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Cyclooxygenase-2 Inhibition for the Prophylaxis and Treatment of Preinvasive Breast Cancer in a Her-2/Neu Mouse Model

2010· article· en· W2169075189 on OpenAlex
Danh Tran‐Thanh, Stephen D. Buttars, Yanxia Wen, Christine Wilson, Susan J. Done

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenueCancer Prevention Research · 2010
Typearticle
Languageen
FieldMedicine
TopicInflammatory mediators and NSAID effects
Canadian institutionsUniversity Health NetworkUniversity of TorontoBC Cancer Agency
FundersCanadian Institutes of Health ResearchU.S. Food and Drug Administration
KeywordsCelecoxibBreast cancerMouse mammary tumor virusMedicineCancerDuctal carcinomaCyclooxygenaseCarcinogenesisCancer researchGenetically modified mouseMammary glandMetastasisAngiogenesisTumor progressionInternal medicinePathologyTransgeneBiologyImmunologyEnzyme

Abstract

fetched live from OpenAlex

Ductal carcinoma in situ (DCIS) is the most common form of preinvasive breast cancer. Several molecular alterations have been identified in DCIS. Among them, cyclooxygenase 2 (COX-2) overexpression has been shown in 60% to 80% of DCIS cases. Celecoxib is a nonsteroidal anti-inflammatory drug that selectively inhibits COX-2. In this study, we evaluated whether COX-2 inhibition by celecoxib can reduce the incidence of preinvasive breast cancer and its progression to invasive breast cancer in a mouse model exhibiting a similar phenotype to human solid-pattern DCIS. We have used the mouse model mouse mammary tumor virus (MMTV)-Neu to investigate this possibility. These mice carry a rat Her-2/Neu transgene and are known to develop DCIS-like lesions. Our results showed that celecoxib (500 ppm) given as prophylaxis was neither able to prevent tumor development nor delay tumor appearance compared with untreated mice. Furthermore, when the drug was given early in tumorigenesis, it did not reduce the progression of preinvasive to invasive tumors nor prevent lung metastasis. Reduction of prostaglandin levels was, however, achieved in mammary tumors of treated mice. In addition, celecoxib treatment caused an increase in apoptosis and decreased vascular endothelial growth factor expression in treated animals. Our results contrast with some previously published studies and highlight the complexity of the relationship between COX-2 and breast cancer.

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.

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 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 score0.269
Threshold uncertainty score0.281

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
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)0.0000.000

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 head0.054
GPT teacher head0.394
Teacher spread0.340 · 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