroporation and then induce them into neuronal cells. Results We successfully isolated sufficient T cells from 20 mL peripheral blood of the donors and reprogrammed these T cells into iPSCs within 4 weeks. These iPSCs could be stably passaged to at least 50 passages, and exhibited the abilities of pluripotency and multiple-lineage differentiation. Notably, under the medium induction for 21 days, these T-cell-derived iPSCs could be differentiated into Nestin (neural progenitor marker)-, GFAP (glial cell marker)-, and MAP2 (neuron cell marker)-positive cells detected by immunofluorescence methods. Conclusion We have developed a safer method to generate integration-free and nonviral human iPSCs from adult somatic cells. This induction method will be useful for the derivation of human integration-free iPSCs and will also be applicable to the generation of iPSCs-derived neuronal cells for drug screening or therapeutics in the near future. more...
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- 2015
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26. Cisplatin-selected resistance is associated with increased motility and stem-like properties via activation of STAT3/Snail axis in atypical teratoid/rhabdoid tumor cells
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Wei Hsiu Liu, Guang-Yuh Chiou, Ming Teh Chen, Mong Lien Wang, Yi Yen Lee, Yi Wei Chen, Yang Hsin Shih, Shih Hwa Chiou, Ming Chao Huang, Pin I. Huang, Hsin I. Ma, and Chian Shiu Chien
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Male ,STAT3 Transcription Factor ,Oncology ,Pathology ,medicine.medical_specialty ,Atypical teratoid/rhabdoid tumor (ATRT) ,medicine.medical_treatment ,Motility ,Antineoplastic Agents ,Mice, SCID ,Drug resistance ,Snail ,oncogenic resistance and cisplatin ,STAT3 ,Mice ,Cell Movement ,Cell Line, Tumor ,biology.animal ,Internal medicine ,parasitic diseases ,medicine ,Animals ,Humans ,General hospital ,Rhabdoid Tumor ,Cisplatin ,Chemotherapy ,biology ,Brain Neoplasms ,medicine.disease ,Drug Resistance, Neoplasm ,Atypical teratoid rhabdoid tumor ,biology.protein ,Heterografts ,Female ,Snail Family Transcription Factors ,Signal Transduction ,Transcription Factors ,Research Paper ,medicine.drug - Abstract
// Wei-Hsiu Liu 1, 2 , Ming-Teh Chen 3, 4, * , Mong-Lien Wang 3, 5 , Yi-Yen Lee 5, 7, * , Guang-Yuh Chiou 6 , Chian-Shiu Chien 3, 9 , Pin-I Huang 5, 8 , Yi-Wei Chen 5, 8 , Ming-Chao Huang 3, 7 , Shih-Hwa Chiou 3, 5, 9 , Yang-Hsin Shih 3, 4 , Hsin-I Ma 1, 2 1 Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan 2 Department of Neurological Surgery, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan 3 School of Medicine, National Yang-Ming University, Taipei, Taiwan 4 Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital & National Yang-Ming University, Taipei, Taiwan 5 Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan 6 College of Biological Science and Technology, National Chiao Tung Univeristy, Taiwan 7 Division of Pediatric Neurosurgery, Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan 8 Cancer Center, Taipei Veterans General Hospital, Taipei, Taiwan 9 Department of Medical Research and Education, Taipei Veterans General Hospital, Taiwan * These authors have contributed equally to this work Correspondence to: Hsin-I Ma, e-mail: uf004693@mail2000.com.tw Keywords: Atypical teratoid/rhabdoid tumor (ATRT), STAT3, Snail, oncogenic resistance and cisplatin Received: August 24, 2014 Accepted: November 11, 2014 Published: January 31, 2015 ABSTRACT Atypical teratoid/rhabdoid tumor (ATRT) is a malignant pediatric brain tumor with great recurrence after complete surgery and chemotherapy. Here, we demonstrate that cisplatin treatment selects not only for resistance but also for a more oncogenic phenotype characterized by high self-renewal and invasive capabilities. These phenomena are likely due to STAT3 upregulatoin which occurred simultaneously with higher expression of Snail, an activator of epithelial–mesenchymal transition (EMT), in ATRT-CisR cells. STAT3 knockdown effectively suppressed Snail expression and blocked motility and invasion in ATRT-CisR cells, while overexpressing Snail reversed these effects. Chromatin immunoprecipitation assay indicated that STAT3 directly bound to Snail promoter. Moreover, STAT3 knockdown effectively suppressed cancer stem-like properties, synergistically enhanced the chemotherapeutic effect, and significantly improved survival rate in ATRT-CisR-transplanted immunocompromised mice. Finally, immunohistochemistrical analysis showed that STAT3 and Snail were coexpressed at high levels in recurrent ATRT tissues. Thus, the STAT3/Snail pathway plays an important role in oncogenic resistance, rendering cells not only drug-resistant but also increasingly oncogenic (invasion, EMT and recurrence). Therefore, the STAT3/Snail could be a target for ATRT treatment. more...
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- 2015
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27. Musashi-1 promotes chemoresistant granule formation by PKR/eIF2α signalling cascade in refractory glioblastoma
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Yuan Tzu Lan, Hsiao Yun Chen, Mong Lien Wang, Wen Liang Lo, Pin I. Huang, Shih Hwa Chiou, Chien Min Lin, Yi Ping Yang, Hsin I. Ma, Kun Ling Tsai, Yi Wei Chen, Yi Yen Lee, Liang Ting Lin, and Ming Teh Chen more...
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0301 basic medicine ,Programmed cell death ,Eukaryotic Initiation Factor-2 ,Mice, Nude ,Nerve Tissue Proteins ,Cytoplasmic Granules ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,eIF-2 Kinase ,Stress granule ,Cancer stem cell ,Cell Line, Tumor ,Gene silencing ,Animals ,Humans ,Arsenic trioxide ,Molecular Biology ,Chemistry ,RNA-Binding Proteins ,Protein kinase R ,Neural stem cell ,Cell biology ,030104 developmental biology ,Drug Resistance, Neoplasm ,Neoplastic Stem Cells ,Molecular Medicine ,Stem cell ,Glioblastoma ,Signal Transduction - Abstract
Musashi-1 (MSI1), one of the RNA-binding proteins, is abundantly found not only in neural stem cells but also in several cancer tissues and has been reported to act as a positive regulator of cancer progression. Growing evidence indicates that PKR and eIF2α play pivotal roles in the stimulation of stress granule formation as well as in the subsequent translation modulation in response to stressful conditions; however, little is known about whether MSI1 is involved in this PKR/eIF2α cancer stem cell-enhancing machinery. In this study, we demonstrated that MSI1 promotes human glioblastoma multiforme (GBM) stem cells and enhances chemoresistance when exposed to sublethal stress. The overexpression of MSI1 leads to a protective effect in mitigating drug-induced cell death, thus facilitating the formation of chemoresistant stress granules (SGs) in response to arsenic trioxide (ATO) treatment. SG components, such as PKR and eIF2α, were dominantly activated and assembled, while ATO was engaged. The activated PKR and eIF2α contribute to the downstream enhancement of stem cell genes, thereby promoting the progression of GBM. The silencing of MSI1 or PKR both obviously withdrew the phenomena. Taken together, our findings indicate that MSI1 plays a leading role in stress granule formation that grants cancer stem cell properties and chemoresistant stress granules in GBM, in response to stressful conditions via the PKR/eIF2α signalling cascade. more...
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- 2017
28. Epigenetic Regulation of the miR142-3p/Interleukin-6 Circuit in Glioblastoma
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Stephanie A. Miller, Kuan Hsuan Chen, Mong Lien Wang, Yi Wei Chen, Dean-Mo LIu, Yueh Chien, Chiung Chyi Shen, Guang-Yuh Chiou, Yang Hsin Shih, Kai Hsi Lu, Shih Hwa Chiou, Chung Ching Chio, Yun Ching Chang, Yi Ping Yang, Pin I. Huang, Mien Chie Hung, Ming Teh Chen, Hsin I. Ma, Yung Luen Yu, and Chian Shiu Chien more...
