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X Demographics
Mendeley readers
Attention Score in Context
| Title |
Long-term acquired everolimus resistance in pancreatic neuroendocrine tumours can be overcome with novel PI3K-AKT-mTOR inhibitors
|
|---|---|
| Published in |
British Journal of Cancer, March 2016
|
| DOI | 10.1038/bjc.2016.25 |
| Pubmed ID | |
| Authors |
Timon Vandamme, Matthias Beyens, Ken Op de Beeck, Fadime Dogan, Peter M van Koetsveld, Patrick Pauwels, Geert Mortier, Christel Vangestel, Wouter de Herder, Guy Van Camp, Marc Peeters, Leo J Hofland |
| Abstract |
The mTOR-inhibitor everolimus improves progression-free survival in advanced pancreatic neuroendocrine tumours (PNETs). However, adaptive resistance to mTOR inhibition is described. QGP-1 and BON-1, two human PNET cell lines, were cultured with increasing concentrations of everolimus up to 22 weeks to reach a dose of 1 μM everolimus, respectively, 1000-fold and 250-fold initial IC50. Using total DNA content as a measure of cell number, growth inhibitory dose-response curves of everolimus were determined at the end of resistance induction and over time after everolimus withdrawal. Response to ATP-competitive mTOR inhibitors OSI-027 and AZD2014, and PI3K-mTOR inhibitor NVP-BEZ235 was studied. Gene expression of 10 PI3K-Akt-mTOR pathway-related genes was evaluated using quantitative real-time PCR (RT-qPCR). Long-term everolimus-treated BON-1/R and QGP-1/R showed a significant reduction in everolimus sensitivity. During a drug holiday, gradual return of everolimus sensitivity in BON-1/R and QGP-1/R led to complete reversal of resistance after 10-12 weeks. Treatment with AZD2014, OSI-027 and NVP-BEZ235 had an inhibitory effect on cell proliferation in both sensitive and resistant cell lines. Gene expression in BON-1/R revealed downregulation of MTOR, RICTOR, RAPTOR, AKT and HIF1A, whereas 4EBP1 was upregulated. In QGP-1/R, a downregulation of HIF1A and an upregulation of ERK2 were observed. Long-term everolimus resistance was induced in two human PNET cell lines. Novel PI3K-AKT-mTOR pathway-targeting drugs can overcome everolimus resistance. Differential gene expression profiles suggest different mechanisms of everolimus resistance in BON-1 and QGP-1. |
X Demographics
The data shown below were collected from the profiles of 5 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 20% |
| Venezuela, Bolivarian Republic of | 1 | 20% |
| Unknown | 3 | 60% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 3 | 60% |
| Practitioners (doctors, other healthcare professionals) | 1 | 20% |
| Scientists | 1 | 20% |
Mendeley readers
The data shown below were compiled from readership statistics for 55 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 55 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 13 | 24% |
| Student > Ph. D. Student | 10 | 18% |
| Student > Bachelor | 10 | 18% |
| Student > Doctoral Student | 4 | 7% |
| Student > Master | 4 | 7% |
| Other | 10 | 18% |
| Unknown | 4 | 7% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 21 | 38% |
| Biochemistry, Genetics and Molecular Biology | 12 | 22% |
| Agricultural and Biological Sciences | 4 | 7% |
| Engineering | 3 | 5% |
| Chemistry | 3 | 5% |
| Other | 3 | 5% |
| Unknown | 9 | 16% |
Attention Score in Context
This research output has an Altmetric Attention Score of 15. 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 21 October 2020.
All research outputs
#2,109,454
of 22,856,968 outputs
Outputs from British Journal of Cancer
#1,117
of 10,432 outputs
Outputs of similar age
#36,106
of 299,392 outputs
Outputs of similar age from British Journal of Cancer
#23
of 104 outputs
Altmetric has tracked 22,856,968 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 90th percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 10,432 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 9.6. This one has done well, scoring higher than 89% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 299,392 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 87% of its contemporaries.
We're also able to compare this research output to 104 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 77% of its contemporaries.