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X Demographics
Mendeley readers
Attention Score in Context
| Title |
Dactolisib (NVP-BEZ235) toxicity in murine brain tumour models
|
|---|---|
| Published in |
BMC Cancer, August 2016
|
| DOI | 10.1186/s12885-016-2712-4 |
| Pubmed ID | |
| Authors |
I. A. Netland, H. E. Førde, L. Sleire, L. Leiss, M. A. Rahman, B. S. Skeie, C. H. Gjerde, P. Ø. Enger, D. Goplen |
| Abstract |
Glioblastomas (GBMs) are highly malignant brain tumours with a poor prognosis, and current cytotoxic regimens provide only a limited survival benefit. The PI3K/Akt/mTOR pathway has been an attractive target for therapy due to its high activation in GBMs as well as other cancers. The dual pan-PI3K/mTOR kinase inhibitor dactolisib (NVP-BEZ235) is an anti-neoplastic compound currently under investigation. However, little is known about its efficacy in human GBMs. We aimed at evaluating the efficacy of dactolisib in human glioblastoma cells, as well as in murine models carrying human GBM xenografts. To assess the effect of dactolisib in vitro, MTS assay, manual cell count, BrdU incorporation and Annexin V staining experiments were used to observe growth and apoptosis. Furthermore, Akt phosphorylation (S473), a downstream target of PI3K, was explored by western blotting. Animal studies utilizing orthotopic xenograft models of glioblastoma were performed in nude rats and NOD/SCID mice to monitor survival benefit or inhibition of tumor growth. We found that dactolisib in vitro shows excellent dose dependent anti-growth properties and increase in apoptosis. Moreover, dose dependent inhibition of Akt phosphorylation (S473), a downstream effect of PI3K, was observed by western blotting. However, in two independent animal studies utilizing nude rats and NOD/SCID mice in orthotopic xenograft models of glioblastoma, we observed no survival benefit or inhibition of tumour growth. Severe side effects were observed, such as elevated levels of blood glucose and the liver enzyme alanine transaminase (ALT), in addition to diarrhoea, hair loss (alopecia), skin rash and accumulation of saliva in the oral cavity. Taken together, our results suggest that despite the anti-neoplastic efficacy of dactolisib in glioma treatment in vitro, its utility in vivo is questionable due to toxicity. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Portugal | 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 30 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 30 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 5 | 17% |
| Researcher | 3 | 10% |
| Student > Master | 3 | 10% |
| Other | 2 | 7% |
| Student > Doctoral Student | 2 | 7% |
| Other | 8 | 27% |
| Unknown | 7 | 23% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 9 | 30% |
| Biochemistry, Genetics and Molecular Biology | 5 | 17% |
| Agricultural and Biological Sciences | 3 | 10% |
| Nursing and Health Professions | 1 | 3% |
| Pharmacology, Toxicology and Pharmaceutical Science | 1 | 3% |
| Other | 4 | 13% |
| Unknown | 7 | 23% |
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 21 August 2016.
All research outputs
#20,337,788
of 22,883,326 outputs
Outputs from BMC Cancer
#6,506
of 8,326 outputs
Outputs of similar age
#299,792
of 343,547 outputs
Outputs of similar age from BMC Cancer
#200
of 278 outputs
Altmetric has tracked 22,883,326 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 8,326 research outputs from this source. They receive a mean Attention Score of 4.3. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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 343,547 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 278 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.