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Record W2999247095 · doi:10.1101/2020.01.10.902148

Chemical-Genetic Interrogation of Nuclear Size Control Reveals Cancer-Specific Effects on Cell Migration and Invasion

2020· preprint· en· W2999247095 on OpenAlexafffund
Andrea Rizzotto, Sylvain Tollis, Nhan T. Pham, Jan Wildenhain, Nikolaj Zuleger, Jeremy Keys, Dzmitry G. Batrakou, Jayne Culley, Sarah Y. Zheng, Jan Lammerding, Neil O. Carragher, Valerie G. Brunton, Manfred Auer, Mike Tyers, Eric C. Schirmer

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2020
Typepreprint
Languageen
FieldMedicine
TopicHormonal Regulation and Hypertension
Canadian institutionsUniversité de MontréalInstitute for Research in Immunology and Cancer
FundersDivision of Chemical, Bioengineering, Environmental, and Transport SystemsMedical Research CouncilCanadian Institutes of Health ResearchDarwin Trust of EdinburghMcGill UniversityU.S. Department of DefenseNational Institutes of HealthNational Science Foundation
KeywordsCancerCancer researchBiologyProstate cancerCellPhenotypeAdenocarcinomaCancer cellAdenocarcinoma of the lungInternal medicineMedicineGeneticsGene

Abstract

fetched live from OpenAlex

Abstract Lower survival rates for many cancer types correlate with increases or decreases in nuclear size/scaling in a tumor-type/tissue-specific manner. Postulating that nuclear size changes confer a fitness advantage on tumor cells, we screened for FDA/EMA-approved compounds that reverse tumor nuclear size changes in cell lines from three such tumor types: prostate adenocarcinoma, colonic adenocarcinoma, and small-cell squamous lung cancer. We found distinct, largely non-overlapping sets of compounds that either rectify or exacerbate nuclear size changes for each tumor type. Nuclear size phenotypes across cell lines clustered particular classes of compounds including serotonin uptake inhibitors, cyclo-oxygenase inhibitors, beta-adrenergic receptor agonists, monoamine oxidase inhibitors, and Na + /K + ATPase inhibitors. Nearly all compounds selected for further investigation inhibited cell migration and/or invasion, suggesting that targeting nuclear size control pathways in chemotherapy regimens could improve patient survival.

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)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.326
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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 head0.015
GPT teacher head0.218
Teacher spread0.202 · 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 designBench or experimental
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

Citations3
Published2020
Admission routes2
Has abstractyes

Explore more

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