Preclinical Evidence that Use of TRAIL in Ewing's Sarcoma and Osteosarcoma Therapy Inhibits Tumor Growth, Prevents Osteolysis, and Increases Animal Survival
Bibliographic record
Abstract
PURPOSE: Osteosarcoma and Ewing's sarcoma are high-grade neoplasms typically arising in the bones of children and adolescents. Despite improvement in therapy, the five-year survival rate is only 20% for patients not responding to treatment or presenting with metastases. Among new therapeutic strategies, the efficacy of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), a member of the TNF superfamily with strong antitumoral activity and minimal toxicity to most normal cells and tissues, was investigated by complementary approaches both in vitro and in preclinical models. EXPERIMENTAL DESIGN: The sensitivity of osteosarcoma and Ewing's sarcoma cell lines to TRAIL was investigated in vitro by determining TRAIL receptor expression together with TRAIL effects on cell viability and apoptosis. Complementary preclinical studies were carried out in respective tumor models by inoculation of osteosarcoma or Ewing's sarcoma tumor cells in paraosseous location. In addition, a model of lung nodule dissemination was developed by i.v. injection of osteosarcoma cells. RESULTS: In vitro, both osteosarcoma and Ewing's sarcoma cells that express the TRAIL death receptors were highly sensitive to TRAIL-induced caspase-8-mediated apoptosis. TRAIL administered in vivo by nonviral gene therapy inhibited primary bone tumor incidence and growth by 87% and prevented tumor-induced osteolysis, leading to a significant 2-fold increase in animal survival 40 days after tumor induction. Furthermore, TRAIL inhibited tumor nodule dissemination in lungs and increased survival in an osteosarcoma model. CONCLUSION: These findings suggest that TRAIL is a promising candidate for the development of new therapeutic strategies in the most frequent malignant primary bone tumors.
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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 | 0.003 | 0.002 |
| 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 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".