Evidence map›Paper›PMID 36835505›Full record

ArticleInternational journal of molecular sciences2023

A Novel Preclinical In Vitro 3D Model of Oral Carcinogenesis for Biomarker Discovery and Drug Testing.

Ravi Teja Chitturi Suryaprakash, Kate Shearston, Camile S Farah, Simon A Fox, Muhammad Munir Iqbal, Ulrich Kadolsky, Xiao Zhong, Alka Saxena, Omar Kujan

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 2 pooled it
3.0field-weighted citation impact, top 8% 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

11 citing papers in PubMed, 2 syntheses or guidelines pooled it, 13 citations in OpenAlex.

  1. Models of Oral Epithelial Dysplasia: A Systematic Review and Temporal Analysis.Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology · 2026
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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

9 authors at 2 institutions in 1 country.

Ravi Teja Chitturi SuryaprakashUWA Dental School, The University of Western Australia, Nedlands, WA 6009, Australia.
Kate ShearstonUWA Dental School, The University of Western Australia, Nedlands, WA 6009, Australia.
Camile S FarahAustralian Centre for Oral Oncology Research and Education, Nedlands, WA 6009, Australia.ORCID 0000-0002-1642-6204
Simon A FoxUWA Dental School, The University of Western Australia, Nedlands, WA 6009, Australia.ORCID 0000-0003-2042-1809
Muhammad Munir IqbalGenomics WA, Harry Perkins Institute of Medical Research, Telethon Kids Institute, The University of Western Australia, Nedlands, WA 6009, Australia.ORCID 0000-0002-8603-5348
Ulrich KadolskyGenomics WA, Harry Perkins Institute of Medical Research, Telethon Kids Institute, The University of Western Australia, Nedlands, WA 6009, Australia.
Xiao ZhongGenomics WA, Harry Perkins Institute of Medical Research, Telethon Kids Institute, The University of Western Australia, Nedlands, WA 6009, Australia.
Alka SaxenaGenomics WA, Harry Perkins Institute of Medical Research, Telethon Kids Institute, The University of Western Australia, Nedlands, WA 6009, Australia.ORCID 0000-0001-5683-0618
Omar KujanUWA Dental School, The University of Western Australia, Nedlands, WA 6009, Australia.ORCID 0000-0002-5951-8280
The Kids Research Institute Australia · AUThe University of Western Australia · AU

Funding

Government of Western Australia Department of Health Grant No. WANMA2021/1
6 · The paper itself

Abstract

This study aimed to develop an in vitro three-dimensional (3D) cell culture model of oral carcinogenesis for the rapid, scalable testing of chemotherapeutic agents. Spheroids of normal (HOK) and dysplastic (DOK) human oral keratinocytes were cultured and treated with 4-nitroquinoline-1-oxide (4NQO). A 3D invasion assay using Matrigel was performed to validate the model. RNA was extracted and subjected to transcriptomic analysis to validate the model and assess carcinogen-induced changes. The VEGF inhibitors pazopanib and lenvatinib were tested in the model and were validated by a 3D invasion assay, which demonstrated that changes induced by the carcinogen in spheroids were consistent with a malignant phenotype. Further validation was obtained by bioinformatic analyses, which showed the enrichment of pathways associated with hallmarks of cancer and VEGF signalling. Overexpression of common genes associated with tobacco-induced oral squamous cell carcinoma (OSCC), such as MMP1, MMP3, MMP9, YAP1, CYP1A1, and CYP1B1, was also observed. Pazopanib and lenvatinib inhibited the invasion of transformed spheroids. In summary, we successfully established a 3D spheroid model of oral carcinogenesis for biomarker discovery and drug testing. This model is a validated preclinical model for OSCC development and would be suitable for testing a range of chemotherapeutic agents.

Indexed as

Antineoplastic AgentsBiomarkers, TumorCarcinogenesisCell Culture Techniques, Three DimensionalMouth NeoplasmsSpheroids, CellularCarcinogensDrug Screening Assays, AntitumorHumansIndazolesPhenylurea CompoundsPyrimidinesQuinolinesSquamous Cell Carcinoma of Head and NeckSulfonamidesTumor Cells, CulturedAntineoplastic AgentsBiomarkers, TumorCarcinogensIndazoleslenvatinibpazopanibPhenylurea CompoundsPyrimidinesQuinolinesSulfonamidesVascular Endothelial Growth Factor Aalcoholchemopreventionlenvatiniboral epithelial dysplasiaoral squamous cell carcinomapazopanibspheroidtobaccoVEGF

Identifiers

PMID36835505
PMCPMC9967961
OpenAlexW4321374291

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.