Evidence map›Paper›PMID 26815725›Full record

ArticleStem cell reviews and reports2016

Disparate Response to Methotrexate in Stem Versus Non-Stem Cells.

Olivia S Beane, Louise E O Darling, Vera C Fonseca, Eric M Darling

Open access · greenAbstract read
In one paragraph

Article in Stem cell reviews and reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.0field-weighted citation impact, top 24% 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

8 citing papers in PubMed, 9 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

4 authors at 2 institutions in 1 country.

Olivia S BeaneCenter for Biomedical Engineering, Brown University, Providence, RI, USA.
Louise E O DarlingDepartment of Biological Sciences, Wellesley College, Wellesley, MA, USA.
Vera C FonsecaDepartment of Molecular Pharmacology, Physiology, & Biotechnology, Brown University, Providence, RI, USA.
Eric M DarlingCenter for Biomedical Engineering, Brown University, Providence, RI, USA. eric_darling@brown.edu.
Brown University · USWellesley College · US

Funding

High-yield, lineage-specific enrichment of living mesenchymal stem cellsR01AR063642 · NIAMS · BROWN UNIVERSITY · PI DARLING, ERIC M · 2013 to 2018
$1.8M
NIAMS NIH HHS R01 AR063642
6 · The paper itself

Abstract

Methotrexate (MTX) is a commonly used chemotherapeutic agent that kills cancer cells by binding dihydrofolate reductase (DHFR) as a competitive inhibitor. Due to its non-selectivity, MTX also impairs normal (non-cancerous) cell function and causes long-term damage to healthy tissue. These consequences have been investigated extensively in bone-derived cells due to their sensitivity to the drug. While DHFR likely plays a role in normal cell response to MTX, research in this area is limited. Moreover, how MTX sensitivity differs among cell types responsible for maintaining connective tissues is unknown. The goal of this study was to investigate the role of DHFR and subsequent nucleotide synthesis in normal cell response to MTX. We also sought to compare adverse effects of MTX among normal cell types to identify sensitive populations and resistant cell sources for regenerative procedures targeting patients undergoing chemotherapy. DHFR overexpression or exogenous amino acid + nucleoside delivery rescued normal cells from adverse MTX effects. Conversely, DHFR knockdown impaired MTX-treated adipose-derived stem cell (ASC) osteogenesis. Proliferation of ASCs and bone marrow stem cells was more resistant to MTX than that of terminally differentiated osteoblasts. However, stem cells became susceptible to the drug after beginning differentiation. These results suggest that the ability of stem cells to survive and to maintain their surrounding tissues likely depends on whether they are in a "stem" state when exposed to MTX. Therapeutic strategies that delay the differentiation of stem cells until clearance of the drug may produce more favorable outcomes in the long-term health of treated tissues.

Indexed as

AdipocytesCell DifferentiationCell ProliferationCells, CulturedCell SurvivalHumansMesenchymal Stem CellsMethotrexateOsteogenesisRegenerationStem CellsTetrahydrofolate DehydrogenaseMethotrexateTetrahydrofolate DehydrogenaseCancerChemotherapyMesenchymal stem cellMethotrexateRegenerative medicine

Identifiers

PMID26815725
PMCPMC4880537
OpenAlexW2297766973

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.