MB-01 * NOTCH1 PROMOTES MYC MEDULLOBLASTOMA METASTASIS, INITIATION AND MAINTENANCE
Bibliographic record
Abstract
Medulloblastoma (MB) is a malignant brain tumor that originates in the cerebellum in children and spreads via the cerebrospinal fluid to the leptomeningeal spaces of the brain and spinal cord. MB is stratified into four distinct groups, according to genetic and clinical features, and patients from group 3 (also known as c-Myc-amplified) have the highest risk of developing metastatic disease and, consequently, poor prognosis. Treatment protocols involve surgery, craniospinal radiation, and high-dose chemotherapy, which frequently cause disabling neurotoxic effects in long-term survivors. We used MB cell lines and primary cells isolated from patients from the c-Myc-amplified group as tools to understand the cellular determinants of leptomeningeal dissemination. Cells isolated from metastatic tumors express 10 times more NICD1 (Notch1 Intracellular Domain), the active form of Notch1, than cells isolated from primary sites (as quantified by western blot and imunohistochemistry), what implies the upregulation of Notch1 signaling pathway in MB metastasis. Moreover, flow cytometry analyses revealed that the cells isolated from metastatic sites express higher levels of full-length Notch1 when compared to cells from primary sites. These differences occur because of the enrichment in the cancer stem cell population at the metastatic sites, as we observed that MB cells isolated from metastatic tumors exhibit higher self-renewal potential than cells from primary tumor sites.
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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 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 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".