Title |
A Novel Anticancer Therapy That Simultaneously Targets Aberrant p53 and Notch Activities in Tumors
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Published in |
PLOS ONE, October 2012
|
DOI | 10.1371/journal.pone.0046627 |
Pubmed ID | |
Authors |
Yuting Yao, Li Wang, He Zhang, Haibo Wang, Xiaoping Zhao, Yidan Zhang, Leilei Zhang, Xianqun Fan, Guanxiang Qian, Ji-Fan Hu, Shengfang Ge |
Abstract |
Notch signaling pathway plays an important role in tumorigenesis by maintaining the activity of self-renewal of cancer stem cells, and therefore, it is hypothesized that interference of Notch signaling may inhibit tumor formation and progression. H101 is a recombinant oncolytic adenovirus that is cytolytic in cells lacking intact p53, but it is unable to eradicate caner stem cells. In this study, we tested a new strategy of tumor gene therapy by combining a Notch1-siRNA with H101 oncolytic adenovirus. In HeLa-S3 tumor cells, the combined therapy blocked the Notch pathway and induced apoptosis in tumors that are p53-inactive. In nude mice bearing xenograft tumors derived from HeLa-S3 cells, the combination of H101/Notch1-siRNA therapies inhibited tumor growth. Moreover, Notch1-siRNA increased Hexon gene expression at both the transcriptional and the translational levels, and promoted H101 replication in tumors, thereby enhancing the oncolytic activity of H101. These data demonstrate the feasibility to combine H101 p53-targted oncolysis and anti-Notch siRNA activities as a novel anti-cancer therapy. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 2 | 67% |
Unknown | 1 | 33% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 3 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 24 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 5 | 21% |
Researcher | 5 | 21% |
Student > Master | 4 | 17% |
Student > Bachelor | 3 | 13% |
Student > Doctoral Student | 2 | 8% |
Other | 3 | 13% |
Unknown | 2 | 8% |
Readers by discipline | Count | As % |
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Biochemistry, Genetics and Molecular Biology | 8 | 33% |
Agricultural and Biological Sciences | 8 | 33% |
Medicine and Dentistry | 2 | 8% |
Immunology and Microbiology | 1 | 4% |
Social Sciences | 1 | 4% |
Other | 1 | 4% |
Unknown | 3 | 13% |