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Data from Dietary Feeding of Silibinin Inhibits Prostate Tumor Growth and Progression in Transgenic Adenocarcinoma of the Mouse Prostate Model

2023· preprint· en· W4361264457 on OpenAlexaff
Komal Raina, Marie‐José Blouin, Rana P. Singh, Noreen Majeed, Gagan Deep, Leyon Varghese, L. Michael Glodé, Norman M. Greenberg, David Hwang, Pinchas Cohen, Michaël Pollak, Rajesh Agarwal

Bibliographic record

Venuenot available
Typepreprint
Languageen
FieldMedicine
TopicSilymarin and Mushroom Poisoning
Canadian institutionsMcGill UniversityJewish General Hospital
Fundersnot available
KeywordsTrampSilibininProstateProstate cancerInternal medicineEndocrinologyAdenocarcinomaGenetically modified mouseProliferating cell nuclear antigenMedicineCancer researchBiologyTransgeneCancerImmunohistochemistryBiochemistry

Abstract

fetched live from OpenAlex

<div>Abstract<p>Herein, for the first time, we evaluated the chemopreventive efficacy of dietary silibinin against prostate cancer (PCa) growth and progression in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice from two different genetic backgrounds [C57BL/6 (TRAMP) × FVB; C57BL/6 (TRAMP) × C57BL/6]. At 4 weeks of age, mice were fed control or 0.1% to 1% silibinin–supplemented diets until 23 to 24 weeks of age. Silibinin-fed groups had a lower tumor grade and higher incidence of prostatic intraepithelial neoplasia (PIN) at the expense of a strong decrease in adenocarcinoma incidence. Prostate tissue showed a 47% (<i>P</i> < 0.001) decrease in proliferating cell nuclear antigen (PCNA)–positive cells and an ∼7-fold (<i>P</i> < 0.001) increase in apoptotic cells at the highest silibinin dose. As potential mechanisms of silibinin efficacy, an ∼50% (<i>P</i> < 0.05) decrease in insulin-like growth factor (IGF) receptor type Iβ and an ∼13-fold (<i>P</i> < 0.001) increase in IGF-binding protein 3 (IGFBP-3) protein levels were also observed. These changes were specific to tumors as they were not reflected in circulating IGF-IGFBP-3 system. Additionally, silibinin decreased protein expression of cyclin-dependent kinases (Cdk) by more than 90% (<i>P</i> < 0.001) with a concomitant increase in Cdk inhibitors, Cip1/p21 and Kip1/p27 (<i>P</i> < 0.05, for both). A dose-dependent decrease was also observed in cyclin B1, cyclin E, and cyclin A protein levels by silibinin. Together, these findings suggest that oral silibinin blocks PCa growth and progression at PIN stage in TRAMP mice via modulation of tumor IGF-IGFBP-3 axis and cell cycle regulation, and therefore it has practical and translational potential in suppressing growth and neoplastic conversion of PIN to PCa in humans. [Cancer Res 2007;67(22):11083–91]</p></div>

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)0.001
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: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.249
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.002
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 head0.100
GPT teacher head0.325
Teacher spread0.225 · 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 designObservational
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 routes1
Has abstractyes

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