Vitamin D3 Administration Induces Nuclear p27 Accumulation, Restores Differentiation, and Reduces Tumor Burden in a Mouse Model of Metastatic Follicular Thyroid Cancer
Bibliographic record
Abstract
We have previously demonstrated in vitro that 1alpha,25-dihydroxyvitamin D3 (calcitriol) treatment increases p27 expression and decreases cell proliferation in cultured thyroid carcinoma cell lines. We hypothesized that in vivo treatment with calcitriol would have a beneficial effect on thyroid carcinoma growth and progression. Five x 10(6) WRO (human thyroid follicular carcinoma derived) cells were implanted in the neck in 4- to 5-wk-old female SCID mice in an orthotopic xenograft model. Animals (n = 15) were treated i.p. three times a week for 21 d with 0.75 microg/kg calcitriol or vehicle. Mice were killed 21 d after tumor implantation, tumor volume was measured, and excised tumor tissue was examined by light microscopy and immunohistochemistry for p27 and thyroglobulin reactivity. Average tumor volume in control mice after 21 d of vehicle treatment was 2002 +/- 207 mm3 compared with a mean tumor volume of 1241 +/- 115 mm3 in animals receiving calcitriol, reflecting a 38% reduction in tumor volume size (P < 0.003). Tumors from vehicle-treated animals demonstrated morphological features of epithelial malignancies with characteristics of insular carcinoma and multiple metastases to the lungs. Tumors excised from calcitriol-treated animals demonstrated signs of differentiation with restoration of thyroglobulin staining. This was associated with a marked accumulation of p27 immunoreactivity in the nuclear compartment. These studies demonstrate that in vivo calcitriol administration can effectively restore p27 accumulation in thyroid carcinoma cells, an effect associated with appreciably enhanced cellular differentiation, reduction in tumor burden, and prevention of metastatic growth.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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.
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 teacher head, 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".