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The regulation of combined treatment-induced cell death with recombinant TRAIL and bortezomib through TRAIL signaling in TRAIL-resistant cells

Overview of attention for article published in BMC Cancer, April 2018
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Title
The regulation of combined treatment-induced cell death with recombinant TRAIL and bortezomib through TRAIL signaling in TRAIL-resistant cells
Published in
BMC Cancer, April 2018
DOI 10.1186/s12885-018-4352-3
Pubmed ID
Authors

Sunhyo Ryu, Yun Jeong Ahn, Chakeong Yoon, Jeong Hwan Chang, Yoonkyung Park, Tae-Hyoung Kim, Amanda R. Howland, Cheryl A. Armstrong, Peter I. Song, Ae Ran Moon

Abstract

Multiple trials have attempted to demonstrate the effective induction of cell death in TRAIL-resistant cancer cells, including using a combined treatment of recombinant TRAIL and various proteasome inhibitors. These studies have yielded limited success, as the mechanism of cell death is currently unidentified. Understanding this mechanism's driving forces may facilitate the induction of cell death in TRAIL-resistant cancer cells. Three kinds of recombinant soluble TRAIL proteins were treated into TRAIL-resistant cells and TRAIL-susceptible cells, with or without bortezomib, to compare their respective abilities to induce cell death. Recombinant TRAIL was treated with bortezomib to investigate whether this combination treatment could induce tumor regression in a mouse syngeneic tumor model. To understand the mechanism of combined treatment-induced cell death, cells were analyzed by flow cytometry and the effects of various cell death inhibitors on cell death rates were examined. ILz:rhTRAIL, a recombinant human TRAIL containing isoleucine zipper hexamerization domain, showed the highest cell death inducing ability both in single treatment and in combination treatment with bortezomib. In both TRAIL-resistant and TRAIL-susceptible cells treated with the combination treatment, an increase in cell death rates was dependent upon both the dose of TRAIL and its intrinsic properties. When a syngeneic mouse tumor model was treated with the combination of ILz:rhTRAIL and bortezomib, significant tumor regression was seen as a result of the effective induction of cancer cell death. The combination treatment-induced cell death was both inhibited by TRAIL blocking antibody and caspase-dependent. However, it was not inhibited by various ER stress inhibitors and autophagy inhibitors. The combination treatment with ILz:rhTRAIL and bortezomib was able to induce cell death in both TRAIL-susceptible and TRAIL-resistant cancer cells through the intracellular TRAIL signaling pathway. The efficiency of cell death was dependent on the properties of TRAIL under the environment provided by bortezomib. The combination treatment-induced cell death was not regulated by bortezomib-induced ER stress response or by autophagy.

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

Geographical breakdown

Country Count As %
Unknown 14 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 3 21%
Student > Bachelor 3 21%
Professor 2 14%
Researcher 2 14%
Librarian 1 7%
Other 2 14%
Unknown 1 7%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 4 29%
Medicine and Dentistry 3 21%
Veterinary Science and Veterinary Medicine 2 14%
Agricultural and Biological Sciences 2 14%
Immunology and Microbiology 1 7%
Other 1 7%
Unknown 1 7%

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 18 April 2018.
All research outputs
#11,396,404
of 12,818,993 outputs
Outputs from BMC Cancer
#3,874
of 4,749 outputs
Outputs of similar age
#234,479
of 270,423 outputs
Outputs of similar age from BMC Cancer
#1
of 1 outputs
Altmetric has tracked 12,818,993 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 4,749 research outputs from this source. They receive a mean Attention Score of 3.9. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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