Evidence map›Paper›PMID 26368816›Full record

ArticlePloS one2015

Treatment with a Small Molecule Mutant IDH1 Inhibitor Suppresses Tumorigenic Activity and Decreases Production of the Oncometabolite 2-Hydroxyglutarate in Human Chondrosarcoma Cells.

Luyuan Li, Ana C Paz, Breelyn A Wilky, Britt Johnson, Karina Galoian, Andrew Rosenberg, Guozhi Hu, Gabriel Tinoco, Olaf Bodamer, Jonathan C Trent

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.

0numbers the graph read from it
0cells of the map it votes in
69citing papers in PubMed
11.0field-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

69 citing papers in PubMed, 106 citations in OpenAlex.

  1. Trial
  2. Review
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  4. Isocitrate dehydrogenase mutations as potential tumour agnostic targets.EJC supplements : EJC : official journal of EORTC, European Organization for Research and Treatment of Cancer ... [et al.] · 2026
    Article
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  8. Review
  9. Article
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  11. Article
  12. Cancers · 2023
    Review
  13. Article
  14. Article
  15. Review
  16. Review
  17. Epigenetic Abnormalities in Chondrosarcoma.International journal of molecular sciences · 2023
    Review
  18. Article
  19. Article
  20. Article

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

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 2 institutions in 1 country.

Luyuan LiDivision of Hematology and Oncology/Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, United States of America; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida, United States of America; Sheila and David Fuente Graduate Program in Cancer Biology, University of Miami Miller School of Medicine, Miami, Florida, United States of America.
Ana C PazDivision of Hematology and Oncology/Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, United States of America; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida, United States of America.
Breelyn A WilkyDivision of Hematology and Oncology/Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, United States of America; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida, United States of America.
Britt JohnsonDepartment of Human Genetics, University of Miami Miller School of Medicine, Miami, Florida, United States of America.
Karina GaloianDepartment of Orthopaedic Surgery, University of Miami Miller School of Medicine, Miami, Florida, United States of America.
Andrew RosenbergDepartment of Pathology, University of Miami Miller School of Medicine, Miami, Florida, United States of America.
Guozhi HuDivision of Hematology and Oncology/Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, United States of America; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida, United States of America.
Gabriel TinocoDivision of Hematology and Oncology/Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, United States of America; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida, United States of America.
Olaf BodamerDepartment of Human Genetics, University of Miami Miller School of Medicine, Miami, Florida, United States of America.
Jonathan C TrentDivision of Hematology and Oncology/Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, United States of America; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida, United States of America; Sheila and David Fuente Graduate Program in Cancer Biology, University of Miami Miller School of Medicine, Miami, Florida, United States of America.
University of Miami · USSylvester Comprehensive Cancer Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Chondrosarcomas are malignant bone tumors that produce cartilaginous matrix. Mutations in isocitrate dehydrogenase enzymes (IDH1/2) were recently described in several cancers including chondrosarcomas. The IDH1 inhibitor AGI-5198 abrogates the ability of mutant IDH1 to produce the oncometabolite D-2 hydroxyglutarate (D-2HG) in gliomas. We sought to determine if treatment with AGI-5198 would similarly inhibit tumorigenic activity and D-2HG production in IDH1-mutant human chondrosarcoma cells. Two human chondrosarcoma cell lines, JJ012 and HT1080 with endogenous IDH1 mutations and a human chondrocyte cell line C28 with wild type IDH1 were employed in our study. Mutation analysis of IDH was performed by PCR-based DNA sequencing, and D-2HG was detected using tandem mass spectrometry. We confirmed that JJ012 and HT1080 harbor IDH1 R132G and R132C mutation, respectively, while C28 has no mutation. D-2HG was detectable in cell pellets and media of JJ012 and HT1080 cells, as well as plasma and urine from an IDH-mutant chondrosarcoma patient, which decreased after tumor resection. AGI-5198 treatment decreased D-2HG levels in JJ012 and HT1080 cells in a dose-dependent manner, and dramatically inhibited colony formation and migration, interrupted cell cycling, and induced apoptosis. In conclusion, our study demonstrates anti-tumor activity of a mutant IDH1 inhibitor in human chondrosarcoma cell lines, and suggests that D-2HG is a potential biomarker for IDH mutations in chondrosarcoma cells. Thus, clinical trials of mutant IDH inhibitors are warranted for patients with IDH-mutant chondrosarcomas.

Indexed as

ApoptosisBenzeneacetamidesCell Line, TumorChondrocytesChondrosarcomaEnzyme InhibitorsGlutaratesHumansImidazolesIsocitrate DehydrogenaseMutation, MissenseAGI-5198alpha-hydroxyglutarateBenzeneacetamidesEnzyme InhibitorsGlutaratesIDH1 protein, humanImidazolesIsocitrate Dehydrogenase

Identifiers

PMID26368816
PMCPMC4569544
OpenAlexW2209736027

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.