Targeting integrin beta 1 using anti-tumorigenic quinazoline derivative in inhibition of glioblastoma cell invasion and survival: An in vitro preclinical study
Bibliographic record
Abstract
Objective: Glioblastoma (GBM) is the most common and malignant brain tumor, with a ~14.5 months median survival rate without disease-modifying curative treatment. After surgical resection, radiation, and adjuvant temozolomide (TMZ) chemotherapy is the first-line treatment of GBM with adverse effects, including bone marrow suppression, genotoxicity, and teratogenicity. Here, we report a synthetic quinazoline derivative that inhibits the growth of GBM cells as a new therapeutic approach.Methods: A potent quinazoline derivative (6-Pyridin-2-yl-5,6-dihydro-benzo[4,5] imidazo[1,2-c] quinazoline) was synthesized by one chemical step with 90% yield, followed by in vitro testing in GBM and neuroblastoma cells.Results: The in vitro studies showed that the quinazoline derivative is highly specific by decreasing GBM cell invasion while inducing cell death and inhibiting the cellular invasion in the three-dimensional Matrigel matrix. This compound is highly specific to GBM cell death compared with other cells. Synthetic quinazoline derivative is non-toxic to normal non-tumorigenic cells but toxic to cancerous cells. Under these experimental conditions, quinazoline derivatives caused inhibition of beta-1 integrin, which is an important cell adhesion molecule required for tumor cell invasion and metastasis, with extracellular matrix-mediated interactions. Furthermore, a synthetic quinazoline derivative decreases oncogenic PKC-epsilon activity in neuroblastoma cells.Conclusions: These studies suggest that a synthetic quinazoline derivative may treat GBM effectively alone or combined with other chemotherapeutic/immunotherapeutic agents.
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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 | 0.003 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.001 | 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 | 0.002 |
| 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".