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Male ,Untranslated region ,Molecular Sequence Data ,Mice, Nude ,medicine.disease_cause ,Epigenesis, Genetic ,Mice ,HMGA2 ,Cell Line, Tumor ,microRNA ,medicine ,Animals ,Humans ,Epigenetics ,Promoter Regions, Genetic ,3' Untranslated Regions ,Molecular Biology ,Mice, Inbred BALB C ,Base Sequence ,biology ,Brain Neoplasms ,Interleukin-6 ,Three prime untranslated region ,SOXB1 Transcription Factors ,HMGA2 Protein ,Cell Biology ,DNA Methylation ,Middle Aged ,Up-Regulation ,MicroRNAs ,Tumor progression ,DNA methylation ,biology.protein ,Cancer research ,Female ,Glioblastoma ,Carcinogenesis - Abstract
Epigenetic regulation plays a critical role in glioblastoma (GBM) tumorigenesis. However, how microRNAs (miRNAs) and cytokines cooperate to regulate GBM tumor progression is still unclear. Here, we show that interleukin-6 (IL-6) inhibits miR142-3p expression and promotes GBM propagation by inducing DNA methyltransferase 1-mediated hypermethylation of the miR142-3p promoter. Interestingly, miR142-3p also suppresses IL-6 secretion by targeting the 3' UTR of IL-6. In addition, miR142-3p also targets the 3' UTR and suppresses the expression of high-mobility group AT-hook 2 (HMGA2), leading to inhibition of Sox2-related stemness. We further show that HMGA2 enhances Sox2 expression by directly binding to the Sox2 promoter. Clinically, GBM patients whose tumors present upregulated IL-6, HMGA2, and Sox2 protein expressions and hypermethylated miR142-3p promoter also demonstrate poor survival outcome. Orthotopic delivery of miR142-3p blocks IL-6/HMGA2/Sox2 expression and suppresses stem-like properties in GBM-xenotransplanted mice. Collectively, we discovered an IL-6/miR142-3p feedback-loop-dependent regulation of GBM malignancy that could be a potential therapeutic target. more...
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- 2013
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29. Gamma knife radiosurgery for lymphoplasmacyte-rich meningioma
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Shih-Chieh Lin, Wan-Yuo Guo, Donald Ming-Tak Ho, Cheng-Chia Lee, Wei-Hsin Wang, Min-Hsiung Chen, Yang Hsin Shih, David Hung-Chi Pan, and Ming-Teh Chen
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medicine.medical_specialty ,medicine.medical_treatment ,Lymphoplasmacyte-rich meningioma ,Gamma knife radiosurgery ,Radiation Dosage ,Radiosurgery ,World health ,Meningioma ,Humans ,Medicine ,Lymphocytes ,Gait Disorders, Neurologic ,Suprasellar region ,business.industry ,Tumor shrinkage ,General Medicine ,Middle Aged ,medicine.disease ,Immunohistochemistry ,Magnetic Resonance Imaging ,Treatment Outcome ,Benign Meningioma ,Female ,Surgery ,Neurology (clinical) ,Radiology ,business - Abstract
Lymphoplasmacyte-rich meningioma with the features of lasmocytoma was first described in 1971 [1]. In 1993, ymphoplasmacyte-rich meningioma was proposed as a variant f meningioma in the World Health Organization classification 2]. Since lymphoplasmacyte-rich meningioma has neoplastic and nflammatory features simultaneously, its biological behavior and rognosis are not so clearly understood. We report a case of ymphoplasmacyte-rich meningioma in a 60-year-old female who nderwent a subtotal surgical resection. However, the residual umor progressed on the suprasellar region one year after opertion, and we arranged Gamma-Knife radiosurgery (GKS) for er. Seven months after GKS, significant tumor shrinkage was oted without any adverse radiation effects (ARE). There is a diference in response to radiation between benign meningiomas nd lymphoplasmacyte-rich meningiomas. This interesting clinical ourse may help us understand more about this rare meningioma. more...
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- 2013
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30. A method for unit recording in the lumbar spinal cord during locomotion of the conscious adult rat
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Hsueh Chen Huang, Min Chi Hsiao, Rune W. Berg, Ming Teh Chen, and Henrich Cheng
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Cord ,Action Potentials ,Monitoring, Ambulatory ,Rats, Sprague-Dawley ,Lumbar ,medicine ,Animals ,Muscle, Skeletal ,Motor Neurons ,CATS ,Neocortex ,Electromyography ,business.industry ,General Neuroscience ,Anatomy ,Spinal cord ,Electrodes, Implanted ,Rats ,Lumbar Spinal Cord ,medicine.anatomical_structure ,Unit recording ,Female ,Implant ,business ,Neuroscience ,Locomotion ,Muscle Contraction - Abstract
Extracellular recordings from single units in the brain, for example the neocortex, have proven feasible in moving, awake rats, but have not yet been possible in the spinal cord. Single-unit activity during locomotor-like activity in reduced preparations from adult cats and rats have provided valuable insights for the development of hypotheses about the organization of functional networks in the spinal cord. However, since reduced preparations could result in spurious conclusions, it is crucial to test these hypotheses in animals that are awake and behaving. Furthermore, unresolved issues such as how muscle force precision is achieved by motoneurons as well as how spinal neurons are spatio-temporally correlated are better to investigate in the conscious and behaving animal. We have therefore developed procedures to implant arrays of extracellular recording electrodes in the lumbar spinal cord of the adult rat for long-term studies. In addition, we implanted pairs of electromyographic electrodes in the hindlimbs for the purpose of monitoring locomotion. With our technique, we obtained stable long-term recordings of spinal units, even during locomotion. We suggest this as a novel method for investigating motor pattern-generating circuitry in the spinal cord. more...
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- 2009
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31. Idiopathic hypereosinophilic syndrome with infiltration of cerebrospinal fluid by immature eosinophils: a case report and literature review
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Ming-Teh Chen, Chiang-Wei Chou, Min-Hsiung Chen, Liang-Shong Lee, Yang Hsin Shih, Sanford P.C. Hsu, and Chun-Fu Lin
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Male ,Pathology ,medicine.medical_specialty ,Antineoplastic Agents ,Hypereosinophilia ,Subdural Space ,Piperazines ,Fatal Outcome ,Cerebrospinal fluid ,Hypereosinophilic Syndrome ,Eosinophilic ,medicine ,Humans ,Treatment Failure ,Subdural space ,Subdural effusion ,Aged ,Respiratory distress ,Hypereosinophilic syndrome ,business.industry ,Prognosis ,medicine.disease ,Cerebrospinal Fluid Shunts ,Subdural Effusion ,Eosinophils ,Pyrimidines ,Imatinib mesylate ,medicine.anatomical_structure ,Benzamides ,Imatinib Mesylate ,Surgery ,Neurology (clinical) ,Intracranial Hypertension ,medicine.symptom ,Tomography, X-Ray Computed ,business - Abstract
Background Idiopathic hypereosinophilic syndrome is characterized by persistent hypereosinophilia with end organ damage and no definite underlying cause. It has been recognized that eosinophils can induce varying degrees of neural damage. There are only a few reports in the literature regarding CSF by eosinophils, and the relationship between hypereosinophilic syndrome and eosinophilic leukemia remains unclear. Case description We report a case of IHS with CSF infiltration by immature eosinophils and significant subdural effusion with underlying brain parenchyma compression. He was treated by inserting a subdural-peritoneal shunt with improvement. Respiratory distress and pulmonary infiltration with eosinophils developed. Imatinib mesylate (Gleevec) was added with improvement, and subsequent CSF study showed normalization of CSF cytology analysis. However, re-collection of subdural fluid developed later and resulted in consciousness disturbance, and the patient died thereafter. Conclusion Idiopathic hypereosinophilic syndrome remains a serious condition with a poor prognosis for most patients. Cerebrospinal fluid infiltration by immature eosinophils is a rare condition in IHS and may lead to poor prognosis, as observed in this patient, despite improved medical management (steroid and imatinib mesylate) and adequate surgical shunting for the subdural effusion. more...
