Component
Methotrexate response of human leukemia xenografts in mice
Context-specific entity; species, compartment and exposure are stated on each claim.
1 recorded relationships. Experimental role, claim status and evidence remain attached to each record.
How nutrients influence it
Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.
Other things that act on it
Enzymes, hormones, genes, and other components with a recorded effect. These are not nutrients, so they do not count toward the arrows above. Each finding names the chapter that recorded it.
How nutrients reach it in more than one step
Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.
Tracing routes…
What it does
Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.
What acts on it
Combined histidine and methotrexate reduced HEL/SEM xenograft size more than either single treatment in the reported main mouse experiment.
Experimental context and source evidence
- evidence_access
- Primary full text
- experimental_model
- NOD-SCID mice with human leukemia xenografts; daily injections for five days, histidine 400 microliters at 46 mg/mL and methotrexate 50 mg/kg.
- limitations
- Main methods specify injections despite dietary terminology in the abstract. No oral human combination trial or treatment recommendation; longer mouse experiments do not establish human safety. Correction record: A 2022 author correction is indexed (PMID 35017686). The publisher-accessible record identifies corrected Fig. 1f, Extended Data Fig. 11, Supplementary Fig. 3 and source data for Figs. 1/2, including an erroneous doxorubicin replicate. Complete correction narrative was not accessible; its full impact is not independently cleared. The original study remains flagged corrected, and no comprehensive safety claim is made. https://www.nature.com/articles/s41586-021-03487-2
- nutrient_topic
- L-Histidine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Histidine
- plain_language
- Changing substrate supply strengthened a drug effect in this animal model.
- primary_references
- Histidine catabolism is a major determinant of methotrexate sensitivity. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29995852/ · DOI 10.1038/s41586-018-0316-7
L-Histidine: supply, catabolism, histamine, receptors and cross-nutrient mechanisms (2026-09-19) · lines 178–184
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · NOD-SCID mice with human leukemia xenografts; daily injections for five days, histidine 400 microliters at 46 mg/mL and methotrexate 50 mg/kg. · source_derived_draft · unverified_draft
## histidine-histidine-mtx-xenograft Changing substrate supply strengthened a drug effect in this animal model. Combined histidine and methotrexate reduced HEL/SEM xenograft size more than either single treatment in the reported main mouse experiment. Model: NOD-SCID mice with human leukemia xenografts; daily injections for five days, histidine 400 microliters at 46 mg/mL and methotrexate 50 mg/kg. Limitations: Main methods specify injections despite dietary terminology in the abstract. No oral human combination trial or treatment recommendation; longer mouse experiments do not establish human safety. Correction record: A 2022 author correction is indexed (PMID 35017686). The publisher-accessible record identifies corrected Fig. 1f, Extended Data Fig. 11, Supplementary Fig. 3 and source data for Figs. 1/2, including an erroneous doxorubicin replicate. Complete correction narrative was not accessible; its full impact is not independently cleared. The original study remains flagged corrected, and no comprehensive safety claim is made. https://www.nature.com/articles/s41586-021-03487-2 Evidence access: Primary full text Histidine catabolism is a major determinant of methotrexate sensitivity. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29995852/ · DOI 10.1038/s41586-018-0316-7
Complete structured claim and evidence
The events it takes part in
A mechanism often involves more than two components. These are the full events, with every participant and its role.
Situations it appears in
Low-supply and faulty-machinery situations recorded in the chapters where this component plays a part.
In the sources
Preserved passages that mention this component, quoted exactly. Open one to read it in context.
Open hypotheses
Proposed ideas that involve this component. They are labeled as hypotheses and do not change any recorded statement.
This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.