Cited 0 times in
Combination of radiotherapy and adenovirus-mediated p53 gene therapy for MDM2-overexpressing hepatocellular carcinoma
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 금웅섭 | - |
dc.date.accessioned | 2015-12-24T09:11:20Z | - |
dc.date.available | 2015-12-24T09:11:20Z | - |
dc.date.issued | 2013 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/135162 | - |
dc.description | Dept. of Medicine/박사 | - |
dc.description.abstract | The p53 gene plays a determinant role in radiation-induced cell death and its protein product is negatively regulated by MDM2. We investigated whether adenovirus-mediated modified p53 gene transfer, which blocks p53-MDM2 binding, is effective for radiation-induced cell death in hepatocellular carcinoma (HCC) at different MDM2 cellular levels. Human hepatocellular carcinoma cell lines expressing MDM2 at low levels (Huh7) and high levels (SK-Hep1) were used. Ad-p53 and Ad-p53vp are replication-deficient adenoviral vectors containing human wild-type or modified p53, respectively. The anti-tumor effect was highest for Ad-p53 + radiotherapy (RT) in the low-level MDM2 cells, whereas this effect was highest for Ad-p53vp + RT in the MDM2-overexpressing cells. In Huh-7 cells, Ad-p53 + RT decreased cell viability (32%) in vitro and inhibited tumor growth (enhancement factor, 1.86) in vivo. Additionally, p21 expression and apoptosis were increased. In contrast, in SK-Hep1 cells, Ad-p53vp + RT showed decreased cell viability (51%) in vitro and inhibition of tumor growth (enhancement factor, 3.07) in vivo. Caspase-3 expression and apoptosis were also increased. Adenovirus-expressing modified p53, which blocks p53-MDM2 binding, was effective in killing tumor cells overexpressing MDM2. Furthermore, the combination strategy for disruption of the p53-MDM2 interaction with RT demonstrated enhanced anti-tumor effects both in vitro and in vivo. | - |
dc.description.statementOfResponsibility | open | - |
dc.publisher | Graduate School, Yonsei University | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.title | Combination of radiotherapy and adenovirus-mediated p53 gene therapy for MDM2-overexpressing hepatocellular carcinoma | - |
dc.title.alternative | MDM2 과발현 간세포암에서 아데노바이러스 이용한 p53 유전자 치료와 방사선 병용치료의 항암 효과 | - |
dc.type | Thesis | - |
dc.contributor.department | Dept. of Radiation Oncology (방사선종양학교실) | - |
dc.contributor.localId | A00273 | - |
dc.contributor.alternativeName | Koom, Woong Sub | - |
dc.contributor.affiliatedAuthor | 금웅섭 | - |
dc.type.local | Dissertation | - |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.