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- 2007
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32. Nuclear Localization Signal-Enhanced Polyurethane-Short Branch Polyethylenimine-Mediated Delivery of Let-7a Inhibited Cancer Stem-Like Properties by Targeting the 3′-UTR of HMGA2 in Anaplastic Astrocytoma
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Yi-Wei Chen, Yun-Chin Chang, Ming-Teh Chen, Pin I. Huang, Hsin-I Ma, Chien-Ying Wang, Wen-Hsing Sung, Yi-Ping Yang, Meng-Yin Yang, Yi-Yen Lee, Yuh-Lih Chang, Wen Liang Lo, Yi-Wen Liao, and Ling-Ming Tseng more...
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Adult ,Cell Survival ,Nuclear Localization Signals ,Polyurethanes ,Biomedical Engineering ,Mice, Nude ,lcsh:Medicine ,Antineoplastic Agents ,Gene delivery ,Astrocytoma ,medicine.disease_cause ,Mice ,Side population ,SOX2 ,Cancer stem cell ,Radiation, Ionizing ,medicine ,Tumor Cells, Cultured ,Animals ,Humans ,Polyethyleneimine ,Side-Population Cells ,Transplantation ,Gene knockdown ,Base Sequence ,Chemistry ,HMGA2 Protein ,lcsh:R ,Cell Biology ,Middle Aged ,Molecular biology ,MicroRNAs ,Cancer cell ,Cancer research ,Neoplastic Stem Cells ,Female ,Cisplatin ,Carcinogenesis ,Sequence Alignment ,Nuclear localization sequence - Abstract
Anaplastic astrocytoma (AA) is a grade III glioma that often occurs in middle-aged patients and presents a uniformly poor prognosis. A small subpopulation of cancer stem cells (CSCs) possessing a self-renewing capacity is reported to be responsible for tumor recurrence and therapeutic resistance. An accumulating amount of microRNAs (miRNA) were found aberrantly expressed in human cancers and regulate CSCs. Efforts have been made to couple miRNAs with nonviral gene delivery approaches to target specific genes in cancer cells. However, the efficiency of delivery of miRNAs to AA-derived CSCs is still an applicability hurdle. The present study aimed to investigate the effectiveness and applicability of nonviral vector-mediated delivery of Let-7a with regard to eradication of AA and AA-derived CSC cells. Herein, our miRNA/mRNA microarray and RT-PCR analysis showed that the expression of Let-7a, a tumor-suppressive miRNA, is inversely correlated with the levels of HMGA2 and Sox2 in the AA side population (SP+) cells. Luciferase reporter assay showed that Let-7a directly targets the 3′-UTRs of HMGA2 in AA-SP+ cells. Knockdown of HMGA2 significantly suppressed the protein expression of Sox2 in AA-SP+ cells, whereas overexpression of HMGA2 upregulated Sox2 expression in AA-SP-. Nuclear localization signal (NLS) peptides can facilitate nuclear targeting of DNA and are used to improve gene delivery. Using polyurethane-short branch polyethylenimine (PU-PEI) as a therapeutic delivery vehicle, we conjugated NLS with Let-7 and successfully delivered it to AA-SP+ cells, resulting in significantly suppressed expression of HMGA2 and Sox2, tumorigenicity, and CSC-like abilities. This treatment facilitated the differentiation of AA-SP+ cells into non-SP CSCs. Furthermore, PU-PEI-mediated delivery of NLS-conjugated Let-7a in AA-SP+ cells suppressed the expression of drug-resistant and antiapoptotic genes, and increased cell sensitivity to radiation. Finally, the in vivo delivery of PU-PEI-NLS-Let-7a significantly suppressed the tumorigenesis of AA-SP+ cells and synergistically improved the survival rate of orthotopically AA-SP+-transplanted immunocompromised mice when combined with radiotherapy. Therefore, PU-PEI-NLS-Let-7a is a potential novel therapeutic approach for AA. more...
- Published
- 2015
33. Exercise suppresses COX-2 pro-inflammatory pathway in vestibular migraine
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Ming Teh Chen, Yann Jang Chen, Wen Cheng Li, Chung Lan Kao, Pin I. Huang, Ming Chao Huang, Yi Ping Yang, and Yi Yen Lee
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Male ,Migraine Disorders ,Population ,Nitric Oxide Synthase Type II ,Inflammation ,Bioinformatics ,Dizziness ,Nitric oxide ,chemistry.chemical_compound ,Immune system ,Malondialdehyde ,medicine ,Humans ,RNA, Messenger ,education ,Exercise ,education.field_of_study ,business.industry ,General Neuroscience ,Interleukin ,Middle Aged ,medicine.disease ,Pathophysiology ,Exercise Therapy ,Oxidative Stress ,chemistry ,Migraine ,Cyclooxygenase 2 ,Anesthesia ,Cytokines ,Tumor necrosis factor alpha ,Female ,medicine.symptom ,business ,Reactive Oxygen Species ,Signal Transduction - Abstract
Migraine and dizziness are relatively common disorders. Patients with dizziness have a higher incidence of migraines than the general population. The discomfort experienced by these patients is often poorly controlled by medication. However, the pathophysiology of vestibular migraine (VM) remains unclear. We hypothesized that patients with VM would experience remission from symptoms after exercise training and that this effect may be mediated through the suppression of cyclooxygenase-2 (COX-2)-mediated inflammation. Thus, the aim of the present study was to investigate the efficacy and possible anti-inflammatory benefits of exercise in patients with VM. We assessed the level of soluble inflammatory mediators in plasma from VM patients and control subjects. Our analysis of cytokine expression in the patients with VM undergoing exercise treatment revealed a significant reduction in pro-inflammatory cytokines and/or cytotoxic factors, such as tumor necrosis factor-α, interleukins, nitric oxide (NO), inducible NO synthase, and reactive oxygen species. In contrast, we found an increase in the level of anti-inflammatory cytokines after exercise. Moreover, the group undergoing exercise training showed significant symptomatic improvement and demonstrated suppressed antioxidant enzyme activity. To summarize, our data suggest that exercise significantly inhibits COX-2 activity, leading to the suppression of pro-inflammatory cytokines and changes in redox status. These results suggest that there is a molecular link between the central nervous system and the immune system. Furthermore, elucidation of the neurobiological mechanisms underlying VM could potentially lead to the development of novel therapeutic interventions for these patients. more...
- Published
- 2015
34. Dynamics of neural coding in the accumbens during extinction and reinstatement of rewarded behavior
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Ming-Teh Chen, Patricia H. Janak, and Tara Caulder
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Male ,Appetitive Behavior ,education.field_of_study ,Neural correlates of consciousness ,Ventral striatum ,Population ,Extinction (psychology) ,Nucleus accumbens ,Nucleus Accumbens ,Extinction, Psychological ,Rats ,Behavioral Neuroscience ,Electrophysiology ,medicine.anatomical_structure ,Reward ,medicine ,Animals ,Conditioning, Operant ,Rats, Long-Evans ,Psychology ,education ,Neural coding ,Reinforcement ,Evoked Potentials ,Neuroscience - Abstract
Neural correlates of reward-seeking behavior are observed in the nucleus accumbens (NAC). The dependence of these correlates upon the presence of a reward was studied by comparing the behavioral correlates observed when the presence of the reward was manipulated within a single behavioral session. Rats were well-trained on a continuous reinforcement instrumental task reinforced by 0.1 ml drops of 5% sucrose. Extracellular single-unit neural activity was recorded from electrode arrays implanted into the NAC when instrumental behavior was and then was not reinforced with sucrose (within-session extinction). A variable delay between the instrumental response and the sucrose delivery allowed for separation of neural activity related to these task events. A spike activity increase around the time of the instrumental response was the most common behavioral correlate, while a decrease in spike activity upon sucrose delivery was the second most common behavioral correlate. Following removal of the reinforcer, subjects continued to perform the instrumental response, allowing for the examination of response-related spike activity under extinction conditions in which the response was no longer reinforced by sucrose. A majority of the response-related neural activity patterns were lost when sucrose was no longer available. New neural responses also were detected during this period. For some subjects, the reinforcer was again made available during the same session. Encoding of the primary behavioral events during this period of reinstated reinforcer was similar, but not identical, to that observed during the first period of reinforced responding. These findings reveal that instrumental task-associated spike activity within the NAC is partially dependent upon the presence of the reinforcer, and that encoding across the population is distinct under reinforced and extinction conditions. more...
