Evidence map›Paper›PMID 29462944›Full record

ArticleInternational journal of molecular sciences2018

Multifaceted Mechanisms of Cisplatin Resistance in Long-Term Treated Urothelial Carcinoma Cell Lines.

Margaretha A Skowron, Margarita Melnikova, Joep G H van Roermund, Andrea Romano, Peter Albers, Juergen Thomale, Wolfgang A Schulz, Günter Niegisch, Michèle J Hoffmann

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
2.8field-weighted citation impact, top 10% 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

28 citing papers in PubMed, 42 citations in OpenAlex.

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  17. Epigenetic Priming and Development of New Combination Therapy Approaches.Methods in molecular biology (Clifton, N.J.) · 2023
    Article
  18. Article
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  20. Molecular mechanism of CD163Annals of translational medicine · 2022
    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

9 authors at 3 institutions in 2 countries.

Margaretha A SkowronDepartment of Urology, Medical Faculty, Heinrich Heine University, 40225 Duesseldorf, Germany. Margaretha.Skowron@hhu.de.ORCID 0000-0003-2152-384X
Margarita MelnikovaInstitute of Cell Biology (Cancer Research), University of Duisburg-Essen Medical School, 45122 Essen, Germany. margarita.melnikova@uni-due.de.
Joep G H van RoermundDepartment of Urology, Maastricht University Medical Centre, 6202AZ Maastricht, The Netherlands. joep.van.roermund@mumc.nl.
Andrea RomanoDepartment of Obstetrics and Gynaecology, GROW-School for Oncology & Developmental Biology, Maastricht University Medical Centre, 6229HX Maastricht, The Netherlands. a.romano@maastrichtuniversity.nl.ORCID 0000-0002-5900-6883
Peter AlbersDepartment of Urology, Medical Faculty, Heinrich Heine University, 40225 Duesseldorf, Germany. peter.albers@med.uni-duesseldorf.de.
Juergen ThomaleInstitute of Cell Biology (Cancer Research), University of Duisburg-Essen Medical School, 45122 Essen, Germany. juergen.thomale@uni-due.de.ORCID 0000-0003-3224-8361
Wolfgang A SchulzDepartment of Urology, Medical Faculty, Heinrich Heine University, 40225 Duesseldorf, Germany. Wolfgang.Schulz@hhu.de.ORCID 0000-0002-2196-463X
Günter NiegischDepartment of Urology, Medical Faculty, Heinrich Heine University, 40225 Duesseldorf, Germany. Guenter.Niegisch@hhu.de.ORCID 0000-0001-6929-8691
Michèle J HoffmannDepartment of Urology, Medical Faculty, Heinrich Heine University, 40225 Duesseldorf, Germany. michele.hoffmann@hhu.de.
Heinrich Heine University Düsseldorf · DEMaastricht University Medical Centre · NLUniversity of Duisburg-Essen · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Therapeutic efficacy of cisplatin-based treatment of late stage urothelial carcinoma (UC) is limited by chemoresistance. To elucidate underlying mechanisms and to develop new approaches for overcoming resistance, we generated long-term cisplatin treated (LTT) UC cell lines, characterised their cisplatin response, and determined the expression of molecules involved in cisplatin transport and detoxification, DNA repair, and apoptosis. Inhibitors of metallothioneins and Survivin were applied to investigate their ability to sensitise towards cisplatin. Cell growth, proliferation, and clonogenicity were examined after cisplatin treatment by MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, EdU (5-ethynyl-2'-deoxyuridine) incorporation assay, and Giemsa staining, respectively. Cell cycle distribution and apoptosis were quantified by flow cytometry. mRNA and protein expressions were measured by real-time quantitative (qRT)-PCR, western blot, or immunofluorescence staining. LTTs recovered rapidly from cisplatin stress compared to parental cells. In LTTs, to various extents, cisplatin exporters and metallothioneins were induced, cisplatin adduct levels and DNA damage were decreased, whereas expression of DNA repair factors and specific anti-apoptotic factors was elevated. Pharmacological inhibition of Survivin, but not of metallothioneins, sensitised LTTs to cisplatin, in an additive manner. LTTs minimise cisplatin-induced DNA damage and evade apoptosis by increased expression of anti-apoptotic factors. The observed diversity among the four LTTs highlights the complexity of cisplatin resistance mechanisms even within one tumour entity, explaining heterogeneity in patient responses to chemotherapy.

Indexed as

Drug Resistance, NeoplasmAntineoplastic AgentsApoptosisCarcinomaCell CycleCell Line, TumorCisplatinDNA DamageHumansMetallothioneinUrinary Bladder NeoplasmsUrotheliumAntineoplastic AgentsCisplatinMetallothioneincisplatinmetallothioneinresistance mechanismsSurvivinurothelial carcinomaYM155

Identifiers

PMID29462944
PMCPMC5855812
OpenAlexW2789444905

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.