Evidence map›Paper›PMID 29661248›Full record

ArticleBMC cancer2018

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

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

Open access · goldAbstract read
In one paragraph

Article in BMC cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.2field-weighted citation impact, top 47% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 7 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 2 countries.

Sunhyo RyuDepartment of Dermatology, University of Colorado Denver School of Medicine, Aurora, CO, 80045, USA.
Yun Jeong AhnDepartment of Biomedical Science and Research Center for Proteinaceous Materials, Chosun University School of Medicine, 309 Pilmoon-Daero, Gwangju, 61452, Republic of Korea.
Chakeong YoonDepartment of Biomedical Science and Research Center for Proteinaceous Materials, Chosun University, Gwangju, South Korea.
Jeong Hwan ChangDepartment of Surgery, Chosun University School of Medicine, Gwangju, South Korea.
Yoonkyung ParkDepartment of Biomedical Science and Research Center for Proteinaceous Materials, Chosun University, Gwangju, South Korea.
Tae-Hyoung KimDepartment of Biochemistry, Chosun University School of Medicine, Gwangju, South Korea.
Amanda R HowlandDepartment of Dermatology, University of Colorado Denver School of Medicine, Aurora, CO, 80045, USA.
Cheryl A ArmstrongDepartment of Dermatology, University of Colorado Denver School of Medicine, Aurora, CO, 80045, USA.
Peter I SongDepartment of Dermatology, University of Colorado Denver School of Medicine, Aurora, CO, 80045, USA. peter.song@ucdenver.edu.
Ae Ran MoonDepartment of Biomedical Science and Research Center for Proteinaceous Materials, Chosun University School of Medicine, 309 Pilmoon-Daero, Gwangju, 61452, Republic of Korea. moonaeran@chosun.ac.kr.
Chosun University · KRUniversity of Colorado Denver · USUniversity of Colorado Anschutz Medical Campus · US

Funding

Chosun University 2014National Research Foundation of Korea NRF-2014K1A1A2064460National Research Foundation of Korea NRF-2015R1D1A3A01020417
6 · The paper itself

Abstract

backgroundMultiple 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.

methodsThree 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.

resultsILz: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.

conclusionsThe 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.

Indexed as

AnimalsApoptosisBortezomibCaspasesCell Line, TumorCell ProliferationDrug Resistance, NeoplasmDrug SynergismHumansMiceSignal TransductionTNF-Related Apoptosis-Inducing LigandXenograft Model Antitumor AssaysBortezomibCaspasesTNF-Related Apoptosis-Inducing LigandTNFSF10 protein, humanApoptosisBortezomibCaspase-dependentCombination treatmentRecombinant TRAIL

Identifiers

PMID29661248
PMCPMC5902847
OpenAlexW2803611315

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.