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Record W4313119801 · doi:10.1093/bjs/znac242.082

O082 Patient derived renal cell carcinoma tumouroids for personalised renal cancer medicine

2022· article· en· W4313119801 on OpenAlexaff
K Bokea, T Azimi, Katerina Stamati, Elnaz Yaghini, S Macrobert, Umber Cheema, Maxine Tran, Andrew Feber, Marilena Loizidou

Bibliographic record

VenueBritish journal of surgery · 2022
Typearticle
Languageen
FieldMedicine
TopicRenal cell carcinoma treatment
Canadian institutionsInstitute of Cancer Research
Fundersnot available
KeywordsPazopanibMedicineRenal cell carcinomaStromal cellCancer researchCabozantinibCancerKidney cancerPathologySunitinibInternal medicine

Abstract

fetched live from OpenAlex

Abstract Introduction Despite the significant advancements in the therapeutic management of renal cell carcinoma (RCC), there is still a pressing need for patient-specific platforms that can predict personalised treatment response. This study aims to optimise renal cancer tumouroids: 3D in vitro models that mimic the tumour density, and incorporate primary cells isolated from RCC surgical specimens and extracellular matrix components to recapitulate the tumour microenvironment. Methods RCC samples were collected post-surgery (n=16), disaggregated using different methods and the isolated cells were grown in 2D and tumouroids. Cell proliferation was compared among different culture conditions by measuring ATP production. Tumouroids were also challenged with a clinically used tyrosine kinase inhibitor, pazopanib. Immunofluorescence and confocal microscopy were used to detect expression of RCC markers and whole-exome sequencing was performed to investigate tumouroids’ resemblance to the parental tumour. Results Patient-derived RCC tumouroids retain the expression of renal cancer associated gene markers, including mutant VHL, and protein markers, including cytokeratins and epithelial-tomesenchymal markers. A non-linear increase in proliferation was observed in the tumouroids which may be indicative of 3D organization and other cellular functions. Tumouroids’ response to pazopanib ranged from none to strong (40%) and tumouroids of higher complexity, that incorporated a stromal compartment, responded stronger than simpler tumouroids (n=3). Conclusion Our results indicate that RCC cells maintain their phenotype and genotype when grown as tumouroids. Future work will compare the response from tumouroids to the responses from both xenografts and the actual patients to determine the suitability of tumouroids as personalised cancer treatment platforms. Take-home message Renal Cell Carcinoma cells isolated from human patients maintain their phenotype and genotype when grown in biomimetic tumouroids and respond to treatment.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow), Insufficient payload (model declined to judge)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.487
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0020.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.042
GPT teacher head0.256
Teacher spread0.214 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2022
Admission routes1
Has abstractyes

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