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Record W4379390159 · doi:10.21203/rs.3.rs-2944450/v1

Association of extensive RNA disruption with natural killer cell-mediated death of K562 chronic myelogenous leukemia cells

2023· preprint· en· W4379390159 on OpenAlexafffund
Isabella Pascheto, Baoqing Guo, Aseem Kumar, Laura B. Pritzker, Amadeo M. Parissenti

Bibliographic record

VenueResearch Square · 2023
Typepreprint
Languageen
FieldImmunology and Microbiology
TopicImmune Cell Function and Interaction
Canadian institutionsHealth Sciences NorthLaurentian University
FundersMitacsEberhard Karls Universität Tübingen
KeywordsK562 cellsProgrammed cell deathCancer researchRNABiologyLeukemiaCellImmunologyApoptosisGeneBiochemistry

Abstract

fetched live from OpenAlex

Abstract Extensive degradation of tumour 28S and 18S ribosomal RNAs, coupled with the accumulation of ribosomal RNA degradation products, is associated with pathologic complete response and improved disease-free-survival in breast cancer patients. Various chemotherapy agents and cellular stressors are known to trigger this process, termed ‘RNA disruption’, in tumour cells. However, it’s unclear whether immunotherapies, with or without chemotherapy administration, also trigger RNA disruption. To address this question, we assessed the ability of natural killer (NK) cells to induce RNA disruption and cell death in K562 chronic myeloid leukemia cells in vitro. We found that NK cells strongly stimulated RNA disruption, cytotoxicity (loss of plasma membrane integrity) and cell death (generation of cells with a subG1 DNA content) in K562 cells. Pre-activation of NK cells with interleukin-2 or pre-treatment of K562 cells with the chemotherapy drug doxorubicin augmented RNA disruption in K562 cells. RNA degradation patterns looked very similar between NK cell-treated and doxorubicin-treated K562 cells. Our observations suggest that RNA disruption is strongly associated with cell death irrespective of the death-inducing stimulus and raise the prospect that tumour RNA disruption may be a useful biomarker for quantifying cancer patients’ response to immunotherapies, with or without co-administration of chemotherapy drugs.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
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 score0.002
Threshold uncertainty score0.005

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
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)0.0020.001

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 head0.028
GPT teacher head0.312
Teacher spread0.284 · 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 source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
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
Published2023
Admission routes2
Has abstractyes

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