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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 (98th percentile)

Mentioned by

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9 news outlets
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6 X users

Citations

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60 Dimensions

Readers on

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48 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.

X Demographics

X Demographics

The data shown below were collected from the profiles of 6 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 48 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 48 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 11 23%
Student > Bachelor 8 17%
Researcher 6 13%
Student > Doctoral Student 3 6%
Student > Master 3 6%
Other 6 13%
Unknown 11 23%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 14 29%
Medicine and Dentistry 10 21%
Pharmacology, Toxicology and Pharmaceutical Science 2 4%
Agricultural and Biological Sciences 2 4%
Chemistry 2 4%
Other 6 13%
Unknown 12 25%
Attention Score in Context

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
#503,495
of 23,005,189 outputs
Outputs from Oncotarget
#147
of 14,344 outputs
Outputs of similar age
#11,983
of 317,570 outputs
Outputs of similar age from Oncotarget
#14
of 1,061 outputs
Altmetric has tracked 23,005,189 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 97th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 14,344 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.6. This one has done particularly well, scoring higher than 98% 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 317,570 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 1,061 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.