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Targeting the cancer stem cell marker, aldehyde dehydrogenase 1, to circumvent cisplatin resistance in NSCLC

Overview of attention for article published in Oncotarget, August 2017
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About this Attention Score

  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (96th percentile)
  • High Attention Score compared to outputs of the same age and source (97th percentile)

Mentioned by

news
9 news outlets
twitter
6 tweeters

Citations

dimensions_citation
36 Dimensions

Readers on

mendeley
34 Mendeley
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Title
Targeting the cancer stem cell marker, aldehyde dehydrogenase 1, to circumvent cisplatin resistance in NSCLC
Published in
Oncotarget, August 2017
DOI 10.18632/oncotarget.19881
Pubmed ID
Authors

Lauren MacDonagh, Michael F. Gallagher, Brendan Ffrench, Claudia Gasch, Eamon Breen, Steven G. Gray, Siobhan Nicholson, Niamh Leonard, Ronan Ryan, Vincent Young, John J. O’Leary, Sinead Cuffe, Stephen P. Finn, Kenneth J. O’Byrne, Martin P. Barr

Abstract

Non-small cell lung cancer (NSCLC) accounts for a large proportion of cancer deaths and is characterized by low treatment response rates and poor overall prognosis. In the absence of specific treatable mutations, cisplatin-based chemotherapy plays an important role in the treatment of this disease. Unfortunately, the development of resistance has become a major therapeutic challenge in the use of this cytotoxic drug. Elucidating the mechanisms underlying this resistance phenotype, may result in the development of novel agents that enhance sensitivity to cisplatin in lung cancer patients. In this study, targeting the cancer stem cell activity of aldehyde dehydrogenase 1 (ALDH1) was investigated as a strategy to overcome chemoresistance in NSCLC. Tumors from NSCLC patients showed an increase in their profile of pluripotent stemness genes. Cisplatin exposure induced the emergence or expansion of an ALDH1-positive subpopulation in cisplatin sensitive and resistant NSCLC cell lines, respectively, further enhancing cisplatin resistance. Using the Aldefluor assay and FACS analysis, ALDH1 subpopulations were isolated and evaluated in terms of stem cell characteristics. Only ALDH1-positive cells exhibited asymmetric division, cisplatin resistance and increased expression of stem cell factors in vitro. Xenograft studies in NOD/SCID mice demonstrated efficient tumorigenesis from low cell numbers of ALDH1-positive and ALDH1-negative subpopulations. Targeting ALDH1 with Diethylaminobenzaldehyde (DEAB) and Disulfiram, significantly re-sensitized resistant lung cancer cells to the cytotoxic effects of cisplatin. Our data demonstrate the existence of a lung CSC population and suggest a role for targeting ALDH1 as a potential therapeutic strategy in re-sensitizing NSCLC cells to the cytotoxic effects of cisplatin.

Twitter Demographics

The data shown below were collected from the profiles of 6 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 34 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 34 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 8 24%
Student > Bachelor 7 21%
Student > Doctoral Student 3 9%
Student > Master 3 9%
Other 2 6%
Other 5 15%
Unknown 6 18%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 10 29%
Medicine and Dentistry 8 24%
Agricultural and Biological Sciences 2 6%
Psychology 1 3%
Economics, Econometrics and Finance 1 3%
Other 4 12%
Unknown 8 24%

Attention Score in Context

This research output has an Altmetric Attention Score of 73. 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 14 October 2017.
All research outputs
#184,818
of 11,927,787 outputs
Outputs from Oncotarget
#96
of 11,533 outputs
Outputs of similar age
#9,662
of 272,852 outputs
Outputs of similar age from Oncotarget
#16
of 778 outputs
Altmetric has tracked 11,927,787 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 98th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 11,533 research outputs from this source. They receive a mean Attention Score of 3.7. 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 272,852 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 96% of its contemporaries.
We're also able to compare this research output to 778 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 97% of its contemporaries.