Vinburnine Sensitizes Radiotherapy Efficacy in Nasopharyngeal Carcinoma by Triggering Pyroptosis and Immune Responses via Activation of EDAR‐NFκB Pathway
Bibliographic record
Abstract
Abstract Radiotherapy combined with chemotherapy is the traditional treatment for nasopharyngeal carcinoma (NPC); however, the side effects of these therapies restrict their clinical application; therefore, identifying appropriate alternative chemotherapy agents is a critical clinical challenge. In this study, an approved drug library is assessed and identified vinburnine as a promising alternative chemotherapy agent that sensitizes NPC to radiotherapy with lower toxicity than cisplatin. Mechanistically, vinburnine directly interacts with ectodysplasin A receptor (EDAR), a member of the Tumor Necrosis Factor (TNF) receptor superfamily, which activates the radiotherapy‐induced Nuclear Factor Kappa B (NFκB) signaling pathway. As a consequence, vinburnine enhances radiotherapy‐induces apoptosis in NPC cells, promotes Gasdermin E (GSDME)‐mediated pyroptosis, and increases the secretion of chemokine (C‐C motif) ligand 5(CCL5) and C‐X3‐C Motif Chemokine Ligand 1 (CX3CL1), which promotes and strengthens T‐cell toxicity against NPC cells. Furthermore, it is found that EDAR expression is significantly greater in patients with nonrecurrent NPC than in those with recurrent disease and that EDAR expression is positively correlated with CD8 + T‐cell infiltration; thus, it may be a potential biomarker for NPC prognosis. Overall, the study revealed that vinburnine is a novel chemotherapeutic agent that increases the sensitivity of NPC to radiotherapy and revealed a novel mechanism by which vinburnine and radiotherapy collaboratively modulate the EDAR‐NFκB‐apoptosis/pyroptosis‐CCL5/CX3CL1 signaling pathway, which provides a promising therapeutic strategy for NPC.
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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".