Mechanism of Genetically-Regulated Response to Bacillus- Calmette Guérin Immunotherapy for Bladder Cancer
Bibliographic record
Abstract
In this study, we investigated host response to Bacillus-Calmette Guérin (BCG) immunotherapy using the murine MM45T bladder tumor cell line. BALB/c (Bcgs allele) and BALB/c.CD2 (CD2) (Bcgr allele) mice were seeded subcutaneously with MM45T cells. Treatment began on day 7 with intra-tumor injections of BCG. Significant decreases in tumor growth in BALB/c (p < 0.05) but not in the CD2 (p = NS) mice were observed 6, 10 and 14 days following treatment. Investigation of the mechanism(s) underlining the difference in the response between the two strains of mice revealed key points, namely: (i) Intraperitoneal injection of BCG led to a significant increase (p < 0.05) in the number of cells recovered 14 days later by peritoneal lavage (in million cells: 5.1 ± 0.7 vs 9.5 ± 0.3 in BALB/c and 5.3 ± 0.4 vs 7.0 ± 0.4 in CD2, PBS vs BCG). (ii) Compositional analysis of the lavages following BCG injection indicated a significant increase in the lymphocyte/macrophage ratio in BALB/c mice as compared to CD2 mice (p < 0.05). (iii) Activated peritoneal macrophage production of nitric oxide (NO) was significantly lower (p < 0.05) in BALB/c than in CD2 (26.8 ± 1.6 vs 38.3 ± 0.7 uM of nitrite respectively) when challenged with lipopolysaccharide. (iv) No difference in the in vitro cytotoxicity against MM45T cells was observed between BALB/c and CD2 macrophages. Our results suggest that differences in the composition of monocytes infiltrating the site of BCG treatment and in the release of substances such as NO by macrophages may be key determinants of the response to BCG immunotherapy for bladder cancer.
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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) | 0.000 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".