EXPLORING THE ROLE OF GAT1 AND GABA IN TEMOZOLOMIDE TREATED GLIOMA
Bibliographic record
Abstract
Abstract Approximately 3000 Canadians a year are diagnosed with the most aggressive and fatal form of brain cancer called glioma. Even with surgical resection, chemotherapy, and radiotherapy these patients have an average survival of less than 20 months. Research in the past has primarily focused on identifying and targeting specific genetic mutations in the tumor. However, it is apparent that the environment surrounding the tumor can influence tumor growth, tumor spread into the brain, and drug resistance. The brain presents many challenges to glioma treatment, one of which is the unique environment in which gliomas grow, which contributes to poor patient outcomes. The interaction between tumor cells, surrounding normal brain tissue, and immune cells supports the aggressiveness of glioma. Using a model of chemosensitive and chemoresistant tumors, we have identified an increase in the GABA transporter GAT1 in the chemosensitive tumor treated with the standard chemotherapy temozolomide. GAT1 is primarily expressed on neurons, but has also been shown to be expressed on astrocytes and immune cells such as macrophages. Our lab has identified that macrophages tend to concentrate in the same region as GAT1 expressing cells within the tumor environment. In addition, multiple papers have shown that an increase in GABA promotes a glioma-promoting immune microenvironment. Thus, we believe that treatment with temozolomide causes an increase in environmental GAT1 expression, resulting in a reuptake of GABA, and promoting a glioma-inhibitory macrophage phenotype. We believe that understanding how the glioma-inhibitory macrophage phenotype occurs will help improve patient outcomes.
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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) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| 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".