Synergistic enhancement of breast cancer cell death using ultrasound-microbubbles in combination with cisplatin
Bibliographic record
Abstract
Cisplatin (CDDP), an anti-cancer agent, can effectively treat several cancerous tumourstumors such as testicular, bladder, and ovarian cancers. CDDP binds to specific DNA bases causing 1,2-intrastrand cross-links, single strand and double strand breaks inducing apoptosis. However, the effectiveness of CDDP is limited in tumourtumors such as breast cancer due to drug resistance. In this study, the application of ultrasound-microbubble (USMB) in improving the therapeutic effect of CDDP in breast cancer cell line is investigated. Human breast cancer (MDA-MB-231) cells in suspension (2×106 cells/mL concentration and 0.6 mL volume) were treated with CDDP (3 µM, 30 µM and 300 µM) and USMB at 0.5 MHz pulse centered frequency, 60 s insonation time, 16 µs pulse duration, 1 kHz pulse repetition frequency, and 1.7% v/v (volume concentration) of Definity microbubble agent. Following USMB treatment, cells were plated in 96-well plates for 24 and 48-hour incubation, after which cell viability was measured using MTT assay (VMTT). Cell viability decreased significantly with the combined treatment of CDDP and USMB compared to CDDP alone (p<0.001) after both 24 and 48-hour incubation. After 24-hour incubation, the VMMT was 40±2%, 32±1% and 18±1% with the combined treatment compared to 96±3%, 81±3% and 63±3% with CDDP alone at 3 µM, 30 µM and 300 µM, respectively. The combined treatment was additive at both concentrations (3 µM, p=0.9957) and (30 µM, p=0.6018) and synergistic at the highest concentration (300 µM, p=0.0169), based on Bliss Independence model with a 95% confidence interval of p<0.05. Furthermore, after 48-hour incubation, the VMTT was 54±3%, 22±1% and 13±1% with the combined treatment compared to 94±9%, 68±3% and 44±2%with CDDP alone at 3 µM, 30 µM and 300 µM, respectively. The combined treatment was still additive at the lowest concentration (3 µM, p=0.6689) and synergistic at the higher concentrations (30 µM, p=0.0001) and (300 µM, p=0.0001) based on Bliss Independence model with a 95% confidence interval of p<0.05 after 48-hour incubation. The combination of ultrasound-microbubble and cisplatin synergistically enhances chemotherapeutic effectiveness in breast cancer cells. However, this enhanced effectiveness, in breast cancer cells (MDA-MB-231), is dependent on incubation time and cisplatin (CDDP) concentration.
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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".