Chemotherapy increases CDA expression and sensitizes malignant pleural mesothelioma cells to capecitabine treatment
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Le résumé fourni par la source
The combination of cisplatin and pemetrexed remains the gold standard chemotherapy for malignant pleural mesothelioma (MPM), although resistance and poor response pose a significant challenge. Cytidine deaminase (CDA) is a key enzyme in the nucleotide salvage pathway and is involved in the adaptive stress response to chemotherapy. The cytidine analog capecitabine and its metabolite 5'-deoxy-5-fluorocytidine (5'-DFCR) are converted via CDA to 5-fluorouracil, which affects DNA and RNA metabolism. This study investigated a schedule-dependent treatment strategy, proposing that initial chemotherapy induces CDA expression, sensitizing cells to subsequent capecitabine treatment. Basal CDA protein expression was low in different mesothelioma cell lines but increased in the corresponding xenografts. Standard chemotherapy increased CDA protein levels in MPM cells in vitro and in vivo in a schedule-dependent manner. This was associated with epithelial-to-mesenchymal transition and with HIF-1alpha expression at the transcriptional level. In addition, pretreatment with cisplatin and pemetrexed in combination sensitized MPM xenografts to capecitabine. Analysis of a tissue microarray (TMA) consisting of samples from 98 human MPM patients revealed that most human MPM samples had negative CDA expression. While survival curves based on CDA expression in matched samples clearly separated, significance was not reached due to the limited sample size. In non-matched samples, CDA expression before but not after neoadjuvant therapy was significantly associated with worse overall survival. In conclusion, chemotherapy increases CDA expression in xenografts, which is consistent with our in vitro results in MPM and lung cancer. A subset of matched patient samples showed increased CDA expression after therapy, suggesting that a schedule-dependent treatment strategy based on chemotherapy and capecitabine may benefit a selected MPM patient population.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Chemotherapy increases CDA expression and sensitizes malignant pleural mesothelioma cells to capecitabine treatment
- Date Crossref
- 06/08/2024
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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University of Bern Department for BioMedical Research pays non établi dans la noticeUniversité ou école supérieure
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University Hospital of Bern pays non établi dans la noticeÉtablissement de santé
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Central South University pays non établi dans la noticeUniversité ou école supérieure
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Hunan Cancer Hospital Hunan Clinical Medical Research Center of Accurate Diagnosis and Treatment for Esophageal Carcinoma pays non établi dans la noticeÉtablissement de santé
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Düsseldorf University Hospital pays non établi dans la noticeÉtablissement de santé
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Heinrich Heine University Düsseldorf pays non établi dans la noticeUniversité ou école supérieure
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University of Lausanne Department of Laboratory Medicine and Pathology pays non établi dans la noticeUniversité ou école supérieure
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Bern University of Applied Sciences pays non établi dans la noticeUniversité ou école supérieure
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Bern University Hospital Department of General Thoracic Surgery pays non établi dans la noticeUniversité ou école supérieure
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Graduate School of Cellular and Biomedical Sciences pays non établi dans la noticeUniversité ou école supérieure
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Heinrich-Heine University and University Hospital of Duesseldorf Institute of Pathology pays non établi dans la noticeUniversité ou école supérieure
Department for BioMedical Research — University of Bern, University Hospital of Bern et Central South University, avec 8 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.