Evidence map›Paper›PMID 27932296›Full record

ArticleEBioMedicine2017

Low Density Lipoproteins Amplify Cytokine-signaling in Chronic Lymphocytic Leukemia Cells.

Lindsay McCaw, Yonghong Shi, Guizhi Wang, You-Jun Li, David E Spaner

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

Article in EBioMedicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
2.0field-weighted citation impact, top 13% 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

25 citing papers in PubMed, 55 citations in OpenAlex.

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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

5 authors at 2 institutions in 2 countries.

Lindsay McCawBiology Platform, Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada; Department of Nutritional Sciences, University of Toronto, Toronto, ON, Canada.
Yonghong ShiBiology Platform, Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada.
Guizhi WangBiology Platform, Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada.
You-Jun LiBiology Platform, Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada; Department of Human Anatomy, College of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, China.
David E SpanerBiology Platform, Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada; Department of Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Medicine, University of Toronto, Toronto, ON M5G 2C4, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 2M9, Canada; Sunnybrook Odette Cancer Center, Toronto, ON M4N 3M5, Canada. Electronic address: spanerd@sri.utoronto.ca.
Sunnybrook Research InstituteSunnybrook Health Science Centre · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Recent studies suggest there is a high incidence of elevated low-density lipoprotein (LDL) levels in Chronic Lymphocytic Leukemia (CLL) patients and a survival benefit from cholesterol-lowering statin drugs. The mechanisms of these observations and the kinds of patients they apply to are unclear. Using an in vitro model of the pseudofollicles where CLL cells originate, LDLs were found to increase plasma membrane cholesterol, signaling molecules such as tyrosine-phosphorylated STAT3, and activated CLL cell numbers. The signaling effects of LDLs were not seen in normal lymphocytes or glycolytic lymphoma cell-lines but were restored by transduction with the nuclear receptor PPARδ, which mediates metabolic activity in CLL cells. Breakdown of LDLs in lysosomes was required for the amplification effect, which correlated with down-regulation of HMGCR expression and long lymphocyte doubling times (LDTs) of 53.6±10.4months. Cholesterol content of circulating CLL cells correlated directly with blood LDL levels in a subgroup of patients. These observations suggest LDLs may enhance proliferative responses of CLL cells to inflammatory signals. Prospective clinical trials are needed to confirm the therapeutic potential of lowering LDL concentrations in CLL, particularly in patients with indolent disease in the "watch-and-wait" phase of management.

Indexed as

Signal TransductionCell Line, TumorCytokinesHumansHydroxymethylglutaryl-CoA Reductase InhibitorsHydroxymethylglutaryl CoA ReductasesLeukemia, Lymphocytic, Chronic, B-CellLipid MetabolismLipoproteins, LDLLymphocytesLysosomesPhosphorylationSTAT3 Transcription FactorVitamin ECytokinesHydroxymethylglutaryl-CoA Reductase InhibitorsHydroxymethylglutaryl CoA ReductasesLipoproteins, LDLSTAT3 Transcription FactorVitamin ECholesterolChronic lymphocytic leukemiaHMGCRJanus kinasesLipoproteinsLysosomal lipaseNuclear receptorsRuxolitinibSTAT3

Identifiers

PMID27932296
PMCPMC5233814
OpenAlexW2559590288

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.