Evidence map›Paper›PMID 31319571›Full record

ArticleCancers2019

In-Vitro and In-Vivo Establishment and Characterization of Bioluminescent Orthotopic Chemotherapy-Resistant Human Osteosarcoma Models in NSG Mice.

Maria Eugénia Marques da Costa, Antonin Marchais, Anne Gomez-Brouchet, Bastien Job, Noémie Assoun, Estelle Daudigeos-Dubus, Olivia Fromigué, Conceição Santos, Birgit Geoerger, Nathalie Gaspar

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.6field-weighted citation impact, top 15% 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

10 citing papers in PubMed, 14 citations in OpenAlex.

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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

10 authors at 4 institutions in 2 countries.

Maria Eugénia Marques da CostaNational Centre for Scientific Research (CNRS), UMR8203, Gustave Roussy, 94805 Villejuif, France.ORCID 0000-0002-1498-603X
Antonin MarchaisNational Centre for Scientific Research (CNRS), UMR8203, Gustave Roussy, 94805 Villejuif, France.
Anne Gomez-BrouchetIUCT-Oncopole, CHU and University of Toulouse, Pathology department, 31100 Toulouse, France.
Bastien JobNational Institute for Health and Medical Research (INSERM), US23, Gustave Roussy, 94805 Villejuif, France.
Noémie AssounNational Centre for Scientific Research (CNRS), UMR8203, Gustave Roussy, 94805 Villejuif, France.
Estelle Daudigeos-DubusNational Centre for Scientific Research (CNRS), UMR8203, Gustave Roussy, 94805 Villejuif, France.
Olivia FromiguéUniversity of Paris Sud, 91400 Orsay, France.ORCID 0000-0002-3050-6155
Conceição SantosDepartment of Biology, Faculty of Sciences, University of Porto, 4000 Porto, Portugal.
Birgit GeoergerNational Centre for Scientific Research (CNRS), UMR8203, Gustave Roussy, 94805 Villejuif, France.ORCID 0000-0003-4361-3643
Nathalie GasparNational Centre for Scientific Research (CNRS), UMR8203, Gustave Roussy, 94805 Villejuif, France. nathalie.gaspar@gustaveroussy.fr.
Université Paris-Sud · FRCentre National de la Recherche Scientifique · FRInserm · FRUniversidade do Porto · PT

Funding

Etoile de Martin OsteomicsFédération Enfants et Santé OsteomicsFoundation For Science and Technology SFRH/BD/89137/2012Ligue Contre le Cancer OsteomicsSFCE OsteomicsUne main Vers l'Espoir association Osteomics
6 · The paper itself

Abstract

Osteosarcoma, the most common bone malignancy with a peak incidence at adolescence, had no survival improvement since decades. Persistent problems are chemo-resistance and metastatic spread. We developed in-vitro osteosarcoma models resistant to chemotherapy and in-vivo bioluminescent orthotopic cell-derived-xenografts (CDX). Continuous increasing drug concentration cultures in-vitro resulted in five methotrexate (MTX)-resistant and one doxorubicin (DOXO)-resistant cell lines. Resistance persisted after drug removal except for MG-63. Different resistance mechanisms were identified, affecting drug transport and action mechanisms specific to methotrexate (RFC/SCL19A1 decrease, DHFR up-regulation) for MTX-resistant lines, or a multi-drug phenomenon (PgP up-regulation) for HOS-R/DOXO. Differential analysis of copy number abnormalities (aCGH) and gene expression (RNAseq) revealed changes of several chromosomic regions translated at transcriptomic level depending on drug and cell line, as well as different pathways implicated in invasive and metastatic potential (e.g., Fas, Metalloproteinases) and immunity (enrichment in HLA cluster genes in 6p21.3) in HOS-R/DOXO. Resistant-CDX models (HOS-R/MTX, HOS-R/DOXO and Saos-2-B-R/MTX) injected intratibially into NSG mice behaved as their parental counterpart at primary tumor site; however, they exhibited a slower growth rate and lower metastatic spread, although they retained resistance and CGH main characteristics without drug pressure. These models represent valuable tools to explore resistance mechanisms and new therapies in osteosarcoma.

Indexed as

bioluminescencebone tumorcell-derived xenograftDHFRdoxorubicinMDR1methotrexateresistance

Identifiers

PMID31319571
PMCPMC6678535
OpenAlexW2958622517

What OpenQuestion holds

Textmetadata
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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.