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- 2004
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35. PT689. Utilization of Psychotic Drugs in Taiwan: An Overview of Outpatient Sector in 2010
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Ya Mei Bai, Cheng Ta Li, Ming Teh Chen, Tung Ping Su, Wen Hang Chang, and Wei Chen Lin
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Pharmacology ,Abstracts ,Tuesday Abstracts ,Psychiatry and Mental health ,medicine.medical_specialty ,Family medicine ,medicine ,Pharmacology (medical) ,Business - Published
- 2016
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36. Risk of meningioma in patients with head injury: A nationwide population-based study
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Ai Seon Kuan, C. J. Teng, Ming Teh Chen, Yung Tai Chen, and Shuu Jiun Wang
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Adult ,Male ,Risk ,medicine.medical_specialty ,Brain tumor ,meningioma ,Cohort Studies ,Meningioma ,Internal medicine ,Meningeal Neoplasms ,medicine ,Craniocerebral Trauma ,Humans ,Cumulative incidence ,In patient ,Aged ,Proportional Hazards Models ,Medicine(all) ,lcsh:R5-920 ,business.industry ,Hazard ratio ,Head injury ,General Medicine ,Middle Aged ,medicine.disease ,Surgery ,Population based study ,Taiwan National Health Insurance Research Database ,population-based study ,Cohort ,Female ,lcsh:Medicine (General) ,business ,head injury - Abstract
Background Head injury has been suggested to correlate with meningioma. However, results of studies investigating the relationship between head injury and meningioma were inconsistent. Therefore, we conducted this study to assess the association between head injury and meningioma, and to determine the possible risk factors. Methods Head injury patients aged 18 years and older, without antecedent diagnosis of brain tumor, and who were followed up for more than 30 days between January 1, 2001, and December 31, 2010, were recruited from the Taiwan National Health Insurance Research Database. Hazard ratios (HRs) of meningioma risk for head injury patients compared with an age- and sex-matched cohort were calculated by Cox proportional regression analysis. The difference in cumulative incidence between head injury patients and the matched cohort was analyzed using the Kaplan–Meier method and tested with the log-rank test. Results Each cohort (i.e., the head injury cohort and the matched cohort) consisted of 75,292 individuals with a mean age of 44.7 years, and 52.3% of these patients were male. The incidence rates of meningioma were 3.99/105 person-years and 3.23/105 person-years in the head injury cohort and the comparison cohort, respectively, with a Charlson Comorbidity Index score-adjusted HR of 1.27 (p = 0.514). There were no associations between head injury and risk of meningioma, neither overall nor in stratified analyses according to severity of head injury, age, and sex of patients. ConclusionHead injury, regardless of severity, patient sex, or age, is unlikely to be a cause of meningioma. more...
- Published
- 2014
37. MicroRNA142-3p promotes tumor-initiating and radioresistant properties in malignant pediatric brain tumors
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Ming Teh Chen, Hsin I. Ma, Yi Ping Yang, Sang Hue Yen, Shih Hwa Chiou, Pin I. Huang, Yi Yen Lee, Yi Wei Chen, Yang Hsin Shih, Mong Lien Wang, Yuan Tzu Lan, and Ming Chao Huang
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Male ,Pathology ,Cell ,lcsh:Medicine ,Mice ,Cell Movement ,Radiation, Ionizing ,Tumor Cells, Cultured ,AC133 Antigen ,Child ,Mice, Inbred BALB C ,Brain Neoplasms ,medicine.anatomical_structure ,Child, Preschool ,Neoplastic Stem Cells ,Female ,Adenylyl Cyclases ,medicine.medical_specialty ,Adolescent ,Cell Survival ,Biomedical Engineering ,Down-Regulation ,Mice, Nude ,Biology ,Antigen ,Cancer stem cell ,Antigens, CD ,Radioresistance ,medicine ,Gene silencing ,Animals ,Humans ,Radiosensitivity ,Embryonic Stem Cells ,Glycoproteins ,Transplantation ,Base Sequence ,Mesenchymal stem cell ,lcsh:R ,Cancer ,Infant ,Mesenchymal Stem Cells ,Cell Biology ,medicine.disease ,MicroRNAs ,Gamma Rays ,Adenylyl Cyclase Inhibitors ,Cancer research ,Peptides ,Medulloblastoma - Abstract
Primary central nervous system (CNS) atypical teratoid/rhabdoid tumor (ATRT) is an extremely malignant pediatric brain tumor observed in infancy and childhood. It has been reported that a subpopulation of CD133+ cells isolated from ATRT tumors present with cancer stem-like and radioresistant properties. However, the exact biomolecular mechanisms of ATRT or CD133-positive ATRT (ATRT-CD133+) cells are still unclear. We have previously shown that ATRT-CD133+ cells have pluripotent differentiation ability and the capability of malignant cells to be highly resistant to ionizing radiation (IR). By using microRNA array and quantitative RT-PCR in this study, we showed that expression of miR142-3p was lower in ATRT-CD133+ cells than in ATRT-CD133- cells. miR142-3p overexpression significantly inhibited the self-renewal and tumorigenicity of ATRT-CD133+ cells. On the contrary, silencing of endogenous miR142-3p dramatically increased the tumor-initiating and stem-like cell capacities in ATRT cells or ATRT-CD133- cells and further promoted the mesenchymal transitional and radioresistant properties of ATRT cells. Most importantly, therapeutic delivery of miR142-3p in ATRT cells effectively reduced its lethality by blocking tumor growth, repressing invasiveness, increasing radiosensitivity, and prolonging survival time in orthotropic-transplanted immunocompromised mice. These results demonstrate the prospect of developing novel miRNA-based strategies to block the stem-like and radioresistant properties of malignant pediatric brain cancer stem cells. more...
