Academic Journal
Validation of hyperthermia as an enhancer of chemotherapeutic efficacy: insights from a bladder cancer organoid model
Title: | Validation of hyperthermia as an enhancer of chemotherapeutic efficacy: insights from a bladder cancer organoid model |
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Authors: | Ying Xu, Guoliang Sun, Tiantian Yang, Huaibiao Li, Poyi Hu, Wanru Luo, Tingke Zhang, Haoran Liu, Guoyi Chen, Zhangqun Ye, Yuqing Wu, Jie Yu, Wanyi Chen, Kai Zhao, Chunyan Liu, Huiping Zhang |
Source: | International Journal of Hyperthermia, Vol 41, Iss 1 (2024) |
Publisher Information: | Taylor & Francis Group, 2024. |
Publication Year: | 2024 |
Collection: | LCC:Medical technology |
Subject Terms: | Hyperthermia chemotherapy, NMIBC, RT4, organoids, bladder cancer, Medical technology, R855-855.5 |
More Details: | Objective This study aimed to evaluate the combined efficacy of hyperthermia and chemotherapy using a bladder cancer organoid model and to explore hyperthermia-related molecular pathways.Method Tumor organoids were generated by embedding RT4 bladder cancer cells into Matrigel. The resulting organoids were treated with pirarubicin or gemcitabine at 37 °C or 42 °C. Proliferation was determined by Ki67 immunofluorescence staining, and apoptosis was assessed using a TdT-mediated dUTP nick end labeling (TUNEL) assay. RNA sequencing was used to identify the differentially expressed genes.Results Bladder cancer organoids were successfully established and exhibited robust proliferative abilities. Treatment with gemcitabine or pirarubicin under hyperthermic conditions caused pronounced structural damage to the organoids and increased cell death compared to that in the normothermically treated group. Furthermore, Ki67 labeling and TUNEL assays showed that the hyperthermia chemotherapy group showed a significantly reduced proliferation rate and high level of apoptosis. Finally, RNA sequencing revealed the IFN-γ signaling pathway to be associated with hyperthermia.Conclusion Overall, hyperthermia combined with chemotherapy exerted better therapeutic effects than those of normothermic chemotherapy in grade 1-2 non-muscle-invasive bladder cancer, potentially through activation of the IFN-γ-JAK-STAT pathway. |
Document Type: | article |
File Description: | electronic resource |
Language: | English |
ISSN: | 02656736 1464-5157 0265-6736 |
Relation: | https://doaj.org/toc/0265-6736; https://doaj.org/toc/1464-5157 |
DOI: | 10.1080/02656736.2024.2316085 |
Access URL: | https://doaj.org/article/a36dc95a13424b298f2c509856c1a223 |
Accession Number: | edsdoj.36dc95a13424b298f2c509856c1a223 |
Database: | Directory of Open Access Journals |
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ISSN: | 02656736 14645157 |
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DOI: | 10.1080/02656736.2024.2316085 |
Published in: | International Journal of Hyperthermia |
Language: | English |