Cited 49 times in
Reversing the intractable nature of pancreatic cancer by selectively targeting ALDH-high, therapy-resistant cancer cells
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 김상겸 | - |
dc.contributor.author | 김한솔 | - |
dc.contributor.author | 김호근 | - |
dc.date.accessioned | 2014-12-18T09:41:30Z | - |
dc.date.available | 2014-12-18T09:41:30Z | - |
dc.date.issued | 2013 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/88645 | - |
dc.description.abstract | Human pancreatic ductal adenocarcinoma (PDAC) is a cancer with a dismal prognosis. The efficacy of PDAC anticancer therapies is often short-lived; however, there is little information on how this disease entity so frequently gains resistance to treatment. We adopted the concept of cancer stem cells (CSCs) to explain the mechanism of resistance and evaluated the efficacy of a candidate anticancer drug to target these therapy-resistant CSCs. We identified a subpopulation of cells in PDAC with CSC features that were enriched for aldehyde dehydrogenase (ALDH), a marker expressed in certain stem/progenitor cells. These cells were also highly resistant to, and were further enriched by, treatment with gemcitabine. Similarly, surgical specimens from PDAC patients showed that those who had undergone preoperative chemo-radiation therapy more frequently displayed cancers with ALDH strongly positive subpopulations compared with untreated patients. Importantly, these ALDH-high cancer cells were sensitive to disulfiram, an ALDH inhibitor, when tested in vitro. Furthermore, in vivo xenograft studies showed that the effect of disulfiram was additive to that of low-dose gemcitabine when applied in combination. In conclusion, human PDAC-derived cells that express high levels of ALDH show CSC features and have a key role in the development of resistance to anticancer therapies. Disulfiram can be used to suppress this therapy-resistant subpopulation. | - |
dc.description.statementOfResponsibility | open | - |
dc.relation.isPartOf | PLOS ONE | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.subject.MESH | Aldehyde Dehydrogenase/antagonists & inhibitors | - |
dc.subject.MESH | Aldehyde Dehydrogenase/metabolism* | - |
dc.subject.MESH | Analysis of Variance | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Blotting, Western | - |
dc.subject.MESH | Carcinoma, Pancreatic Ductal/drug therapy* | - |
dc.subject.MESH | Cell Line, Tumor | - |
dc.subject.MESH | Deoxycytidine/analogs & derivatives | - |
dc.subject.MESH | Deoxycytidine/pharmacology | - |
dc.subject.MESH | Disulfiram/pharmacology* | - |
dc.subject.MESH | Drug Delivery Systems/methods | - |
dc.subject.MESH | Drug Resistance, Neoplasm/physiology* | - |
dc.subject.MESH | Flow Cytometry | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Immunohistochemistry | - |
dc.subject.MESH | Mice | - |
dc.subject.MESH | Neoplastic Stem Cells/enzymology* | - |
dc.subject.MESH | Pancreatic Neoplasms/drug therapy* | - |
dc.subject.MESH | Real-Time Polymerase Chain Reaction | - |
dc.title | Reversing the intractable nature of pancreatic cancer by selectively targeting ALDH-high, therapy-resistant cancer cells | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Pathology (병리학) | - |
dc.contributor.googleauthor | Sang Kyum Kim | - |
dc.contributor.googleauthor | Honsoul Kim | - |
dc.contributor.googleauthor | Da-hye Lee | - |
dc.contributor.googleauthor | Tae-shin Kim | - |
dc.contributor.googleauthor | Tackhoon Kim | - |
dc.contributor.googleauthor | Chaeuk Chung | - |
dc.contributor.googleauthor | Gou Young Koh | - |
dc.contributor.googleauthor | Hoguen Kim | - |
dc.contributor.googleauthor | Dae-Sik Lim | - |
dc.identifier.doi | 10.1371/journal.pone.0078130 | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.contributor.localId | A00520 | - |
dc.contributor.localId | A01099 | - |
dc.contributor.localId | A01183 | - |
dc.relation.journalcode | J02540 | - |
dc.identifier.eissn | 1932-6203 | - |
dc.identifier.pmid | 24194908 | - |
dc.subject.keyword | Aldehyde Dehydrogenase/antagonists & inhibitors | - |
dc.subject.keyword | Aldehyde Dehydrogenase/metabolism* | - |
dc.subject.keyword | Analysis of Variance | - |
dc.subject.keyword | Animals | - |
dc.subject.keyword | Blotting, Western | - |
dc.subject.keyword | Carcinoma, Pancreatic Ductal/drug therapy* | - |
dc.subject.keyword | Cell Line, Tumor | - |
dc.subject.keyword | Deoxycytidine/analogs & derivatives | - |
dc.subject.keyword | Deoxycytidine/pharmacology | - |
dc.subject.keyword | Disulfiram/pharmacology* | - |
dc.subject.keyword | Drug Delivery Systems/methods | - |
dc.subject.keyword | Drug Resistance, Neoplasm/physiology* | - |
dc.subject.keyword | Flow Cytometry | - |
dc.subject.keyword | Humans | - |
dc.subject.keyword | Immunohistochemistry | - |
dc.subject.keyword | Mice | - |
dc.subject.keyword | Neoplastic Stem Cells/enzymology* | - |
dc.subject.keyword | Pancreatic Neoplasms/drug therapy* | - |
dc.subject.keyword | Real-Time Polymerase Chain Reaction | - |
dc.contributor.alternativeName | Kim, Sang Kyum | - |
dc.contributor.alternativeName | Kim, Hon Soul | - |
dc.contributor.alternativeName | Kim, Ho Keun | - |
dc.contributor.affiliatedAuthor | Kim, Sang Kyum | - |
dc.contributor.affiliatedAuthor | Kim, Hon Soul | - |
dc.contributor.affiliatedAuthor | Kim, Ho Keun | - |
dc.rights.accessRights | free | - |
dc.citation.volume | 8 | - |
dc.citation.number | 10 | - |
dc.citation.startPage | e78130 | - |
dc.identifier.bibliographicCitation | PLOS ONE, Vol.8(10) : e78130, 2013 | - |
dc.identifier.rimsid | 33381 | - |
dc.type.rims | ART | - |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.