- Published
- 2014
38. In Vivo Extracellular Recording of Striatal Neurons in the Awake Rat Following Unilateral 6-Hydroxydopamine Lesions
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Marisela Morales, Patricia H. Janak, Ming-Teh Chen, Donald J. Woodward, and Barry J. Hoffer
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Male ,Apomorphine ,Dopamine ,Action Potentials ,Striatum ,Motor Activity ,Lesion ,chemistry.chemical_compound ,Developmental Neuroscience ,Dopaminergic Cell ,Animals ,Medicine ,Anesthesia ,Chloral Hydrate ,Parkinson Disease, Secondary ,Wakefulness ,Oxidopamine ,Neurons ,Hydroxydopamine ,Receptors, Dopamine D2 ,business.industry ,Dopaminergic ,Corpus Striatum ,Rats, Inbred F344 ,Electrodes, Implanted ,Rats ,Disease Models, Animal ,medicine.anatomical_structure ,nervous system ,Neurology ,chemistry ,Neuron ,medicine.symptom ,business ,Microelectrodes ,Neuroscience ,medicine.drug - Abstract
The purpose of this study was to further understand the functional effects of dopaminergic input to the dorsal striatum and to compare the effects of dopaminergic lesions in awake and anesthetized animals. We examined the effects of unilateral 6-hydroxydopamine (6-OHDA) lesions of the ascending dopaminergic bundle on the firing properties of dorsal striatal neurons in the awake freely moving rat using chronically implanted microwire electrode arrays. We recorded extracellular activity of striatal neurons under baseline conditions and following the systemic injection of apomorphine in awake and anesthetized subjects. Firing rates were higher in the hemisphere ipsilateral to the 6-OHDA lesion compared to rates of neurons from the contralateral unlesioned hemisphere. Striatal firing rates from sham and no-surgery control rats were, in general, higher than those from the contralateral unlesioned striatum of experimental subjects. Apomorphine (0.05 mg/kg, sc) normalized the differences in firing rates in lesioned animals by increasing firing of neurons within the contralateral unlesioned side, while simultaneously decreasing firing of neurons within the ipsilateral lesioned side. Mean firing rates were substantially higher in awake animals than in subjects anesthetized with chloral hydrate, perhaps reflecting anesthesia-induced decreases in excitatory input to striatal neurons. Chloral hydrate anesthesia decreased firing rates of neurons in the lesioned, unlesioned, and control striata to a similar degree, although absolute firing rates of neurons from the 6-OHDA-lesioned striata remained elevated over all other groups. Unilateral 6-OHDA lesions also altered the pattern of spike output in the awake animal as indicated by an increase in the number of bursts per minute following dopaminergic deafferentation. This and other burst parameters were altered by apomorphine. Our findings show that effects of dopaminergic deafferentation can be measured in the awake behaving animal; this model should prove useful for testing the behavioral and functional effects of experimental manipulations designed to reduce or reverse the effects of dopaminergic cell loss. In addition, these results suggest that the contralateral changes in striatal function which occur in the unilateral dopaminergic lesion model should be considered when evaluating experimental results. more...
- Published
- 2001
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39. Intratumoral decorin gene delivery by AAV vector inhibits brain glioblastomas and prolongs survival of animals by inducing cell differentiation
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Shi Yuan Cheng, Xiao Xiao, Hao Ai Shui, Hsin I. Ma, Ying Hsiu Lai, Ming Teh Chen, Yi Ping Yang, Jun Ming Han, Chi Hsien Wang, and Dueng-Yuan Hueng
- Subjects
Proteomics ,Proteome ,Decorin ,Cellular differentiation ,viruses ,lcsh:Chemistry ,Transduction (genetics) ,Transduction, Genetic ,Electrophoresis, Gel, Two-Dimensional ,lcsh:QH301-705.5 ,Spectroscopy ,decorin ,Brain Neoplasms ,Brain ,Cell Differentiation ,General Medicine ,Dependovirus ,3. Good health ,Computer Science Applications ,Tumor Burden ,2-D electrophoresis ,Blotting, Western ,Genetic Vectors ,Brain tumor ,Mice, Nude ,dsAAV ,glioblastoma multiforme ,proteomics ,Biology ,Gene delivery ,Catalysis ,Article ,Inorganic Chemistry ,Glioma ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Physical and Theoretical Chemistry ,Molecular Biology ,Organic Chemistry ,Genetic Therapy ,medicine.disease ,Molecular biology ,Survival Analysis ,Xenograft Model Antitumor Assays ,carbohydrates (lipids) ,lcsh:Biology (General) ,lcsh:QD1-999 ,Apoptosis ,Cell culture ,Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ,Cancer research ,Glioblastoma - Abstract
Glioblastoma multiforme (GBM) is the most malignant cancer in the central nervous system with poor clinical prognosis. In this study, we investigated the therapeutic effect of an anti-cancer protein, decorin, by delivering it into a xenograft U87MG glioma tumor in the brain of nude mice through an adeno-associated viral (AAV2) gene delivery system. Decorin expression from the AAV vector in vitro inhibited cultured U87MG cell growth by induction of cell differentiation. Intracranial injection of AAV-decorin vector to the glioma-bearing nude mice in vivo significantly suppressed brain tumor growth and prolonged survival when compared to control non-treated mice bearing the same U87MG tumors. Proteomics analysis on protein expression profiles in the U87MG glioma cells after AAV-mediated decorin gene transfer revealed up- and down-regulation of important proteins. Differentially expressed proteins between control and AAV-decorin-transduced cells were identified through MALDI-TOF MS and database mining. We found that a number of important proteins that are involved in apoptosis, transcription, chemotherapy resistance, mitosis, and fatty acid metabolism have been altered as a result of decorin overexpression. These findings offer valuable insight into the mechanisms of the anti-glioblastoma effects of decorin. In addition, AAV-mediated decorin gene delivery warrants further investigation as a potential therapeutic approach for brain tumors. more...
- Published
- 2013
40. Inhibition of cancer stem cell-like properties and reduced chemoradioresistance of glioblastoma using microRNA145 with cationic polyurethane-short branch PEI
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Wen Liang Lo, Yang Hsin Shih, Yuh Lih Chang, Yueh Chien, Shih Hwa Chiou, Ming Teh Chen, Guang-Yuh Chiou, Jong Yuh Cherng, Yi Wei Chen, Pin I. Huang, Yi Ping Yang, and Mong Lien Wang
- Subjects
Male ,Molecular Sequence Data ,Polyurethanes ,Biophysics ,Down-Regulation ,Bioengineering ,Biology ,medicine.disease_cause ,Radiation Tolerance ,Biomaterials ,SOX2 ,Cancer stem cell ,Glioma ,microRNA ,medicine ,Temozolomide ,Humans ,Polyethyleneimine ,neoplasms ,3' Untranslated Regions ,Aged ,Regulation of gene expression ,Base Sequence ,Gene Expression Profiling ,SOXB1 Transcription Factors ,Gene Transfer Techniques ,Cancer ,Middle Aged ,medicine.disease ,Molecular biology ,nervous system diseases ,Dacarbazine ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,Cell Transformation, Neoplastic ,Mechanics of Materials ,Drug Resistance, Neoplasm ,embryonic structures ,Ceramics and Composites ,Cancer research ,Neoplastic Stem Cells ,Female ,Carcinogenesis ,Glioblastoma ,Octamer Transcription Factor-3 ,medicine.drug - Abstract
Glioblastomas (GBMs) are the most common primary brain tumors with poor prognosis. CD133 has been considered a putative marker of cancer stem cells (CSCs) in malignant cancers, including GBMs. MicroRNAs (miRNAs), highly conserved small RNA molecules, may target oncogenes and have potential as a therapeutic strategy against cancer. However, the role of miRNAs in GBM-associated CSCs remains mostly unclear. In this study, our miRNA/mRNA-microarray and RT-PCR analysis showed that the expression of miR145 (a tumor-suppressive miRNA) is inversely correlated with the levels of Oct4 and Sox2 in GBM-CD133 + cells and malignant glioma specimens. We demonstrated that miR145 negatively regulates GBM tumorigenesis by targeting Oct4 and Sox2 in GBM-CD133 + . Using polyurethane-short branch polyethylenimine (PU-PEI) as a therapeutic-delivery vehicle, PU-PEI-mediated miR145 delivery to GBM-CD133 + significantly inhibited their tumorigenic and CSC-like abilities and facilitated their differentiation into CD133 − -non-CSCs. Furthermore, PU-PEI-miR145-treated GBM-CD133 + effectively suppressed the expression of drug-resistance and anti-apoptotic genes and increased the sensitivity of the cells to radiation and temozolomide. Finally, the in vivo delivery of PU-PEI-miR145 alone significantly suppressed tumorigenesis with stemness, and synergistically improved the survival rate when used in combination with radiotherapy and temozolomide in orthotopic GBM-CD133 + -transplanted immunocompromised mice. Therefore, PU-PEI-miR145 is a novel therapeutic approach for malignant brain tumors. more...
