Evidence map›Paper›PMID 29753460›Full record

ArticleSurgery2018

Synthetic high-density lipoprotein nanoconjugate targets neuroblastoma stem cells, blocking migration and self-renewal.

Chitra Subramanian, Peter T White, Rui Kuai, Avinaash Kalidindi, Valerie P Castle, James J Moon, Barbara N Timmermann, Anna Schwendeman, Mark S Cohen

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Surgery, 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
0.8field-weighted citation impact, top 27% 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, 10 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
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

9 authors at 2 institutions in 1 country.

Chitra SubramanianDepartment of Surgery, University of Michigan, Ann Arbor, MI.
Peter T WhiteDepartment of Surgery, University of Michigan, Ann Arbor, MI.
Rui KuaiDepartment of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI; Biointerfaces Institute, University of Michigan, Ann Arbor, MI.
Avinaash KalidindiDepartment of Surgery, University of Michigan, Ann Arbor, MI.
Valerie P CastleDepartment of Pediatrics, University of Michigan, Ann Arbor, MI.
James J MoonDepartment of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI; Biointerfaces Institute, University of Michigan, Ann Arbor, MI.
Barbara N TimmermannDepartment of Medicinal Chemistry, University of Kansas, Lawrence, KS.
Anna SchwendemanDepartment of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI; Biointerfaces Institute, University of Michigan, Ann Arbor, MI.
Mark S CohenDepartment of Surgery, University of Michigan, Ann Arbor, MI; Department of Pharmacology, University of Michigan, Ann Arbor, MI. Electronic address: cohenmar@med.umich.edu.
University of Michigan · USUniversity of Kansas · US

Funding

XenograftP30CA046592 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI THEODORE S LAWRENCE · 1988 to 2026
$178.2M
University of Michigan Surgical Oncology Research Training ProgramT32CA009672 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI JACQUELINE SARA JERUSS, WEIPING ZOU · 1991 to 2026
$6.0M
Synthetic HDL_a potential sepsis therapyR01GM113832 · NIGMS · UNIVERSITY OF KENTUCKY · PI LI, XIANG-AN, SCHWENDEMAN, ANNA · 2015 to 2019
$3.0M
Development and Evaluation of Purine and Coumarin Based Hsp90 Inhibitors`U01CA120458 · NCI · UNIVERSITY OF KANSAS LAWRENCE · PI BLAGG, BRIAN S J · 2007 to 2014
$2.6M
Biomaterials for treatment of head and neck cancerR01CA173292 · NCI · UNIVERSITY OF KANSAS LAWRENCE · PI FORREST, MARCUS LAIRD · 2013 to 2017
$1.4M
Optimization and Investigation of Cruentaren A analogsR01CA216919 · NCI · UNIVERSITY OF NOTRE DAME · PI BLAGG, BRIAN S J, COHEN, MARK STEVEN · 2017 to 2021
$1.4M
NCI NIH HHS P30 CA046592NCI NIH HHS R01 CA173292NCI NIH HHS R01 CA216919NCI NIH HHS T32 CA009672NCI NIH HHS U01 CA120458NIGMS NIH HHS R01 GM113832
6 · The paper itself

Abstract

backgroundPathways critical for neuroblastoma cancer stem cell function are targeted by 4,19,27-triacetyl withalongolide A (WGA-TA). Because neuroblastoma cells and their cancer stem cells highly overexpress the scavenger receptor class B type 1 receptor that binds to synthetic high-density lipoprotein, we hypothesized that a novel mimetic synthetic high-density lipoprotein nanoparticle would be an ideal carrier for the delivery of 4,19,27-triacetyl withalongolide to neuroblastoma and neuroblastoma cancer stem cells.

methodsExpression of scavenger receptor class B type 1 in validated human neuroblastoma cells was evaluated by quantitative polymerase chain reaction (qPCR) and Western blot. In vitro cellular uptake of synthetic high-density lipoprotein nanoparticles was observed with a fluorescence microscope. In vivo biodistribution of synthetic high-density lipoprotein nanoparticles was investigated with IVIS imaging. Self-renewal and migration/invasion were assessed by sphere formation and Boyden chamber assays, respectively. Viability was analyzed by CellTiter-Glo assay. Cancer stem cell markers were evaluated by flow cytometry.

resultsqPCR and Western blot analysis revealed a higher level of scavenger receptor class B type 1 expression and drug uptake in N-myc amplified neuroblastoma cells. In vitro uptake of synthetic high-density lipoprotein was almost completely blocked by excess synthetic high-density lipoprotein. The synthetic high-density lipoprotein nanoparticles mainly accumulated in the tumor and liver, but not in other organs. Synthetic HDL-4,19,27-triacetyl withalongolide showed a 1,000-fold higher potency than the carrier (synthetic high-density lipoprotein) alone (P < .01) to kill neuroblastoma cells. Additionally, a dose-dependent decrease in sphere formation, invasion, migration, and cancer stem cell markers was observed after treatment of neuroblastoma cells with synthetic high-density lipoprotein-4,19,27-triacetyl withalongolide A.

conclusionSynthetic high-density lipoprotein is a promising platform to improve the delivery of anticancer drug 4,19,27-triacetyl withalongolide A to neuroblastomas and neuroblastoma cancer stem cells through SR-B1 targeting in vitro and in vivo.

Identifiers

PMID29753460
PMCPMC6814450
OpenAlexW2802861156

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.