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Record W4241427629 · doi:10.1093/neuonc/nov061.132

PM-10 * GENETICALLY ENGINEERED MOUSE MODELS OF CHOROID PLEXUS TUMORS

2015· article· en· W4241427629 on OpenAlexaff
J. Wang, Diana M. Merino, Brian L. Murphy, Girish Dhall, Erin N. Kiehna, Alex Judkins, D. W. Ellison, C. Eberhart, Scott R. VandenBerg, David Malkin, Richard J. Gilbertson, M. Roussel, R. Wechsler-Reya

Bibliographic record

VenueNeuro-Oncology · 2015
Typearticle
Languageen
FieldMathematics
TopicMathematical Biology Tumor Growth
Canadian institutionsHospital for Sick Children
Fundersnot available
KeywordsChoroid plexusGenetically engineeredGenetically modified organismBiologyComputational biologyGeneticsNeuroscienceGene

Abstract

fetched live from OpenAlex

Choroid plexus tumors are the most common brain tumors in children under one year of age, accounting for up to 20% of brain tumors in that age group. These tumors exhibit a range of malignancies, from relatively benign choroid plexus papillomas (CPPs) to extremely aggressive choroid plexus carcinomas (CPCs), which despite intensive therapy, have a dismal prognosis. More effective treatments for these tumors depend on animal models that can be used to study tumor biology. We have created animal models of choroid plexus tumors by crossing mice carrying Cre-inducible alleles of Myc (LSL-MycT58A) and Cre-deletable alleles of p53 (p53flox) to animals that express Cre recombinase in neural stem cells or progenitors (Atoh1-Cre or Blbp-Cre). The progeny of these crosses develop choroid plexus tumors with high penetrance: activation of Myc alone results in CPPs, and concomitant deletion of p53 accelerates tumor growth and malignancy, culminating in formation of CPCs. Histological analysis indicates that mouse CPPs and CPCs resemble their human counterparts, and that CPCs (but not CPPs) exhibit reduced expression of normal choroid plexus epithelial markers and loss of tight junction proteins. Gene expression profiling reveals that CPPs and CPCs have altered expression of cell cycle regulators, and exhibit hallmarks of genomic instability and DNA damage responses. CPCs, but not CPPs, also exhibit abnormal telomere function and have increased expression of stem cell markers and hypoxia-induced genes. These studies provide important insight into the mechanisms of choroid plexus tumorigenesis, and yield valuable animal models that can be used to identify novel therapies for patients with aggressive choroid plexus tumors.

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 imitation

Not 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.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.003
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Theoretical or conceptual · Consensus signal: Theoretical or conceptual
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.269
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.003
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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.

Opus teacher head0.072
GPT teacher head0.313
Teacher spread0.241 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designTheoretical or conceptual
Domainnot available
GenreEmpirical

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".

Quick stats

Citations1
Published2015
Admission routes1
Has abstractyes

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