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Record W7132945375

Defining Synthetic Lethal Pathways in ATRT-MYC Tumours

2021· dissertation· W7132945375 on OpenAlexaff
Elizabeth A. Richardson

Bibliographic record

VenueTSpace · 2021
Typedissertation
Language
FieldBiochemistry, Genetics and Molecular Biology
TopicChromatin Remodeling and Cancer
Canadian institutionsUniversity of Toronto
Fundersnot available
KeywordsDasatinibHistone deacetylase inhibitorVorinostatIn vivoCell cycleHistone deacetylaseDoxorubicinCell cycle checkpoint
DOInot available

Abstract

fetched live from OpenAlex

Atypical Rhabdoid Teratoid Tumours (ATRTs) are malignant embryonal brain tumours, of which the ATRT-MYC subgroup are particularly invasive and treatment-resistant with poor clinical outcomes. The purpose of this study is to investigate the cellular effects of the multi-tyrosine kinase inhibitor Dasatinib on ATRT-MYC tumours in vitro, as well as identify and characterize drug compounds that act synergistically with Dasatinib. Here I show that Dasatinib has a cytostatic, but not cytotoxic effect at IC50 concentrations. Proliferative impairment observed is most consistent with senescence and G1/S cell cycle arrest. Vorinostat, a histone deacetylase inhibitor, was found to act synergistically with Dasatinib at near-IC50 doses; combination showed cytostatic effects, with increased senescence markers and impaired cell cycle progression. In conclusion, while Dasatinib and Vorinostat combination did not elicit cell death, it effectively suppressed ATRT-MYC proliferation. Further study of Dasatinib-Vorinostat combination is warranted in vivo as a potential therapy for this highly lethal disease.

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 score0.046
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0010.001
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 head0.013
GPT teacher head0.302
Teacher spread0.289 · 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

Citations0
Published2021
Admission routes1
Has abstractyes

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