Cancer Prognosis According to Parthanatos Features
Bibliographic record
Abstract
SUMMARY For nearly 50 years, translational research studies aimed at improving chemotherapy-induced killing of cancer cells have focused on the induction of apoptosis. Here we show that a PARP-1-mediated programmed cell death mechanism “parthanatos” is associated with the successful, front-line treatment of a common cancer. Peripheral blood mononuclear cells (PBMCs) from healthy human donors (10 of 10 tested), as well as primary cancer cells from approximately 50% of acute myeloid leukemia (AML) patients (n = 18 of 39 tested, French-American-British (FAB) subtypes M4 and M5) exhibited two distinctive features of parthanatos upon treatment with a front-line drug combination of cytarabine and an anthracycline. Statistically significant improvements in survival rates were observed in the parthanatos positive versus parthanatos negative AML patient groups (HR = 0.22 – 0.38, p = 0.002 – 0.05). Near-median expression of PARP1 mRNA was associated with a 50% longer survival time (HR = 0.66, p = 0.01), and the poly [ADP-ribose] polymerase (PARP) inhibitor Olaparib exhibited antagonistic activities against ara-C and idarubicin in primary blood monocytes from healthy donors as well as primary cancer isolates from ~50% of AML patients. Together these results suggest that PARP activity is a prognostic biomarker for AML subtypes M4 and M5 and support the relevance of parthanatos in curative chemotherapy of AML. In Brief Messikommer and co-workers report that PARP-1-mediated programmed cell death is associated with successful, front-line treatment of acute myeloid leukemia (AML). Highlights The first-line cancer drug cytarabine (ara-C) induces parthanatos or apoptosis, depending on the specific AML cell line being treated. OCI-AML3 cells undergo parthanatos or apoptosis, depending on the specific drug being added. The presence of two parthanatos features in primary cancer cells from AML patients (n = 18 of 39 tested) having French-American-British (FAB) subclassifications M4 or M5 is associated with four-fold improved survival (HR = 0.23, p = 0.01) following curative chemotherapy with ara-C and an anthracycline. The poly [ADP-ribose] polymerase (PARP) inhibitor Olaparib exhibits antagonistic activities against ara-C and idarubicin in primary blood monocytes from healthy donors as well as primary cancer isolates from ~50% of AML patients. Near-median expression of PARP1 mRNA is associated with a 50% increase in survival time (HR = 0.66, p = 0.01) of AML patients following chemotherapy with ara-C and idarubicin. GRAPHICAL ABSTRACT
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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 | 0.001 |
| 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) | 0.005 | 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".