Evidence map›Paper›PMID 34439353›Full record

ArticleCancers2021

Selective Targeting of Class I Histone Deacetylases in a Model of Human Osteosarcoma.

Haydee M Torres, Ashley M VanCleave, Mykayla Vollmer, Dakota L Callahan, Austyn Smithback, Josephine M Conn, Tania Rodezno-Antunes, Zili Gao, Yuxia Cao, Yohannes Afeworki and 1 more

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.7field-weighted citation impact, top 31% 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

6 citing papers in PubMed, 9 citations in OpenAlex.

  1. Whole-Exome Analysis and Osteosarcoma: A Game Still Open.International journal of molecular sciences · 2024
    Review
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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

11 authors at 5 institutions in 1 country.

Haydee M TorresCancer Biology & Immunotherapies Group at Sanford Research, Sioux Falls, SD 57104, USA.ORCID 0000-0002-9912-6230
Ashley M VanCleaveCancer Biology & Immunotherapies Group at Sanford Research, Sioux Falls, SD 57104, USA.ORCID 0000-0002-2033-1822
Mykayla VollmerMedical Student Research Program, University of South Dakota, Vermillion, SD 57069, USA.
Dakota L CallahanSanford Program for Undergraduate Research, University of Sioux Falls, Sioux Falls, SD 57104, USA.
Austyn SmithbackSanford PROMISE Scholar Program, Harrisburg High School, Sioux Falls, SD 57104, USA.
Josephine M ConnSanford Program for Undergraduate Research, Carleton College, Northfield, MN 55057, USA.
Tania Rodezno-AntunesCancer Biology & Immunotherapies Group at Sanford Research, Sioux Falls, SD 57104, USA.
Zili GaoFlow Cytometry Core at Sanford Research, Sioux Falls, SD 57104, USA.
Yuxia CaoCancer Biology & Immunotherapies Group at Sanford Research, Sioux Falls, SD 57104, USA.
Yohannes AfeworkiFunctional Genomics & Bioinformatics Core Facility at Sanford Research, Sioux Falls, SD 57104, USA.ORCID 0000-0002-1126-1527
Jianning TaoCancer Biology & Immunotherapies Group at Sanford Research, Sioux Falls, SD 57104, USA.ORCID 0000-0001-5678-9272
Sanford Research · USSouth Dakota State University · USCarleton College · USUniversity of Sioux Falls · USUniversity of South Dakota · US

Funding

Yeast 2 HybridP20GM103620 · NIGMS · SANFORD RESEARCH/USD · PI ROUX, KYLE J · 2013 to 2023
$24.2M
The Impact of PD-1 Inhibition on Immune-Response to ChemoradiotherapyP20GM103548 · NIGMS · SANFORD RESEARCH/USD · PI EGLAND, KRISTI A · 2012 to 2020
$20.8M
Geographical Management of Cancer Health Disparities Region 6 GMaP6 Research Stimulus AwardNIGMS NIH HHS P20 GM103548NIGMS NIH HHS P20 GM103620NIH HHS P20 GM103548NIH HHS P20 GM103620NIH HHS P30CA042014-31S2
6 · The paper itself

Abstract

Dysregulation of histone deacetylases (HDACs) is associated with the pathogenesis of human osteosarcoma, which may present an epigenetic vulnerability as well as a therapeutic target. Domatinostat (4SC-202) is a next-generation class I HDAC inhibitor that is currently being used in clinical research for certain cancers, but its impact on human osteosarcoma has yet to be explored. In this study, we report that 4SC-202 inhibits osteosarcoma cell growth in vitro and in vivo. By analyzing cell function in vitro, we show that the anti-tumor effect of 4SC-202 involves the combined induction of cell-cycle arrest at the G2/M phase and apoptotic program, as well as a reduction in cell invasion and migration capabilities. We also found that 4SC-202 has little capacity to promote osteogenic differentiation. Remarkably, 4SC-202 revised the global transcriptome and induced distinct signatures of gene expression in vitro. Moreover, 4SC-202 decreased tumor growth of established human tumor xenografts in immunodeficient mice in vivo. We further reveal key targets regulated by 4SC-202 that contribute to tumor cell growth and survival, and canonical signaling pathways associated with progression and metastasis of osteosarcoma. Our study suggests that 4SC-202 may be exploited as a valuable drug to promote more effective treatment of patients with osteosarcoma and provide molecular insights into the mechanism of action of class I HDAC inhibitors.

Indexed as

4SC-202domatinostatepigeneticshistone deacetylase inhibitorosteoblast-like differentiationosteosarcomasignaling pathwaystranscriptomexenografts

Identifiers

PMID34439353
PMCPMC8394112
OpenAlexW3193636802

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.