Evidence map›Paper›PMID 24496871›Full record

ArticleCancer2014

Design, development, and validation of a high-throughput drug-screening assay for targeting of human leukemia.

Katja Karjalainen, Renata Pasqualini, Jorge E Cortes, Steven M Kornblau, Benjamin Lichtiger, Susan O'Brien, Hagop M Kantarjian, Richard L Sidman, Wadih Arap, Erkki Koivunen

Open access · bronzeAbstract read
In one paragraph

Article in Cancer, 2014. 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
–field-weighted citation impact, top 85% 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, 4 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

10 authors at 3 institutions in 2 countries.

Katja KarjalainenDavid H. Koch Center, The University of Texas MD Anderson Cancer Center, Houston, Texas; Department of Biological and Environmental Sciences, Division of Biochemistry, The University of Helsinki, Helsinki, Finland.
Renata Pasqualini
Jorge E Cortes
Steven M Kornblau
Benjamin Lichtiger
Susan O'Brien
Hagop M Kantarjian
Richard L Sidman
Wadih Arap
Erkki Koivunen
The University of Texas MD Anderson Cancer Center · USBeth Israel Deaconess Medical Center · USHelsinki Institute of Physics · FI

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8M
NCI NIH HHS P30 CA016672
6 · The paper itself

Abstract

backgroundThe authors developed an ex vivo methodology to perform drug library screening against human leukemia.

methodsThe strategy for this screening relied on human blood or bone marrow cultures under hypoxia; under these conditions, leukemia cells deplete oxygen faster than normal cells, causing a hemoglobin oxygenation shift. Several advantages were observed: 1) partial recapitulation of the leukemia microenvironment, 2) use of native hemoglobin oxygenation as a real-time sensor/reporter, 3) cost-effectiveness, 4) species specificity, and 5) a format that enables high-throughput screening.

resultsFor a proof of concept, a chemical library (size, approximately 20,000 compounds) was screened against human leukemia cells. Seventy compounds were identified ("hit" rate, 0.35%; Z-factor = 0.71) that had activity, and 20 compounds were examined to identify 18 true-positive compounds (90%). Finally, the results demonstrated that carbonohydraxonic diamide group-containing compounds are potent antileukemia agents that induce cell death in leukemia cells and in patient-derived samples.

conclusionsThe current results indicated that this unique functional assay can identify novel drug candidates and can help with the development of future applications in personalized drug selection for patients with leukemia.

Indexed as

Drug Screening Assays, AntitumorSmall Molecule LibrariesHigh-Throughput Screening AssaysHumansLeukemiaOxygenOxygenSmall Molecule Librariesbloodbone marrowchemical librarydrug screeninghypoxialeukemia targetingtumor microenvironment

Identifiers

PMID24496871
PMCPMC4457455
OpenAlexW2155822347

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.