Enhanced efficacy with azacytidine and oncolytic BHV-1 in a tolerized cotton rat model of breast adenocarcinoma
Bibliographic record
Abstract
Oncolytic viruses selectively replicate in cancer cells by exploiting biochemical differences between normal and tumor cells. Treatment with epigenetic modifiers such as 5-Azacytidine, a DNA methyltransferase inhibitor, increases the replication and cytotoxicity of oncolytic viruses in vivo and in vitro. The cotton rat is an attractive animal to study oncolytic viruses, as syngeneic models of breast adenocarcinoma and osteosarcoma are well established, and many features of primary and secondary tumor growth recapitulate human disease. Treatment of LCRT breast cancer cells with 5-Azacytidine increases bovine herpesvirus type 1 (BHV-1)-mediated cytotoxicity in vitro, with Chou-Talalay analysis indicating a very strong synergy. In vivo, BHV-1 monotherapy delayed tumor growth but did not improve survival of cotton rats with subcutaneous breast adenocarcinomas. However, combination therapy significantly decreased the incidence of secondary lesions, with enhanced tumor cell clearance and evidence of immune cell infiltration compared to BHV-1 monotherapy. Together, these results warrant further investigation of BHV-1 combination therapy with epigenetic modifiers for the treatment of breast cancer, particularly in the context of the prevention and treatment of secondary lesions. Oncolytic viruses selectively replicate in cancer cells by exploiting biochemical differences between normal and tumor cells. Treatment with epigenetic modifiers such as 5-Azacytidine, a DNA methyltransferase inhibitor, increases the replication and cytotoxicity of oncolytic viruses in vivo and in vitro. The cotton rat is an attractive animal to study oncolytic viruses, as syngeneic models of breast adenocarcinoma and osteosarcoma are well established, and many features of primary and secondary tumor growth recapitulate human disease. Treatment of LCRT breast cancer cells with 5-Azacytidine increases bovine herpesvirus type 1 (BHV-1)-mediated cytotoxicity in vitro, with Chou-Talalay analysis indicating a very strong synergy. In vivo, BHV-1 monotherapy delayed tumor growth but did not improve survival of cotton rats with subcutaneous breast adenocarcinomas. However, combination therapy significantly decreased the incidence of secondary lesions, with enhanced tumor cell clearance and evidence of immune cell infiltration compared to BHV-1 monotherapy. Together, these results warrant further investigation of BHV-1 combination therapy with epigenetic modifiers for the treatment of breast cancer, particularly in the context of the prevention and treatment of secondary lesions.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 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".