Potential Utility of BimS as a Novel Apoptotic Therapeutic Molecule
Bibliographic record
Abstract
We have previously demonstrated a 1000-fold induction of gene expression exclusive to Epstein-Barr virus (EBV)-positive nasopharyngeal carcinoma (NPC) cells using an adenoviral vector (ad5.oriP). This platform allows us to explore tumor-specific gene therapy with BimS (ad5.oriP.BimS), a potent proapoptotic Bcl-2 family member. Ad5.oriP.BimS (25 infectious units (ifu)/cell) reduced C666-1 viability in a time- and dose-dependent manner to 15% survival. The effect was enhanced with radiation (6 Gy). Three days after infection, the proportion of apoptotic cells increased from 3.5% (control) to 47.5% (25 ifu/cell). Confocal microscopy demonstrated Bim colocalization to the mitochondria within 18 h of ad5.oriP.BimS infection. Ad5.oriP.BimS induced a 2.8-, 2.1-, and 1.85-fold increase in caspase-3, -8, and -9 activities, respectively. When C666-1 cells were infected with ad5.oriP.BimS (20 ifu/cell), no tumors formed in 7/9 mice followed for 100 days. Six intratumoral injections of ad5.oriP.BimS (1.5 x 10(9) ifu/dose) in combination with radiation were sufficient to cause almost complete disappearance of established C666-1 or C15 xenograft tumors. Intravenous injections of ad5.oriP.BimS (10(9) ifu) induced mild perturbation in liver function tests, associated with hepatocyte apoptoses and mitoses. This vector appears to be safe and effectively cytotoxic to EBV-positive NPC cells both in vitro and in vivo, mediated primarily through the induction of apoptosis.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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 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".