P11.40 Development of an implantable multifunctional biodevice (GlioGel) in the treatment of recurrent glioblastoma
Bibliographic record
Abstract
Abstract BACKGROUND Glioblastoma (GBM) is a devastating disease with a median survival of 14–16 months. This poor prognosis can be explained by 3 factors. First, the infiltrative nature of the disease prohibits a complete removal of the tumor. Second, some of the tumor cells are brain tumor stem cells, which are highly migratory and highly resistant to treatments. Finally, the presence of the blood-brain barrier prohibits entry of therapeutics. This situation implies that new treatment approaches must be directed toward the infiltrated brain surrounding the resection cavity. To bypass this problem and improve the potency of adjuvant treatment, we have designed a new “GlioGel-device” that will have the ability to: 1- attract the migrating tumor cells into or nearby the device, and 2- subsequently deliver chemotherapy to the locally pooled tumor cells and 3- irradiate these cells with radioisotopes embedded in the GlioGel. MATERIAL AND METHODS In vitro proof of principle of chemoattraction was investigated by agarose drops method releasing chemokines molecules (CCL2, CCL11, CXCL10) with F98 and U87MG GBM cells. In vivo experiments evaluated the efficiency of chemokines and doxorubicin released by the implanted GlioGel on the tumor behaviour in our Fischer-F98 rat glioma model. An histology of tumour behaviour exposed to chemokines and survival of GBM rats treated with doxorubicin were analysed. RESULTS In vitro preliminary results for chemoattraction assays show that up to 2 times more cells invade the gel when it releases chemoattractant compared to PBS. The In vivo chemotherapy experiments with a fast, medium and slow release of doxorubicin from the GlioGel show that a local dose that represent a 1300-fold smaller dose than a normal intravenous systemic dose gave a significant reduction in tumour growth (median survival) compared to a control group. We investigated the effect provided by the GlioGel impregnated with chemokines on tumor cells migration, after implantation in the Fischer-F98 rat glioma model. CONCLUSION This preliminary study shows the ability of GlioGel releasing chemokines and doxorubicin to respectively attract and kill orthotopic glioblastoma cells. These encouraging results will be completed with a combination of short-range (high LET) radiation by embedded radioisotope into the GlioGel aiming for synergistic combination to eradicate as much tumour cells as possible, while limiting systemic side effects.
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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) | 0.001 | 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".