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Effect of sulfasalazine on human neuroblastoma: analysis of sepiapterin reductase (SPR) as a new therapeutic target

Overview of attention for article published in BMC Cancer, June 2015
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About this Attention Score

  • Above-average Attention Score compared to outputs of the same age (64th percentile)
  • Good Attention Score compared to outputs of the same age and source (76th percentile)

Mentioned by

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5 tweeters

Citations

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13 Dimensions

Readers on

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29 Mendeley
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Title
Effect of sulfasalazine on human neuroblastoma: analysis of sepiapterin reductase (SPR) as a new therapeutic target
Published in
BMC Cancer, June 2015
DOI 10.1186/s12885-015-1447-y
Pubmed ID
Authors

Lisette P. Yco, Dirk Geerts, Gabor Mocz, Jan Koster, André S. Bachmann

Abstract

Neuroblastoma (NB) is an aggressive childhood malignancy in children up to 5 years of age. High-stage tumors frequently relapse even after aggressive multimodal treatment, and then show therapy resistance, typically resulting in patient death. New molecular-targeted compounds that effectively suppress tumor growth and prevent relapse with more efficacy are urgently needed. We and others previously showed that polyamines (PA) like spermidine and spermine are essential for NB tumorigenesis and that DFMO, an inhibitor of the key PA synthesis gene product ODC, is effective both in vitro and in vivo, securing its evaluation in NB clinical trials. To find additional compounds interfering with PA biosynthesis, we tested sulfasalazine (SSZ), an FDA-approved salicylate-based anti-inflammatory and immune-modulatory drug, recently identified to inhibit sepiapterin reductase (SPR). We earlier presented evidence for a physical interaction between ODC and SPR and we showed that RNAi-mediated knockdown of SPR expression significantly reduced native ODC enzyme activity and impeded NB cell proliferation. Human NB mRNA expression datasets in the public domain were analyzed using the R2 platform. Cell viability, isobologram, and combination index analyses as a result of SSZ treatment with our without DFMO were carried out in NB cell cultures. Molecular protein-ligand docking was achieved using the GRAMM algorithm. Statistical analyses were performed with the Kruskal-Wallis test, 2log Pearson test, and Student's t test. In this study, we show the clinical relevance of SPR in human NB tumors. We found that high SPR expression is significantly correlated to unfavorable NB characteristics like high age at diagnosis, MYCN amplification, and high INSS stage. SSZ inhibits the growth of NB cells in vitro, presumably due to the inhibition of SPR as predicted by computational docking of SSZ into SPR. Importantly, the combination of SSZ with DFMO produces synergistic antiproliferative effects in vitro. The results suggest the use of SSZ in combination with DFMO for further experiments, and possible prioritization as a novel therapy for the treatment of NB patients.

Twitter Demographics

The data shown below were collected from the profiles of 5 tweeters 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 29 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Peru 1 3%
Unknown 28 97%

Demographic breakdown

Readers by professional status Count As %
Student > Master 9 31%
Researcher 7 24%
Student > Bachelor 4 14%
Other 3 10%
Student > Doctoral Student 1 3%
Other 1 3%
Unknown 4 14%
Readers by discipline Count As %
Agricultural and Biological Sciences 6 21%
Biochemistry, Genetics and Molecular Biology 4 14%
Medicine and Dentistry 3 10%
Neuroscience 2 7%
Immunology and Microbiology 2 7%
Other 6 21%
Unknown 6 21%

Attention Score in Context

This research output has an Altmetric Attention Score of 3. 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 28 June 2015.
All research outputs
#5,755,979
of 11,338,088 outputs
Outputs from BMC Cancer
#1,194
of 4,155 outputs
Outputs of similar age
#81,548
of 234,962 outputs
Outputs of similar age from BMC Cancer
#40
of 182 outputs
Altmetric has tracked 11,338,088 research outputs across all sources so far. This one is in the 48th percentile – i.e., 48% of other outputs scored the same or lower than it.
So far Altmetric has tracked 4,155 research outputs from this source. They receive a mean Attention Score of 3.7. This one has gotten more attention than average, scoring higher than 70% 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 234,962 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 64% of its contemporaries.
We're also able to compare this research output to 182 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 76% of its contemporaries.