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Interaction between riboflavin and BCRP‐mediated drug transport in the mammary gland (844.2)

2014· article· en· W1502294434 on OpenAlexaff
John Leon‐Cheon, Liana Dedina, Mingdong Yang, Patricia A. Harper, Shinya Ito

Bibliographic record

VenueThe FASEB Journal · 2014
Typearticle
Languageen
FieldMedicine
TopicOral health in cancer treatment
Canadian institutionsHospital for Sick ChildrenUniversity of Toronto
Fundersnot available
KeywordsCimetidineAbcg2RiboflavinChemistryPharmacologyExcretionBreast milkTopotecanVitaminEndocrinologyInternal medicineTransporterMedicineATP-binding cassette transporterBiochemistryChemotherapy

Abstract

fetched live from OpenAlex

Breastfeeding provides numerous benefits to a child’s growth and development. However, in a lactating mother, expression of Breast Cancer Resistance Protein (BCRP) is significantly increased in the mammary gland. BCRP is an efflux transporter and is responsible for the transport of many different substrates from natural carcinogens (ex. PhIP found in charred meats) to chemotherapeutic drugs. As a result, this poses a risk of exposure to potentially harmful BCRP substrates from a mother’s milk to her child. We hypothesized that riboflavin, a vitamin substrate for BCRP, can act as a potential competitor for BCRP‐mediated excretion of drugs/toxins into milk. We used intravenous topotecan and cimetidine at a dose of 1 and 5 mg/kg as model BCRP substrates in lactating mice. In mice pretreated with 5 mg/kg riboflavin, excretion of topotecan and cimetidine into milk at 30 min postdose was significantly reduced. Mean topotecan levels in the milk were 883 ng/ml (SD: ±465; n=10) in the control and 682 ng/ml (SD: ±316; n=10; p<0.01) in the riboflavin treatment group. For cimetidine, the mean milk levels were 1941 ng/ml (SD: ±387; n=7) in the control, compared to 1555 ng/ml (SD: ±192; n=7; p<0.05) in the riboflavin‐pretreated mice. The milk‐to‐plasma ratios of topotecan and cimetidine in riboflavin‐pretreated mice also showed a significant 35% and 26% decrease respectively. In conclusion, our findings indicate that riboflavin administration does reduce the excretion of other BCRP substrates into a mother’s milk. Grant Funding Source : Supported by CIHR

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: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.007

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)0.0010.000

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 head0.027
GPT teacher head0.316
Teacher spread0.289 · 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 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
Published2014
Admission routes1
Has abstractyes

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