Transglutaminase 2 as a Possible Chemotherapeutic Target in Glioblastoma Multiforme
Bibliographic record
Abstract
Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults. Despite advances in therapies, patients with GBM still have a 14 month median survival rate after treatment. A common feature of GBM tumors is the presence of hypoxic microenvironments due to insufficient perfusion; which ranges from 4 to <1% oxygen. It has been reported that cells in these hypoxic regions show increased resistance to current therapies used to treat GBM patients. Therefore, it is important to define molecular mechanisms that help the cells survive in hypoxia. One possible therapeutic target is the multifunctional protein transglutaminase 2 (TG2), which plays a role in promoting cell proliferation and survival in various tissues. Interestingly, increased expression of TG2 in GBM tumors correlates with shorter survival times. The goal of this project is to determine if TG2 affects GBM proliferation and survival, in both normoxia and hypoxia, and whether we can use NC9, a novel TG2 inhibitor, as a chemotherapeutic agent in GBM cells. We found that NC9 effectively inhibits colony formation of GBM cells in a TG2‐dependent manner. Results from an EdU incorporation assay show that NC9 decreases the proliferation rate of GBM cells in both normoxic and hypoxic conditions. Markers for the NF‐κB proliferation pathway showed a marked reduction as a result of NC9 treatment. NC9 was not toxic to primary cortical neurons or astrocytes at the concentrations used, which is encouraging for clinical potential. Our results suggest that TG2 is involved in GBM proliferation and NC9, or its derivatives, have the potential to be clinically used for the treatment of GBM.
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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 | 0.000 |
| 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".