Traitement de l’adénocarcinome du pancréas avec le virus de la stomatite vésiculaire codant pour le transgène GM-CSF
Bibliographic record
Abstract
BACKGROUND Pancreatic cancer is the 8th most frequent cancer found in Canada for women and the 10th most frequent for men. Pancreatic ductal adenocarcinoma (PDAC) is the most frequent subtype of pancreatic cancer. Its survival rate is only at 8 % over 5 years, which makes it one of the most fatal cancers. Between 40 to 60 % of patients will receive their diagnosis at a late stage of their disease, which is inoperable. Surgery is presently the only option to cure patients. The standard of care for patients that are not operable is Folfirinox, a chemotherapeutic agent that is sometimes able to debulk the primary tumor to allow for tumor resection. However, the majority of patients cannot withstand chemotherapy for their PDAC due to severe cytotoxic side effects. In our laboratory, we are developing virotherapy as an alternative treatment option for PDAC patients. We are working with an oncolytic vesicular stomatitis virus armed with the transgene GM-CSF (VSV-GM-CSF) and we believe that it could kill cancer cells through cell lysis and induce an immune response to give pancreatic cancer patients a better chance of survival. AIMS Our goal was to compare the response in vitro and in vivo to different PDAC treatments such as Folfirinox alone, virus alone and a combination of the two. METHODS The human pancreatic cancer cell lines Mia-PaCa-2 and Panc01 as well as the mouse cell lines Panc02 and KPC were used for our experiment. We used 3 different viruses; one with the human transgene (VSVd51-hGM-CSF), one with the mouse transgene (VSVd51-mGM-CSF) and finally the parental virus with no transgene (VSVd51). We used a different virus for the mouse and the human because the GM-CSF protein is only 70% homologous between the two species. The functionality of our virus was confirmed using a cytotoxic assay, a replication assay and a ELISA to ensure the production of GM-CSF. The immunogenic cell death cause by the virus was analyzed by western blot to measure HMGB1 and HSP90, by flow cytometry for calreticuline and luminometric assay for ATP. For our in vivo model, we orthotopically implanted Panc02 directly into the mouse pancreas, followed by treatment with VSV-mGM-CSF, Folfirinox or the combination. RESULTS We can confirm that our virus armed with a transgene has the ability to kill, to reproduce itself and to produce the GM-CSF protein. In vitro data suggests that VSV-GM-CSF is better to induce cell death than chemotherapy and that a combination of the two therapies is also better than Folfirinox alone. In vivo, with no significant data, VSV-GM-CSF seems to be better than Folfirinox and the combination of the two for mice survival. This means that the virus could become an alternative treatment for PDAC patients in the future.
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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) | 0.001 | 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".