Priming of bone marrow stromal cells with the epigenetic modifier decitabine overcomes stroma-mediated resistance to bortezomib in multiple myeloma cells.
Bibliographic record
Abstract
Abstract Title of the project Priming of bone marrow stromal cells with the epigenetic modifier decitabine overcomes stroma-mediated resistance to bortezomib in multiple myeloma cells. Introduction. In multiple myeloma (MM), the malignant plasma cells reside in the bone marrow microenvironment. Within this environment, MM cells are protected against anti-myeloma drugs through interaction with bone marrow mesenchymal stromal cells (MSCs). This form of stroma-mediated protection may partly explain poor treatment response in some MM patients. One approach to overcome this resistance is using a combination of drugs which target both the cancer cells and disrupt the above interaction at the same time. In this project we investigated whether pre-treatment (priming) of MSCs with an epigenetic modifier decitabine could overcome the above resistance when MM cells are exposed to the anti-myeloma drug bortezomib (BTZ). Methods. The luciferase-tagged MM cell line (U266) and the bone marrow MSC line (HS.5) were cultivated and maintained in their specific culture media. First, HS.5 cells were seeded on 96-well plates and treated with different doses of decitabine for 24h. Then, the decitabine was removed and wells washed, U266 cells were added on top of the HS.5 cells (co-culture), BTZ was added to the wells and plate incubation continued for another 24h. Finally, luminescence of the 96-well plate was measured using a luminescence plate reader to calculate % cytotoxicity. Results. MM cells’ death by BTZ was the highest in the absence of HS.5 cells (n=3, mean=67%), however, it was significantly reduced when MM cells were co-cultured with HS.5 cells (n=3, mean=44.5%, p<0.001) implying stroma-induced drug resistance. On the other hand, when HS.5 cells were primed with decitabine, cell death in MM cells was increased to the level close to MM cells’ death in monoculture (n=3, mean= 63.5%, p=0.171) indicating rescue effect of decitabine treatment of HS.5 cells.Conclusions. Our findings indicate that MSCs may at least partly employ an epigenetic mechanism to induce resistance to drugs in MM cells via direct interaction with latter cells. However, further investigation is ongoing to establish whether this could be a potential underlying mechanism.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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 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".