Evidence map›Paper›PMID 28536927›Full record

ArticleCellular oncology (Dordrecht, Netherlands)2017

Involvement of the DNA mismatch repair system in cisplatin sensitivity of testicular germ cell tumours.

Christiane Rudolph, Cecilie Melau, John E Nielsen, Kristina Vile Jensen, Dekang Liu, Javier Pena-Diaz, Ewa Rajpert-De Meyts, Lene Juel Rasmussen, Anne Jørgensen

Abstract read
In one paragraph

Article in Cellular oncology (Dordrecht, Netherlands), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
4.0field-weighted citation impact, top 6% 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

20 citing papers in PubMed, 35 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Biomarkers for Salvage Therapy in Testicular Germ Cell Tumors.International journal of molecular sciences · 2023
    Review
  5. Review
  6. Review
  7. Article
  8. Review
  9. Article
  10. Mismatch repair deficiency occurs very rarely in seminomas.Translational andrology and urology · 2021
    Article
  11. Review
  12. Article
  13. Frontiers in oncology · 2020
    Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review
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

9 authors at 2 institutions in 1 country.

Christiane RudolphUniversity Department of Growth and Reproduction (Rigshospitalet), Blegdamsvej 9, 2100, Copenhagen, Denmark.
Cecilie MelauUniversity Department of Growth and Reproduction (Rigshospitalet), Blegdamsvej 9, 2100, Copenhagen, Denmark.
John E NielsenUniversity Department of Growth and Reproduction (Rigshospitalet), Blegdamsvej 9, 2100, Copenhagen, Denmark.
Kristina Vile JensenUniversity Department of Growth and Reproduction (Rigshospitalet), Blegdamsvej 9, 2100, Copenhagen, Denmark.
Dekang LiuDepartment of Cellular and Molecular Medicine, Center for Healthy Aging, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen, Denmark.
Javier Pena-DiazDepartment of Cellular and Molecular Medicine, Center for Healthy Aging, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen, Denmark.
Ewa Rajpert-De MeytsUniversity Department of Growth and Reproduction (Rigshospitalet), Blegdamsvej 9, 2100, Copenhagen, Denmark.
Lene Juel RasmussenDepartment of Cellular and Molecular Medicine, Center for Healthy Aging, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen, Denmark.
Anne JørgensenUniversity Department of Growth and Reproduction (Rigshospitalet), Blegdamsvej 9, 2100, Copenhagen, Denmark. aj@rh.regionh.dk.ORCID http://orcid.org/0000-0002-6409-198X
University of Copenhagen · DKRigshospitalet · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundTesticular germ cell tumours (TGCT) are highly sensitive to cisplatin-based chemotherapy, but patients with tumours containing differentiated teratoma components are less responsive to this treatment. The cisplatin sensitivity in TGCT has previously been linked to the embryonic phenotype in the majority of tumours, although the underlying mechanism largely remains to be elucidated. The aim of this study was to investigate the role of the DNA mismatch repair (MMR) system in the cisplatin sensitivity of TGCT.

methodsThe expression pattern of key MMR proteins, including MSH2, MSH6, MLH1 and PMS2, were investigated during testis development and in the pathogenesis of TGCT, including germ cell neoplasia in situ (GCNIS). The TGCT-derived cell line NTera2 was differentiated using retinoic acid (10 μM, 6 days) after which MMR protein expression and activity, as well as cisplatin sensitivity, were investigated in both undifferentiated and differentiated cells. Finally, the expression of MSH2 was knocked down by siRNA in NTera2 cells after which the effect on cisplatin sensitivity was examined.

resultsMMR proteins were expressed in proliferating cells in the testes, while in malignant germ cells MMR protein expression was found to coincide with the expression of the pluripotency factor OCT4, with no or low expression in the more differentiated yolk sac tumours, choriocarcinomas and teratomas. In differentiated NTera2 cells we found a significantly (p < 0.05) lower expression of the MMR and pluripotency factors, as well as a reduced MMR activity and cisplatin sensitivity, compared to undifferentiated NTera2 cells. Also, we found that partial knockdown of MSH2 expression in undifferentiated NTera2 cells resulted in a significantly (p < 0.001) reduced cisplatin sensitivity.

conclusionThis study reports, for the first time, expression of the MMR system in fetal gonocytes, from which GCNIS cells are derived. Our findings in primary TGCT specimens and TGCT-derived cells suggest that a reduced sensitivity to cisplatin in differentiated TGCT components could result from a reduced expression of MMR proteins, in particular MSH2 and MLH1, which are involved in the recognition of cisplatin adducts and in activation of the DNA damage response pathway to initiate apoptosis.

Indexed as

Antineoplastic AgentsApoptosisCell Line, TumorCisplatinDNA-Binding ProteinsDNA Mismatch RepairGene Expression Regulation, NeoplasticHumansMaleMismatch Repair Endonuclease PMS2MutL Protein Homolog 1MutS Homolog 2 ProteinNeoplasms, Germ Cell and EmbryonalRNA InterferenceTesticular NeoplasmsAntineoplastic AgentsCisplatinDNA-Binding ProteinsG-T mismatch-binding proteinMismatch Repair Endonuclease PMS2MLH1 protein, humanMSH2 protein, humanMutL Protein Homolog 1MutS Homolog 2 ProteinPMS2 protein, humanCisplatinGerm cell neoplasiaMismatch repairPluripotencyTesticular cancer

Identifiers

PMID28536927
PMCPMC13001569
OpenAlexW2617355063

What OpenQuestion holds

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Registered trials

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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.