Evidence map›Paper›PMID 25653139›Full record

ArticleNature communications2015

Quantitative high throughput screening using a primary human three-dimensional organotypic culture predicts in vivo efficacy.

Hilary A Kenny, Madhu Lal-Nag, Erin A White, Min Shen, Chun-Yi Chiang, Anirban K Mitra, Yilin Zhang, Marion Curtis, Elizabeth M Schryver, Sam Bettis and 5 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Nature communications, 2015. 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 90 papers.

0numbers the graph read from it
0cells of the map it votes in
90citing papers in PubMed
10.8field-weighted citation impact, top 1% 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

90 citing papers in PubMed, 177 citations in OpenAlex.

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30 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 4 institutions in 1 country.

Hilary A KennyDepartment of Obstetrics and Gynecology/Section of Gynecologic Oncology, University of Chicago, 5841 South Maryland Avenue, MC2050, Chicago, Illinois 60637, USA.
Madhu Lal-NagDivision of Preclinical Innovation, National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, 9800 Medical Center Drive, Building B, Rockville, Maryland 20850, USA.
Erin A WhiteDepartment of Obstetrics and Gynecology/Section of Gynecologic Oncology, University of Chicago, 5841 South Maryland Avenue, MC2050, Chicago, Illinois 60637, USA.
Min ShenDivision of Preclinical Innovation, National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, 9800 Medical Center Drive, Building B, Rockville, Maryland 20850, USA.
Chun-Yi ChiangDepartment of Obstetrics and Gynecology/Section of Gynecologic Oncology, University of Chicago, 5841 South Maryland Avenue, MC2050, Chicago, Illinois 60637, USA.
Anirban K MitraDepartment of Obstetrics and Gynecology/Section of Gynecologic Oncology, University of Chicago, 5841 South Maryland Avenue, MC2050, Chicago, Illinois 60637, USA.
Yilin ZhangDepartment of Obstetrics and Gynecology/Section of Gynecologic Oncology, University of Chicago, 5841 South Maryland Avenue, MC2050, Chicago, Illinois 60637, USA.
Marion CurtisDepartment of Obstetrics and Gynecology/Section of Gynecologic Oncology, University of Chicago, 5841 South Maryland Avenue, MC2050, Chicago, Illinois 60637, USA.
Elizabeth M SchryverDepartment of Obstetrics and Gynecology/Section of Gynecologic Oncology, University of Chicago, 5841 South Maryland Avenue, MC2050, Chicago, Illinois 60637, USA.
Sam BettisInstitute of Genomics and Systems Biology, University of Chicago, 5841 South Maryland Avenue, MC2050, Chicago, Illinois 60637, USA.
Ajit JadhavDivision of Preclinical Innovation, National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, 9800 Medical Center Drive, Building B, Rockville, Maryland 20850, USA.
Matthew B BoxerDivision of Preclinical Innovation, National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, 9800 Medical Center Drive, Building B, Rockville, Maryland 20850, USA.
Zhuyin Li1] Division of Preclinical Innovation, National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, 9800 Medical Center Drive, Building B, Rockville, Maryland 20850, USA [2] Lead Discovery and Optimization, Bristol-Myers Squibb, 5 Research Parkway, Wallingford, Connecticut 06492, USA.
Marc FerrerDivision of Preclinical Innovation, National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, 9800 Medical Center Drive, Building B, Rockville, Maryland 20850, USA.
Ernst LengyelDepartment of Obstetrics and Gynecology/Section of Gynecologic Oncology, University of Chicago, 5841 South Maryland Avenue, MC2050, Chicago, Illinois 60637, USA.
University of Chicago · USNational Institutes of Health · USBristol-Myers Squibb (United States) · USNational Center for Advancing Translational Sciences · US

Funding

Trans-NIH RNAi Facility (TNRF)ZICTR000041 · NCATS · NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES · PI CHENG, KEN · 2015 to 2025
$9.4M
Regulation of Adhesion and Proteolysis in Ovarian CancerR01CA111882 · NCI · UNIVERSITY OF CHICAGO · PI LENGYEL, ERNST · 2006 to 2016
$2.8M
Adaptation of an Organotypic 3 Dimensional Culture for High-Throughput ScreeningR21NS075702 · NINDS · UNIVERSITY OF CHICAGO · PI LENGYEL, ERNST · 2011 to 2011
$156k
NCI NIH HHS R01 CA111882NIMH NIH HHS U54 MH084681NINDS NIH HHS R21 NS075702
6 · The paper itself

Abstract

The tumour microenvironment contributes to cancer metastasis and drug resistance. However, most high throughput screening (HTS) assays for drug discovery use cancer cells grown in monolayers. Here we show that a multilayered culture containing primary human fibroblasts, mesothelial cells and extracellular matrix can be adapted into a reliable 384- and 1,536-multi-well HTS assay that reproduces the human ovarian cancer (OvCa) metastatic microenvironment. We validate the identified inhibitors in secondary in vitro and in vivo biological assays using three OvCa cell lines: HeyA8, SKOV3ip1 and Tyk-nu. The active compounds directly inhibit at least two of the three OvCa functions: adhesion, invasion and growth. In vivo, these compounds prevent OvCa adhesion, invasion and metastasis, and improve survival in mouse models. Collectively, these data indicate that a complex three-dimensional culture of the tumour microenvironment can be adapted for quantitative HTS and may improve the disease relevance of assays used for drug screening.

Indexed as

AnimalsAntineoplastic AgentsBenzophenanthridinesBiguanidesCantharidinCell AdhesionCell MovementCell ProliferationCoculture TechniquesEpithelial CellsEscinExtracellular MatrixFemaleFibroblastsHigh-Throughput Screening AssaysHumansalexidineAntineoplastic AgentsBenzophenanthridinesBiguanidesCantharidinEscinIsoquinolinesProchlorperazinesanguinarineTomatine

Identifiers

PMID25653139
PMCPMC4427252
OpenAlexW2020216997

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.