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FTY720 inhibits mesothelioma growth in vitro and in a syngeneic mouse model

Overview of attention for article published in Journal of Translational Medicine, March 2017
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About this Attention Score

  • In the top 5% of all research outputs scored by Altmetric
  • One of the highest-scoring outputs from this source (#7 of 2,119)
  • High Attention Score compared to outputs of the same age (99th percentile)
  • High Attention Score compared to outputs of the same age and source (98th percentile)

Mentioned by

news
53 news outlets
twitter
1 tweeter

Citations

dimensions_citation
18 Dimensions

Readers on

mendeley
31 Mendeley
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Title
FTY720 inhibits mesothelioma growth in vitro and in a syngeneic mouse model
Published in
Journal of Translational Medicine, March 2017
DOI 10.1186/s12967-017-1158-z
Pubmed ID
Authors

Agata Szymiczek, Sandra Pastorino, David Larson, Mika Tanji, Laura Pellegrini, Jiaming Xue, Shuangjing Li, Carlotta Giorgi, Paolo Pinton, Yasutaka Takinishi, Harvey I. Pass, Hideki Furuya, Giovanni Gaudino, Andrea Napolitano, Michele Carbone, Haining Yang

Abstract

Malignant mesothelioma (MM) is a very aggressive type of cancer, with a dismal prognosis and inherent resistance to chemotherapeutics. Development and evaluation of new therapeutic approaches is highly needed. Immunosuppressant FTY720, approved for multiple sclerosis treatment, has recently raised attention for its anti-tumor activity in a variety of cancers. However, its therapeutic potential in MM has not been evaluated yet. Cell viability and anchorage-independent growth were evaluated in a panel of MM cell lines and human mesothelial cells (HM) upon FTY720 treatment to assess in vitro anti-tumor efficacy. The mechanism of action of FTY720 in MM was assessed by measuring the activity of phosphatase protein 2A (PP2A)-a major target of FTY720. The binding of the endogenous inhibitor SET to PP2A in presence of FTY720 was evaluated by immunoblotting and immunoprecipitation. Signaling and activation of programmed cell death were evaluated by immunoblotting and flow cytometry. A syngeneic mouse model was used to evaluate anti-tumor efficacy and toxicity profile of FTY720 in vivo. We show that FTY720 significantly suppressed MM cell viability and anchorage-independent growth without affecting normal HM cells. FTY720 inhibited the phosphatase activity of PP2A by displacement of SET protein, which appeared overexpressed in MM, as compared to HM cells. FTY720 promoted AKT dephosphorylation and Bcl-2 degradation, leading to induction of programmed cell death, as demonstrated by caspase-3 and PARP activation, as well as by cytochrome c and AIF intracellular translocation. Moreover, FTY720 administration in vivo effectively reduced tumor burden in mice without apparent toxicity. Our preclinical data indicate that FTY720 is a potentially promising therapeutic agent for MM treatment.

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 31 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 31 100%

Demographic breakdown

Readers by professional status Count As %
Student > Doctoral Student 6 19%
Student > Ph. D. Student 6 19%
Professor > Associate Professor 2 6%
Researcher 2 6%
Professor 1 3%
Other 2 6%
Unknown 12 39%
Readers by discipline Count As %
Medicine and Dentistry 5 16%
Biochemistry, Genetics and Molecular Biology 3 10%
Pharmacology, Toxicology and Pharmaceutical Science 3 10%
Neuroscience 2 6%
Immunology and Microbiology 1 3%
Other 3 10%
Unknown 14 45%

Attention Score in Context

This research output has an Altmetric Attention Score of 419. 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 10 April 2017.
All research outputs
#15,673
of 9,665,907 outputs
Outputs from Journal of Translational Medicine
#7
of 2,119 outputs
Outputs of similar age
#1,247
of 255,355 outputs
Outputs of similar age from Journal of Translational Medicine
#1
of 65 outputs
Altmetric has tracked 9,665,907 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 99th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 2,119 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.6. This one has done particularly well, scoring higher than 99% 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 255,355 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 99% of its contemporaries.
We're also able to compare this research output to 65 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 98% of its contemporaries.