The distribution of anti-cancer drugs in relation to blood vessels in solid tumors
Bibliographic record
Abstract
1496 Anti-cancer drugs gain access to solid tumors via the circulatory system, and must penetrate the extravascular space to reach all cancer cells to cause lethal toxicity. There is limited but consistent evidence that drug resistance may be caused by limited delivery of anti-cancer drugs through the solid tumor microenvironment. Consequently, we are studying the distribution of common anti-cancer drugs in solid tumors of mice to address the hypothesis that their poor penetration through tissue is a major factor that limits the effectiveness of chemotherapy. The fluorescent agent Hoechst 33342 was used to model drug penetration. Tumor-bearing mice were injected intravenously with Hoechst 33342 and with EF5 to mark hypoxic cells. Tumors were resected from mice 20 minutes following injection and frozen in liquid nitrogen. Cryostat sections were stained for vascular endothelial cells with an antimouse CD31 monoclonal antibody, and with anti-EF5 to label hypoxic cells. Using an inverted fluorescence microscope the sections were imaged to generate a Hoechst 33342/ CD31-Cy3/EF-Cy5 fluorescence color composite that effectively relates Hoechst 33342 distribution to the vasculature and to hypoxic cells within a given cross-section. Image analysis shows a mean fifteen-fold decrease in the concentration of Hoechst 33342 over a 100 μm distance from blood vessels, and low to undetectable levels in hypoxic regions. Current experiments are modeling the distribution of the fluorescent anti-cancer drug doxorubicin.
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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".