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Novel adjuvants from seaweed impede autophagy signaling in therapy-resistant residual pancreatic cancer

Overview of attention for article published in Journal of Biomedical Science, April 2015
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Title
Novel adjuvants from seaweed impede autophagy signaling in therapy-resistant residual pancreatic cancer
Published in
Journal of Biomedical Science, April 2015
DOI 10.1186/s12929-015-0132-4
Pubmed ID
Authors

Sheeja Aravindan, Satish Kumar Ramraj, Somasundaram T Somasundaram, Natarajan Aravindan

Abstract

Identifying the drug-deliverables that target autophagy is crucial to finding a cure for pancreatic cancer (PC), as activated autophagy is associated with poor patient outcomes. Our recent studies recognized the anti-PC potential of an antioxidant-rich collection of seaweed polyphenols and identified potential compounds for the treatment of PC. Accordingly, we investigated whether such compounds could regulate autophagy in therapy-resistant PC cells in vitro and in residual PC in vivo. Human Panc-3.27 and MiaPaCa-2 cells were exposed to fractionated irradiation (FIR) with/without ethyl acetate (EA) polyphenol from Spatoglossum asperum (SA-EA), Padina tetrastromatica (PT-EA), or Hormophysa triquerta (HT-EA). The cells were subjected to QPCR to examine transcriptional alterations in the following autophagy functional regulators: ATG3, ATG5, ATG7, ATG12, LC3A, LC3B, Beclin, Myd88, HMGB1, Rage, and TLRs 1-9. Using a clinically relevant mouse model of residual PC, we use tissue microarray (TMA) and immunohistochemistry (IHC) procedures to investigate the potential of polyphenol(s) to target ATG3, ATG5, ATG12, LC3A, LC3B, BECN1, and SURIVIN after clinical radiotherapy. Radiation significantly increased the transcription of autophagy functional regulators in both cell lines. Seaweed polyphenols completely suppressed the transcription of all investigated autophagy regulators in both cell-lines. Gene silencing approach defined the role of LC3B in radiation-induced cell survival in this setting. TMA-IHC analysis revealed the complete regulation of ATG3, ATG5, ATG12, LC3A, LC3B, BECN1, and SURVIVIN in residual PC following SA-EA, PT-EA, and HT-EA treatment. These data demonstrate the autophagy blue print in therapy-resistant PC cells for the first time. Moreover, the data strongly suggest that the selected polyphenols could serve as effective adjuvants for current PC treatment modalities and may inhibit tumor relapse by comprehensively targeting therapy-orchestrated autophagy in residual cells.

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Mendeley readers

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 4 12%
Other 3 9%
Student > Bachelor 3 9%
Student > Master 3 9%
Researcher 3 9%
Other 7 21%
Unknown 11 32%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 6 18%
Agricultural and Biological Sciences 6 18%
Medicine and Dentistry 5 15%
Pharmacology, Toxicology and Pharmaceutical Science 1 3%
Computer Science 1 3%
Other 4 12%
Unknown 11 32%
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 11 March 2016.
All research outputs
#17,285,668
of 25,374,647 outputs
Outputs from Journal of Biomedical Science
#753
of 1,101 outputs
Outputs of similar age
#169,706
of 279,643 outputs
Outputs of similar age from Journal of Biomedical Science
#6
of 13 outputs
Altmetric has tracked 25,374,647 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 1,101 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 11.0. This one is in the 23rd percentile – i.e., 23% 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 279,643 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 30th percentile – i.e., 30% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 13 others from the same source and published within six weeks on either side of this one. This one is in the 46th percentile – i.e., 46% of its contemporaries scored the same or lower than it.