Exploration of Patient-Derived Pancreatic Ductal Adenocarcinoma Ex Vivo Tissue for Treatment Response
Patient-derived tissue culture models are valuable tools to investigate drug effects and targeted treatment approaches. Resected tumor slices cultured ex vivo have recently gained interest in precision medicine, since they reflect the complex microenvironment of cancer tissue. In this study, we exam...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-01-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/12/1/167 |
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| author | Tímea Szekerczés Arun Kumar Selvam Carlos Fernández Moro Soledad Pouso Elduayen Joakim Dillner Mikael Björnstedt Mehran Ghaderi |
| author_facet | Tímea Szekerczés Arun Kumar Selvam Carlos Fernández Moro Soledad Pouso Elduayen Joakim Dillner Mikael Björnstedt Mehran Ghaderi |
| author_sort | Tímea Szekerczés |
| collection | DOAJ |
| description | Patient-derived tissue culture models are valuable tools to investigate drug effects and targeted treatment approaches. Resected tumor slices cultured ex vivo have recently gained interest in precision medicine, since they reflect the complex microenvironment of cancer tissue. In this study, we examined the treatment response to an internally developed ex vivo tissue culture model from pancreatic ductal adenocarcinoma (PDAC) and in vitro analysis. Seven PDAC tissues were cultured and subsequently treated with indole-3-pyruvic acid (IPA). IPA, which is known as an agonist of the aryl hydrocarbon receptor (AHR) pathway, has antioxidant properties. Genome-wide transcriptome sequencing analysis revealed activation of AHR pathway genes (CYP1A1 and CYP1B1, <i>p</i> ≤ 0.05). Additionally, significant upregulation of AHR repressor genes AHRR and TiPARP was also observed (<i>p</i> ≤ 0.05), which is indicative of the negative feedback loop activation of AHR pathway signaling. The overall transcriptomic response to IPA indicated that the tissues are biologically active and respond accordingly to exogenous treatment. Cell culture analysis confirmed the significant induction of selected AHR genes by IPA. A morphological examination of the paraffin-embedded formalin-fixed tissue did not show obvious signs of IPA treatment related to tumor cell damage. This study is a proof of concept that ex vivo patient-derived tissue models offer a valuable tool in precision medicine to monitor the effect of personalized treatments. |
| first_indexed | 2024-03-09T13:46:33Z |
| format | Article |
| id | doaj.art-c7ee6b00f8b6433d815adca6369bc29f |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-09T13:46:33Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-c7ee6b00f8b6433d815adca6369bc29f2023-11-30T20:59:17ZengMDPI AGAntioxidants2076-39212023-01-0112116710.3390/antiox12010167Exploration of Patient-Derived Pancreatic Ductal Adenocarcinoma Ex Vivo Tissue for Treatment ResponseTímea Szekerczés0Arun Kumar Selvam1Carlos Fernández Moro2Soledad Pouso Elduayen3Joakim Dillner4Mikael Björnstedt5Mehran Ghaderi6Division of Pathology, Department of Laboratory Medicine, Karolinska Institutet, 141 52 Huddinge, SwedenDivision of Pathology, Department of Laboratory Medicine, Karolinska Institutet, 141 52 Huddinge, SwedenDivision of Pathology, Department of Laboratory Medicine, Karolinska Institutet, 141 52 Huddinge, SwedenDepartment of Clinical Pathology and Cancer Diagnostics, Karolinska University Hospital, 141 86 Stockholm, SwedenDivision of Pathology, Department of Laboratory Medicine, Karolinska Institutet, 141 52 Huddinge, SwedenDivision of Pathology, Department of Laboratory Medicine, Karolinska Institutet, 141 52 Huddinge, SwedenDivision of Pathology, Department of Laboratory Medicine, Karolinska Institutet, 141 52 Huddinge, SwedenPatient-derived tissue culture models are valuable tools to investigate drug effects and targeted treatment approaches. Resected tumor slices cultured ex vivo have recently gained interest in precision medicine, since they reflect the complex microenvironment of cancer tissue. In this study, we examined the treatment response to an internally developed ex vivo tissue culture model from pancreatic ductal adenocarcinoma (PDAC) and in vitro analysis. Seven PDAC tissues were cultured and subsequently treated with indole-3-pyruvic acid (IPA). IPA, which is known as an agonist of the aryl hydrocarbon receptor (AHR) pathway, has antioxidant properties. Genome-wide transcriptome sequencing analysis revealed activation of AHR pathway genes (CYP1A1 and CYP1B1, <i>p</i> ≤ 0.05). Additionally, significant upregulation of AHR repressor genes AHRR and TiPARP was also observed (<i>p</i> ≤ 0.05), which is indicative of the negative feedback loop activation of AHR pathway signaling. The overall transcriptomic response to IPA indicated that the tissues are biologically active and respond accordingly to exogenous treatment. Cell culture analysis confirmed the significant induction of selected AHR genes by IPA. A morphological examination of the paraffin-embedded formalin-fixed tissue did not show obvious signs of IPA treatment related to tumor cell damage. This study is a proof of concept that ex vivo patient-derived tissue models offer a valuable tool in precision medicine to monitor the effect of personalized treatments.https://www.mdpi.com/2076-3921/12/1/167patient-derived PDAC explantsAHR pathwayindole-3-pyruvic acid |
| spellingShingle | Tímea Szekerczés Arun Kumar Selvam Carlos Fernández Moro Soledad Pouso Elduayen Joakim Dillner Mikael Björnstedt Mehran Ghaderi Exploration of Patient-Derived Pancreatic Ductal Adenocarcinoma Ex Vivo Tissue for Treatment Response Antioxidants patient-derived PDAC explants AHR pathway indole-3-pyruvic acid |
| title | Exploration of Patient-Derived Pancreatic Ductal Adenocarcinoma Ex Vivo Tissue for Treatment Response |
| title_full | Exploration of Patient-Derived Pancreatic Ductal Adenocarcinoma Ex Vivo Tissue for Treatment Response |
| title_fullStr | Exploration of Patient-Derived Pancreatic Ductal Adenocarcinoma Ex Vivo Tissue for Treatment Response |
| title_full_unstemmed | Exploration of Patient-Derived Pancreatic Ductal Adenocarcinoma Ex Vivo Tissue for Treatment Response |
| title_short | Exploration of Patient-Derived Pancreatic Ductal Adenocarcinoma Ex Vivo Tissue for Treatment Response |
| title_sort | exploration of patient derived pancreatic ductal adenocarcinoma ex vivo tissue for treatment response |
| topic | patient-derived PDAC explants AHR pathway indole-3-pyruvic acid |
| url | https://www.mdpi.com/2076-3921/12/1/167 |
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