Abstract B24: Detection of O6- and N7-methylguanine adducts by LC/MS in brain tumor tissues obtained from patients treated with temozolomide.
Bibliographic record
Abstract
Abstract The current standard of care for glioblastoma includes surgery, radiotherapy and chemotherapeutic agents such as temozolomide (TMZ), a DNA methylating compound. The cytotoxic effects of TMZ have been linked to guanine methylation at the N7 and O6 positions. These adducts are not currently used as markers of TMZ efficacy. Using liquid chromatography/mass spectrometry (LC/MS), we have established a sensitive analytical assay to directly detect both N7- and O6-methylguanine adducts from DNA following TMZ treatment. A limit of detection below 1 fmol was observed for O6-methylguanine, while N7-methylguanine was observed below 5 fmol. O6- and N7-methylguanine were successfully detected by LC/MS in tumour and normal brain tissue samples from patients treated with a neoadjuvant TMZ regimen for 14 days (75 mg/m2). Variations in levels of both methylated guanines were detected between patients as well as within different locations of the same tumour sample. This technique provides a direct detection of the damage inflicted by TMZ. This could potentially indicate the efficacy of the drug, allowing for prompt analysis and response. It also holds potential for determining efficacy of treatment dose, schedule and possible concomitant drugs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr B24.
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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".