MEDU-29. A NOVEL MOUSE MODEL OF PI3 KINASE PATHWAY IN METASTATIC SHH MEDULLOBLASTOMA
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Bibliographic record
Abstract
Sleeping Beauty transposon mutagenesis in Shh medulloblastomas enabled us to identify that Pten was a common insertion site in both primary tumor and matched spinal metastases, suggesting PI3 kinase pathway is important for the progression of Shh medulloblastoma, in particular, for its metastasis. And PI3K-addiction could be one of mechanisms for the resistance to SHH signaling inhibitors seen in SHH medulloblastoma patients. To dissect the role of PI3 kinase pathway during the development of metastatic Shh medulloblastoma, and to establish an in vivo model for pre-clinical trials for PI3K pathway inhibitors on metastatic SHH medulloblastoma, we recently generate a novel targeted mutant mouse model Rosa-Tetoff-lsl-Pik3CAH1047R –t2a-Fluc. In this mouse model, a Dox-off and Cre-LoxP dual system mediates the spatial-temporal specific expression of Pik3CAH1047R, and the tumor cells could be visualized by bioluminescent imaging (BLI). We have crossed Rosa-Tetoff-lsl-Pik3CAH1047R –t2a-Fluc mouse with Math1Cre and Ptc heterozygous deletion mice to generate Pik3CAH1047R/Math1Cre/Ptc triple mice. Preliminary results showed that in the absence of Doxycycline the triple mice developed massive metastases at the frontal brain and spinal cord. More mice are generated and aged for detail experiments. In summary, we established a novel mouse model to express Pik3CAH1047R in a spatial-temporal specific manner, and the mutant Pik3CA greatly promoted Shh medulloblastoma metastasis to the spinal cord and frontal brain.
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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 it