Deciphering the Biological Differences between Micro-metastasis and Macro-metastasis in Medulloblastoma
Bibliographic record
Abstract
Medulloblastoma is a common paediatric brain tumor, arising within the hindbrain and affecting approximately 18-20% of children diagnosed with brain cancer. Metastasis is present in 40% of patients during initial diagnosis and is almost exclusive to the leptomeninges of the brain and spinal cord. Unfortunately, despite such high incidence and poor prognosis, leptomeningeal metastatic disease remains poorly understood and lacks effective therapies.The objective of my studies is to investigate the biology between micro- and macro-metastatic stages in medulloblastoma. My hypothesis is that the progression of a micro- to a macro-metastasis is dependent on a biological switch in which its inhibition carries therapeutic potential. In transgenic mice, I observed metastases of various sizes and with statistical modeling, I confirmed that there were two populations – micro- and macro-metastases. Using single-cell sequencing, I revealed that the two populations differed in their lipid metabolism and that alterations in the lipid composition of animals influenced metastatic burden. With such results, I proposed that micro-metastases are metabolically plastic – the ability to use one metabolite for multiple purposes – and must undergo a transition to become metabolically flexible – the ability to use multiple metabolites – prior to developing as macro-metastases. In addition to understanding the progression, I investigated the evolutionary trajectory of micro- and macro-metastases. Contradictory to expectations, I found that primary tumors and macro-metastases are more similar to each other than either primary tumors to micro-metastases, or micro- and macro-metastases to each other. Therefore, a proposed model for metastatic progression is the primary tumor gives rise to both micro- and macro-metastases, and the macro-metastases are capable of seeding more micro-metastases. Finally, I briefly explored the microenvironments of micro- and macro-metastases and found evidence of macrophages in association with micro-metastases. Overall, the results of my doctoral studies have contributed to the expansion of our knowledge in medulloblastoma metastasis.
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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 | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".