Chemoresistance in Pancreatic Cancer The Role of Adipose-Derived Mesenchymal Stem Cells and Key Resistance Genes /
Drug resistance is a significant challenge in pancreatic ductal adenocarcinoma (PDAC), where stromal elements such as adipose-derived mesenchymal stem cells (ASCs) contribute to a chemoresistant tumor microenvironment (TME). This study explored the effects of oxaliplatin (OXP) and 5-fluorouracil (5-...
Elmentve itt :
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| Dokumentumtípus: | Cikk |
| Megjelent: |
2025
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| Sorozat: | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
26 No. 1 |
| Tárgyszavak: | |
| doi: | 10.3390/ijms26010390 |
| mtmt: | 35667146 |
| Online Access: | http://publicatio.bibl.u-szeged.hu/35509 |
| LEADER | 02841nab a2200337 i 4500 | ||
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| 008 | 250114s2025 hu o 000 eng d | ||
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| 024 | 7 | |a 10.3390/ijms26010390 |2 doi | |
| 024 | 7 | |a 35667146 |2 mtmt | |
| 040 | |a SZTE Publicatio Repozitórium |b hun | ||
| 041 | |a eng | ||
| 100 | 1 | |a Parvaneh Shahram | |
| 245 | 1 | 0 | |a Chemoresistance in Pancreatic Cancer |h [elektronikus dokumentum] : |b The Role of Adipose-Derived Mesenchymal Stem Cells and Key Resistance Genes / |c Parvaneh Shahram |
| 260 | |c 2025 | ||
| 300 | |a 28 | ||
| 490 | 0 | |a INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES |v 26 No. 1 | |
| 520 | 3 | |a Drug resistance is a significant challenge in pancreatic ductal adenocarcinoma (PDAC), where stromal elements such as adipose-derived mesenchymal stem cells (ASCs) contribute to a chemoresistant tumor microenvironment (TME). This study explored the effects of oxaliplatin (OXP) and 5-fluorouracil (5-FU) on PDAC cells (Capan-1) and ASCs to investigate the mechanisms of chemoresistance. While OXP and 5-FU reduced Capan-1 viability in a dose- and time-dependent manner, ASCs demonstrated high resistance, maintaining > 90% viability even at cytotoxic doses. Transcriptomic analyses revealed OXP-induced transcriptional reprogramming in ASCs, with over 7000 differentially expressed genes, highlighting the pathways related to DNA damage response, cell cycle regulation, and stress-related signaling. In contrast, 5-FU elicited limited transcriptional changes, affecting only 192 genes. Cytokine proteome profiling revealed that OXP-treated ASCs significantly influenced the tumor microenvironment by promoting immune evasion (via IL-4, GM-CSF, IP-10, and GROα) and driving extracellular matrix remodeling (through EMMPRIN and DPPIV). In contrast, 5-FU induced comparatively weaker effects, primarily limited to hypoxia-related pathways. Although OXP reduced angiogenic factors, it paradoxically activated pro-survival pathways, thereby enhancing ASC-mediated tumor support. These findings underscore ASCs as modulators of chemoresistance via secretome alterations and stress adaptation. Therefore, future strategies should prioritize the precise targeting of tumor cells while also focusing on the development of personalized treatments to achieve durable therapeutic responses in PDAC. | |
| 650 | 4 | |a Biológiai tudományok | |
| 650 | 4 | |a Általános orvostudomány | |
| 700 | 0 | 1 | |a Miklós Vanda |e aut |
| 700 | 0 | 1 | |a Páhi Zoltán Gábor |e aut |
| 700 | 0 | 1 | |a Szűcs Diána |e aut |
| 700 | 0 | 1 | |a Monostori Tamás |e aut |
| 700 | 0 | 1 | |a Póliska Szilárd |e aut |
| 700 | 0 | 1 | |a Venglovecz Viktória |e aut |
| 700 | 0 | 1 | |a Pankotai Tibor |e aut |
| 700 | 0 | 1 | |a Kemény Lajos |e aut |
| 700 | 0 | 1 | |a Veréb Zoltán |e aut |
| 856 | 4 | 0 | |u http://publicatio.bibl.u-szeged.hu/35509/1/Parvaneh.pdf |z Dokumentum-elérés |