Evidence map›Paper›PMID 26381901›Full record

ArticleJournal of controlled release : official journal of the Controlled Release Society2015

Delivery of tumor-homing TRAIL sensitizer with long-acting TRAIL as a therapy for TRAIL-resistant tumors.

Yumin Oh, Magdalena Swierczewska, Tae Hyung Kim, Sung Mook Lim, Ha Na Eom, Jae Hyung Park, Dong Hee Na, Kwangmeyung Kim, Kang Choon Lee, Martin G Pomper and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of controlled release : official journal of the Controlled Release Society, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 pooled it
1.5field-weighted citation impact, top 18% 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

10 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Review
  5. Article
  6. Protein PEGylation for cancer therapy: bench to bedside.Journal of cell communication and signaling · 2019
    Review
  7. Article
  8. Review
  9. Mechanisms of tumor cell resistance to the current targeted-therapy agents.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016
    Review
  10. 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

11 authors at 4 institutions in 2 countries.

Yumin OhRussell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins School of Medicine, Baltimore, MD, USA; Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Magdalena SwierczewskaRussell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins School of Medicine, Baltimore, MD, USA; Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Tae Hyung KimRussell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins School of Medicine, Baltimore, MD, USA; Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Sung Mook LimCollege of Pharmacy, Sungkyunkwan University, Suwon, South Korea.
Ha Na EomCollege of Pharmacy, Sungkyunkwan University, Suwon, South Korea.
Jae Hyung ParkDepartment of Polymer Science and Engineering, Sungkyunkwan University, Suwon, South Korea.
Dong Hee NaCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, South Korea.
Kwangmeyung KimCenter for Theragnosis, Korea Institute of Science of Technology, Seoul, South Korea.
Kang Choon LeeCollege of Pharmacy, Sungkyunkwan University, Suwon, South Korea.
Martin G PomperRussell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins School of Medicine, Baltimore, MD, USA; Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD, USA.
Seulki LeeRussell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins School of Medicine, Baltimore, MD, USA; Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, MD, USA; Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD, USA. Electronic address: seulki@jhmi.edu.
Johns Hopkins University · USSungkyunkwan University · KRKorea Institute of Science and Technology · KRKyungpook National University · KR

Funding

T32: Predoctoral and Postdoctoral Training Program in Nanotechnology for Cancer ResearchT32CA153952 · NCI · JOHNS HOPKINS UNIVERSITY · PI Denis Wirtz · 2015 to 2026
$3.5M
T-32 NIH Postdoctoral Training Program in Nanotechnology for Cancer Medicine NTCMT32CA130840 · NCI · JOHNS HOPKINS UNIVERSITY · PI WIRTZ, DENIS · 2008 to 2012
$1.2M
Development of preclinical HTS for discovery of drugs modulating apoptosisR00EB013450 · NIBIB · JOHNS HOPKINS UNIVERSITY · PI LEE, SEULKI · 2013 to 2015
$718k
NCI NIH HHS CA130460NCI NIH HHS PC131920NCI NIH HHS T32 CA130840NCI NIH HHS T32 CA153952NIBIB NIH HHS R00 EB013450NIBIB NIH HHS R00EB013450
6 · The paper itself

Abstract

Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) has attracted great interest as a cancer therapy because it selectively induces death receptor (DR)-mediated apoptosis in cancer cells while sparing normal tissue. However, recombinant human TRAIL demonstrates limited therapeutic efficacy in clinical trials, possibly due to TRAIL-resistance of primary cancers and its inherent short half-life. Here we introduce drug delivery approaches to maximize in vivo potency of TRAIL in TRAIL-resistant tumor xenografts by (1) extending the half-life of the ligand with PEGylated TRAIL (TRAILPEG) and (2) concentrating a TRAIL sensitizer, selected from in vitro screening, in tumors via tumor-homing nanoparticles. Antitumor efficacy of TRAILPEG with tumor-homing sensitizer was evaluated in HCT116 and HT-29 colon xenografts. Western blot, real-time PCR, immunohistochemistry and cell viability assays were employed to investigate mechanisms of action and antitumor efficacy of the combination. We discovered that doxorubicin (DOX) sensitizes TRAIL-resistant HT-29 colon cancer cells to TRAIL by upregulating mRNA expression of DR5 by 60% in vitro. Intravenously administered free DOX does not effectively upregulate DR5 in tumor tissues nor demonstrate synergy with TRAILPEG in HT-29 xenografts, but rather introduces significant systemic toxicity. Alternatively, when DOX was encapsulated in hyaluronic acid-based nanoparticles (HAC/DOX) and intravenously administered with TRAILPEG, DR-mediated apoptosis was potentiated in HT-29 tumors by upregulating DR5 protein expression by 70% and initiating both extrinsic and intrinsic apoptotic pathways with reduced systemic toxicity compared to HAC/DOX or free DOX combined with TRAILPEG (80% vs. 40% survival rate; 75% vs. 34% tumor growth inhibition). This study demonstrates a unique approach to overcome TRAIL-based therapy drawbacks using sequential administration of a tumor-homing TRAIL sensitizer and long-acting TRAILPEG.

Indexed as

AnimalsAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsApoptosisCaspasesCell SurvivalChemistry, PharmaceuticalColonic NeoplasmsDoxorubicinDrug Resistance, NeoplasmEnzyme ActivationHalf-LifeHCT116 CellsHEK293 CellsHT29 CellsHumansAntineoplastic AgentsCaspasesDoxorubicinHyaluronic AcidPolyethylene GlycolsReceptors, TNF-Related Apoptosis-Inducing LigandTNF-Related Apoptosis-Inducing LigandTNFSF10 protein, humanApoptosisDeath receptorsNanomedicineTRAILTRAIL sensitizers

Identifiers

PMID26381901
PMCPMC4688186
OpenAlexW1641691935

What OpenQuestion holds

Textmetadata
LicenceTDM
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.