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Dasatinib enhances tumor growth in gemcitabine-resistant orthotopic bladder cancer xenografts

Overview of attention for article published in BMC Research Notes, September 2016
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Title
Dasatinib enhances tumor growth in gemcitabine-resistant orthotopic bladder cancer xenografts
Published in
BMC Research Notes, September 2016
DOI 10.1186/s13104-016-2256-3
Pubmed ID
Authors

Stefan Vallo, Martin Michaelis, Kilian M. Gust, Peter C. Black, Florian Rothweiler, Hans-Michael Kvasnicka, Roman A. Blaheta, Maximilian P. Brandt, Felix Wezel, Axel Haferkamp, Jindrich Cinatl

Abstract

Systemic chemotherapy with gemcitabine and cisplatin is standard of care for patients with metastatic urothelial bladder cancer. However, resistance formation is common after initial response. The protein Src is known as a proto-oncogene, which is overexpressed in various human cancers. Since there are controversial reports about the role of Src in bladder cancer, we evaluated the efficacy of the Src kinase inhibitor dasatinib in the urothelial bladder cancer cell line RT112 and its gemcitabine-resistant sub-line RT112(r)GEMCI(20) in vitro and in vivo. RT112 urothelial cancer cells were adapted to growth in the presence of 20 ng/ml gemcitabine (RT112(r)GEMCI(20)) by continuous cultivation at increasing drug concentrations. Cell viability was determined by MTT assay, cell growth kinetics were determined by cell count, protein levels were measured by western blot, and cell migration was evaluated by scratch assays. In vivo tumor growth was tested in a murine orthotopic xenograft model using bioluminescent imaging. Dasatinib exerted similar effects on Src signaling in RT112 and RT112(r)GEMCI(20) cells but RT112(r)GEMCI(20) cells were less sensitive to dasatinib-induced anti-cancer effects (half maximal inhibitory concentration (IC50) of dasatinib in RT112 cells: 349.2 ± 67.2 nM; IC50 of dasatinib in RT112(r)GEMCI(20) cells: 1081.1 ± 239.2 nM). Dasatinib inhibited migration of chemo-naive and gemcitabine-resistant cells. Most strikingly, dasatinib treatment reduced RT112 tumor growth and muscle invasion in orthotopic xenografts, while it was associated with increased size and muscle-invasive growth in RT112(r)GEMCI(20) tumors. Dasatinib should be considered with care for the treatment of urothelial cancer, in particular for therapy-refractory cases.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 14 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 14 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 3 21%
Professor 2 14%
Student > Postgraduate 2 14%
Researcher 2 14%
Student > Master 1 7%
Other 0 0%
Unknown 4 29%
Readers by discipline Count As %
Medicine and Dentistry 8 57%
Biochemistry, Genetics and Molecular Biology 2 14%
Unknown 4 29%

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 June 2022.
All research outputs
#14,414,673
of 21,468,133 outputs
Outputs from BMC Research Notes
#2,220
of 4,138 outputs
Outputs of similar age
#178,514
of 293,290 outputs
Outputs of similar age from BMC Research Notes
#1
of 1 outputs
Altmetric has tracked 21,468,133 research outputs across all sources so far. This one is in the 22nd percentile – i.e., 22% of other outputs scored the same or lower than it.
So far Altmetric has tracked 4,138 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.4. This one is in the 34th percentile – i.e., 34% 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 293,290 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 30th percentile – i.e., 30% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 1 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them