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Dietary Methyl Donor Depletion Protects Against Intestinal Tumorigenesis in <i>Apc</i> <i>Min</i> /+ Mice

2012· article· en· W2098537038 on OpenAlex
Krishna Kadaveru, Petr Protiva, Emily J. Greenspan, Young‐In Kim, Daniel W. Rosenberg

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.

Bibliographic record

VenueCancer Prevention Research · 2012
Typearticle
Languageen
FieldMedicine
TopicFolate and B Vitamins Research
Canadian institutionsUniversity of Toronto
FundersNational Cancer Institute
KeywordsCarcinogenesisChemistryCarcinogenCancer researchInternal medicineBiologyEndocrinologyCell biologyCancerMedicineBiochemistry

Abstract

fetched live from OpenAlex

Despite recent population data, the influence of dietary folate supplementation on colon cancer risk remains controversial. This study examines the effects of folate deficiency, in combination with choline, methionine, and vitamin B12 depletion, on intestinal tumorigenesis in Apc(Min/+) mice. Methyl donor sufficient (MDS) and deficient (MDD) diets were started at five or 10 weeks of age and tumors evaluated at 16 weeks. MDD suppressed intestinal tumor formation in Apc(Min/+) mice (~80%) when started at five weeks of age. The protective effect was lost when MDD was initiated at 10 weeks of age, indicating an important time dependency on cancer suppression. Concomitant with cancer protection, MDD restricted body weight gain. Therefore, a second study was conducted in which MDS was given ad libitum or pair-fed with MDD. Although small intestinal tumors were reduced 54% in pair-fed MDS mice, MDD caused a further reduction (96%). In colon, although MDD did not affect tumor numbers, tumor size was reduced. Gene expression profiling of normal-appearing colonic mucosa after 11 weeks on MDD identified a total of 493 significantly downregulated genes relative to the MDS group. Pathway analysis placed many of these genes within general categories of inflammatory signaling and cell-cycle regulation, consistent with recently published human data obtained during folate depletion. Further studies are warranted to investigate the complex interplay of methyl donor status and cancer protection in high-risk populations.

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)0.004
metaresearch head score (Gemma)0.001
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: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.339
Threshold uncertainty score0.710

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0040.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.002
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
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 head0.143
GPT teacher head0.445
Teacher spread0.302 · 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