- Published
- 2011
41. Targeting autophagy enhances BO-1051-induced apoptosis in human malignant glioma cells
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Tsann-Long Su, Yu Chih Chen, Li Hsin Chen, Pei Chen Hsieh, Chian Shiu Chien, Yang Hsin Shih, Pang-Hsien Tu, Hsin I. Ma, Bo Hua Jiang, Yi-Hui Lin, Shih Hwa Chiou, Pei Ming Chu, and Ming Teh Chen
- Subjects
Cancer Research ,Human glioma ,Cell Survival ,MAP Kinase Signaling System ,Phase contrast microscopy ,Blotting, Western ,Cell Culture Techniques ,Antineoplastic Agents ,Apoptosis ,Toxicology ,law.invention ,Microscopy, Electron, Transmission ,law ,Glioma ,medicine ,Autophagy ,Humans ,Pharmacology (medical) ,Microscopy, Phase-Contrast ,Pharmacology ,Membrane potential ,Membrane Potential, Mitochondrial ,Dose-Response Relationship, Drug ,Molecular Structure ,Chemistry ,Brain Neoplasms ,TOR Serine-Threonine Kinases ,medicine.disease ,Blot ,Oncology ,Microscopy, Fluorescence ,Cell culture ,Immunology ,Nitrogen Mustard Compounds ,Cancer research ,Proto-Oncogene Proteins c-akt - Abstract
BO-1051 is an N-mustard derivative that is conjugated with DNA-affinic 9-anilinoacridine. Since BO-1051 was reported to have strong anticancer activity, we investigated the effect and underlying mechanism of BO-1051 in human glioma cell lines.Human glioma cell lines U251MG and U87MG were studied with BO-1051 or the combination of BO-1051 and autophagic inhibitors. Growth inhibition was assessed by MTT assay. Apoptosis was measured by annexin V staining followed by flow cytometry and immunoblotting for apoptosis-related molecules. Induction of autophagy was detected by acridine orange labeling, electron microscopy, LC3 localization and its conversion. Transfection of shRNA was used to determine the involvement of Beclin1 in apoptotic cell death.MTT assay showed that BO-1051 suppressed the viability of four glioma cell lines (U251MG, U87MG, GBM-3 and DBTRG-05MG) in a dose-dependent manner. The IC(50) values of BO-1051 for the glioma cells were significantly lower than the values for primary neurons cultures and normal fibroblast cells. Moreover, BO-1051 not only induced apoptotic cell death, but also enhanced autophagic flux via inhibition of Akt/mTOR and activation of Erk1/2. Importantly, suppression of autophagy by 3-methyladenine or bafilomycin A1 significantly increased BO-1051-induced apoptotic cell death in U251MG and U87MG cells. In addition, the proportion of apoptotic cells after BO-1051 treatment was enhanced by co-treatment with shRNA against Beclin1.BO-1051 induced both apoptosis and autophagy, and inhibition of autophagy significantly augmented the cytotoxic effect of BO-1051. Thus, a combination of BO-1051 and autophagic inhibitors offers a potentially new therapeutic modality for the treatment of malignant glioma. more...
- Published
- 2011
42. Resveratrol suppresses tumorigenicity and enhances radiosensitivity in primary glioblastoma tumor initiating cells by inhibiting the STAT3 axis
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Chin Hong Chang, Ming Teh Chen, Guang-Yuh Chiou, Yuh Lih Chang, Hsin I. Ma, Yang Hsin Shih, Chuan Chih Hsu, Charn Jung Chang, Shih Hwa Chiou, Lo Lin Tsai, Pin I. Huang, Cheng Chia Yu, Chin Tien Wang, Ling Ming Tseng, Yi Ping Yang, and Ming Hsiung Chen more...
- Subjects
Male ,STAT3 Transcription Factor ,Physiology ,Clinical Biochemistry ,Cell ,Mice, SCID ,Biology ,Resveratrol ,Astrocytoma ,urologic and male genital diseases ,chemistry.chemical_compound ,Mice ,In vivo ,Radioresistance ,Stilbenes ,medicine ,Tumor Cells, Cultured ,Animals ,Humans ,Radiosensitivity ,STAT3 ,Aged ,urogenital system ,Brain Neoplasms ,Cell Biology ,Chemoradiotherapy ,Middle Aged ,Antineoplastic Agents, Phytogenic ,Xenograft Model Antitumor Assays ,female genital diseases and pregnancy complications ,In vitro ,nervous system diseases ,medicine.anatomical_structure ,chemistry ,Apoptosis ,Cancer research ,biology.protein ,Female ,Glioblastoma ,Signal Transduction - Abstract
Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor. Patients diagnosed with GBM have a poor prognosis, and it has been reported that tumor malignancy and GBM recurrence are promoted by STAT3 signaling. As resveratrol (RV), a polyphenol in grapes, is reported to be a potent and non-toxic cancer-preventive compound, the aim of this study was to investigate the therapeutic effect and molecular mechanisms of RV on GBM-derived radioresistant tumor initiating cells (TIC). Firstly, our results showed that primary GBM-CD133(+) TIC presented high tumorigenic and radiochemoresistant properties as well as increased protein levels of phosphorylated STAT3. We consistently observed that treatment with shRNA-STAT3 (sh-STAT3) or AG490, a STAT3 inhibitor, significantly inhibited the cancer stem-like cell properties and radioresistance of GBM-CD133(+) in vitro and in vivo. Furthermore, treatment of GBM-CD133(+) with 100 µM RV induced apoptosis and enhanced radiosensitivity by suppressing STAT3 signaling. Microarray results suggested that RV or AG490 inhibited the stemness gene signatures of GBM-CD133(+) and facilitated the differentiation of GBM-CD133(+) into GBM-CD133(-) or astrocytoma cells. Finally, xenotransplant experiments indicated that RV or sh-STAT3 therapy could significantly improve the survival rate and synergistically enhance the radiosensitivity of radiation-treated GBM-TIC. In summary, RV can reduce in vivo tumorigenicity and enhance the sensitivity of GBM-TIC to radiotherapies through the STAT3 pathway. more...
- Published
- 2011
43. Gamma knife radiosurgery for central neurocytoma: retrospective analysis of fourteen cases with a median follow-up period of sixty-five months
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Yang Hsin Shih, David Hung-Chi Pan, Meng Chao Chen, Tai-Tong Wong, Ling Wei Wang, Wan-Yuo Guo, Chii-Wann Lin, Ming Teh Chen, Wen Yuh Chung, Kang Du Liu, Yu Shu Yen, Hsiu Mei Wu, and Cheng Ying Shiau
- Subjects
Adult ,Male ,Adolescent ,medicine.medical_treatment ,Gamma knife radiosurgery ,Radiosurgery ,Median follow-up ,Central neurocytoma ,Retrospective analysis ,Medicine ,Humans ,Neurocytoma ,Retrospective Studies ,business.industry ,Brain Neoplasms ,Microsurgery ,medicine.disease ,Radiation therapy ,Treatment Outcome ,Child, Preschool ,Surgery ,Female ,Neurology (clinical) ,business ,Nuclear medicine ,Follow-Up Studies - Abstract
Object: Central neurocytoma (CN) is considered to be a benign neuronal tumor with possible atypical behavior. Microsurgery, radiation therapy (RT) and radiosurgery all have been used in treating this rare disease during the past decade. In this study, the authors present the experience with gamma knife radiosurgery (GKRS) on 14 patients with CN during a median follow-up period of 65 months and document the safety and efficacy of GKRS in the treatment of CN. Methods: Between November 1997 and December 2009, 14 patients pathologically diagnosed with CN were treated with GKRS. Follow-up magnetic resonance imaging (MRI) was performed at 6-month intervals. Tumor volume and adverse radiation effects (ARE) were documented to evaluate tumor response to GKRS. The Karnofsky Performance Scale (KPS) and neurological status were used to assess clinical outcome. The mean radiation dose prescribed to the tumor margin was 12.1 Gy (ranging from 11 to 13 Gy). The mean tumor volume was 19.6 ml (ranging from 3.5 to 48.9 ml). The mean follow-up period was 70 months (ranging from 30 to 140 months), and the median follow-up period was 65 months. Results: Tumor shrinkage was found in all patients at the final MRI follow-up. The mean volume reduction was 69% (ranging from 47 to 87%). No tumor progression, ARE or radiation-related toxicity developed in any of the cases. The KPS scores of all patients were the same or had increased, and the neurological functions were all stable without deterioration at the final follow-up. Conclusion: In our observations, GKRS was found to be an effective and safe alternative as adjuvant therapy for pathology-confirmed CN. The tumor volume and functional outcome can be controlled with a favorable result in long-term observation. Compared with RT and microsurgery, GKRS plays an important role in the treatment of CN as a minimally invasive technique with low morbidity. Regular long-term MRI follow-up should be mandatory to document the tumor response and possible recurrence. Multicenter consortia should be considered for further investigation and evaluation of GKRS for such a rare tumor. more...
