| Title |
Effect of siRNA pre-Exposure on Subsequent Response to siRNA Therapy
|
|---|---|
| Published in |
Pharmaceutical Research, July 2015
|
| DOI | 10.1007/s11095-015-1741-z |
| Pubmed ID | |
| Authors |
Hamidreza Montazeri Aliabadi, Parvin Mahdipoor, Cezary Kucharsky, Nicole Chan, Hasan Uludağ |
| Abstract |
An alternative cancer therapy based on RNA interference (RNAi) has shown considerable promise but the possibility of resistance development is not known. This study explored the possibility of therapeutic resistance against siRNA nanoparticles in human cancer cells. Two approaches to siRNA treatment were undertaken using lipid-modified polyethylenimines, a single high concentration (shock) and repeated increasing concentrations (gradual). The targets were Mcl-1, RPS6KA5 and KSP in MDA-MB-435 cells. There was no evidence of resistance development in shock-treated cells, while the decrease in mRNA levels of targeted proteins was not as robust in naïve cells in gradual treatment. However, silencing efficiency was restored after a 7-day recovery period when expression of suppressed proteins returned to normal levels. Cellular uptake of siRNA was not affected by pre-treatments. Other mediators involved in cell survival and proliferation were altered in siRNA-treated cells, but only JUN silencing led to a heightened loss of viability. In vivo experiments demonstrated similar silencing efficiency at mRNA level after repeat doses. Human cancer cells responded to repeat siRNA nanoparticles in a similar fashion after a temporary initial alteration and little, if any, resistance was evident against repeated siRNA treatments. |
X Demographics
The data shown below were collected from the profiles of 4 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 4 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 50% |
| Science communicators (journalists, bloggers, editors) | 2 | 50% |
Mendeley readers
The data shown below were compiled from readership statistics for 12 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 12 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Master | 3 | 25% |
| Student > Ph. D. Student | 2 | 17% |
| Student > Bachelor | 1 | 8% |
| Other | 1 | 8% |
| Researcher | 1 | 8% |
| Other | 0 | 0% |
| Unknown | 4 | 33% |
| Readers by discipline | Count | As % |
|---|---|---|
| Engineering | 2 | 17% |
| Pharmacology, Toxicology and Pharmaceutical Science | 1 | 8% |
| Biochemistry, Genetics and Molecular Biology | 1 | 8% |
| Immunology and Microbiology | 1 | 8% |
| Agricultural and Biological Sciences | 1 | 8% |
| Other | 2 | 17% |
| Unknown | 4 | 33% |
Attention Score in Context
This research output has an Altmetric Attention Score of 2. 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 12 August 2016.
All research outputs
#14,231,577
of 22,816,807 outputs
Outputs from Pharmaceutical Research
#2,158
of 2,857 outputs
Outputs of similar age
#135,485
of 263,437 outputs
Outputs of similar age from Pharmaceutical Research
#13
of 27 outputs
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We're also able to compare this research output to 27 others from the same source and published within six weeks on either side of this one. This one is in the 44th percentile – i.e., 44% of its contemporaries scored the same or lower than it.