Caenorhabditis elegans as animal model to investigate the cellular mechanism of resistance for the chemotherapeutic agent cisplatin
Bibliographic record
Abstract
In the last three decades, cisplatin has been one of the most widely prescribed drugs being an effective treatment for many cancer types. Despite its effectiveness, many patients are intrinsically resistant to cisplatin-based therapies and an important fraction of tumors eventually develop chemoresistance to this agent. In this study we consolidate C. elegans as a pluricellular model (I) to better understand the biological response to cisplatin-based chemotherapy to finally to map cellular pathways capable of modulating the response to cisplatin and (II) to functionally validate candidate genes involved in the such response to cisplatin.\n\n\t\t\t\t We discover that cisplatin-induced damage provokes in worms specific cell-type apoptotic activation and induces a systemic response promoting the activation of a set of redox-stress responsive genes whose transcription is mediated by the evolutionary conserved Insulin-IGF-like receptor signaling pathway (IIS) transcription factors SKN-1/Nrf2 and DAF-16/FOXO. In addition, altering both IIS-pathway-related genes and some of their targets leads to modify the response to cisplatin. Accordingly, this study demonstrates the importance of redox homeostasis in the resistance to cisplatin, and the central role of Nrf2/SKN-1 and FOXO/DAF-16 as modulators of cisplatin resistance acquisition through this mechanism, which is conserved from worms to mammals.\n\n\t\t\t\t We also demonstrated, after an RNAi based approach using C. elegans, that several genes present at the 9q32-q33.1 human region, such as the glucosyl ceramide synthase or the copper transporter, were able to individually alter the response to cisplatin. Moreover, we demonstrated the relevance of the glucosylceramide synthase activity as a biological mechanism that mediate tumor cell protection against cisplatin exposure in tumorgraft models, highlighting the relevance of targeting glucosylceramide synthase as a novel approach to resensitize tumors to cisplatin. This confirms the translational value of C. elegans in cisplatin-based research, which could fill the gap between in vitro and preclinical studies.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".