- Published
- 2009
44. Posterior inferior cerebellar artery with extracranial origin harboring an extracranial aneurysm
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Min-Hsiung Chen, Sanford P.C. Hsu, Liang-Shong Lee, Ming-Teh Chen, Yang Hsin Shih, Chun-Fu Lin, and Hsin Hung Chen
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Adult ,Male ,medicine.medical_specialty ,Subarachnoid hemorrhage ,Vertebral artery ,Fourth ventricle ,Neurosurgical Procedures ,Subarachnoid Space ,Aneurysm ,medicine.artery ,Cerebellum ,medicine ,Humans ,cardiovascular diseases ,Foramen Magnum ,Cervical Atlas ,Vertebral Artery ,Fourth Ventricle ,Medulla Oblongata ,medicine.diagnostic_test ,business.industry ,Intracranial Aneurysm ,Digital subtraction angiography ,Subarachnoid Hemorrhage ,medicine.disease ,Hydrocephalus ,Cerebral Angiography ,Posterior inferior cerebellar artery ,Intraventricular hemorrhage ,Treatment Outcome ,cardiovascular system ,Surgery ,Neurology (clinical) ,Radiology ,business ,Tomography, X-Ray Computed ,Spinal Canal ,Vascular Surgical Procedures - Abstract
Background We report on a rare case of a saccular aneurysm on the TM segment of the right PICA. The aneurysm was located at the nonbifurcation region of the PICA. Case description The patient underwent a brain CT scan that revealed a diffuse SAH and an IVH in the fourth ventricle with obstructive hydrocephalus. After external ventricular drainage to relieve the hydrocephalus, the aneurysm was demonstrated by cerebral digital subtraction angiography. Conclusions The origin of the PICA aneurysm was extracranial and intradural, illustrating a rare location of such type of aneurysm. more...
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- 2007
45. Hippocampal Desynchronization of Functional Connectivity Prior to the Onset of Status Epilepticus in Pilocarpine-Treated Rats
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Yang Hsin Shih, Yung Yang Lin, Chou P. Hung, Ming-Teh Chen, and Chi-Han Wang
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Male ,Central Nervous System ,Time Factors ,Anatomy and Physiology ,Electroencephalography Phase Synchronization ,Action Potentials ,lcsh:Medicine ,Hippocampus ,Local field potential ,Hippocampal formation ,Rats, Sprague-Dawley ,Behavioral Neuroscience ,Status Epilepticus ,Temporal Lobe Epilepsy ,Molecular Cell Biology ,lcsh:Science ,Neurons ,education.field_of_study ,Multidisciplinary ,Pilocarpine ,Animal Models ,Electrophysiology ,Neurology ,Anesthesia ,Medicine ,Cellular Types ,medicine.symptom ,Research Article ,medicine.drug ,Population ,Status epilepticus ,Neurological System ,Temporal lobe ,Model Organisms ,Seizures ,medicine ,Animals ,education ,Biology ,Epilepsy ,lcsh:R ,Rats ,nervous system ,Rat ,lcsh:Q ,Nerve Net ,Neuroscience - Abstract
Status epilepticus (SE), a pro-epileptogenic brain insult in rodent models of temporal lobe epilepsy, is successfully induced by pilocarpine in some, but not all, rats. This study aimed to identify characteristic alterations within the hippocampal neural network prior to the onset of SE. Sixteen microwire electrodes were implanted into the left hippocampus of male Sprague-Dawley rats. After a 7-day recovery period, animal behavior, hippocampal neuronal ensemble activities, and local field potentials (LFP) were recorded before and after an intra-peritoneal injection of pilocarpine (350 mg/kg). The single-neuron firing, population neuronal correlation, and coincident firing between neurons were compared between SE (n = 9) and nonSE rats (n = 12). A significant decrease in the strength of functional connectivity prior to the onset of SE, as measured by changes in coincident spike timing between pairs of hippocampal neurons, was exclusively found in SE rats. However, single-neuron firing and LFP profiles did not show a significant difference between SE and nonSE rats. These results suggest that desynchronization in the functional circuitry of the hippocampus, likely associated with a change in synaptic strength, may serve as an electrophysiological marker prior to SE in pilocarpine-treated rats. more...
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- 2012
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46. WSSFN Society News
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John Bringas, Kang-Du Liu, Won Seok Chang, Aviva Abosch, Chii-Wann Lin, Adrian P. Kells, Ming Ge, Hsiu-Mei Wu, Hae Yu Kim, Lisa Tansey, Meng-Chao Chen, Seong Ho Kim, Lin Tchia Yeng, Alastair J. Martin, Shunro Endo, Young Hwan Ahn, Mitchel S. Berger, Ling-Wei Wang, Erich Talamoni Fonoff, Devashish Shrivastava, Wan-Yuo Guo, David Hung-Chi Pan, Nakamasa Hayashi, Peter G. Piferi, Hideo Hamada, Akshay Gupte, Nobuhiro Dougu, Wen-han Hu, Sang Seok Yeo, István Valálik, Geoffrey Bates, Sung Ho Jang, Cheng-Ying Shiau, Clement Hamani, Kai Zhang, Su Min Son, Paul S. Larson, Kortaro Tanaka, András Csókay, László Bognár, Tai-Tong Wong, Ákos Jobbágy, Yu-Shu Yen, Fan-gang Meng, Manoel Jacobsen Teixeira, Krystof S. Bankiewicz, Ming-Teh Chen, R. Mark Richardson, Wen-Yuh Chung, Yoshiharu Taguchi, Dong Wan Kang, Jeong-Han Kang, Young Seok Park, Satz Mengensatzproduktion, Druck Reinhardt Druck Basel, Daniel Ciampi de Andrade, Kathryn H. Rosenbluth, Jian-guo Zhang, Shutaro Takashima, Yu Ma, Maggie A. Spaniol, Takashi Asahi, Philip A. Starr, Jin Woo Chang, Marco Antonio Marcolin, Joo Pyung Kim, An-chao Yang, and Yang-Hsin Shih more...
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Political science ,Media studies ,Surgery ,Neurology (clinical) ,News media - Published
- 2005
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47. ESSFN Society News
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Shunro Endo, Yu-Shu Yen, Ming-Teh Chen, István Valálik, Erich Talamoni Fonoff, Devashish Shrivastava, Sung Ho Jang, R. Mark Richardson, Lin Tchia Yeng, Kai Zhang, Mitchel S. Berger, Paul S. Larson, Alastair J. Martin, Su Min Son, László Bognár, Chii-Wann Lin, Akshay Gupte, Joo Pyung Kim, Kang-Du Liu, Manoel Jacobsen Teixeira, Peter G. Piferi, Nakamasa Hayashi, Won Seok Chang, Fan-gang Meng, Wan-Yuo Guo, Meng-Chao Chen, Geoffrey Bates, Adrian P. Kells, András Csókay, David Hung-Chi Pan, Wen-han Hu, Krystof S. Bankiewicz, Jian-guo Zhang, Aviva Abosch, Druck Reinhardt Druck Basel, Daniel Ciampi de Andrade, Nobuhiro Dougu, Hsiu-Mei Wu, Philip A. Starr, Lisa Tansey, An-chao Yang, Ákos Jobbágy, Sang Seok Yeo, Hideo Hamada, Yang-Hsin Shih, Dong Wan Kang, Young Seok Park, Satz Mengensatzproduktion, Yoshiharu Taguchi, Maggie A. Spaniol, Ling-Wei Wang, Marco Antonio Marcolin, Jeong-Han Kang, Shutaro Takashima, Tai-Tong Wong, Hae Yu Kim, Young Hwan Ahn, Cheng-Ying Shiau, Clement Hamani, John Bringas, Kathryn H. Rosenbluth, Wen-Yuh Chung, Seong Ho Kim, Ming Ge, Yu Ma, Takashi Asahi, Kortaro Tanaka, and Jin Woo Chang more...
