Validation of hyperthermia as an enhancer of chemotherapeutic efficacy: insights from a bladder cancer organoid model

Bibliographic Details
Title: Validation of hyperthermia as an enhancer of chemotherapeutic efficacy: insights from a bladder cancer organoid model
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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More Details
ISSN:02656736
14645157
DOI:10.1080/02656736.2024.2316085
Published in:International Journal of Hyperthermia
Language:English