TMOD-02. DIFFUSE GLIOMATOSIS IN MOUSE MODEL OF GFAP TISSUE SPECIFIC KNOCK IN OF EGFRvIII AND KNOCK OUT OF p19 ARF
Bibliographic record
Abstract
We generated a transgenic mouse harboring EGFRvIII knock in and homozygous p19 ARF deletion restricted to glial cells. The mice developed diffuse glioma with some tumors showing classical histological pseudopalisading necrosis and hyper vascularity. Transgenic mice develop tumors as early as 1 month and 53% of mice die by 6 months of age. MRIs reveal that mice develop ventriculomegaly and external hydrocephalus when tumor cell infiltration grows exophytic and presents with accumulations of neoplastic cells in association with leptomeninges, in addition to the brain and spinal cord parenchyma. Immunohistochemical analysis shows a strong glial component; tumors display positive GFAP, S100 staining and negative NeuN, synaptophysin staining. Three primary cell cultures were isolated as adherent and neurospheres from mice with tumors. During in vitro culture, EGFRvIII expression was lost in 2 of 3 lines, similar to seen in humans GBMs. Results were confirmed by Western blot and RT-PCR. Intracranial injection with EGFRvIII positive lines resulted in tumors in NODSCID mice. Immunohistochemistry staining of xenografts show that cells retained EGFRvIII expression, thus reinforcing that the importance of tissue microenvironment in maintaining genomic drivers. We present phenotype and genomic profile of a new transgenic model of glioma, with a prominent phenotype of leptomeningeal spread, potentially serving as a model for this important manifestation of human tumors.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 0.002 |
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".