Evidence map›Paper›PMID 30460772›Full record

ArticleJournal of cellular and molecular medicine2019

Deciphering the molecular effects of romidepsin on germ cell tumours: DHRS2 is involved in cell cycle arrest but not apoptosis or induction of romidepsin effectors.

Daniel Nettersheim, Daniel Berger, Sina Jostes, Margaretha Skowron, Hubert Schorle

Open access · goldAbstract read
In one paragraph

Article in Journal of cellular and molecular medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
0.8field-weighted citation impact, top 27% 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

18 citing papers in PubMed, 21 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. The BRCT Domain from the Homologue of the Oncogene PES1 inInternational journal of molecular sciences · 2022
    Article
  8. Article
  9. Review
  10. Review
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Cancers · 2020
    Article
  17. DHRS2 mediates cell growth inhibition induced by Trichothecin in nasopharyngeal carcinoma.Journal of experimental & clinical cancer research : CR · 2019
    Article
  18. 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

5 authors at 1 institution in 1 country.

Daniel NettersheimDepartment of Urology, Urological Research Lab, Translational Urooncology, University Medical School Düsseldorf, Düsseldorf, Germany.ORCID 0000-0002-4483-845X
Daniel BergerDepartment of Developmental Pathology, Institute of Pathology, University Medical School Bonn, Bonn, Germany.
Sina JostesDepartment of Developmental Pathology, Institute of Pathology, University Medical School Bonn, Bonn, Germany.
Margaretha SkowronDepartment of Urology, Urological Research Lab, Translational Urooncology, University Medical School Düsseldorf, Düsseldorf, Germany.
Hubert SchorleDepartment of Developmental Pathology, Institute of Pathology, University Medical School Bonn, Bonn, Germany.
University of Bonn · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Testicular germ cell tumours (GCTs) mostly affect young men at age 17-40. Although high cure rates can be achieved by orchiectomy and chemotherapy, GCTs can still be a lethal threat to young patients with metastases or therapy resistance. Thus, alternative treatment options are needed. Based on studies utilising GCT cell lines, the histone deacetylase inhibitor romidepsin is a promising therapeutic option, showing high toxicity at very low doses towards cisplatin-resistant GCT cells, but not fibroblasts or Sertoli cells. In this study, we extended our analysis of the molecular effects of romidepsin to deepen our understanding of the underlying mechanisms. Patients will benefit from these analyses, since detailed knowledge of the romidepsin effects allows for a better risk and side-effect assessment. We screened for changes in histone acetylation of specific lysine residues and analysed changes in the DNA methylation landscape after romidepsin treatment of the GCT cell lines TCam-2, 2102EP, NCCIT and JAR, while human fibroblasts were used as controls. In addition, we focused on the role of the dehydrogenase/reductase DHRS2, which was strongly up-regulated in romidepsin treated cells, by generating DHRS2-deficient TCam-2 cells using CRISPR/Cas9 gene editing. We show that DHRS2 is dispensable for up-regulation of romidepsin effectors (GADD45B, DUSP1, ZFP36, ATF3, FOS, CDKN1A, ID2) but contributes to induction of cell cycle arrest. Finally, we show that a combinatory treatment of romidepsin plus the gluccocorticoid dexamethasone further boosts expression of the romidepsin effectors and reduces viability of GCT cells more strongly than under single agent treatment. Thus, romidepsin and dexamethasone might represent a new combinatorial approach for treatment of GCT.

Indexed as

Antibiotics, AntineoplasticApoptosisCarbonyl Reductase (NADPH)Cell Cycle CheckpointsCell Line, TumorCell ProliferationCisplatinDepsipeptidesDexamethasoneHistone Deacetylase InhibitorsHumansNeoplasms, Germ Cell and EmbryonalTesticular NeoplasmsUp-RegulationAntibiotics, AntineoplasticCarbonyl Reductase (NADPH)CisplatinDepsipeptidesDexamethasoneDHRS2 protein, humanHistone Deacetylase InhibitorsromidepsinDHRS2/HEP27epigenetic therapygerm cell tumourhistone deacetylase inhibitorromidepsin

Identifiers

PMID30460772
PMCPMC6307807
OpenAlexW2900790986

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.