MB-16NOTCH1 PROMOTES GROUP 3 MEDULLOBLASTOMA METASTASIS, INITIATION AND SELF-RENEWAL
Bibliographic record
Abstract
Medulloblastoma is the most common pediatric malignant brain. Group 3, the most aggressive molecular subgroup of medulloblastoma, arises in the cerebellum and/or floor of the 4th ventricle and frequently disseminates through the cerebrospinal fluid (CSF) to different regions of the brain and spinal cord. The presence and stage of metastasis (tumor cells in the CSF and in the spinal subarachnoid space) are directly related to the overall survival and progression-free survival of medulloblastoma patients. The mechanisms of dissemination through the CSF are very poorly understood and the pathways involved in medulloblastoma maintenance are unknown. We show that Notch1 pathway regulates group 3 medulloblastoma metastasis, initiation and self-renewal. Notch1 expressing cells are not only the self-renewing group 3 medulloblastoma tumor initiating cells but also are the cells which initiate spinal metastasis. Group 3 medulloblastoma spinal metastasis present increased expression of Notch1 and modulation of Notch1 intracellular domain (NICD1) expression is directly related to medulloblastoma metastasis and survival rate of tumor-bearing mice. In addition, sorted Notch1-negative group 3 medulloblastoma cells were unable to produce detectable metastasis in the first passage in vivo and to generate primary tumors in the second passage in vivo, whereas Notch1-positive cells robustly formed brain tumors and spinal metastasis upon in vivo passages. These findings identify Notch1-positive cells as the medulloblastoma stem cells. Notch1 is a pivotal driver of group 3 medulloblastoma initiation and progression, supporting the development of therapies targeting this pathway.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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".