Mouse Models to Interrogate the Implications of the Differentiation Status in the Ontogeny of Gliomas
Bibliographic record
Abstract
Diana Marcela Muñoz 1 , Abhijit Guha 1,2 1 The Arthur and Sonia Labatt Brain Tumor Research Centre, Hospital for Sick Children Research Institute, University of Toronto, Toronto, Ontario, Canada, M5G 1L7 2 Division of Neurosurgery, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada, M5T 2S8 Received: August 31, 2011; Accepted: September 1, 2011; Published: September 3, 2011; Keywords: Glioblastoma Multiforme (GBM), Tumor Heterogeneity, Tumor Microenvironment, Brain Tumor Stem Cells (BTSC) Correspondence: Abhijit Guha, email: // // Abstract Glioblastoma Multiforme (GBM) is the most common and lethal of human primary central nervous system (CNS) tumors, with a median survival of 14-16 months despite optimal surgery, radiation and chemotherapy. A reason for this dismal prognosis is insufficient understanding of the ontogeny of GBMs, which are highly heterogeneous at a pathological level. This pathological diversity, between and within GBMs as well as varying grades of gliomas, has not been fully explained solely on the grounds of oncogenic stimulus. Interaction with the tumor microenvironment is likely a source of this pathological heterogeneity, as well as the inherent characteristics of the tumor cell of origin. Currently, controversy exists on whether the initial transformed cell is a differentiated astrocyte, progenitor or neural stem cell. Putative Cancer Stem Cells (CSCs), which have features of normal stem cell plus the ability to recapitulate the tumor phenotype in vivo in small numbers, have been identified from a variety of solid human cancers, including GBMs. Evidence suggesting that regions harboring normal stem cells in the adult CNS, such as the subventricular zone and the dentate gyrus, are more prone to viral and chemical oncogenesis, is supportive of the hypothesis that brain tumors arise from stem cells. However, it is still to be determined whether the appearance of brain tumor stem cells (BTSC) is the cause or consequence of tumor initiation and progression. This review discusses emerging evidence highlighting the relevance of the state of differentiation and regional heterogeneity in the ontogeny of GBM. This is an area of high interest in cancer in general, with potential significant therapeutic and prognostic implications.
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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) | 0.001 | 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".