Vitamin D Receptor-Dependent Inhibition of Mammary Tumor Growth by EB1089 and Ultraviolet Radiation in Vivo
Bibliographic record
Abstract
1,25-Dihydroxyvitamin D(3) (1,25D), the biologically active form of vitamin D(3), exerts antiproliferative and proapoptotic effects in multiple transformed cell types, and thus, the vitamin D signaling pathway represents a potential anticancer target. Although chronic treatment with 1,25D induces hypercalcemia, synthetic vitamin D analogs have been developed that inhibit tumor growth in vivo with minimal elevation of serum calcium. Furthermore, vitamin D is synthesized in skin exposed to UV light, and this route of vitamin D elevation is not associated with hypercalcemia. In this study, we examined whether enhancement of vitamin D status via exogenous (EB1089, a 1,25D analog) or endogenous (UV exposure) approaches could exert antitumor effects without hypercalcemia. We used mammary xenografts with differential vitamin D receptor (VDR) expression to examine whether the antitumor effects of either therapy are receptor mediated. We present evidence that both EB1089 and UV exposure inhibit tumor growth via induction of growth arrest and apoptosis. These antitumor effects were observed only in xenografts containing VDR-positive tumor cells; heterogeneous tumors containing VDR-negative tumor cells and VDR-positive stromal and endothelial cells were unresponsive to both therapies. No evidence for antiangiogenic effects of EB1089 were detected in this model system. Neither EB1089 nor UV was associated with overt toxicity, but keratinocyte proliferation was increased in UV-exposed skin. These data provide proof of principle that UV exposure modulates tumor growth via elevation of vitamin D signaling and that therapeutic approaches designed to target the vitamin D pathway will be effective only if tumor cells express functional VDR.
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 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".