Distribution of photosensitizers in bladder cancer spheroids: implications for intravesical instillation of photosensitizers for photodynamic therapy of bladder cancer.
Bibliographic record
Abstract
PURPOSE: Uniform intratumor distribution of sufficient photosensitizer is one of the important aspects of photodynamic therapy for solid tumors. METHODS: Multicellular spheroids derived from a human transitional cell carcinoma cell line (MGHU3) were used as a surrogate system of tiny solid tumors to study intratumor distribution of photosensitizers. Photosensitizers included Photofrin, hypocrellins (HBEA-R1/R2, HBBA-R2), aluminum phthalocyanine chloride (AlPC), benzoporphyrin derivative monoacid ring A (BPD-MA), protoporphyrin-IX (PpIX), and liposomal formulations of HBBA-R2 and BPD-MA. Spheroids were incubated with various doses of the above drugs for 1-4 hours, and were examined by confocal microscopy. RESULTS: Histology showed all cells were healthy in spheroids less than 400 microm in diameter. Scanning electron microscopy showed tight cell-to-cell interdigitation in spheroids. HBEA-R1/R2 distributed more uniformly in spheroids than other drugs. Free hypocrellins and BPD-MA penetrated spheroids centripetally deeper than AlPC, Photofrin, and PpIX. Liposomal HBBA-R2 and BPD-MA penetrated less than their free formulations. CONCLUSIONS: The spheroids mimic solid tumors prior to neovascularization. Based on drug distribution in spheroids, hypocrellins and BPD-MA appear superior to Photofrin, AlPC and PpIX for intravesical administration for bladder cancer phototherapy.
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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) | 0.001 | 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".