Localized release of extracellular ATP by ultrasound and microbubbles for enhancing cancer immunotherapy
Bibliographic record
Abstract
Introduction: Extracellular ATP (eATP) is a damage-associated molecular pattern (DAMP) which plays a critical role in the activation of the NLRP3 inflammasome, an important mediator of the innate immune response. Ultrasound (US) and microbubbles (MB) have been shown to release ATP in muscle locally [1]. Our hypothesis is that US+MB could release ATP in tumor microenvironment following by the activation of pro-inflammatory immune response. The eATP release following US+MB and its quantification in muscle and 4T1 model will be presented. Methods: eATP quantification in vitro: 4T1 cells were incubated with D-luciferin (250 μM), luciferase (0.7 μM) and MB (5x106MB/ml) and the eATP signal was measured by bioluminescence (BLI) using Optix MX2. eATP quantificationinvivo: We quantified eATP in mice hindlimbs ( n=6) and 4T1 subcutaneous tumors ( n=8). After IP injection of D-luciferin (3 mg) and IV infusion of luciferase (270 μg) and MB (Definity, 4 μL/min), the mice received US treatment (1 MHz, 5000 cycles, 800 kPa) using a therapeutic probe for 10 min. The therapy was guided by US contrast imaging and the eATP signal was measured by BLI. A positive control was performed by IM administration of ATP (250 μM) in the hindlimb ( n=3). Results and conclusion: US+MB treatment released ATPinvitroand the signal increased with the number of cycle and pressure. Following the IM injection of ATP (250 μM), we detected a BLI signal at 4 min that was higher than baseline but was back to baseline level at 8 min. In muscle, After US+MB, the signal was 5.5 folds greater in the treated side compared to the non-treated side at 15 min and persisted until 75 min post-treatment. In tumors, we observed a significant increase in eATP signal post-US+MB in the treated side at 15 min that persisted up to 45 min post-treatment compared to the control side. In conclusion, US+MB treatment releases ATP in muscle and in 4T1 tumors which persisted longer in time compared to a direct intramuscular injection. The immune response characterization in 4T1 tumors after US+MB is in progress.
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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 | 0.000 | 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 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".