Effect of Tirapazamine, Metformin or Mild Hyperthermia on Recovery From Radiation-Induced Damage in Pimonidazole-Unlabeled Quiescent Tumor Cells
Bibliographic record
Abstract
BACKGROUND: The aim of the study was to examine the effect of tirapazamine (TPZ) on recovery from radiation-induced damage in pimonidazole-unlabeled quiescent (Q) tumor cells compared with that of metformin (Met) or mild temperature hyperthermia (MTH). METHODS: Proliferating (P) cells in EL4 tumors were labeled by continuous 5-bromo-2'-deoxyuridine (BrdU) administration. Tumors received γ-rays at 1 h after pimonidazole administration followed by Met or TPZ treatment or MTH. Twenty-four hours later, the responses of Q and total (P + Q) cells and those of the pimonidazole-unlabeled cells were assessed with micronucleation and apoptosis frequencies using immunofluorescence staining for BrdU and apoptosis frequency using immunofluorescence staining for pimonidazole, respectively. RESULTS: With γ-rays only, the pimonidazole-unlabeled cell fraction showed significantly enhanced radio-sensitivity compared with the whole cell fraction more remarkably in Q than total cells. However, a significantly greater decrease in radio-sensitivity in the pimonidazole-unlabeled than the whole cell fraction, evaluated using a delayed assay, was more clearly observed in Q than total cells. Post-irradiation MTH or Met treatment more clearly repressed the decrease in radio-sensitivity in the Q than total cells. Post-irradiation TPZ administration produced a large radio-sensitizing effect on both total and Q cells, especially on Q cells. In pimonidazole-unlabeled cell fractions in both total and Q cells, TPZ suppressed the reduction in sensitivity much more efficiently than MTH or Met without any radio-sensitizing effect. CONCLUSION: Post-irradiation TPZ administration has the potential to both suppress recovery from radiation-induced damage and enhance the radio-sensitivity both in total and Q tumor cells. Post-irradiation TPZ administration may be useful for controlling tumors.
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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 | 0.001 | 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".