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Record W2857918608 · doi:10.1038/s41467-018-05266-6

Stromal PTEN determines mammary epithelial response to radiotherapy

2018· article· en· W2857918608 on OpenAlexaff
Gina M. Sizemore, Subhasree Balakrishnan, Katie Thies, Anisha M. Hammer, Steven T. Sizemore, Anthony J. Trimboli, Maria C. Cuitiño, Sarah Steck, Gary Tozbikian, Raleigh D. Kladney, Neelam Shinde, Manjusri Das, Dongju Park, Sarmila Majumder, Shiva Krishnan, Lianbo Yu, Soledad Fernández, Arnab Chakravarti, Peter G. Shields, Julia White, Thomas J. Rosol, Thomas Ludwig, Morag Park, Gustavo Leone, Michael C. Ostrowski

Bibliographic record

VenueNature Communications · 2018
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicPI3K/AKT/mTOR signaling in cancer
Canadian institutionsMcGill University Health Centre
FundersNational Cancer InstituteU.S. Department of Health and Human ServicesNational Institutes of HealthHollings Cancer Center, Medical University of South CarolinaPelotoniaU.S. Department of Defense
KeywordsPTENTensinStromal cellCancer researchBreast cancerStromaParacrine signallingCarcinogenesisMedicineEpidermal growth factor receptorPathologyCancerBiologyRadiation therapyEpitheliumMammary glandOncologyInternal medicinePI3K/AKT/mTOR pathwayReceptorSignal transductionCell biologyImmunohistochemistry

Abstract

fetched live from OpenAlex

The importance of the tumor-associated stroma in cancer progression is clear. However, it remains uncertain whether early events in the stroma are capable of initiating breast tumorigenesis. Here, we show that in the mammary glands of non-tumor bearing mice, stromal-specific phosphatase and tensin homolog (Pten) deletion invokes radiation-induced genomic instability in neighboring epithelium. In these animals, a single dose of whole-body radiation causes focal mammary lobuloalveolar hyperplasia through paracrine epidermal growth factor receptor (EGFR) activation, and EGFR inhibition abrogates these cellular changes. By analyzing human tissue, we discover that stromal PTEN is lost in a subset of normal breast samples obtained from reduction mammoplasty, and is predictive of recurrence in breast cancer patients. Combined, these data indicate that diagnostic or therapeutic chest radiation may predispose patients with decreased stromal PTEN expression to secondary breast cancer, and that prophylactic EGFR inhibition may reduce this risk.

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 score0.006

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)0.0020.000

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 head0.014
GPT teacher head0.326
Teacher spread0.312 · 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

Citations26
Published2018
Admission routes1
Has abstractyes

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