Pharmacological Ascorbate Enhances Chemotherapies in Pancreatic Ductal Adenocarcinoma
| العنوان: | Pharmacological Ascorbate Enhances Chemotherapies in Pancreatic Ductal Adenocarcinoma |
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| المؤلفون: | Brianne R. O'Leary, Elena K. Ruppenkamp, Garett J. Steers, Juan Du, Rory S. Carroll, Brett A. Wagner, Garry R. Buettner, Joseph J. Cullen |
| المصدر: | Pancreas. 51:684-693 |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Paclitaxel, Hepatology, Endocrinology, Diabetes and Metabolism, Leucovorin, Antineoplastic Agents, Ascorbic Acid, Irinotecan, Oxaliplatin, Pancreatic Neoplasms, Mice, Endocrinology, Antineoplastic Combined Chemotherapy Protocols, Internal Medicine, Animals, Humans, Fluorouracil, Carcinoma, Pancreatic Ductal |
| الوصف: | Pharmacological ascorbate (P-AscH - , high-dose, intravenous vitamin C) has shown promise as an adjuvant therapy for pancreatic ductal adenocarcinoma (PDAC) treatment. The objective of this study was to determine the effects of P-AscH - when combined with PDAC chemotherapies.Clonogenic survival, combination indices, and DNA damage were determined in human PDAC cell lines treated with P-AscH - in combination with 5-fluorouracil, paclitaxel, or FOLFIRINOX (combination of leucovorin, 5-fluorouracil, irinotecan, oxaliplatin). Tumor volume changes, overall survival, blood analysis, and plasma ascorbate concentration were determined in vivo in mice treated with P-AscH - with or without FOLFIRINOX.P-AscH - combined with 5-fluorouracil, paclitaxel, or FOLFIRINOX significantly reduced clonogenic survival in vitro. The DNA damage, measured by γH2AX protein expression, was increased after treatment with P-AscH - , FOLFIRINOX, and their combination. In vivo, tumor growth rate was significantly reduced by P-AscH - , FOLFIRINOX, and their combination. Overall survival was significantly increased by the combination of P-AscH - and FOLFIRINOX. Treatment with P-AscH - increased red blood cell and hemoglobin values but had no effect on white blood cell counts. Plasma ascorbate concentrations were significantly elevated in mice treated with P-AscH - with or without FOLFIRINOX.The addition of P-AscH - to standard of care chemotherapy has the potential to be an effective adjuvant for PDAC treatment. |
| تدمد: | 1536-4828 0885-3177 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::75923ece290a778c672b09d484796b09 https://doi.org/10.1097/mpa.0000000000002086 |
| رقم الأكسشن: | edsair.doi.dedup.....75923ece290a778c672b09d484796b09 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15364828 08853177 |
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