The SRG rat as a novel host for an orthotopic patient-derived xenograft model of breast cancer brain metastasis
Bibliographic record
Abstract
Patient-derived xenograft (PDX) models are essential for understanding the pathophysiology and developing treatment strategies for breast cancer brain metastasis (BCBM). While immunodeficient mouse models allow for human BCBM growth, their small size limits host survival, neurological imaging and therapeutic interventions. This study evaluated the immunodeficient SRG rat (Sprague Dawley Rag2-/-; Il2rg-/-) as a new intermediate-sized host for orthotopic modeling of human BCBM. The primary goal was to determine if the SRG rat brain presents a hospitable environment for orthotopic growth of patient BCBM cells. A secondary goal was to compare phenotypes of the patient and xenografted tumors. Adult SRG rats received stereotactic intracerebral implants of 1 million engineered patient BCBM cells. Bioluminesence imaging (BLI) and magnetic resonance imaging (MRI) provided metabolic and anatomic monitoring of tumor growth. Post-mortem histological analysis compared biomarker profiles in original patient and xenograft tumors. Orthotopic patient-derived BCBM tumors progressed in all SRG rats within 5 weeks post-implantation. BLI radiance increased 125-fold over the study period. MRI revealed tumor-induced brain edema and both patient and xenograft BCBMs exhibited pronounced vascularity and gadolinium enhancement. Histopathology confirmed that xenograft tumors maintained high proliferation indices and biomarker expression consistent with the parent tumor. The SRG rat provided a reliable intermediate-sized host for orthotopic growth of patient-derived BCBM xenografts, offering advantages over existing models for studying tumor behavior and therapeutic responses.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".