Evidence map›Paper›PMID 41673140›Full record

ArticleScientific reports2026

Validation of chemoresistance phenotypes in pleural mesothelioma across 2D, 3D, and in vivo models.

Huaikai Shi, Sakthi Priya Selvamani, Richard Zelei, Ling Zhuang, Dongwei Wang, Ben Johnson, Vivek Dharwal, Duo Xu, Yiwei Wang, Tristan Rutland and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. 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

15 authors.

Huaikai Shi *Asbestos and Dust Diseases Research Institute, Gate 3 Hospital Road, Concord, Sydney, NSW, 2139, Australia. peter.shi@addri.org.au.ORCID http://orcid.org/0000-0002-8269-2981
Sakthi Priya Selvamani *Asbestos and Dust Diseases Research Institute, Gate 3 Hospital Road, Concord, Sydney, NSW, 2139, Australia.
Richard ZeleiAsbestos and Dust Diseases Research Institute, Gate 3 Hospital Road, Concord, Sydney, NSW, 2139, Australia.
Ling ZhuangAsbestos and Dust Diseases Research Institute, Gate 3 Hospital Road, Concord, Sydney, NSW, 2139, Australia.
Dongwei WangAsbestos and Dust Diseases Research Institute, Gate 3 Hospital Road, Concord, Sydney, NSW, 2139, Australia.
Ben JohnsonAsbestos and Dust Diseases Research Institute, Gate 3 Hospital Road, Concord, Sydney, NSW, 2139, Australia.
Vivek DharwalAsbestos and Dust Diseases Research Institute, Gate 3 Hospital Road, Concord, Sydney, NSW, 2139, Australia.
Duo XuDivision of Thoracic Surgery, David Geffen School of Medicine at UCLA, Los Angeles, USA.
Yiwei WangJiangsu Provincial Engineering Research Centre of TCM External Medication Development and Application, Nanjing University of Chinese Medicine, Nanjing, 210023, Jiangsu, China.
Tristan RutlandWestern Sydney University, Campbeltown, NSW, 2751, Australia.
Sonja KlebePathology, Flinders Health and Medical Research Institute, Flinders University, Bedford Park, SA, 5042, Australia.
Steven KaoAsbestos and Dust Diseases Research Institute, Gate 3 Hospital Road, Concord, Sydney, NSW, 2139, Australia.
Anthony LintonAsbestos and Dust Diseases Research Institute, Gate 3 Hospital Road, Concord, Sydney, NSW, 2139, Australia.
Elham Hosseini-BeheshtiAsbestos and Dust Diseases Research Institute, Gate 3 Hospital Road, Concord, Sydney, NSW, 2139, Australia.
Yuen Yee ChengSchool of Biomedical Engineering, Faculty of Engineering and Information Technology, The University of Technology Sydney, 15 Broadway, Ultimo, NSW, 2007, Australia. yuenyee.cheng@uts.edu.au.ORCID http://orcid.org/0000-0001-7060-0624

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Pleural mesothelioma (PM) is a highly aggressive cancer with limited treatment efficacy and poor prognosis. Conventional two-dimensional (2D) culture models fail to replicate the tumour microenvironment (TME), limiting their translational relevance. Here, we establish a three-dimensional (3D) spheroid model to investigate chemotherapy resistance across different PM subtypes. Compared to 2D cultures, 3D spheroids display enhanced resistance to cisplatin-pemetrexed, with elevated IC₅₀ values, reduced apoptosis, and altered cell cycle profiles. Seahorse metabolic analysis of 3D spheroids demonstrate a suppressed metabolic phenotype, characterised by reduced oxidative phosphorylation (OCR). However, the glycolytic capacity was not upregulated, consistent with the hypoxic and nutrient-limited conditions observed in mesothelioma lesions. In parallel, molecular profiling identifies subtype-specific miRNA signatures that closely align with patient-derived datasets. Proteomic analysis of 3D cultures identifies upregulation of PI3K/AKT and Notch/VEGF signalling, implicating these pathways in treatment resistance. Histological assessment of xenografts further confirms 3D model fidelity in capturing tumour fibrosis, necrosis, and response to therapy. These findings position the 3D spheroid system as a robust and physiologically relevant platform for modelling drug resistance and guiding therapeutic development in PM.

Indexed as

Antineoplastic AgentsDrug Resistance, NeoplasmMesotheliomaPleural NeoplasmsAnimalsApoptosisCell Line, TumorCisplatinGene Expression Regulation, NeoplasticHumansMiceMicroRNAsPemetrexedPhenotypeProteomicsSignal TransductionAntineoplastic AgentsCisplatinMicroRNAsPemetrexed

Identifiers

PMID41673140
PMCPMC12972125

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.