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X Demographics
Mendeley readers
Attention Score in Context
| Title |
OSU-2S/Sorafenib Synergistic Antitumor Combination against Hepatocellular Carcinoma: The Role of PKCδ/p53
|
|---|---|
| Published in |
Frontiers in Pharmacology, November 2016
|
| DOI | 10.3389/fphar.2016.00463 |
| Pubmed ID | |
| Authors |
Hany A. Omar, Mai F. Tolba, Jui-Hsiang Hung, Taleb H. Al-Tel |
| Abstract |
Background: Sorafenib (Nexavar(®)) is an FDA-approved systemic therapy for advanced hepatocellular carcinoma (HCC). However, the low efficacy and adverse effects at high doses limit the clinical application of sorafenib and strongly recommend its combination with other agents aiming at ameliorating its drawbacks. OSU-2S, a PKCδ activator, was selected as a potential candidate anticancer agent to be combined with sorafenib to promote the anti-cancer activity through synergistic interaction. Methods: The antitumor effects of sorafenib, OSU-2S and their combination were assessed by MTT assay, caspase activation, Western blotting, migration/invasion assays in four different HCC cell lines. The synergistic interactions were determined by Calcusyn analysis. PKCδ knockdown was used to elucidate the role of PKCδ activation as a mechanism for the synergy. The knockdown/over-expression of p53 was used to explain the differential sensitivity of HCC cell lines to sorafenib and/or OSU-2S. Results: OSU-2S synergistically enhanced the anti-proliferative effects of sorafenib in the four used HCC cell lines with combination indices <1. This effect was accompanied by parallel increases in caspase 3/7 activity, PARP cleavage, PKCδ activation and inhibition of HCC cell migration/invasion. In addition, PKCδ knockdown abolished the synergy between sorafenib and OSU-2S. Furthermore, p53 restoration in Hep3B cells through the over-expression rendered them more sensitive to both agents while p53 knockdown from HepG2 cells increased their resistance to both agents. Conclusion: OSU-2S augments the anti-proliferative effect of sorafenib in HCC cell lines, in part, through the activation of PKCδ. The p53 status in HCC cells predicts their sensitivity toward both sorafenib and OSU-2S. The proposed combination represents a therapeutically relevant approach that can lead to a new HCC therapeutic protocol. |
X Demographics
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 23 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 23 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 5 | 22% |
| Other | 3 | 13% |
| Unspecified | 3 | 13% |
| Lecturer | 2 | 9% |
| Researcher | 2 | 9% |
| Other | 3 | 13% |
| Unknown | 5 | 22% |
| Readers by discipline | Count | As % |
|---|---|---|
| Unspecified | 3 | 13% |
| Biochemistry, Genetics and Molecular Biology | 3 | 13% |
| Pharmacology, Toxicology and Pharmaceutical Science | 2 | 9% |
| Medicine and Dentistry | 2 | 9% |
| Chemical Engineering | 1 | 4% |
| Other | 5 | 22% |
| Unknown | 7 | 30% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 01 December 2016.
All research outputs
#20,355,479
of 22,903,988 outputs
Outputs from Frontiers in Pharmacology
#10,131
of 16,202 outputs
Outputs of similar age
#349,990
of 415,970 outputs
Outputs of similar age from Frontiers in Pharmacology
#96
of 157 outputs
Altmetric has tracked 22,903,988 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 16,202 research outputs from this source. They receive a mean Attention Score of 5.0. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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We're also able to compare this research output to 157 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.