Evidence map›Paper›PMID 26668189›Full record

ArticleMolecular cancer therapeutics2016

A Novel Inhibitor of Topoisomerase I Is Selectively Toxic for a Subset of Non-Small Cell Lung Cancer Cell Lines.

Iryna O Zubovych, Anirudh Sethi, Aditya Kulkarni, Vural Tagal, Michael G Roth

Abstract read
In one paragraph

Article in Molecular cancer therapeutics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed, 5 citations in OpenAlex.

  1. 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

5 authors at 1 institution in 1 country.

Iryna O ZubovychDepartment of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas.
Anirudh SethiDepartment of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas.
Aditya KulkarniDepartment of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas.
Vural TagalDepartment of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas.
Michael G RothDepartment of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas. michael.roth@utsouthwestern.edu.
The University of Texas Southwestern Medical Center · US

Funding

UT Southwestern Medical Center Simmons Comprehensive Cancer CenterP30CA142543 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI Sandi Leigh Pruitt · 2010 to 2026
$53.7M
Lung cancer oncogenotype-selective drug target discoveryU01CA176284 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI MACMILLAN, JOHN B, MINNA, JOHN D. · 2013 to 2016
$2.8M
EXTRAMURAL RESEARCH FACILITIES CONSTRUCTIONC06RR015437 · NCRR · UNIVERSITY OF TEXAS SW MED CTR/DALLAS · PI ADAMS, PERRIE M · 2000 to 2000
$2.0M
CCR NIH HHS RC2148255NCI NIH HHS P30 CA142543NCI NIH HHS U01 CA176284NCI NIH HHS U01CA176284NCRR NIH HHS C06 RR015437NCRR NIH HHS C06-RR15437
6 · The paper itself

Abstract

SW044248, identified through a screen for chemicals that are selectively toxic for non-small cell lung cancer (NSCLC) cell lines, was found to rapidly inhibit macromolecular synthesis in sensitive, but not in insensitive, cells. SW044248 killed approximately 15% of a panel of 74 NSCLC cell lines and was nontoxic to immortalized human bronchial cell lines. The acute transcriptional response to SW044248 in sensitive HCC4017 cells correlated significantly with inhibitors of topoisomerases and SW044248 inhibited topoisomerase 1 (Top1) but not topoisomerase 2. SW044248 inhibited Top1 differently from camptothecin and camptothecin did not show the same selective toxicity as SW044248. Elimination of Top1 by siRNA partially protected cells from SW044248, although removing Top1 was itself eventually toxic. Cells resistant to SW044248 responded to the compound by upregulating CDKN1A and siRNA to CDKN1A sensitized those cells to SW044248. Thus, at least part of the differential sensitivity of NSCLC cells to SW044248 is the ability to upregulate CDKN1A.

Indexed as

Antineoplastic AgentsCarcinoma, Non-Small-Cell LungCell Line, TumorCyclin-Dependent Kinase Inhibitor p21DNA DamageDNA ReplicationDose-Response Relationship, DrugHumansIndolesInhibitory Concentration 50Lung NeoplasmsProtein BiosynthesisStress, PhysiologicalTopoisomerase I InhibitorsTranscription FactorsTranscription, GeneticAntineoplastic AgentsCyclin-Dependent Kinase Inhibitor p21ELF2 protein, humanIndolesSW044248Topoisomerase I InhibitorsTranscription FactorsTriazines

Identifiers

PMID26668189
PMCPMC4707128
OpenAlexW2219630070

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.