X-linked inhibitor regulating TRAIL-induced apoptosis in chemoresistant human primary glioblastoma cells.
Bibliographic record
Abstract
INTRODUCTION: The X-chromosome-linked inhibitor of apoptosis protein (XIAP) prevents apoptosis from activated transmembrane death receptors and confers tumour resistance to irradiation and chemotherapy. Despite the important oncologic implications, data concerning glioblastoma in this regard are few and isolated. The objective of this study was to examine the role of XIAP in the signalling pathway of TRAIL (tumour necrosis factor-related apoptosis-inducing ligand)-mediated apoptosis in chemoresistant human glioblastoma cells. METHOD: Downregulators of XIAP, low-dose cisplatin, etoposide (VP 16) or second mitochondria-derived activator of caspase (Smac)-Tat peptide, were applied to 2 chemoresistant glioblastoma cell lines of fresh isolates to identify the impact of these sensitizing agents on the cytotoxicity of TRAIL. Hoechst staining for apoptotic nuclear morphology and Western blot analysis for the corresponding levels of proteins that regulate apoptotic pathways including XIAP were performed. The involvement of mitochondrial pathways marked by the release of cytochrome c or Smac/direct IAP (inhibitor of apoptosis protein)-binding protein with low P1 (DIABLO), or both, was assessed by confocal fluorescence microscopy. RESULTS: Downregulators of XIAP induced apoptosis in a dose-dependent manner with TRAIL in 1 chemoresistant glioblastoma cell line. Here, XIAP downregulation modulated by Smac-Tat peptide resulted in increased TRAIL-induced cell death. In addition, TRAIL was shown to enhance the translocation of Smac/DIABLO from mitochondria to the cytosol in cells that underwent apoptosis, which in turn neutralized XIAP activity. In comparison, the second chemoresistant glioblastoma cell line showed no regulatory XIAP effect. This finding correlates with the upstream effect of mutant p53 and BCL-X(L) status that were upregulated in this chemoresistant cell line. CONCLUSION: These results support the use of selective or tailored therapeutic strategies that synergistically sensitize chemoresistant glioblastoma to TRAIL-mediated apoptosis by administering appropriate XIAP downregulating agents.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| 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) | 0.002 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".