Evidence map›Paper›PMID 22560972›Full record

ArticleNuclear medicine and biology2012

The effects of 5-fluoruracil treatment on 3'-fluoro-3'-deoxythymidine (FLT) transport and metabolism in proliferating and non-proliferating cultures of human tumor cells.

David A Plotnik, Lena J McLaughlin, Kenneth A Krohn, Jeffrey L Schwartz

Abstract read
In one paragraph

Article in Nuclear medicine and biology, 2012. 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
0.6field-weighted citation impact, top 30% 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, 13 citations in OpenAlex.

  1. Article
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  3. Response Monitoring with [Molecular imaging and biology · 2017
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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 1 institution in 1 country.

David A PlotnikDepartment of Radiation Oncology, University of Washington, Box 356069 Seattle, WA 98195, USA.
Lena J McLaughlin
Kenneth A Krohn
Jeffrey L Schwartz
University of Washington · US

Funding

RadiochemistryP01CA042045 · NCI · UNIVERSITY OF WASHINGTON · PI LINK, JEANNE MEYERS · 1986 to 2015
$23.2M
PET Proliferation TracersR01CA118130 · NCI · UNIVERSITY OF WASHINGTON · PI SCHWARTZ, JEFFREY L. · 2008 to 2012
$1.7M
NCI NIH HHS CA118130NCI NIH HHS P01 CA042045NCI NIH HHS R01 CA118130
6 · The paper itself

Abstract

unlabelled3'-Fluoro-3'-deoxythymidine (FLT) positron emission tomography (PET) has been proposed for imaging thymidylate synthase (TS) inhibition. Agents that target TS and shut down de novo synthesis of thymidine monophosphate increase the uptake and retention of FLT in vitro and in vivo because of a compensating increase in the salvage pathway. Increases in both thymidine kinase-1 (TK1) and the equilibrative nucleoside transporter hENT1 have been reported to underlie this effect. We examined whether the effects of one TS inhibitor, 5-fluorouracil (5FU), on FLT uptake require proliferating cells and whether the effects are limited to increasing TK1 activity.

methodsThe effects of 5FU on FLT transport and metabolism, TK1 activity, and cell cycle progression were evaluated in the human tumor cell line, A549, maintained as either a proliferating or non-proliferating culture.

resultsThere were dose-dependent increases in FLT uptake that peaked after a 10 μM 5FU exposure and then declined to baseline levels or below at higher doses in both proliferating and non-proliferating cultures. The dose-dependence for FLT uptake was mirrored by changes in TK1 activity. S phase fraction did not correlate with FLT uptake in proliferating cultures. Chemical inhibition of hENT1 reduced overall levels of FLT uptake but did not affect the low dose increase in FLT uptake.

conclusions5FU only affects FLT uptake in proliferating A549 cells and increases in FLT uptake are directly related to increased TK1 activity. Our studies did not support a role for hENT1 in the increased uptake of FLT after exposure to 5FU. Our studies with A549 cells support the suggestion that FLT-PET could provide a measure of TS inhibition in vivo.

Indexed as

Antineoplastic AgentsBiological TransportCell CycleCell Line, TumorCell ProliferationDideoxynucleosidesFluorouracilHumansThymidine KinasealovudineAntineoplastic AgentsDideoxynucleosidesFluorouracilThymidine Kinasethymidine kinase 1

Identifiers

PMID22560972
PMCPMC3435469
OpenAlexW2033000117

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.