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Changes in mitochondrial stability during the progression of the Barrett’s esophagus disease sequence

Overview of attention for article published in BMC Cancer, July 2016
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Title
Changes in mitochondrial stability during the progression of the Barrett’s esophagus disease sequence
Published in
BMC Cancer, July 2016
DOI 10.1186/s12885-016-2544-2
Pubmed ID
Authors

N. J. O’Farrell, R. Feighery, S. L. Picardo, N. Lynam-Lennon, M. Biniecka, S. A. McGarrigle, J. J. Phelan, F. MacCarthy, D. O’Toole, E. J. Fox, N. Ravi, J. V. Reynolds, J. O’Sullivan

Abstract

Barrett's esophagus follows the classic step-wise progression of metaplasia-dysplasia-adenocarcinoma. While Barrett's esophagus is a leading known risk factor for esophageal adenocarcinoma, the pathogenesis of this disease sequence is poorly understood. Mitochondria are highly susceptible to mutations due to high levels of reactive oxygen species (ROS) coupled with low levels of DNA repair. The timing and levels of mitochondria instability and dysfunction across the Barrett's disease progression is under studied. Using an in-vitro model representing the Barrett's esophagus disease sequence of normal squamous epithelium (HET1A), metaplasia (QH), dysplasia (Go), and esophageal adenocarcinoma (OE33), random mitochondrial mutations, deletions and surrogate markers of mitochondrial function were assessed. In-vivo and ex-vivo tissues were also assessed for instability profiles. Barrett's metaplastic cells demonstrated increased levels of ROS (p < 0.005) and increased levels of random mitochondrial mutations (p < 0.05) compared with all other stages of the Barrett's disease sequence in-vitro. Using patient in-vivo samples, Barrett's metaplasia tissue demonstrated significantly increased levels of random mitochondrial deletions (p = 0.043) compared with esophageal adenocarcinoma tissue, along with increased expression of cytoglobin (CYGB) (p < 0.05), a gene linked to oxidative stress, compared with all other points across the disease sequence. Using ex-vivo Barrett's metaplastic and matched normal patient tissue explants, higher levels of cytochrome c (p = 0.003), SMAC/Diablo (p = 0.008) and four inflammatory cytokines (all p values <0.05) were secreted from Barrett's metaplastic tissue compared with matched normal squamous epithelium. We have demonstrated that increased mitochondrial instability and markers of cellular and mitochondrial stress are early events in the Barrett's disease sequence.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 16 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 16 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 3 19%
Student > Doctoral Student 2 13%
Student > Ph. D. Student 2 13%
Professor 1 6%
Other 1 6%
Other 2 13%
Unknown 5 31%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 5 31%
Medicine and Dentistry 3 19%
Agricultural and Biological Sciences 2 13%
Engineering 1 6%
Unknown 5 31%
Attention Score in Context

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 17 October 2017.
All research outputs
#16,927,921
of 24,892,887 outputs
Outputs from BMC Cancer
#4,464
of 8,812 outputs
Outputs of similar age
#243,463
of 371,666 outputs
Outputs of similar age from BMC Cancer
#111
of 257 outputs
Altmetric has tracked 24,892,887 research outputs across all sources so far. This one is in the 21st percentile – i.e., 21% of other outputs scored the same or lower than it.
So far Altmetric has tracked 8,812 research outputs from this source. They receive a mean Attention Score of 4.6. This one is in the 39th percentile – i.e., 39% of its peers scored the same or lower than it.
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 371,666 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 26th percentile – i.e., 26% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 257 others from the same source and published within six weeks on either side of this one. This one is in the 44th percentile – i.e., 44% of its contemporaries scored the same or lower than it.