Evidence map›Paper›PMID 21257818›Full record

ArticleMolecular cancer research : MCR2011

An image-based, high-throughput screening assay for molecules that induce excess DNA replication in human cancer cells.

Wenge Zhu, Chrissie Y Lee, Ronald L Johnson, Jennifer Wichterman, Ruili Huang, Melvin L DePamphilis

Erratum issuedOpen access · bronzeAbstract readEvaluation StudyValidation Study
In one paragraph

Article in Molecular cancer research : MCR, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
0.5field-weighted citation impact, top 33% 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

13 citing papers in PubMed, 16 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Regulation of Mammalian DNA Replication via the Ubiquitin-Proteasome System.Advances in experimental medicine and biology · 2017
    Review
  9. Article
  10. Article
  11. Genomic instability in cancer.Cold Spring Harbor perspectives in biology · 2013
    Review
  12. Review
  13. Article
4 · The record

Corrections and comments

  • Erratum issued
5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Wenge ZhuNational Institute of Child Health and Human Development, NIH, Bethesda, MD 20892-2753, USA.
Chrissie Y Lee
Ronald L Johnson
Jennifer Wichterman
Ruili Huang
Melvin L DePamphilis
Eunice Kennedy Shriver National Institute of Child Health and Human Development · US

Funding

NIH Chemical Genomics CenterZIBHG200319 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI AUSTIN, CHRISTOPHER P · 2010 to 2011
$55.9M
Initiation Of DNA Replication In Mammalian ChromosomesZIAHD000506 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI DEPAMPHILIS, MELVIN · 2009 to 2023
$15.4M
DNA Replication Control and Its Application to Selective Killing of Cancer CellsR00CA136555 · NCI · GEORGE WASHINGTON UNIVERSITY · PI ZHU, WENGE · 2010 to 2012
$732k
Intramural NIH HHS Z99 HD999999NCI NIH HHS 4R00CA136555NCI NIH HHS R00 CA136555
6 · The paper itself

Abstract

Previous studies have shown DNA re-replication can be induced in cells derived from human cancers under conditions in which it is not possible for cells derived from normal tissues. Because DNA re-replication induces cell death, this strategy could be applied to the discovery of potential anticancer therapeutics. Therefore, an imaging assay amenable to high-throughput screening was developed that measures DNA replication in excess of four genomic equivalents in the nuclei of intact cells and indexes cell proliferation. This assay was validated by screening a library of 1,280 bioactive molecules on both normal and tumor-derived cells where it proved more sensitive than current methods for detecting excess DNA replication. This screen identified known inducers of excess DNA replication, such as inhibitors of microtubule dynamics, and novel compounds that induced excess DNA replication in both normal and cancer cells. In addition, two compounds were identified that induced excess DNA replication selectively in cancer cells and one that induced endocycles selectively in cancer cells. Thus, this assay provides a new approach to the discovery of compounds useful for investigating the regulation of genome duplication and for the treatment of cancer.

Indexed as

Antineoplastic AgentsCell DeathCell Line, TumorCell ProliferationDisulfiramDNA ReplicationDrug Screening Assays, AntitumorHigh-Throughput Screening AssaysHumansIndolesNeoplasmsPargylineSmall Molecule LibrariesSulfonamides3-phenylpropargylamineAntineoplastic AgentsDisulfiramIndolesPargylineSmall Molecule LibrariesSU 6656Sulfonamides

Identifiers

PMID21257818
PMCPMC3060295
OpenAlexW2149900291

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.