Abstract 364: Oxaliplatin and 5-fluorouracil cause therapy-induced senescence in low-grade serous ovarian cancer cells
Notice bibliographique
Résumé
Abstract A critical concern with managing low-grade serous ovarian cancer (LGSOC) is the lack of response to standard carboplatin-paclitaxel chemotherapy; less than 30% of patients respond to such initial chemotherapy. Oxaliplatin (OXP) and 5-Fluorouracil (5-FU) combination treatment is a standard treatment regimen against colorectal cancer (CRC); however, it could be repurposed for use against LGSOC. p53 wildtype CRC tumours have been shown to respond better to OXP & 5-FU suggesting that LGSOC, which is well-characterized to also be p53 wildtype, would also respond effectively to this treatment. Consequently, in this study, we utilized three LGSOC cell lines: VOA6406, VOA7681, and VOA1056. We determined the cytotoxic effects of treatment with OXP & 5-FU; viability, proliferation, clonogenic capacity, and drug-withdrawal recovery were assessed. Results showed a dramatic decrease in cell proliferation in the short-and-long term, without a reduction in cell viability. This effect was confirmed further by measuring Ki67, a marker of cell proliferation; OXP & 5-FU-treated cells showed a significant reduction in Ki67 labelling. The persistence in viability alongside the reduced cell proliferation in cells treated with OXP & 5-FU led us to hypothesize that this drug combination induces senescence in LGSOC cells. A critical aspect of senescence is the arrest of the cell cycle. A propidium iodide-based cell cycle assay, along with western blotting to measure expression of p53, p21, and pRb, demonstrated that the LGSOC cells treated with OXP & 5-FU were arresting at the G1-S phase. Morphology alterations and lysosomal swelling were measured via expression of senescence-associated β-galactosidase (SA-β-gal); OXP & 5-FU-treated LGSOC cells demonstrated a marked increase in SA-β-gal as well as a distinct flattening of cell morphology. Consistent with hallmarks of senescence, anti-apoptotic proteins Bcl-2 and Mcl-1, were elevated upon treatment with OXP & 5-FU. A compelling increase in reactive oxygen species (ROS) production, as well as an elevated expression of caveolin-1, suggest a senescence-induction pathway dependent on oxidative stress. The use of a known ROS quencher, α-tocopherol, confirmed this pathway, as it partially rescued the senescence phenotype induced by OXP & 5-FU. The use of OXP & 5-FU to induce senescence in LGSOC shows promise as an alternate treatment option for this rare disease. We will further study if facilitating a “one-two punch theory” could be used against LGSOC, whereby OXP & 5-FU induces senescence, which could be subsequently “cleared” by a senolytic drug. Citation Format: Rewati Prakash, Alicia A. Goyeneche, Edith Zorychta, Shuk On Annie Leung, Lucy Gilbert, Carlos Telleria. Oxaliplatin and 5-fluorouracil cause therapy-induced senescence in low-grade serous ovarian cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 364.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,001 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».