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Schedule-dependent increased efficiency of pemetrexed-ionizing radiation combination therapy elicits a differential DNA damage response in lung cancer cells

Overview of attention for article published in Cancer Cell International, September 2016
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Mentioned by

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1 tweeter

Citations

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3 Dimensions

Readers on

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6 Mendeley
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Title
Schedule-dependent increased efficiency of pemetrexed-ionizing radiation combination therapy elicits a differential DNA damage response in lung cancer cells
Published in
Cancer Cell International, September 2016
DOI 10.1186/s12935-016-0346-x
Pubmed ID
Authors

Patrick Dorn, Colin Charles Tièche, Ren-Wang Peng, Laurène Froment, Ralph Alexander Schmid, Thomas Michael Marti

Abstract

Lung cancer causes the most cancer deaths worldwide, thus there is a urgent need to develop new treatment options. Concurrent chemoradiotherapy has become a common strategy for the treatment of non-resectable solid tumors including non-small cell lung cancer. Pemetrexed is a folic acid antagonist that inhibits the synthesis of precursor nucleotides, whereas ionizing radiation induces DNA damage, the repair of which is dependent on sufficiently high nucleotide levels. In the clinical setting, the pemetrexed-ionizing radiation combination therapy is administered concomitantly. We hypothesized that prolonged pretreatment with pemetrexed could be beneficial, as prior depletion of nucleotide pools could sensitize cancer cells to subsequent irradiation. Non-small cell lung cancer A549 cells were treated with 1 µM pemetrexed for 72 h. In addition, cells were exposed to five gray ionizing radiation either 1, 48 or 71 h after the initiation of the pemetrexed treatment. Cell growth, senescence induction, cell cycle distribution and DNA damage marker accumulation were analysed at different time points during the treatment and the recovery phase. Stand-alone treatments of five gray ionizing radiation and 1 µM pemetrexed resulted in an intermediate cell growth inhibition of A549 cells and were therefore applied as the combination regimen. Prolonged pemetrexed pretreatment for 71 h resulted in a significant S-phase accumulation. Irradiation and prolonged pemetrexed pretreatment maximally delayed long term cell growth. Additionally, senescence was augmented and recovery from treatment-induced DNA damage was most prominently delayed by prolonged pemetrexed pretreatment. Pretreatment with pemetrexed increases anticancer efficiency of pemetrexed-ionizing radiation combination therapy, which correlates with a persistence of treatment-induced DNA damage. Therefore, this study warrants further investigations to elucidate whether a similar adaptation to the standard treatment regimen could enhance the effectiveness of the non-small cell lung cancer clinical treatment regimen.

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

Geographical breakdown

Country Count As %
Unknown 6 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 1 17%
Student > Ph. D. Student 1 17%
Student > Bachelor 1 17%
Researcher 1 17%
Other 1 17%
Other 0 0%
Unknown 1 17%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 2 33%
Pharmacology, Toxicology and Pharmaceutical Science 1 17%
Medicine and Dentistry 1 17%
Unknown 2 33%

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 07 September 2016.
All research outputs
#4,447,166
of 8,342,643 outputs
Outputs from Cancer Cell International
#100
of 320 outputs
Outputs of similar age
#139,141
of 252,571 outputs
Outputs of similar age from Cancer Cell International
#4
of 6 outputs
Altmetric has tracked 8,342,643 research outputs across all sources so far. This one is in the 27th percentile – i.e., 27% of other outputs scored the same or lower than it.
So far Altmetric has tracked 320 research outputs from this source. They receive a mean Attention Score of 3.4. This one has gotten more attention than average, scoring higher than 56% 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 252,571 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 35th percentile – i.e., 35% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 6 others from the same source and published within six weeks on either side of this one. This one has scored higher than 2 of them.