You are seeing a free-to-access but limited selection of the activity Altmetric has collected about this research output.
Click here to find out more.
X Demographics
Mendeley readers
Attention Score in Context
| Title |
Abemaciclib Is Active in Preclinical Models of Ewing Sarcoma via Multipronged Regulation of Cell Cycle, DNA Methylation, and Interferon Pathway Signaling
|
|---|---|
| Published in |
Clinical Cancer Research, December 2018
|
| DOI | 10.1158/1078-0432.ccr-18-1256 |
| Pubmed ID | |
| Authors |
Michele Dowless, Caitlin D. Lowery, Terry Shackleford, Matthew Renschler, Jennifer Stephens, Robert Flack, Wayne Blosser, Simone Gupta, Julie Stewart, Yue Webster, Jack Dempsey, Alle B. VanWye, Philip Ebert, Philip Iversen, Jonathan B. Olsen, Xueqian Gong, Sean Buchanan, Peter Houghton, Louis Stancato |
| Abstract |
Ewing's sarcoma (ES) is a rare and highly malignant cancer that occurs in the bone and surrounding tissue of children and adolescents. The EWS/ETS fusion transcription factor that drives ES pathobiology was previously demonstrated to modulate cyclin D1 expression. In this study we evaluated abemaciclib, a small molecule CDK4 and CDK6 (CDK4 and 6) inhibitor currently under clinical investigation in pediatric solid tumors, in preclinical models of ES. Using western blot, high content imaging, flow cytometry, ELISA, RNAseq, and CpG methylation assays, we characterized the in vitro response of ES cell lines to abemaciclib. We then evaluated abemaciclib in vivo in cell line-derived and patient-derived xenograft (CDX and PDX, respectively) mouse models of ES as either a monotherapy or in combination with chemotherapy. Abemaciclib induced quiescence in ES cell lines via a G1 cell cycle block, characterized by decreased proliferation and reduction of Ki67 and FOXM1 expression and RB phosphorylation. In addition, abemaciclib reduced DNMT1 expression and promoted an inflammatory immune response as measured by cytokine secretion, antigen presentation, and interferon pathway upregulation. Single agent abemaciclib reduced ES tumor volume in preclinical mouse models and, when given in combination with doxorubicin or temozolomide plus irinotecan, durable disease control was observed. Collectively, our data demonstrate that the anti-tumor effects of abemaciclib in preclinical ES models are multifaceted and include cell cycle inhibition, DNA demethylation, and immunogenic changes. |
X Demographics
The data shown below were collected from the profiles of 2 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 | 50% |
| Unknown | 1 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 38 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 38 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 8 | 21% |
| Researcher | 8 | 21% |
| Student > Ph. D. Student | 6 | 16% |
| Student > Master | 3 | 8% |
| Professor > Associate Professor | 2 | 5% |
| Other | 1 | 3% |
| Unknown | 10 | 26% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 10 | 26% |
| Medicine and Dentistry | 9 | 24% |
| Agricultural and Biological Sciences | 4 | 11% |
| Physics and Astronomy | 1 | 3% |
| Pharmacology, Toxicology and Pharmaceutical Science | 1 | 3% |
| Other | 0 | 0% |
| Unknown | 13 | 34% |
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 03 December 2018.
All research outputs
#18,647,094
of 23,100,534 outputs
Outputs from Clinical Cancer Research
#11,476
of 12,668 outputs
Outputs of similar age
#324,971
of 436,742 outputs
Outputs of similar age from Clinical Cancer Research
#215
of 241 outputs
Altmetric has tracked 23,100,534 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 12,668 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 10.9. This one is in the 5th percentile – i.e., 5% 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 436,742 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 14th percentile – i.e., 14% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 241 others from the same source and published within six weeks on either side of this one. This one is in the 5th percentile – i.e., 5% of its contemporaries scored the same or lower than it.