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medicine.medical_specialty ,Political science ,medicine ,Media studies ,Surgery ,Medical physics ,Neurology (clinical) ,News media - Published
- 2004
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48. Intratumoral Decorin Gene Delivery by AAV Vector Inhibits Brain Glioblastomas and Prolongs Survival of Animals by Inducing Cell Differentiation.
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Hsin-I Ma, Dueng-Yuan Hueng, Hao-Ai Shui, Jun-Ming Han, Chi-Hsien Wang, Ying-Hsiu Lai, Shi-Yuan Cheng, Xiao Xiao, Ming-Teh Chen, and Yi-Ping Yang
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DECORIN ,CELL differentiation ,LABORATORY mice ,ANIMAL models of tumors ,PROTEOMICS ,CANCER chemotherapy - Abstract
Glioblastoma multiforme (GBM) is the most malignant cancer in the central nervous system with poor clinical prognosis. In this study, we investigated the therapeutic effect of an anti-cancer protein, decorin, by delivering it into a xenograft U87MG glioma tumor in the brain of nude mice through an adeno-associated viral (AAV2) gene delivery system. Decorin expression from the AAV vector in vitro inhibited cultured U87MG cell growth by induction of cell differentiation. Intracranial injection of AAV-decorin vector to the glioma-bearing nude mice in vivo significantly suppressed brain tumor growth and prolonged survival when compared to control non-treated mice bearing the same U87MG tumors. Proteomics analysis on protein expression profiles in the U87MG glioma cells after AAV-mediated decorin gene transfer revealed up- and down-regulation of important proteins. Differentially expressed proteins between control and AAV-decorin-transduced cells were identified through MALDI-TOF MS and database mining. We found that a number of important proteins that are involved in apoptosis, transcription, chemotherapy resistance, mitosis, and fatty acid metabolism have been altered as a result of decorin overexpression. These findings offer valuable insight into the mechanisms of the anti-glioblastoma effects of decorin. In addition, AAV-mediated decorin gene delivery warrants further investigation as a potential therapeutic approach for brain tumors. [ABSTRACT FROM AUTHOR] more...
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- 2014
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49. Nanomedicine-Based Neuroprotective Strategies in Patient Specific-iPSC and Personalized Medicine.
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Shih-Fan Jang, Wei-Hsiu Liu, Wen-Shin Song, Kuan-Lin Chiang, Hsin-I Ma, Chung-Lan Kao, and Ming-Teh Chen
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NANOMEDICINE ,NEUROPROTECTIVE agents ,DRUG bioavailability ,MESOPOROUS materials ,NANOPARTICLES analysis - Abstract
In recent decades, nanotechnology has attracted major interests in view of drug delivery systems and therapies against diseases, such as cancer, neurodegenerative diseases, and many others. Nanotechnology provides the opportunity for nanoscale particles or molecules (so called "Nanomedicine") to be delivered to the targeted sites, thereby, reducing toxicity (or side effects) and improving drug bioavailability. Nowadays, a great deal of nano-structured particles/vehicles has been discovered, including polymeric nanoparticles, lipid-based nanoparticles, and mesoporous silica nanoparticles. Nanomedical utilizations have already been well developed in many different aspects, including disease treatment, diagnostic, medical devices designing, and visualization (i.e., cell trafficking). However, while quite a few successful progressions on chemotherapy using nanotechnology have been developed, the implementations of nanoparticles on stem cell research are still sparsely populated. Stem cell applications and therapies are being considered to offer an outstanding potential in the treatment for numbers of maladies. Human induced pluripotent stem cells (iPSCs) are adult cells that have been genetically reprogrammed to an embryonic stem cell-like state. Although the exact mechanisms underlying are still unclear, iPSCs are already being considered as useful tools for drug development/screening and modeling of diseases. Recently, personalized medicines have drawn great attentions in biological and pharmaceutical studies. Generally speaking, personalized medicine is a therapeutic model that offers a customized healthcare/cure being tailored to a specific patient based on his own genetic information. Consequently, the combination of nanomedicine and iPSCs could actually be the potent arms for remedies in transplantation medicine and personalized medicine. This review will focus on current use of nanoparticles on therapeutical applications, nanomedicine-based neuroprotective manipulations in patient specific-iPSCs and personalized medicine. [ABSTRACT FROM AUTHOR] more...
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- 2014
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50. Enhancement of radiosensitivity in human glioblastoma cells by the DNA N-mustard alkylating agent BO-1051 through augmented and sustained DNA damage response.
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Pei-Ming Chu, Shih-Hwa Chiou, Tsann-Long Su, Yi-Jang Lee, Li-Hsin Chen, Yi-Wei Chen, Sang-Hue Yen, Ming-Teh Chen, Ming-Hsiung Chen, Yang-Hsin Shih, Pang-Hsien Tu, Hsin-I. Ma, Chu, Pei-Ming, Chiou, Shih-Hwa, Su, Tsann-Long, Lee, Yi-Jang, Chen, Li-Hsin, Chen, Yi-Wei, Yen, Sang-Hue, and Chen, Ming-Teh more...
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DNA ,RADIATION ,RADIOTHERAPY ,GLIOMAS ,CELL lines - Abstract
Background: 1-{4-[Bis(2-chloroethyl)amino]phenyl}-3-[2-methyl-5-(4-methylacridin-9-ylamino)phenyl]urea (BO-1051) is an N-mustard DNA alkylating agent reported to exhibit antitumor activity. Here we further investigate the effects of this compound on radiation responses of human gliomas, which are notorious for the high resistance to radiotherapy.Methods: The clonogenic assay was used to determine the IC50 and radiosensitivity of human glioma cell lines (U87MG, U251MG and GBM-3) following BO-1051. DNA histogram and propidium iodide-Annexin V staining were used to determine the cell cycle distribution and the apoptosis, respectively. DNA damage and repair state were determined by γ-H2AX foci, and mitotic catastrophe was measure using nuclear fragmentation. Xenograft tumors were measured with a caliper, and the survival rate was determined using Kaplan-Meier method.Results: BO-1051 inhibited growth of human gliomas in a dose- and time-dependent manner. Using the dosage at IC50, BO-1051 significantly enhanced radiosensitivity to different extents [The sensitizer enhancement ratio was between 1.24 and 1.50 at 10% of survival fraction]. The radiosensitive G2/M population was raised by BO-1051, whereas apoptosis and mitotic catastrophe were not affected. γ-H2AX foci was greatly increased and sustained by combined BO-1051 and γ-rays, suggested that DNA damage or repair capacity was impaired during treatment. In vivo studies further demonstrated that BO-1051 enhanced the radiotherapeutic effects on GBM-3-beared xenograft tumors, by which the sensitizer enhancement ratio was 1.97. The survival rate of treated mice was also increased accordingly.Conclusions: These results indicate that BO-1051 can effectively enhance glioma cell radiosensitivity in vitro and in vivo. It suggests that BO-1051 is a potent radiosensitizer for treating human glioma cells. [ABSTRACT FROM AUTHOR] more...- Published
- 2011
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