A sensitive assay for the evaluation of cytotoxicity and its pharmacologic modulation in human solid tumor-derived cell lines exposed to cancer-therapeutic agents.
Bibliographic record
Abstract
PURPOSE: Reliable in vitro cytotoxicity assays are essential for determining the responses of human normal and cancer-derived cells to therapeutic agents and also for the identification and pre-clinical evaluation of new drugs capable of selectively augmenting the susceptibility of cancer cells to conventional therapies. The clonogenic survival assay is considered as the "gold standard" in this regard because it measures the sum of all modes of cell death, encompassing both early and late events such as delayed growth arrest. In this assay, however, the impact of cell-to-cell communication is disregarded because the cells are plated out at very low densities. In addition, here we provide evidence that human breast cancer cell lines cannot be reliably evaluated by clonogenic assays. We developed a novel long-term, High Density Survival (HDS), assay that circumvents the various intrinsic shortcomings of the conventional cytotoxicity assays. METHODS: In the HDS assay, the cells are maintained at a high density for 24 h prior to, and for 24 h after, exposure to a DNA-damaging agent to facilitate intercellular communication. After a carefully scheduled subculturing for approximately 7 days, cultures are assessed for the extent of growth. RESULTS: The degree of radiosensitivity and cisplatin sensitivity evaluated by the HDS assay in human cancer cells was comparable to that measured by the clonogenic assay. Pharmacological inhibitors of CaMKII and/or PI3K signaling elicited a greater degree of radiosensitization when determined by the HDS assay than the clonogenic assay. In all these experiments, there was no relationship between the degree of cytotoxicity measured by the clonogenic survival and viability assays. In the HDS assay, all seven human breast cancer cell lines that we tested exhibited a high degree of radioresistance. CONCLUSIONS: The novel HDS assay appears to be a powerful tool for evaluating cancer cell responses to therapeutic agents under conditions which incorporate some aspects of intercellular communication.
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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 | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 0.002 |
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".