https://scholars.lib.ntu.edu.tw/handle/123456789/541946
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.author | Ho I.-L. | en_US |
dc.contributor.author | Kuo K.-L. | en_US |
dc.contributor.author | Liu S.-H.-. | en_US |
dc.contributor.author | HONG-CHIANG CHANG | en_US |
dc.contributor.author | Hsieh J.-T. | en_US |
dc.contributor.author | Wu J.-T. | en_US |
dc.contributor.author | CHIH-KANG CHIANG | en_US |
dc.contributor.author | WEI-CHOU LIN | en_US |
dc.contributor.author | YU-CHIEH TSAI | en_US |
dc.contributor.author | Chou C.-T. | en_US |
dc.contributor.author | Hsu C.-H. | en_US |
dc.contributor.author | YEONG-SHIAU PU | en_US |
dc.contributor.author | Shi C.-S. | en_US |
dc.contributor.author | KUO-HOW HUANG | en_US |
dc.creator | Ho I.-L.;Kuo K.-L.;Liu S.-H.-.;Hong-Chiang Chang;Hsieh J.-T.;Wu J.-T.;Chiang C.-K.;Lin W.-C.;Tsai Y.-C.;Chou C.-T.;Hsu C.-H.;Pu Y.-S.;Shi C.-S.;Huang K.-H. | - |
dc.date.accessioned | 2021-01-26T02:27:39Z | - |
dc.date.available | 2021-01-26T02:27:39Z | - |
dc.date.issued | 2015 | - |
dc.identifier.issn | 2045-2322 | - |
dc.identifier.uri | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84948388929&doi=10.1038%2fsrep16948&partnerID=40&md5=8fad9e7673211d2b46c07e00ad5a8dff | - |
dc.identifier.uri | https://scholars.lib.ntu.edu.tw/handle/123456789/541946 | - |
dc.description.abstract | Cisplatin-based chemotherapy is the primary treatment for metastatic bladder urothelial carcinoma. However, the response rate is only 40-65%. This study investigated the anti-tumor effect and underlying mechanisms of the combination of cisplatin and the NEDD8-activating enzyme inhibitor MLN4924 in human bladder urothelial carcinoma. The combination of cisplatin and MLN4924 exerted synergistic cytotoxicity on two high-grade bladder urothelial carcinoma cell lines, NTUB1 and T24 (combination index <1). MLN4924 also potentiated the cisplatin-induced apoptosis and activation of caspase-3 and -7, phospho-histone H2A.X and PARP. c-Jun N-terminal kinase (JNK) activation and a down-regulation of B-cell lymphoma-extra large (Bcl-xL) were also observed during cisplatin and MLN4924 treatment. Inhibition of JNK activation partially restored cell viability and Bcl-xL expression. Bcl-xL overexpression also rescued cell viability. MLN4924 significantly potentiated cisplatin-induced tumor suppression in urothelial carcinoma xenograft mice. In summary, MLN4924 synergistically enhanced the anti-tumor effect of cisplatin via an increase in DNA damage, JNK activation and down-regulation of Bcl-xL in urothelial carcinoma cells. These findings provide a new therapeutic strategy for the treatment of bladder cancer. | - |
dc.publisher | Nature Publishing Group | - |
dc.relation.ispartof | Scientific Reports | - |
dc.subject.classification | [SDGs]SDG3 | - |
dc.subject.other | ((1S,2S,4R)-4-(4-((1S)-2,3-dihydro-1H-inden-1-ylamino)-7H-pyrrolo(2,3-d)pyrimidin-7-yl)-2-hydroxycyclopentyl)methyl sulphamate; antineoplastic agent; BCL2L1 protein, human; CASP3 protein, human; CASP7 protein, human; caspase 3; caspase 7; cisplatin; cyclopentane derivative; drug combination; H2AFX protein, human; histone; mitogen activated protein kinase kinase 4; NEDD8 protein, human; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase; protein bcl x; pyrimidine derivative; ubiquitin; animal; antagonists and inhibitors; apoptosis; cancer grading; Carcinoma, Transitional Cell; drug combination; drug effects; drug potentiation; drug screening; gene expression regulation; genetics; human; metabolism; mouse; nude mouse; pathology; signal transduction; tumor cell line; Urinary Bladder Neoplasms; Animals; Antineoplastic Agents; Apoptosis; bcl-X Protein; Carcinoma, Transitional Cell; Caspase 3; Caspase 7; Cell Line, Tumor; Cisplatin; Cyclopentanes; Drug Combinations; Drug Synergism; Gene Expression Regulation, Neoplastic; Histones; Humans; MAP Kinase Kinase 4; Mice; Mice, Nude; Neoplasm Grading; Poly(ADP-ribose) Polymerases; Pyrimidines; Signal Transduction; Ubiquitins; Urinary Bladder Neoplasms; Xenograft Model Antitumor Assays | - |
dc.title | MLN4924 synergistically enhances cisplatin-induced cytotoxicity via jnk and bcl-xl pathways in human urothelial carcinoma | en_US |
dc.type | journal article | en |
dc.identifier.doi | 10.1038/srep16948 | - |
dc.identifier.pmid | 26592553 | - |
dc.identifier.scopus | 2-s2.0-84948388929 | - |
dc.relation.pages | 16948 | - |
dc.relation.journalvolume | 5 | - |
item.cerifentitytype | Publications | - |
item.fulltext | no fulltext | - |
item.openairecristype | http://purl.org/coar/resource_type/c_6501 | - |
item.openairetype | journal article | - |
item.grantfulltext | none | - |
crisitem.author.dept | Urology-NTUH | - |
crisitem.author.dept | Toxicology | - |
crisitem.author.dept | Integrated Diagnostics and Therapeutics-NTUH | - |
crisitem.author.dept | Internal Medicine | - |
crisitem.author.dept | Internal Medicine-NTUH | - |
crisitem.author.dept | Institute of Food Safety and Health | - |
crisitem.author.dept | Center for Biotechnology | - |
crisitem.author.dept | Pathology | - |
crisitem.author.dept | Pathology-NTUH | - |
crisitem.author.dept | Oncology | - |
crisitem.author.dept | Oncology-NTUH | - |
crisitem.author.dept | Urology | - |
crisitem.author.dept | Urology-NTUH | - |
crisitem.author.dept | Surgical Oncology-NTUCC | - |
crisitem.author.dept | Urology-NTUHBP | - |
crisitem.author.dept | Urology | - |
crisitem.author.dept | Urology-NTUH | - |
crisitem.author.dept | Surgical Oncology-NTUCC | - |
crisitem.author.orcid | 0000-0001-5411-6680 | - |
crisitem.author.orcid | 0000-0001-9021-4616 | - |
crisitem.author.orcid | 0000-0003-2857-3479 | - |
crisitem.author.orcid | 0000-0002-9285-7655 | - |
crisitem.author.orcid | 0000-0002-2859-3966 | - |
crisitem.author.orcid | 0000-0002-0989-0578 | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
crisitem.author.parentorg | College of Public Health | - |
crisitem.author.parentorg | Others: University-Level Research Centers | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
crisitem.author.parentorg | National Taiwan University Cancer Center (NTUCC) | - |
crisitem.author.parentorg | NTU BioMedical Park Hospital | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
crisitem.author.parentorg | National Taiwan University Cancer Center (NTUCC) | - |
顯示於: | 醫學系 |
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